Skip to main content
Erschienen in: Cancer and Metastasis Reviews 4/2019

06.12.2019

Immunotherapy in pediatric acute lymphoblastic leukemia

verfasst von: Hiroto Inaba, Ching-Hon Pui

Erschienen in: Cancer and Metastasis Reviews | Ausgabe 4/2019

Einloggen, um Zugang zu erhalten

Abstract

The 5-year survival rate for children and adolescents with acute lymphoblastic leukemia (ALL) has improved to more than 90% in high-income countries. However, further increases in the intensity of conventional chemotherapy would be associated with significant adverse effects; therefore, novel approaches are necessary. The last decade has seen significant advances in targeted therapy with immunotherapy and molecular therapeutics, as well as advances in risk stratification for therapy based on somatic and germline genetic analysis and monitoring of minimal residual disease. For immunotherapy, the approval of antibody-based therapy (with blinatumomab in 2014 and inotuzumab ozogamicin in 2017) and T cell–based therapy (with tisagenlecleucel in 2017) by the US Food and Drug Administration has significantly improved the response rate and outcomes in patients with relapsed/refractory B-ALL. These strategies have also been tested in the frontline setting, and immunotherapy against a new ALL-associated antigen has been developed. Incorporating effective immunotherapy into ALL therapy would enable the intensity of conventional chemotherapy to be decreased and thereby reduce associated toxicity, leading to further improvement in survival and quality of life for patients with ALL.
Literatur
1.
Zurück zum Zitat Pui, C. H., Nichols, K. E., & Yang, J. J. (2019). Somatic and germline genomics in paediatric acute lymphoblastic leukaemia. Nature Reviews Clinical Oncology, 16(4), 227–240.PubMed Pui, C. H., Nichols, K. E., & Yang, J. J. (2019). Somatic and germline genomics in paediatric acute lymphoblastic leukaemia. Nature Reviews Clinical Oncology, 16(4), 227–240.PubMed
2.
Zurück zum Zitat Pui, C. H., Yang, J. J., Hunger, S. P., Pieters, R., Schrappe, M., Biondi, A., Vora, A., Baruchel, A., Silverman, L. B., Schmiegelow, K., Escherich, G., Horibe, K., Benoit, Y. C., Izraeli, S., Yeoh, A. E., Liang, D. C., Downing, J. R., Evans, W. E., Relling, M. V., & Mullighan, C. G. (2015). Childhood acute lymphoblastic leukemia: progress through collaboration. Journal of Clinical Oncology, 33(27), 2938–2948.PubMedPubMedCentral Pui, C. H., Yang, J. J., Hunger, S. P., Pieters, R., Schrappe, M., Biondi, A., Vora, A., Baruchel, A., Silverman, L. B., Schmiegelow, K., Escherich, G., Horibe, K., Benoit, Y. C., Izraeli, S., Yeoh, A. E., Liang, D. C., Downing, J. R., Evans, W. E., Relling, M. V., & Mullighan, C. G. (2015). Childhood acute lymphoblastic leukemia: progress through collaboration. Journal of Clinical Oncology, 33(27), 2938–2948.PubMedPubMedCentral
4.
Zurück zum Zitat Pui, C. H., Campana, D., Pei, D., Bowman, W. P., Sandlund, J. T., Kaste, S. C., et al. (2009). Treating childhood acute lymphoblastic leukemia without cranial irradiation. New England Journal of Medicine, 360(26), 2730–2741. Pui, C. H., Campana, D., Pei, D., Bowman, W. P., Sandlund, J. T., Kaste, S. C., et al. (2009). Treating childhood acute lymphoblastic leukemia without cranial irradiation. New England Journal of Medicine, 360(26), 2730–2741.
5.
Zurück zum Zitat Teachey, D. T., & Pui, C. H. (2019). Comparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia. The Lancet Oncology, 20(3), e142–e154.PubMed Teachey, D. T., & Pui, C. H. (2019). Comparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia. The Lancet Oncology, 20(3), e142–e154.PubMed
6.
Zurück zum Zitat Löffler, A., Kufer, P., Lutterbüse, R., Zettle, F., Daniel, P. T., Schwenkenbecher, J. M., et al. (2000). A recombinant bispecific single-chain antibody, CD19 x CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes. Blood, 95(96), 2098–2103.PubMed Löffler, A., Kufer, P., Lutterbüse, R., Zettle, F., Daniel, P. T., Schwenkenbecher, J. M., et al. (2000). A recombinant bispecific single-chain antibody, CD19 x CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes. Blood, 95(96), 2098–2103.PubMed
7.
Zurück zum Zitat Bargou, R., Leo, E., Zugmaier, G., Klinger, M., Goebeler, M., Knop, S., Noppeney, R., Viardot, A., Hess, G., Schuler, M., Einsele, H., Brandl, C., Wolf, A., Kirchinger, P., Klappers, P., Schmidt, M., Riethmüller, G., Reinhardt, C., Baeuerle, P. A., & Kufer, P. (2008). Tumor regression in cancer patients by very low doses of a T cell–engaging antibody. Science, 321(5891), 974–977.PubMed Bargou, R., Leo, E., Zugmaier, G., Klinger, M., Goebeler, M., Knop, S., Noppeney, R., Viardot, A., Hess, G., Schuler, M., Einsele, H., Brandl, C., Wolf, A., Kirchinger, P., Klappers, P., Schmidt, M., Riethmüller, G., Reinhardt, C., Baeuerle, P. A., & Kufer, P. (2008). Tumor regression in cancer patients by very low doses of a T cell–engaging antibody. Science, 321(5891), 974–977.PubMed
8.
Zurück zum Zitat Topp, M. S., Kufer, P., Gökbuget, N., Goebeler, M., Klinger, M., Neumann, S., et al. (2011). Targeted therapy with the T-cell–engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. Journal of Clinical Oncology, 29(18), 2493–2498.PubMed Topp, M. S., Kufer, P., Gökbuget, N., Goebeler, M., Klinger, M., Neumann, S., et al. (2011). Targeted therapy with the T-cell–engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. Journal of Clinical Oncology, 29(18), 2493–2498.PubMed
9.
Zurück zum Zitat Topp, M. S., Gökbuget, N., Zugmaier, G., Degenhard, E., Goebeler, M. E., Klinger, M., Neumann, S. A., Horst, H. A., Raff, T., Viardot, A., Stelljes, M., Schaich, M., Köhne-Volland, R., Brüggemann, M., Ottmann, O. G., Burmeister, T., Baeuerle, P. A., Nagorsen, D., Schmidt, M., Einsele, H., Riethmüller, G., Kneba, M., Hoelzer, D., Kufer, P., & Bargou, R. C. (2012). Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood, 120(26), 5185–5187.PubMed Topp, M. S., Gökbuget, N., Zugmaier, G., Degenhard, E., Goebeler, M. E., Klinger, M., Neumann, S. A., Horst, H. A., Raff, T., Viardot, A., Stelljes, M., Schaich, M., Köhne-Volland, R., Brüggemann, M., Ottmann, O. G., Burmeister, T., Baeuerle, P. A., Nagorsen, D., Schmidt, M., Einsele, H., Riethmüller, G., Kneba, M., Hoelzer, D., Kufer, P., & Bargou, R. C. (2012). Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood, 120(26), 5185–5187.PubMed
10.
Zurück zum Zitat Topp, M. S., Gökbuget, N., Stein, A. S., Zugmaier, G., O’Brien, S., Bargou, R. C., et al. (2015). Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. The Lancet Oncology, 16(1), 57–66.PubMed Topp, M. S., Gökbuget, N., Stein, A. S., Zugmaier, G., O’Brien, S., Bargou, R. C., et al. (2015). Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. The Lancet Oncology, 16(1), 57–66.PubMed
11.
Zurück zum Zitat Kantarjian, H. M., Stein, A. S., Bargou, R. C., Grande Garcia, C., Larson, R. A., Stelljes, M., Gökbuget, N., Zugmaier, G., Benjamin, J. E., Zhang, A., Jia, C., & Topp, M. S. (2016). Blinatumomab treatment of older adults with relapsed/refractory B-precursor acute lymphoblastic leukemia: results from 2 phase 2 studies. Cancer, 122(14), 2178–2185.PubMed Kantarjian, H. M., Stein, A. S., Bargou, R. C., Grande Garcia, C., Larson, R. A., Stelljes, M., Gökbuget, N., Zugmaier, G., Benjamin, J. E., Zhang, A., Jia, C., & Topp, M. S. (2016). Blinatumomab treatment of older adults with relapsed/refractory B-precursor acute lymphoblastic leukemia: results from 2 phase 2 studies. Cancer, 122(14), 2178–2185.PubMed
12.
Zurück zum Zitat Stein, A. S., Kantarjian, H., Gökbuget, N., Bargou, R., Litzow, M. R., Rambaldi, A., Ribera, J. M., Zhang, A., Zimmerman, Z., Zugmaier, G., & Topp, M. S. (2019). Blinatumomab for acute lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation. Biology of Blood and Marrow Transplantation, 25(8), 1498–1504.PubMed Stein, A. S., Kantarjian, H., Gökbuget, N., Bargou, R., Litzow, M. R., Rambaldi, A., Ribera, J. M., Zhang, A., Zimmerman, Z., Zugmaier, G., & Topp, M. S. (2019). Blinatumomab for acute lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation. Biology of Blood and Marrow Transplantation, 25(8), 1498–1504.PubMed
13.
Zurück zum Zitat Przepiorka, D., Ko, C. W., Deisseroth, A., Yancey, C. L., Candau-Chacon, R., Chiu, H. J., Gehrke, B. J., Gomez-Broughton, C., Kane, R. C., Kirshner, S., Mehrotra, N., Ricks, T. K., Schmiel, D., Song, P., Zhao, P., Zhou, Q., Farrell, A. T., & Pazdur, R. (2015). FDA approval: blinatumomab. Clinical Cancer Research, 21(18), 4035–4039.PubMed Przepiorka, D., Ko, C. W., Deisseroth, A., Yancey, C. L., Candau-Chacon, R., Chiu, H. J., Gehrke, B. J., Gomez-Broughton, C., Kane, R. C., Kirshner, S., Mehrotra, N., Ricks, T. K., Schmiel, D., Song, P., Zhao, P., Zhou, Q., Farrell, A. T., & Pazdur, R. (2015). FDA approval: blinatumomab. Clinical Cancer Research, 21(18), 4035–4039.PubMed
14.
Zurück zum Zitat Kantarjian, H., Stein, A., Gökbuget, N., Fielding, A. K., Schuh, A. C., Ribera, J. M., et al. (2017). Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. New England Journal of Medicine, 376(9), 836–847. Kantarjian, H., Stein, A., Gökbuget, N., Fielding, A. K., Schuh, A. C., Ribera, J. M., et al. (2017). Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. New England Journal of Medicine, 376(9), 836–847.
15.
Zurück zum Zitat Gökbuget, N., Dombret, H., Bonifacio, M., Reichle, A., Graux, C., Faul, C., et al. (2018). Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood, 131(14), 1522–1531.PubMedPubMedCentral Gökbuget, N., Dombret, H., Bonifacio, M., Reichle, A., Graux, C., Faul, C., et al. (2018). Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood, 131(14), 1522–1531.PubMedPubMedCentral
16.
Zurück zum Zitat Brown, P. (2018). Blinatumomab for MRD+ B-ALL: The evidence strengthens. Blood, 131(14), 1497–1498.PubMed Brown, P. (2018). Blinatumomab for MRD+ B-ALL: The evidence strengthens. Blood, 131(14), 1497–1498.PubMed
17.
Zurück zum Zitat Jen, E. Y., Xu, Q., Schetter, A., Przepiorka, D., Shen, Y. L., Roscoe, D., et al. (2019). FDA approval: blinatumomab for patients with B-cell precursor acute lymphoblastic leukemia in morphologic remission with minimal residual disease. Clinical Cancer Research, 25(2), 473–477.PubMed Jen, E. Y., Xu, Q., Schetter, A., Przepiorka, D., Shen, Y. L., Roscoe, D., et al. (2019). FDA approval: blinatumomab for patients with B-cell precursor acute lymphoblastic leukemia in morphologic remission with minimal residual disease. Clinical Cancer Research, 25(2), 473–477.PubMed
18.
Zurück zum Zitat Martinelli, G., Boissel, N., Chevallier, P., Ottmann, O., Gökbuget, N., Topp, M. S., Fielding, A. K., Rambaldi, A., Ritchie, E. K., Papayannidis, C., Sterling, L. R., Benjamin, J., & Stein, A. (2017). Complete hematologic and molecular response in adult patients with relapsed/refractory Philadelphia chromosome–positive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab: results from a phase II, single-arm, multicenter study. Journal of Clinical Oncology, 35(16), 1795–1802.PubMed Martinelli, G., Boissel, N., Chevallier, P., Ottmann, O., Gökbuget, N., Topp, M. S., Fielding, A. K., Rambaldi, A., Ritchie, E. K., Papayannidis, C., Sterling, L. R., Benjamin, J., & Stein, A. (2017). Complete hematologic and molecular response in adult patients with relapsed/refractory Philadelphia chromosome–positive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab: results from a phase II, single-arm, multicenter study. Journal of Clinical Oncology, 35(16), 1795–1802.PubMed
19.
Zurück zum Zitat Assi, R., Kantarjian, H., Short, N. J., Daver, N., Takahashi, K., Garcia-Manero, G., et al. (2017). Safety and efficacy of blinatumomab in combination with a tyrosine kinase inhibitor for the treatment of relapsed Philadelphia chromosome–positive leukemia. Clinical Lymphoma, Myeloma, and Leukemia, 17(12), 897–901. Assi, R., Kantarjian, H., Short, N. J., Daver, N., Takahashi, K., Garcia-Manero, G., et al. (2017). Safety and efficacy of blinatumomab in combination with a tyrosine kinase inhibitor for the treatment of relapsed Philadelphia chromosome–positive leukemia. Clinical Lymphoma, Myeloma, and Leukemia, 17(12), 897–901.
20.
Zurück zum Zitat Klinger, M., Brandl, C., Zugmaier, G., Hijazi, Y., Bargou, R. C., Topp, M. S., Gökbuget, N., Neumann, S., Goebeler, M., Viardot, A., Stelljes, M., Brüggemann, M., Hoelzer, D., Degenhard, E., Nagorsen, D., Baeuerle, P. A., Wolf, A., & Kufer, P. (2012). Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell–engaging CD19/CD3-bispecific BiTE antibody blinatumomab. Blood, 119(26), 6226–6233.PubMed Klinger, M., Brandl, C., Zugmaier, G., Hijazi, Y., Bargou, R. C., Topp, M. S., Gökbuget, N., Neumann, S., Goebeler, M., Viardot, A., Stelljes, M., Brüggemann, M., Hoelzer, D., Degenhard, E., Nagorsen, D., Baeuerle, P. A., Wolf, A., & Kufer, P. (2012). Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell–engaging CD19/CD3-bispecific BiTE antibody blinatumomab. Blood, 119(26), 6226–6233.PubMed
21.
Zurück zum Zitat Zugmaier, G., Gökbuget, N., Klinger, M., Viardot, A., Stelljes, M., Neumann, S., Horst, H. A., Marks, R., Faul, C., Diedrich, H., Reichle, A., Brüggemann, M., Holland, C., Schmidt, M., Einsele, H., Bargou, R. C., & Topp, M. S. (2015). Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment. Blood, 126(24), 2578–2584.PubMedPubMedCentral Zugmaier, G., Gökbuget, N., Klinger, M., Viardot, A., Stelljes, M., Neumann, S., Horst, H. A., Marks, R., Faul, C., Diedrich, H., Reichle, A., Brüggemann, M., Holland, C., Schmidt, M., Einsele, H., Bargou, R. C., & Topp, M. S. (2015). Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment. Blood, 126(24), 2578–2584.PubMedPubMedCentral
22.
Zurück zum Zitat von Stackelberg, A., Locatelli, F., Zugmaier, G., Handgretinger, R., Tripplett, T. M., Rizzari, C., et al. (2016). Phase I/phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. Journal of Clinical Oncology, 34(36), 4381–4389. von Stackelberg, A., Locatelli, F., Zugmaier, G., Handgretinger, R., Tripplett, T. M., Rizzari, C., et al. (2016). Phase I/phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. Journal of Clinical Oncology, 34(36), 4381–4389.
24.
Zurück zum Zitat Elitzur, S., Arad-Cohen, N., Barzilai-Birenboim, S., Ben-Harush, M., Bielorai, B., Elhasid, R., Feuerstein, T., Gilad, G., Gural, A., Kharit, M., Litichever, N., Nirel, R., Weinreb, S., Wolach, O., Toren, A., Izraeli, S., & Jacoby, E. (2019). Blinatumomab as a bridge to further therapy in cases of overwhelming toxicity in pediatric B-cell precursor acute lymphoblastic leukemia: report from the Israeli Study Group of Childhood Leukemia. Pediatric Blood & Cancer, 66(10), e27898. Elitzur, S., Arad-Cohen, N., Barzilai-Birenboim, S., Ben-Harush, M., Bielorai, B., Elhasid, R., Feuerstein, T., Gilad, G., Gural, A., Kharit, M., Litichever, N., Nirel, R., Weinreb, S., Wolach, O., Toren, A., Izraeli, S., & Jacoby, E. (2019). Blinatumomab as a bridge to further therapy in cases of overwhelming toxicity in pediatric B-cell precursor acute lymphoblastic leukemia: report from the Israeli Study Group of Childhood Leukemia. Pediatric Blood & Cancer, 66(10), e27898.
25.
Zurück zum Zitat Keating, A. K., Gossai, N., Phillips, C. L., Maloney, K., Campbell, K., Doan, A., Bhojwani, D., Burke, M. J., & Verneris, M. R. (2019). Reducing minimal residual disease with blinatumomab prior to HCT for pediatric patients with acute lymphoblastic leukemia. Blood Advances, 3(13), 1926–1929.PubMedPubMedCentral Keating, A. K., Gossai, N., Phillips, C. L., Maloney, K., Campbell, K., Doan, A., Bhojwani, D., Burke, M. J., & Verneris, M. R. (2019). Reducing minimal residual disease with blinatumomab prior to HCT for pediatric patients with acute lymphoblastic leukemia. Blood Advances, 3(13), 1926–1929.PubMedPubMedCentral
26.
Zurück zum Zitat Topp, M. S., Zimmerman, Z., Cannell, P., Dombret, H., Maertens, J., Stein, A., Franklin, J., Tran, Q., Cong, Z., & Schuh, A. C. (2018). Health-related quality of life in adults with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab. Blood, 131(26), 2906–2914.PubMedPubMedCentral Topp, M. S., Zimmerman, Z., Cannell, P., Dombret, H., Maertens, J., Stein, A., Franklin, J., Tran, Q., Cong, Z., & Schuh, A. C. (2018). Health-related quality of life in adults with relapsed/refractory acute lymphoblastic leukemia treated with blinatumomab. Blood, 131(26), 2906–2914.PubMedPubMedCentral
27.
Zurück zum Zitat Prescribing information. Blincyto® (blinatumomab) injection. Prescribing information. Blincyto® (blinatumomab) injection.
28.
Zurück zum Zitat Jain, T., & Litzow, M. R. (2018). No free rides: management of toxicities of novel immunotherapies in ALL, including financial. Hematology, American Society of Hematology Education Program, 2018(1), 25–34. Jain, T., & Litzow, M. R. (2018). No free rides: management of toxicities of novel immunotherapies in ALL, including financial. Hematology, American Society of Hematology Education Program, 2018(1), 25–34.
29.
Zurück zum Zitat Teachey, D. T., Rheingold, S. R., Maude, S. L., Zugmaier, G., Barrett, D. M., Seif, A. E., Nichols, K. E., Suppa, E. K., Kalos, M., Berg, R. A., Fitzgerald, J. C., Aplenc, R., Gore, L., & Grupp, S. A. (2013). Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood, 121(26), 5154–5157.PubMedPubMedCentral Teachey, D. T., Rheingold, S. R., Maude, S. L., Zugmaier, G., Barrett, D. M., Seif, A. E., Nichols, K. E., Suppa, E. K., Kalos, M., Berg, R. A., Fitzgerald, J. C., Aplenc, R., Gore, L., & Grupp, S. A. (2013). Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood, 121(26), 5154–5157.PubMedPubMedCentral
30.
Zurück zum Zitat Maschmeyer, G., De Greef, J., Mellinghoff, S. C., Nosari, A., Thiebaut-Bertrand, A., Bergeron, A., et al. (2019). Infections associated with immunotherapeutic and molecular targeted agents in hematology and oncology. A position paper by the European Conference on Infections In Leukemia (ECIL). Leukemia, 33(4), 844–862.PubMedPubMedCentral Maschmeyer, G., De Greef, J., Mellinghoff, S. C., Nosari, A., Thiebaut-Bertrand, A., Bergeron, A., et al. (2019). Infections associated with immunotherapeutic and molecular targeted agents in hematology and oncology. A position paper by the European Conference on Infections In Leukemia (ECIL). Leukemia, 33(4), 844–862.PubMedPubMedCentral
31.
Zurück zum Zitat Duell, J., Dittrich, M., Bedke, T., Mueller, T., Eisele, F., Rosenwald, A., et al. (2017). Frequency of regulatory T cells determines the outcome of the T-cell-engaging antibody blinatumomab in patients with B-precursor ALL. Leukemia, 31(10), 2181–2190.PubMedPubMedCentral Duell, J., Dittrich, M., Bedke, T., Mueller, T., Eisele, F., Rosenwald, A., et al. (2017). Frequency of regulatory T cells determines the outcome of the T-cell-engaging antibody blinatumomab in patients with B-precursor ALL. Leukemia, 31(10), 2181–2190.PubMedPubMedCentral
32.
Zurück zum Zitat Ghiringhelli, F., Menard, C., Puig, P. E., Ladoire, S., Roux, S., Martin, F., Solary, E., le Cesne, A., Zitvogel, L., & Chauffert, B. (2007). Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunology, Immunotherapy, 56(5), 641–648.PubMed Ghiringhelli, F., Menard, C., Puig, P. E., Ladoire, S., Roux, S., Martin, F., Solary, E., le Cesne, A., Zitvogel, L., & Chauffert, B. (2007). Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunology, Immunotherapy, 56(5), 641–648.PubMed
33.
Zurück zum Zitat Beyer, M., Kochanek, M., Darabi, K., Popov, A., Jensen, M., Endl, E., Knolle, P. A., Thomas, R. K., von Bergwelt-Baildon, M., Debey, S., Hallek, M., & Schultze, J. L. (2005). Reduced frequencies and suppressive function of CD4+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine. Blood, 106(6), 2018–2025.PubMed Beyer, M., Kochanek, M., Darabi, K., Popov, A., Jensen, M., Endl, E., Knolle, P. A., Thomas, R. K., von Bergwelt-Baildon, M., Debey, S., Hallek, M., & Schultze, J. L. (2005). Reduced frequencies and suppressive function of CD4+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine. Blood, 106(6), 2018–2025.PubMed
34.
Zurück zum Zitat Piccaluga, P. P., Arpinati, M., Candoni, A., Laterza, C., Paolini, S., Gazzola, A., Sabattini, E., Visani, G., & Pileri, S. A. (2011). Surface antigens analysis reveals significant expression of candidate targets for immunotherapy in adult acute lymphoid leukemia. Leukemia & Lymphoma, 52(2), 325–327. Piccaluga, P. P., Arpinati, M., Candoni, A., Laterza, C., Paolini, S., Gazzola, A., Sabattini, E., Visani, G., & Pileri, S. A. (2011). Surface antigens analysis reveals significant expression of candidate targets for immunotherapy in adult acute lymphoid leukemia. Leukemia & Lymphoma, 52(2), 325–327.
35.
Zurück zum Zitat Tedder, T. F., Tuscano, J., Sato, S., & Kehrl, J. H. (1997). CD22, a B lymphocyte–specific adhesion molecule that regulates antigen receptor signaling. Annual Review of Immunology, 15, 481–504.PubMed Tedder, T. F., Tuscano, J., Sato, S., & Kehrl, J. H. (1997). CD22, a B lymphocyte–specific adhesion molecule that regulates antigen receptor signaling. Annual Review of Immunology, 15, 481–504.PubMed
36.
Zurück zum Zitat DiJoseph, J. F., Armellino, D. C., Boghaert, E. R., Khandke, K., Dougher, M. M., Sridharan, L., et al. (2004). Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies. Blood, 103(5), 1807–1814.PubMed DiJoseph, J. F., Armellino, D. C., Boghaert, E. R., Khandke, K., Dougher, M. M., Sridharan, L., et al. (2004). Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies. Blood, 103(5), 1807–1814.PubMed
37.
Zurück zum Zitat Sievers, E. L., Larson, R. A., Stadtmauer, E. A., Estely, E., Löwenberg, B., Dombret, H., et al. (2001). Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. Journal of Clinical Oncology, 19(13), 3244–3254.PubMed Sievers, E. L., Larson, R. A., Stadtmauer, E. A., Estely, E., Löwenberg, B., Dombret, H., et al. (2001). Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. Journal of Clinical Oncology, 19(13), 3244–3254.PubMed
38.
Zurück zum Zitat Zein, N., Sinha, A. M., McGahren, W. J., & Ellestad, G. A. (1988). Calicheamicin gamma 1I: an antitumor antibiotic that cleaves double-stranded DNA site specifically. Science, 240(4856), 1198–1201.PubMed Zein, N., Sinha, A. M., McGahren, W. J., & Ellestad, G. A. (1988). Calicheamicin gamma 1I: an antitumor antibiotic that cleaves double-stranded DNA site specifically. Science, 240(4856), 1198–1201.PubMed
39.
Zurück zum Zitat Kantarjian, H., Thomas, D., Jorgensen, J., Jabbour, E., Kebriaei, P., Rytting, M., et al. (2012). Inotuzumab ozogamicin, an anti-CD22–calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. The Lancet Oncology, 13(4), 403–411.PubMed Kantarjian, H., Thomas, D., Jorgensen, J., Jabbour, E., Kebriaei, P., Rytting, M., et al. (2012). Inotuzumab ozogamicin, an anti-CD22–calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. The Lancet Oncology, 13(4), 403–411.PubMed
40.
Zurück zum Zitat Kantarjian, H., Thomas, D., Jorgensen, J., Kebriaei, P., Jabbour, E., Rytting, M., York, S., Ravandi, F., Garris, R., Kwari, M., Faderl, S., Cortes, J., Champlin, R., & O’Brien, S. (2013). Results of inotuzumab ozogamicin, a CD22 monoclonal antibody, in refractory and relapsed acute lymphocytic leukemia. Cancer, 119(15), 2728–2736.PubMed Kantarjian, H., Thomas, D., Jorgensen, J., Kebriaei, P., Jabbour, E., Rytting, M., York, S., Ravandi, F., Garris, R., Kwari, M., Faderl, S., Cortes, J., Champlin, R., & O’Brien, S. (2013). Results of inotuzumab ozogamicin, a CD22 monoclonal antibody, in refractory and relapsed acute lymphocytic leukemia. Cancer, 119(15), 2728–2736.PubMed
41.
Zurück zum Zitat DeAngelo, D. J., Stock, W., Stein, A. S., Shustov, A., Liedtke, M., Schiffer, C. A., et al. (2017). Inotuzumab ozogamicin in adults with relapsed or refractory CD22-positive acute lymphoblastic leukemia: a phase 1/2 study. Blood Advances, 1(15), 1167–1180.PubMedPubMedCentral DeAngelo, D. J., Stock, W., Stein, A. S., Shustov, A., Liedtke, M., Schiffer, C. A., et al. (2017). Inotuzumab ozogamicin in adults with relapsed or refractory CD22-positive acute lymphoblastic leukemia: a phase 1/2 study. Blood Advances, 1(15), 1167–1180.PubMedPubMedCentral
42.
Zurück zum Zitat Kantarjian, H. M., DeAngelo, D. J., Stelljes, M., Martinelli, G., Liedtke, M., Stock, W., et al. (2016). Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. New England Journal of Medicine, 375(8), 740–753. Kantarjian, H. M., DeAngelo, D. J., Stelljes, M., Martinelli, G., Liedtke, M., Stock, W., et al. (2016). Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. New England Journal of Medicine, 375(8), 740–753.
43.
Zurück zum Zitat Leslie, M. (2017). ADC approval likely to spur more research. Cancer Discovery, 7(10), 1054–1055. Leslie, M. (2017). ADC approval likely to spur more research. Cancer Discovery, 7(10), 1054–1055.
44.
Zurück zum Zitat Jabbour, E., Ravandi, F., Kebriaei, P., Huang, X., Short, N. J., Thomas, D., Sasaki, K., Rytting, M., Jain, N., Konopleva, M., Garcia-Manero, G., Champlin, R., Marin, D., Kadia, T., Cortes, J., Estrov, Z., Takahashi, K., Patel, Y., Khouri, M. R., Jacob, J., Garris, R., O’Brien, S., & Kantarjian, H. (2018). Salvage chemoimmunotherapy with inotuzumab ozogamicin combined with mini–hyper-CVD for patients with relapsed or refractory Philadelphia chromosome–negative acute lymphoblastic leukemia: a phase 2 clinical trial. JAMA Oncology, 4(2), 230–234.PubMed Jabbour, E., Ravandi, F., Kebriaei, P., Huang, X., Short, N. J., Thomas, D., Sasaki, K., Rytting, M., Jain, N., Konopleva, M., Garcia-Manero, G., Champlin, R., Marin, D., Kadia, T., Cortes, J., Estrov, Z., Takahashi, K., Patel, Y., Khouri, M. R., Jacob, J., Garris, R., O’Brien, S., & Kantarjian, H. (2018). Salvage chemoimmunotherapy with inotuzumab ozogamicin combined with mini–hyper-CVD for patients with relapsed or refractory Philadelphia chromosome–negative acute lymphoblastic leukemia: a phase 2 clinical trial. JAMA Oncology, 4(2), 230–234.PubMed
45.
Zurück zum Zitat Bhojwani, D., Sposto, R., Shah, N. N., Rodriguez, V., Yuan, C., Stetler-Stevenson, M., O’Brien, M. M., McNeer, J., Quereshi, A., Cabannes, A., Schlegel, P., Rossig, C., Dalla-Pozza, L., August, K., Alexander, S., Bourquin, J. P., Zwaan, M., Raetz, E. A., Loh, M. L., & Rheingold, S. R. (2019). Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. Leukemia, 33(4), 884–892.PubMed Bhojwani, D., Sposto, R., Shah, N. N., Rodriguez, V., Yuan, C., Stetler-Stevenson, M., O’Brien, M. M., McNeer, J., Quereshi, A., Cabannes, A., Schlegel, P., Rossig, C., Dalla-Pozza, L., August, K., Alexander, S., Bourquin, J. P., Zwaan, M., Raetz, E. A., Loh, M. L., & Rheingold, S. R. (2019). Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. Leukemia, 33(4), 884–892.PubMed
46.
Zurück zum Zitat Kantarjian, H. M., Su, Y., Jabbour, E. J., Bhattacharyya, H., Yan, E., Cappelleri, J. C., & Marks, D. I. (2018). Patient-reported outcomes from a phase 3 randomized controlled trial of inotuzumab ozogamicin versus standard therapy for relapsed/refractory acute lymphoblastic leukemia. Cancer, 124(10), 2151–2160.PubMed Kantarjian, H. M., Su, Y., Jabbour, E. J., Bhattacharyya, H., Yan, E., Cappelleri, J. C., & Marks, D. I. (2018). Patient-reported outcomes from a phase 3 randomized controlled trial of inotuzumab ozogamicin versus standard therapy for relapsed/refractory acute lymphoblastic leukemia. Cancer, 124(10), 2151–2160.PubMed
47.
Zurück zum Zitat Kantarjian, H. M., DeAngelo, D. J., Advani, A. S., Stelljes, M., Kebriaei, P., Cassday, R. D., et al. (2017). Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study. The Lancet Haematology, 4(8), e387–e398.PubMed Kantarjian, H. M., DeAngelo, D. J., Advani, A. S., Stelljes, M., Kebriaei, P., Cassday, R. D., et al. (2017). Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study. The Lancet Haematology, 4(8), e387–e398.PubMed
48.
Zurück zum Zitat Guffroy, M., Falahatpisheh, H., Biddle, K., Kreeger, J., Obert, L., Walters, K., Goldstein, R., Boucher, G., Coskran, T., Reagan, W., Sullivan, D., Huang, C., Sokolowski, S., Giovanelli, R., Gerber, H. P., Finkelstein, M., & Khan, N. (2017). Liver microvascular injury and thrombocytopenia of antibody–calicheamicin conjugates in cynomolgus monkeys—mechanism and monitoring. Clinical Cancer Research, 23(7), 1760–1770.PubMed Guffroy, M., Falahatpisheh, H., Biddle, K., Kreeger, J., Obert, L., Walters, K., Goldstein, R., Boucher, G., Coskran, T., Reagan, W., Sullivan, D., Huang, C., Sokolowski, S., Giovanelli, R., Gerber, H. P., Finkelstein, M., & Khan, N. (2017). Liver microvascular injury and thrombocytopenia of antibody–calicheamicin conjugates in cynomolgus monkeys—mechanism and monitoring. Clinical Cancer Research, 23(7), 1760–1770.PubMed
49.
Zurück zum Zitat Taksin, A. L., Legrand, O., Raffoux, E., de Revel, T., Thomas, X., Contentin, N., Bouabdallah, R., Pautas, C., Turlure, P., Reman, O., Gardin, C., Varet, B., de Botton, S., Pousset, F., Farhat, H., Chevret, S., Dombret, H., & Castaigne, S. (2007). High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: A prospective study of the alfa group. Leukemia, 21(1), 66–71.PubMed Taksin, A. L., Legrand, O., Raffoux, E., de Revel, T., Thomas, X., Contentin, N., Bouabdallah, R., Pautas, C., Turlure, P., Reman, O., Gardin, C., Varet, B., de Botton, S., Pousset, F., Farhat, H., Chevret, S., Dombret, H., & Castaigne, S. (2007). High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: A prospective study of the alfa group. Leukemia, 21(1), 66–71.PubMed
50.
Zurück zum Zitat Wadleigh, M., Richardson, P. G., Zahrieh, D., Lee, S. J., Cutler, C., Ho, V., Alyea, E. P., Antin, J. H., Stone, R. M., Soiffer, R. J., & DeAngelo, D. (2003). Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation. Blood, 102(5), 1578–8152.PubMed Wadleigh, M., Richardson, P. G., Zahrieh, D., Lee, S. J., Cutler, C., Ho, V., Alyea, E. P., Antin, J. H., Stone, R. M., Soiffer, R. J., & DeAngelo, D. (2003). Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation. Blood, 102(5), 1578–8152.PubMed
51.
Zurück zum Zitat Jabbour, E. J., Sasaki, K., Ravandi, F., Short, N. J., Garcia-Manero, G., Daver, N., Kadia, T., Konopleva, M., Jain, N., Cortes, J., Issa, G. C., Jacob, J., Kwari, M., Thompson, P., Garris, R., Pemmaraju, N., Yilmaz, M., O’Brien, S. M., & Kantarjian, H. M. (2019). Inotuzumab ozogamicin in combination with low-intensity chemotherapy (mini-HCVD) with or without blinatumomab versus standard intensive chemotherapy (HCVAD) as frontline therapy for older patients with Philadelphia chromosome–negative acute lymphoblastic leukemia: a propensity score analysis. Cancer, 125(15), 2579–2586.PubMed Jabbour, E. J., Sasaki, K., Ravandi, F., Short, N. J., Garcia-Manero, G., Daver, N., Kadia, T., Konopleva, M., Jain, N., Cortes, J., Issa, G. C., Jacob, J., Kwari, M., Thompson, P., Garris, R., Pemmaraju, N., Yilmaz, M., O’Brien, S. M., & Kantarjian, H. M. (2019). Inotuzumab ozogamicin in combination with low-intensity chemotherapy (mini-HCVD) with or without blinatumomab versus standard intensive chemotherapy (HCVAD) as frontline therapy for older patients with Philadelphia chromosome–negative acute lymphoblastic leukemia: a propensity score analysis. Cancer, 125(15), 2579–2586.PubMed
52.
Zurück zum Zitat Jabbour, E., Sasaki, K., Ravandi, F., Huang, X., Short, N. J., Khouri, M., Kebriaei, P., Burger, J., Khoury, J., Jorgensen, J., Jain, N., Konopleva, M., Garcia-Manero, G., Kadia, T., Cortes, J., Jacob, J., Montalbano, K., Garris, R., O’Brien, S., & Kantarjian, H. M. (2018). Chemoimmunotherapy with inotuzumab ozogamicin combined with mini-hyper-CVD, with or without blinatumomab, is highly effective in patients with Philadelphia chromosome–negative acute lymphoblastic leukemia in first salvage. Cancer, 124(20), 4044–4055.PubMed Jabbour, E., Sasaki, K., Ravandi, F., Huang, X., Short, N. J., Khouri, M., Kebriaei, P., Burger, J., Khoury, J., Jorgensen, J., Jain, N., Konopleva, M., Garcia-Manero, G., Kadia, T., Cortes, J., Jacob, J., Montalbano, K., Garris, R., O’Brien, S., & Kantarjian, H. M. (2018). Chemoimmunotherapy with inotuzumab ozogamicin combined with mini-hyper-CVD, with or without blinatumomab, is highly effective in patients with Philadelphia chromosome–negative acute lymphoblastic leukemia in first salvage. Cancer, 124(20), 4044–4055.PubMed
53.
Zurück zum Zitat Paul, M. R., Wong, V., Aristizabal, P., & Kuo, D. J. (2019). Treatment of recurrent refractory pediatric pre-B acute lymphoblastic leukemia using inotuzumab ozogamicin monotherapy resulting in CD22 antigen expression loss as a mechanism of therapy resistance. Journal of Pediatric Hematology/Oncology, 41(8), e546–e549.PubMedPubMedCentral Paul, M. R., Wong, V., Aristizabal, P., & Kuo, D. J. (2019). Treatment of recurrent refractory pediatric pre-B acute lymphoblastic leukemia using inotuzumab ozogamicin monotherapy resulting in CD22 antigen expression loss as a mechanism of therapy resistance. Journal of Pediatric Hematology/Oncology, 41(8), e546–e549.PubMedPubMedCentral
54.
Zurück zum Zitat Imai, C., Mihara, K., Andreansky, M., Nicholson, I. C., Pui, C. H., Geiger, T. L., & Campana, D. (2004). Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia. Leukemia, 18(4), 676–684.PubMed Imai, C., Mihara, K., Andreansky, M., Nicholson, I. C., Pui, C. H., Geiger, T. L., & Campana, D. (2004). Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia. Leukemia, 18(4), 676–684.PubMed
55.
Zurück zum Zitat Brentjens, R. J., Santos, E., Nikhamin, Y., Yeh, R., Matsushita, M., La Perle, K., et al. (2007). Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts. Clinical Cancer Research, 13(18 part 1), 5426–5435.PubMed Brentjens, R. J., Santos, E., Nikhamin, Y., Yeh, R., Matsushita, M., La Perle, K., et al. (2007). Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts. Clinical Cancer Research, 13(18 part 1), 5426–5435.PubMed
56.
Zurück zum Zitat Brudno, J. N., Somerville, R. P., Shi, V., Rose, J. J., Halverson, D. C., Fowler, D. H., Gea-Banacloche, J. C., Pavletic, S. Z., Hickstein, D. D., Lu, T. L., Feldman, S. A., Iwamoto, A. T., Kurlander, R., Maric, I., Goy, A., Hansen, B. G., Wilder, J. S., Blacklock-Schuver, B., Hakim, F. T., Rosenberg, S. A., Gress, R. E., & Kochenderfer, J. N. (2016). Allogeneic T cells that express an anti-CD19 chimeric antigen receptor induce remissions of B-cell malignancies that progress after allogeneic hematopoietic stem-cell transplantation without causing graft-versus-host disease. Journal of Clinical Oncology, 34(10), 1112–1121.PubMedPubMedCentral Brudno, J. N., Somerville, R. P., Shi, V., Rose, J. J., Halverson, D. C., Fowler, D. H., Gea-Banacloche, J. C., Pavletic, S. Z., Hickstein, D. D., Lu, T. L., Feldman, S. A., Iwamoto, A. T., Kurlander, R., Maric, I., Goy, A., Hansen, B. G., Wilder, J. S., Blacklock-Schuver, B., Hakim, F. T., Rosenberg, S. A., Gress, R. E., & Kochenderfer, J. N. (2016). Allogeneic T cells that express an anti-CD19 chimeric antigen receptor induce remissions of B-cell malignancies that progress after allogeneic hematopoietic stem-cell transplantation without causing graft-versus-host disease. Journal of Clinical Oncology, 34(10), 1112–1121.PubMedPubMedCentral
57.
Zurück zum Zitat Grupp, S. A., Kalos, M., Barrett, D., Aplenc, R., Porter, D. L., Rheingold, S. R., et al. (2013). Chimeric antigen receptor–modified T cells for acute lymphoid leukemia. New England Journal of Medicine, 368(16), 1509–1518. Grupp, S. A., Kalos, M., Barrett, D., Aplenc, R., Porter, D. L., Rheingold, S. R., et al. (2013). Chimeric antigen receptor–modified T cells for acute lymphoid leukemia. New England Journal of Medicine, 368(16), 1509–1518.
58.
Zurück zum Zitat Maude, S. L., Frey, N., Shaw, P. A., Aplenc, R., Barrett, D. M., Bunin, N. J., Chew, A., Gonzalez, V. E., Zheng, Z., Lacey, S. F., Mahnke, Y. D., Melenhorst, J. J., Rheingold, S. R., Shen, A., Teachey, D. T., Levine, B. L., June, C. H., Porter, D. L., & Grupp, S. A. (2014). Chimeric antigen receptor T cells for sustained remissions in leukemia. New England Journal of Medicine, 371(16), 1507–1517. Maude, S. L., Frey, N., Shaw, P. A., Aplenc, R., Barrett, D. M., Bunin, N. J., Chew, A., Gonzalez, V. E., Zheng, Z., Lacey, S. F., Mahnke, Y. D., Melenhorst, J. J., Rheingold, S. R., Shen, A., Teachey, D. T., Levine, B. L., June, C. H., Porter, D. L., & Grupp, S. A. (2014). Chimeric antigen receptor T cells for sustained remissions in leukemia. New England Journal of Medicine, 371(16), 1507–1517.
59.
Zurück zum Zitat Maude, S. L., Laetsch, T. W., Buechner, J., Rives, S., Boyer, M., Bittencourt, H., Bader, P., Verneris, M. R., Stefanski, H. E., Myers, G. D., Qayed, M., de Moerloose, B., Hiramatsu, H., Schlis, K., Davis, K. L., Martin, P. L., Nemecek, E. R., Yanik, G. A., Peters, C., Baruchel, A., Boissel, N., Mechinaud, F., Balduzzi, A., Krueger, J., June, C. H., Levine, B. L., Wood, P., Taran, T., Leung, M., Mueller, K. T., Zhang, Y., Sen, K., Lebwohl, D., Pulsipher, M. A., & Grupp, S. A. (2018). Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. New England Journal of Medicine, 378(5), 439–448. Maude, S. L., Laetsch, T. W., Buechner, J., Rives, S., Boyer, M., Bittencourt, H., Bader, P., Verneris, M. R., Stefanski, H. E., Myers, G. D., Qayed, M., de Moerloose, B., Hiramatsu, H., Schlis, K., Davis, K. L., Martin, P. L., Nemecek, E. R., Yanik, G. A., Peters, C., Baruchel, A., Boissel, N., Mechinaud, F., Balduzzi, A., Krueger, J., June, C. H., Levine, B. L., Wood, P., Taran, T., Leung, M., Mueller, K. T., Zhang, Y., Sen, K., Lebwohl, D., Pulsipher, M. A., & Grupp, S. A. (2018). Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. New England Journal of Medicine, 378(5), 439–448.
60.
Zurück zum Zitat Lee, D. W., Kochenderfer, J. N., Stetler-Stevenson, M., Cui, Y. K., Delbrook, C., Feldman, S. A., et al. (2015). T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. The Lancet, 385(9967), 517–528. Lee, D. W., Kochenderfer, J. N., Stetler-Stevenson, M., Cui, Y. K., Delbrook, C., Feldman, S. A., et al. (2015). T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. The Lancet, 385(9967), 517–528.
61.
Zurück zum Zitat Park, J. H., Rivière, I., Gonen, M., Wang, X., Sénéchal, B., Curran, K. J., Curran, K. J., Sauter, C., Wang, Y., Santomasso, B., Mead, E., Roshal, M., Maslak, P., Davila, M., Brentjens, R. J., & Sadelain, M. (2018). Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. New England Journal of Medicine, 378(5), 449–459. Park, J. H., Rivière, I., Gonen, M., Wang, X., Sénéchal, B., Curran, K. J., Curran, K. J., Sauter, C., Wang, Y., Santomasso, B., Mead, E., Roshal, M., Maslak, P., Davila, M., Brentjens, R. J., & Sadelain, M. (2018). Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. New England Journal of Medicine, 378(5), 449–459.
62.
Zurück zum Zitat Pulsipher, M. A. (2018). Are CAR T cells better than antibody or HCT therapy in B-ALL? Hematology, American Society of Hematology Education Program, 2018(1), 16–24. Pulsipher, M. A. (2018). Are CAR T cells better than antibody or HCT therapy in B-ALL? Hematology, American Society of Hematology Education Program, 2018(1), 16–24.
63.
Zurück zum Zitat Davila, M. L., Riviere, I., Wang, X., Bartido, S., Park, J., Curran, K., et al. (2014). Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Science Translational Medicine, 6(224), 224ra2. Davila, M. L., Riviere, I., Wang, X., Bartido, S., Park, J., Curran, K., et al. (2014). Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Science Translational Medicine, 6(224), 224ra2.
64.
Zurück zum Zitat Summers, C., Annesley, C., Bleakley, M., Dahlberg, A., Jensen, M. C., & Gardner, R. (2018). Long term follow-up after SCRI-CAR19v1 reveals late recurrences as well as a survival advantage to consolidation with HCT after CAR T cell induced remission [abstract]. Blood, 132(supplement 1), 967. Summers, C., Annesley, C., Bleakley, M., Dahlberg, A., Jensen, M. C., & Gardner, R. (2018). Long term follow-up after SCRI-CAR19v1 reveals late recurrences as well as a survival advantage to consolidation with HCT after CAR T cell induced remission [abstract]. Blood, 132(supplement 1), 967.
65.
Zurück zum Zitat Talekar, M. K., Maude, S. L., Hucks, G. E., Motley, L. S., Callahan, C., White, C. M., et al. (2017). Effect of chimeric antigen receptor-modified T (CAR-T) cells on responses in children with non-CNS extramedullary relapse of CD19+ acute lymphoblastic leukemia (ALL) [abstract]. Journal of Clinical Oncology, 35(15 supplement), 10507. Talekar, M. K., Maude, S. L., Hucks, G. E., Motley, L. S., Callahan, C., White, C. M., et al. (2017). Effect of chimeric antigen receptor-modified T (CAR-T) cells on responses in children with non-CNS extramedullary relapse of CD19+ acute lymphoblastic leukemia (ALL) [abstract]. Journal of Clinical Oncology, 35(15 supplement), 10507.
68.
Zurück zum Zitat June, C. H., & Sadelain, M. (2018). Chimeric antigen receptor therapy. New England Journal of Medicine, 379(1), 64–73. June, C. H., & Sadelain, M. (2018). Chimeric antigen receptor therapy. New England Journal of Medicine, 379(1), 64–73.
69.
Zurück zum Zitat Teachey, D. T., Lacey, S. F., Shaw, P. A., Melenhorst, J. J., Maude, S. L., Frey, N., Pequignot, E., Gonzalez, V. E., Chen, F., Finklestein, J., Barrett, D. M., Weiss, S. L., Fitzgerald, J. C., Berg, R. A., Aplenc, R., Callahan, C., Rheingold, S. R., Zheng, Z., Rose-John, S., White, J. C., Nazimuddin, F., Wertheim, G., Levine, B. L., June, C. H., Porter, D. L., & Grupp, S. A. (2016). Identification of predictive biomarkers for cytokine release syndrome after chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Cancer Discovery, 6(6), 664–679.PubMedPubMedCentral Teachey, D. T., Lacey, S. F., Shaw, P. A., Melenhorst, J. J., Maude, S. L., Frey, N., Pequignot, E., Gonzalez, V. E., Chen, F., Finklestein, J., Barrett, D. M., Weiss, S. L., Fitzgerald, J. C., Berg, R. A., Aplenc, R., Callahan, C., Rheingold, S. R., Zheng, Z., Rose-John, S., White, J. C., Nazimuddin, F., Wertheim, G., Levine, B. L., June, C. H., Porter, D. L., & Grupp, S. A. (2016). Identification of predictive biomarkers for cytokine release syndrome after chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Cancer Discovery, 6(6), 664–679.PubMedPubMedCentral
71.
Zurück zum Zitat Gust, J., Hay, K. A., Hanafi, L. A., Li, D., Myerson, D., Gonzalez-Cuyar, F., et al. (2017). Endothelial activation and blood-brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells. Cancer Discovery, 7(12), 1404–1419.PubMedPubMedCentral Gust, J., Hay, K. A., Hanafi, L. A., Li, D., Myerson, D., Gonzalez-Cuyar, F., et al. (2017). Endothelial activation and blood-brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells. Cancer Discovery, 7(12), 1404–1419.PubMedPubMedCentral
72.
Zurück zum Zitat Santomasso, B. D., Park, J. H., Salloum, D., Riviere, I., Flynn, J., Mead, E., Halton, E., Wang, X., Senechal, B., Purdon, T., Cross, J. R., Liu, H., Vachha, B., Chen, X., DeAngelis, L., Li, D., Bernal, Y., Gonen, M., Wendel, H. G., Sadelain, M., & Brentjens, R. J. (2018). Clinical and biological correlates of neurotoxicity associated with CAR T-cell therapy in patients with B-cell acute lymphoblastic leukemia. Cancer Discovery, 8(8), 958–971.PubMedPubMedCentral Santomasso, B. D., Park, J. H., Salloum, D., Riviere, I., Flynn, J., Mead, E., Halton, E., Wang, X., Senechal, B., Purdon, T., Cross, J. R., Liu, H., Vachha, B., Chen, X., DeAngelis, L., Li, D., Bernal, Y., Gonen, M., Wendel, H. G., Sadelain, M., & Brentjens, R. J. (2018). Clinical and biological correlates of neurotoxicity associated with CAR T-cell therapy in patients with B-cell acute lymphoblastic leukemia. Cancer Discovery, 8(8), 958–971.PubMedPubMedCentral
73.
Zurück zum Zitat Lee, D. W., Santomasso, B. D., Locke, F. L., Ghobadi, A., Turtle, C. J., Brudno, J. N., Maus, M. V., Park, J. H., Mead, E., Pavletic, S., Go, W. Y., Eldjerou, L., Gardner, R. A., Frey, N., Curran, K. J., Peggs, K., Pasquini, M., DiPersio, J., van den Brink, M., Komanduri, K. V., Grupp, S. A., & Neelapu, S. S. (2019). ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biology of Blood and Marrow Transplantation, 25(4), 625–638.PubMed Lee, D. W., Santomasso, B. D., Locke, F. L., Ghobadi, A., Turtle, C. J., Brudno, J. N., Maus, M. V., Park, J. H., Mead, E., Pavletic, S., Go, W. Y., Eldjerou, L., Gardner, R. A., Frey, N., Curran, K. J., Peggs, K., Pasquini, M., DiPersio, J., van den Brink, M., Komanduri, K. V., Grupp, S. A., & Neelapu, S. S. (2019). ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biology of Blood and Marrow Transplantation, 25(4), 625–638.PubMed
74.
Zurück zum Zitat Hill, J. A., Li, D., Hay, K. A., Green, M. L., Cherian, S., Chen, X., Riddell, S. R., Maloney, D. G., Boeckh, M., & Turtle, C. J. (2018). Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy. Blood, 131(1), 121–130.PubMedPubMedCentral Hill, J. A., Li, D., Hay, K. A., Green, M. L., Cherian, S., Chen, X., Riddell, S. R., Maloney, D. G., Boeckh, M., & Turtle, C. J. (2018). Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy. Blood, 131(1), 121–130.PubMedPubMedCentral
75.
Zurück zum Zitat Laetsch, T. W., Maude, S. L., Milone, M. C., Davis, K. L., Krueger, J., Cardena, A. M., et al. (2018). False-positive results with select HIV-1 NAT methods following lentivirus-based tisagenlecleucel therapy. Blood, 131(23), 2596–2598.PubMedPubMedCentral Laetsch, T. W., Maude, S. L., Milone, M. C., Davis, K. L., Krueger, J., Cardena, A. M., et al. (2018). False-positive results with select HIV-1 NAT methods following lentivirus-based tisagenlecleucel therapy. Blood, 131(23), 2596–2598.PubMedPubMedCentral
76.
Zurück zum Zitat Bhoj, V. G., Arhontoulis, D., Wertheim, G., Capobianchi, J., Callahan, C. A., Ellebrecht, C. T., et al. (2016). Persistence of long-lived plasma cells and humoral immunity in individuals responding to CD19-directed CAR T-cell therapy. Blood, 128(3), 360–370.PubMedPubMedCentral Bhoj, V. G., Arhontoulis, D., Wertheim, G., Capobianchi, J., Callahan, C. A., Ellebrecht, C. T., et al. (2016). Persistence of long-lived plasma cells and humoral immunity in individuals responding to CD19-directed CAR T-cell therapy. Blood, 128(3), 360–370.PubMedPubMedCentral
77.
Zurück zum Zitat Long, A. H., Haso, W. M., Shern, J. F., Wanhainen, K. M., Murgai, M., Ingaramo, M., Smith, J. P., Walker, A. J., Kohler, M. E., Venkateshwara, V. R., Kaplan, R. N., Patterson, G. H., Fry, T. J., Orentas, R. J., & Mackall, C. L. (2015). 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nature Medicine, 21(6), 581–590.PubMedPubMedCentral Long, A. H., Haso, W. M., Shern, J. F., Wanhainen, K. M., Murgai, M., Ingaramo, M., Smith, J. P., Walker, A. J., Kohler, M. E., Venkateshwara, V. R., Kaplan, R. N., Patterson, G. H., Fry, T. J., Orentas, R. J., & Mackall, C. L. (2015). 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nature Medicine, 21(6), 581–590.PubMedPubMedCentral
78.
Zurück zum Zitat Feucht, J., Sun, J., Eyquem, J., Ho, Y. J., Zhao, Z., Leibold, J., Dobrin, A., Cabriolu, A., Hamieh, M., & Sadelain, M. (2019). Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency. Nature Medicine, 25(1), 82–88.PubMed Feucht, J., Sun, J., Eyquem, J., Ho, Y. J., Zhao, Z., Leibold, J., Dobrin, A., Cabriolu, A., Hamieh, M., & Sadelain, M. (2019). Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency. Nature Medicine, 25(1), 82–88.PubMed
79.
Zurück zum Zitat Maude, S. L., Teachey, D. T., Porter, D. L., & Grupp, S. A. (2015). CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Blood, 125(26), 4017–4023.PubMedPubMedCentral Maude, S. L., Teachey, D. T., Porter, D. L., & Grupp, S. A. (2015). CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Blood, 125(26), 4017–4023.PubMedPubMedCentral
80.
Zurück zum Zitat Ghorashian, S., Kramer, A. M., Onuoha, S., Wright, G., Bartram, J., Richardson, R., Albon, S. J., Casanovas-Company, J., Castro, F., Popova, B., Villanueva, K., Yeung, J., Vetharoy, W., Guvenel, A., Wawrzyniecka, P. A., Mekkaoui, L., Cheung, G. W., Pinner, D., Chu, J., Lucchini, G., Silva, J., Ciocarlie, O., Lazareva, A., Inglott, S., Gilmour, K. C., Ahsan, G., Ferrari, M., Manzoor, S., Champion, K., Brooks, T., Lopes, A., Hackshaw, A., Farzaneh, F., Chiesa, R., Rao, K., Bonney, D., Samarasinghe, S., Goulden, N., Vora, A., Veys, P., Hough, R., Wynn, R., Pule, M. A., & Amrolia, P. J. (2019). Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR. Nature Medicine, 25(9), 1408–1414.PubMed Ghorashian, S., Kramer, A. M., Onuoha, S., Wright, G., Bartram, J., Richardson, R., Albon, S. J., Casanovas-Company, J., Castro, F., Popova, B., Villanueva, K., Yeung, J., Vetharoy, W., Guvenel, A., Wawrzyniecka, P. A., Mekkaoui, L., Cheung, G. W., Pinner, D., Chu, J., Lucchini, G., Silva, J., Ciocarlie, O., Lazareva, A., Inglott, S., Gilmour, K. C., Ahsan, G., Ferrari, M., Manzoor, S., Champion, K., Brooks, T., Lopes, A., Hackshaw, A., Farzaneh, F., Chiesa, R., Rao, K., Bonney, D., Samarasinghe, S., Goulden, N., Vora, A., Veys, P., Hough, R., Wynn, R., Pule, M. A., & Amrolia, P. J. (2019). Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR. Nature Medicine, 25(9), 1408–1414.PubMed
81.
Zurück zum Zitat Gardner, R. A., Finney, O., Annesley, C., Brakke, H., Summers, C., Leger, K., Bleakley, M., Brown, C., Mgebroff, S., Kelly-Spratt, K. S., Hoglund, V., Lindgren, C., Oron, A. P., Li, D., Riddell, S. R., Park, J. R., & Jensen, M. C. (2017). Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood, 129(25), 3322–3331.PubMedPubMedCentral Gardner, R. A., Finney, O., Annesley, C., Brakke, H., Summers, C., Leger, K., Bleakley, M., Brown, C., Mgebroff, S., Kelly-Spratt, K. S., Hoglund, V., Lindgren, C., Oron, A. P., Li, D., Riddell, S. R., Park, J. R., & Jensen, M. C. (2017). Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood, 129(25), 3322–3331.PubMedPubMedCentral
82.
Zurück zum Zitat Maude, S. L., Barrett, D. M., Rheingold, S. R., Aplenc, R., Teachey, D. T., Callahan, C., et al. (2016). Efficacy of humanized CD19-targeted chimeric antigen receptor (CAR)-modified T cells in children and young adults with relapsed/refractory acute lymphoblastic leukemia [abstract]. Blood, 128, 217. Maude, S. L., Barrett, D. M., Rheingold, S. R., Aplenc, R., Teachey, D. T., Callahan, C., et al. (2016). Efficacy of humanized CD19-targeted chimeric antigen receptor (CAR)-modified T cells in children and young adults with relapsed/refractory acute lymphoblastic leukemia [abstract]. Blood, 128, 217.
83.
Zurück zum Zitat Rossig, C., Pule, M., Altvater, B., Saiagh, S., Wright, G., Ghorashian, S., Clifton-Hadley, L., Champion, K., Sattar, Z., Popova, B., Hackshaw, A., Smith, P., Roberts, T., Biagi, E., Dreno, B., Rousseau, R., Kailayangiri, S., Ahlmann, M., Hough, R., Kremens, B., Sauer, M. G., Veys, P., Goulden, N., Cummins, M., & Amrolia, P. J. (2017). Vaccination to improve the persistence of CD19CAR gene-modified T cells in relapsed pediatric acute lymphoblastic leukemia. Leukemia, 31(5), 1087–1095.PubMed Rossig, C., Pule, M., Altvater, B., Saiagh, S., Wright, G., Ghorashian, S., Clifton-Hadley, L., Champion, K., Sattar, Z., Popova, B., Hackshaw, A., Smith, P., Roberts, T., Biagi, E., Dreno, B., Rousseau, R., Kailayangiri, S., Ahlmann, M., Hough, R., Kremens, B., Sauer, M. G., Veys, P., Goulden, N., Cummins, M., & Amrolia, P. J. (2017). Vaccination to improve the persistence of CD19CAR gene-modified T cells in relapsed pediatric acute lymphoblastic leukemia. Leukemia, 31(5), 1087–1095.PubMed
84.
Zurück zum Zitat Singh, N., Perazzelli, J., Grupp, S. A., & Barrett, D. M. (2016). Early memory phenotypes drive T cell proliferation in patients with pediatric malignancies. Science Translational Medicine, 8(320), 320ra3.PubMed Singh, N., Perazzelli, J., Grupp, S. A., & Barrett, D. M. (2016). Early memory phenotypes drive T cell proliferation in patients with pediatric malignancies. Science Translational Medicine, 8(320), 320ra3.PubMed
85.
Zurück zum Zitat Sabatino, M., Hu, J., Sommariva, M., Gautam, S., Fellowes, V., Hocker, J. D., Dougherty, S., Qin, H., Klebanoff, C. A., Fry, T. J., Gress, R. E., Kochenderfer, J. N., Stroncek, D. F., Ji, Y., & Gattinoni, L. (2016). Generation of clinical-grade CD19-specific CAR-modified CD8+ memory stem cells for the treatment of human B-cell malignancies. Blood, 128(4), 519–528.PubMedPubMedCentral Sabatino, M., Hu, J., Sommariva, M., Gautam, S., Fellowes, V., Hocker, J. D., Dougherty, S., Qin, H., Klebanoff, C. A., Fry, T. J., Gress, R. E., Kochenderfer, J. N., Stroncek, D. F., Ji, Y., & Gattinoni, L. (2016). Generation of clinical-grade CD19-specific CAR-modified CD8+ memory stem cells for the treatment of human B-cell malignancies. Blood, 128(4), 519–528.PubMedPubMedCentral
86.
Zurück zum Zitat Orlando, E. J., Han, X., Tribouley, C., Wood, P. A., Leary, R. J., Riester, M., Levine, J. E., Qayed, M., Grupp, S. A., Boyer, M., de Moerloose, B., Nemecek, E. R., Bittencourt, H., Hiramatsu, H., Buechner, J., Davies, S. M., Verneris, M. R., Nguyen, K., Brogdon, J. L., Bitter, H., Morrissey, M., Pierog, P., Pantano, S., Engelman, J. A., & Winckler, W. (2018). Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia. Nature Medicine, 24(10), 1504–1506.PubMed Orlando, E. J., Han, X., Tribouley, C., Wood, P. A., Leary, R. J., Riester, M., Levine, J. E., Qayed, M., Grupp, S. A., Boyer, M., de Moerloose, B., Nemecek, E. R., Bittencourt, H., Hiramatsu, H., Buechner, J., Davies, S. M., Verneris, M. R., Nguyen, K., Brogdon, J. L., Bitter, H., Morrissey, M., Pierog, P., Pantano, S., Engelman, J. A., & Winckler, W. (2018). Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia. Nature Medicine, 24(10), 1504–1506.PubMed
87.
Zurück zum Zitat Sotillo, E., Barrett, D. M., Black, K. L., Bagashev, A., Oldridge, D., Wu, G., Sussman, R., Lanauze, C., Ruella, M., Gazzara, M. R., Martinez, N. M., Harrington, C. T., Chung, E. Y., Perazzelli, J., Hofmann, T. J., Maude, S. L., Raman, P., Barrera, A., Gill, S., Lacey, S. F., Melenhorst, J. J., Allman, D., Jacoby, E., Fry, T., Mackall, C., Barash, Y., Lynch, K. W., Maris, J. M., Grupp, S. A., & Thomas-Tikhonenko, A. (2015). Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discovery, 5(12), 1282–1295.PubMedPubMedCentral Sotillo, E., Barrett, D. M., Black, K. L., Bagashev, A., Oldridge, D., Wu, G., Sussman, R., Lanauze, C., Ruella, M., Gazzara, M. R., Martinez, N. M., Harrington, C. T., Chung, E. Y., Perazzelli, J., Hofmann, T. J., Maude, S. L., Raman, P., Barrera, A., Gill, S., Lacey, S. F., Melenhorst, J. J., Allman, D., Jacoby, E., Fry, T., Mackall, C., Barash, Y., Lynch, K. W., Maris, J. M., Grupp, S. A., & Thomas-Tikhonenko, A. (2015). Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discovery, 5(12), 1282–1295.PubMedPubMedCentral
88.
Zurück zum Zitat Jacoby, E., Nguyen, S. M., Fountaine, T. J., Welp, K., Gryder, B., Qin, H., et al. (2016). CD19 CAR immune pressure induces B-precursor acute lymphoblastic leukaemia lineage switch exposing inherent leukaemic plasticity. Nature Communications, 7, 12320.PubMedPubMedCentral Jacoby, E., Nguyen, S. M., Fountaine, T. J., Welp, K., Gryder, B., Qin, H., et al. (2016). CD19 CAR immune pressure induces B-precursor acute lymphoblastic leukaemia lineage switch exposing inherent leukaemic plasticity. Nature Communications, 7, 12320.PubMedPubMedCentral
89.
Zurück zum Zitat Gardner, R., Wu, D., Cherian, S., Fang, M., Hanafi, L. A., Finney, O., Smithers, H., Jensen, M. C., Riddell, S. R., Maloney, D. G., & Turtle, C. J. (2016). Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy. Blood, 127(20), 2406–2410.PubMedPubMedCentral Gardner, R., Wu, D., Cherian, S., Fang, M., Hanafi, L. A., Finney, O., Smithers, H., Jensen, M. C., Riddell, S. R., Maloney, D. G., & Turtle, C. J. (2016). Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy. Blood, 127(20), 2406–2410.PubMedPubMedCentral
90.
Zurück zum Zitat Oberley, M. J., Gaynon, P. S., Bhojwani, D., Pulsipher, M. A., Gardner, R. A., Hiemenz, M. C., Ji, J., Han, J., O’Gorman, M. R. G., Wayne, A. S., & Raca, G. (2018). Myeloid lineage switch following chimeric antigen receptor T-cell therapy in a patient with TCF3-ZNF384 fusion-positive B-lymphoblastic leukemia. Pediatric Blood & Cancer, 65(9), e27265. Oberley, M. J., Gaynon, P. S., Bhojwani, D., Pulsipher, M. A., Gardner, R. A., Hiemenz, M. C., Ji, J., Han, J., O’Gorman, M. R. G., Wayne, A. S., & Raca, G. (2018). Myeloid lineage switch following chimeric antigen receptor T-cell therapy in a patient with TCF3-ZNF384 fusion-positive B-lymphoblastic leukemia. Pediatric Blood & Cancer, 65(9), e27265.
91.
Zurück zum Zitat Nagel, I., Bartels, M., Duell, J., Oberg, H. H., Ussat, S., Bruckmueller, H., Ottmann, O., Pfeifer, H., Trautmann, H., Gökbuget, N., Caliebe, A., Kabelitz, D., Kneba, M., Horst, H. A., Hoelzer, D., Topp, M. S., Cascorbi, I., Siebert, R., & Brüggemann, M. (2017). Hematopoietic stem cell involvement in BCR-ABL1–positive ALL as a potential mechanism of resistance to blinatumomab therapy. Blood, 130(18), 2027–2031.PubMedPubMedCentral Nagel, I., Bartels, M., Duell, J., Oberg, H. H., Ussat, S., Bruckmueller, H., Ottmann, O., Pfeifer, H., Trautmann, H., Gökbuget, N., Caliebe, A., Kabelitz, D., Kneba, M., Horst, H. A., Hoelzer, D., Topp, M. S., Cascorbi, I., Siebert, R., & Brüggemann, M. (2017). Hematopoietic stem cell involvement in BCR-ABL1–positive ALL as a potential mechanism of resistance to blinatumomab therapy. Blood, 130(18), 2027–2031.PubMedPubMedCentral
92.
Zurück zum Zitat Rayes, A., McMasters, R. L., & O’Brien, M. M. (2016). Lineage switch in MLL-rearranged infant leukemia following CD19-directed therapy. Pediatric Blood & Cancer, 63(6), 1113–1115. Rayes, A., McMasters, R. L., & O’Brien, M. M. (2016). Lineage switch in MLL-rearranged infant leukemia following CD19-directed therapy. Pediatric Blood & Cancer, 63(6), 1113–1115.
93.
Zurück zum Zitat Balducci, E., Nivaggioni, V., Boudjarane, J., Bouriche, L., Rahal, I., Bernot, D., Alazard, E., Duployez, N., Grardel, N., Arnoux, I., Lafage-Pochitaloff, M., Michel, G., Nadel, B., & Loosveld, M. (2017). Lineage switch from B acute lymphoblastic leukemia to acute monocytic leukemia with persistent t(4;11)(q21;q23) and cytogenetic evolution under CD19-targeted therapy. Annals of Hematology, 96(9), 1579–1581.PubMed Balducci, E., Nivaggioni, V., Boudjarane, J., Bouriche, L., Rahal, I., Bernot, D., Alazard, E., Duployez, N., Grardel, N., Arnoux, I., Lafage-Pochitaloff, M., Michel, G., Nadel, B., & Loosveld, M. (2017). Lineage switch from B acute lymphoblastic leukemia to acute monocytic leukemia with persistent t(4;11)(q21;q23) and cytogenetic evolution under CD19-targeted therapy. Annals of Hematology, 96(9), 1579–1581.PubMed
94.
Zurück zum Zitat Cohen, A., Petsche, D., Grunberger, T., & Freedman, M. H. (1992). Interleukin 6 induces myeloid differentiation of a human biphenotypic leukemic cell line. Leukemia Research, 16(8), 751–760.PubMed Cohen, A., Petsche, D., Grunberger, T., & Freedman, M. H. (1992). Interleukin 6 induces myeloid differentiation of a human biphenotypic leukemic cell line. Leukemia Research, 16(8), 751–760.PubMed
95.
Zurück zum Zitat Alexander, T. B., Gu, Z., Iacobucci, I., Dickerson, K., Choi, J. K., Xu, B., Payne-Turner, D., Yoshihara, H., Loh, M. L., Horan, J., Buldini, B., Basso, G., Elitzur, S., de Haas, V., Zwaan, C. M., Yeoh, A., Reinhardt, D., Tomizawa, D., Kiyokawa, N., Lammens, T., de Moerloose, B., Catchpoole, D., Hori, H., Moorman, A., Moore, A. S., Hrusak, O., Meshinchi, S., Orgel, E., Devidas, M., Borowitz, M., Wood, B., Heerema, N. A., Carrol, A., Yang, Y. L., Smith, M. A., Davidsen, T. M., Hermida, L. C., Gesuwan, P., Marra, M. A., Ma, Y., Mungall, A. J., Moore, R. A., Jones, S. J. M., Valentine, M., Janke, L. J., Rubnitz, J. E., Pui, C. H., Ding, L., Liu, Y., Zhang, J., Nichols, K. E., Downing, J. R., Cao, X., Shi, L., Pounds, S., Newman, S., Pei, D., Guidry Auvil, J. M., Gerhard, D. S., Hunger, S. P., Inaba, H., & Mullighan, C. G. (2018). The genetic basis and cell of origin of mixed phenotype acute leukaemia. Nature, 562(7727), 373–379.PubMedPubMedCentral Alexander, T. B., Gu, Z., Iacobucci, I., Dickerson, K., Choi, J. K., Xu, B., Payne-Turner, D., Yoshihara, H., Loh, M. L., Horan, J., Buldini, B., Basso, G., Elitzur, S., de Haas, V., Zwaan, C. M., Yeoh, A., Reinhardt, D., Tomizawa, D., Kiyokawa, N., Lammens, T., de Moerloose, B., Catchpoole, D., Hori, H., Moorman, A., Moore, A. S., Hrusak, O., Meshinchi, S., Orgel, E., Devidas, M., Borowitz, M., Wood, B., Heerema, N. A., Carrol, A., Yang, Y. L., Smith, M. A., Davidsen, T. M., Hermida, L. C., Gesuwan, P., Marra, M. A., Ma, Y., Mungall, A. J., Moore, R. A., Jones, S. J. M., Valentine, M., Janke, L. J., Rubnitz, J. E., Pui, C. H., Ding, L., Liu, Y., Zhang, J., Nichols, K. E., Downing, J. R., Cao, X., Shi, L., Pounds, S., Newman, S., Pei, D., Guidry Auvil, J. M., Gerhard, D. S., Hunger, S. P., Inaba, H., & Mullighan, C. G. (2018). The genetic basis and cell of origin of mixed phenotype acute leukaemia. Nature, 562(7727), 373–379.PubMedPubMedCentral
96.
Zurück zum Zitat Hamieh, M., Dobrin, A., Cabriolu, A., van der Stegen, S. J. C., Giavridis, T., Mansilla-Soto, J., et al. (2019). CAR T cell trogocytosis and cooperative killing regulate tumour antigen escape. Nature, 568(7750), 112–116.PubMedPubMedCentral Hamieh, M., Dobrin, A., Cabriolu, A., van der Stegen, S. J. C., Giavridis, T., Mansilla-Soto, J., et al. (2019). CAR T cell trogocytosis and cooperative killing regulate tumour antigen escape. Nature, 568(7750), 112–116.PubMedPubMedCentral
97.
Zurück zum Zitat Ruella, M., Xu, J., Barrett, D. M., Fraietta, J. A., Reich, T. J., Ambrose, D. E., Klichinsky, M., Shestova, O., Patel, P. R., Kulikovskaya, I., Nazimuddin, F., Bhoj, V. G., Orlando, E. J., Fry, T. J., Bitter, H., Maude, S. L., Levine, B. L., Nobles, C. L., Bushman, F. D., Young, R. M., Scholler, J., Gill, S. I., June, C. H., Grupp, S. A., Lacey, S. F., & Melenhorst, J. J. (2018). Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell. Nature Medicine, 24(10), 1499–1503.PubMedPubMedCentral Ruella, M., Xu, J., Barrett, D. M., Fraietta, J. A., Reich, T. J., Ambrose, D. E., Klichinsky, M., Shestova, O., Patel, P. R., Kulikovskaya, I., Nazimuddin, F., Bhoj, V. G., Orlando, E. J., Fry, T. J., Bitter, H., Maude, S. L., Levine, B. L., Nobles, C. L., Bushman, F. D., Young, R. M., Scholler, J., Gill, S. I., June, C. H., Grupp, S. A., Lacey, S. F., & Melenhorst, J. J. (2018). Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell. Nature Medicine, 24(10), 1499–1503.PubMedPubMedCentral
98.
Zurück zum Zitat Braig, F., Brandt, A., Goebeler, M., Tony, H. P., Kurze, A. K., Nollau, P., Bumm, T., Böttcher, S., Bargou, R. C., & Binder, M. (2017). Resistance to anti-CD19/CD3 BiTE in acute lymphoblastic leukemia may be mediated by disrupted CD19 membrane trafficking. Blood, 129(1), 100–104.PubMed Braig, F., Brandt, A., Goebeler, M., Tony, H. P., Kurze, A. K., Nollau, P., Bumm, T., Böttcher, S., Bargou, R. C., & Binder, M. (2017). Resistance to anti-CD19/CD3 BiTE in acute lymphoblastic leukemia may be mediated by disrupted CD19 membrane trafficking. Blood, 129(1), 100–104.PubMed
99.
Zurück zum Zitat Haso, W., Lee, D. W., Shah, N. N., Stetler-Stevenson, M., Yuan, C. M., Pastan, I. H., Dimitrov, D. S., Morgan, R. A., FitzGerald, D., Barrett, D. M., Wayne, A. S., Mackall, C. L., & Orentas, R. J. (2013). Anti-CD22–chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood, 121(7), 1165–1174.PubMedPubMedCentral Haso, W., Lee, D. W., Shah, N. N., Stetler-Stevenson, M., Yuan, C. M., Pastan, I. H., Dimitrov, D. S., Morgan, R. A., FitzGerald, D., Barrett, D. M., Wayne, A. S., Mackall, C. L., & Orentas, R. J. (2013). Anti-CD22–chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood, 121(7), 1165–1174.PubMedPubMedCentral
100.
Zurück zum Zitat Qin, H., Cho, M., Haso, W., Zhang, L., Tasian, S. K., Oo, H. Z., Negri, G. L., Lin, Y., Zou, J., Mallon, B. S., Maude, S., Teachey, D. T., Barrett, D. M., Orentas, R. J., Daugaard, M., Sorensen, P. H., Grupp, S. A., & Fry, T. J. (2015). Eradication of B-ALL using chimeric antigen receptor-expressing T cells targeting the TSLPR oncoprotein. Blood, 126(5), 629–639.PubMedPubMedCentral Qin, H., Cho, M., Haso, W., Zhang, L., Tasian, S. K., Oo, H. Z., Negri, G. L., Lin, Y., Zou, J., Mallon, B. S., Maude, S., Teachey, D. T., Barrett, D. M., Orentas, R. J., Daugaard, M., Sorensen, P. H., Grupp, S. A., & Fry, T. J. (2015). Eradication of B-ALL using chimeric antigen receptor-expressing T cells targeting the TSLPR oncoprotein. Blood, 126(5), 629–639.PubMedPubMedCentral
101.
Zurück zum Zitat Fry, T. J., Shah, N. N., Orentas, R. J., Stetler-Stevenson, M., Yuan, C. M., Ramakrishna, S., Wolters, P., Martin, S., Delbrook, C., Yates, B., Shalabi, H., Fountaine, T. J., Shern, J. F., Majzner, R. G., Stroncek, D. F., Sabatino, M., Feng, Y., Dimitrov, D. S., Zhang, L., Nguyen, S., Qin, H., Dropulic, B., Lee, D. W., & Mackall, C. L. (2018). CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nature Medicine, 24(1), 20–28.PubMed Fry, T. J., Shah, N. N., Orentas, R. J., Stetler-Stevenson, M., Yuan, C. M., Ramakrishna, S., Wolters, P., Martin, S., Delbrook, C., Yates, B., Shalabi, H., Fountaine, T. J., Shern, J. F., Majzner, R. G., Stroncek, D. F., Sabatino, M., Feng, Y., Dimitrov, D. S., Zhang, L., Nguyen, S., Qin, H., Dropulic, B., Lee, D. W., & Mackall, C. L. (2018). CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nature Medicine, 24(1), 20–28.PubMed
102.
Zurück zum Zitat Ramakrishna, S., Highfill, S. L., Walsh, Z., Nguyen, S. M., Lei, H., Shern, J. F., Qin, H., Kraft, I. L., Stetler-Stevenson, M., Yuan, C. M., Hwang, J. D., Feng, Y., Zhu, Z., Dimitrov, D., Shah, N. N., & Fry, T. J. (2019). Modulation of target antigen density improves CAR T-cell functionality and persistence. Clinical Cancer Research, 25(17), 5329–5341.PubMedPubMedCentral Ramakrishna, S., Highfill, S. L., Walsh, Z., Nguyen, S. M., Lei, H., Shern, J. F., Qin, H., Kraft, I. L., Stetler-Stevenson, M., Yuan, C. M., Hwang, J. D., Feng, Y., Zhu, Z., Dimitrov, D., Shah, N. N., & Fry, T. J. (2019). Modulation of target antigen density improves CAR T-cell functionality and persistence. Clinical Cancer Research, 25(17), 5329–5341.PubMedPubMedCentral
104.
Zurück zum Zitat Schneider, D., Xiong, Y., Wu, D., Nölle, V., Schmitz, S., Haso, W., et al. (2017). A tandem CD19/CD20 CAR lentiviral vector drives on-target and off-target antigen modulation in leukemia cell lines. Journal for Immunotherapy of Cancer, 5, 42.PubMedPubMedCentral Schneider, D., Xiong, Y., Wu, D., Nölle, V., Schmitz, S., Haso, W., et al. (2017). A tandem CD19/CD20 CAR lentiviral vector drives on-target and off-target antigen modulation in leukemia cell lines. Journal for Immunotherapy of Cancer, 5, 42.PubMedPubMedCentral
105.
Zurück zum Zitat Ruella, M., Barrett, D. M., Kenderian, S. S., Shestova, O., Hofmann, T. J., Perazelli, J., et al. (2016). Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies. The Journal of Clinical Investigation, 126(10), 3814–3826.PubMedPubMedCentral Ruella, M., Barrett, D. M., Kenderian, S. S., Shestova, O., Hofmann, T. J., Perazelli, J., et al. (2016). Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies. The Journal of Clinical Investigation, 126(10), 3814–3826.PubMedPubMedCentral
106.
Zurück zum Zitat Flowers, C. R., & Ramsey, S. D. (2018). What can cost-effectiveness analysis tell us about chimeric antigen receptor T-cell therapy for relapsed acute lymphoblastic leukemia? Journal of Clinical Oncology, 36(32), 3183–3185. Flowers, C. R., & Ramsey, S. D. (2018). What can cost-effectiveness analysis tell us about chimeric antigen receptor T-cell therapy for relapsed acute lymphoblastic leukemia? Journal of Clinical Oncology, 36(32), 3183–3185.
107.
Zurück zum Zitat Lin, J. K., Lerman, B. J., Barnes, J. I., Boursiquot, B. C., Tan, Y. J., Robinson, A. Q. L., et al. (2018). Cost effectiveness of chimeric antigen receptor T-cell therapy in relapsed or refractory pediatric B-cell acute lymphoblastic leukemia. Journal of Clinical Oncology, 36(32), 3192–3202.PubMed Lin, J. K., Lerman, B. J., Barnes, J. I., Boursiquot, B. C., Tan, Y. J., Robinson, A. Q. L., et al. (2018). Cost effectiveness of chimeric antigen receptor T-cell therapy in relapsed or refractory pediatric B-cell acute lymphoblastic leukemia. Journal of Clinical Oncology, 36(32), 3192–3202.PubMed
108.
Zurück zum Zitat Whittington, M. D., McQueen, R. B., Ollendorf, D. A., Kumar, V. M., Chapman, R. H., Tice, J. A., et al. (2018). Long-term survival and value of chimeric antigen receptor T-cell therapy for pediatric patients with relapsed or refractory leukemia. JAMA Pediatrics, 172(12), 1161–1168.PubMedPubMedCentral Whittington, M. D., McQueen, R. B., Ollendorf, D. A., Kumar, V. M., Chapman, R. H., Tice, J. A., et al. (2018). Long-term survival and value of chimeric antigen receptor T-cell therapy for pediatric patients with relapsed or refractory leukemia. JAMA Pediatrics, 172(12), 1161–1168.PubMedPubMedCentral
109.
Zurück zum Zitat Sarkar, R. R., Gloude, N. J., Schiff, D., & Murphy, J. D. (2019). Cost-effectiveness of chimeric antigen receptor T-cell therapy in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia. Journal of the National Cancer Institute, 111(7), 719–726.PubMed Sarkar, R. R., Gloude, N. J., Schiff, D., & Murphy, J. D. (2019). Cost-effectiveness of chimeric antigen receptor T-cell therapy in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia. Journal of the National Cancer Institute, 111(7), 719–726.PubMed
110.
Zurück zum Zitat Laetsch, T. W., Myers, G. D., Baruchel, A., Dietz, A. C., Pulsipher, M. A., Bittencourt, H., et al. (2019). Patient-reported quality of life after tisagenlecleucel infusion in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: a global, single-arm, phase 2 trial. The Lancet Oncology. https://doi.org/10.1016/S1470-2045(19)30493-0.PubMedPubMedCentral Laetsch, T. W., Myers, G. D., Baruchel, A., Dietz, A. C., Pulsipher, M. A., Bittencourt, H., et al. (2019). Patient-reported quality of life after tisagenlecleucel infusion in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: a global, single-arm, phase 2 trial. The Lancet Oncology. https://​doi.​org/​10.​1016/​S1470-2045(19)30493-0.PubMedPubMedCentral
111.
Zurück zum Zitat Mamonkin, M., Rouce, R. H., Tashiro, H., & Brenner, M. K. (2015). A T-cell–directed chimeric antigen receptor for the selective treatment of T-cell malignancies. Blood, 126(8), 983–992.PubMedPubMedCentral Mamonkin, M., Rouce, R. H., Tashiro, H., & Brenner, M. K. (2015). A T-cell–directed chimeric antigen receptor for the selective treatment of T-cell malignancies. Blood, 126(8), 983–992.PubMedPubMedCentral
112.
Zurück zum Zitat Sánchez-Martínez, D., Baroni, M. L., Gutierrez-Agüera, F., Roca-Ho, H., Blanch-Lombarte, O., González-García, S., Torrebadell, M., Junca, J., Ramírez-Orellana, M., Velasco-Hernández, T., Bueno, C., Fuster, J. L., Prado, J. G., Calvo, J., Uzan, B., Cools, J., Camos, M., Pflumio, F., Toribio, M. L., & Menéndez, P. (2019). Fratricide-resistant CD1a-specific CAR T cells for the treatment of cortical T-cell acute lymphoblastic leukemia. Blood, 133(21), 2291–2304.PubMedPubMedCentral Sánchez-Martínez, D., Baroni, M. L., Gutierrez-Agüera, F., Roca-Ho, H., Blanch-Lombarte, O., González-García, S., Torrebadell, M., Junca, J., Ramírez-Orellana, M., Velasco-Hernández, T., Bueno, C., Fuster, J. L., Prado, J. G., Calvo, J., Uzan, B., Cools, J., Camos, M., Pflumio, F., Toribio, M. L., & Menéndez, P. (2019). Fratricide-resistant CD1a-specific CAR T cells for the treatment of cortical T-cell acute lymphoblastic leukemia. Blood, 133(21), 2291–2304.PubMedPubMedCentral
113.
Zurück zum Zitat Gomes-Silva, D., Srinivasan, M., Sharma, S., Lee, C. M., Wagner, D. L., Davis, T. H., Rouce, R. H., Bao, G., Brenner, M. K., & Mamonkin, M. (2017). CD7-edited T cells expressing a CD7-specific CAR for the therapy of T-cell malignancies. Blood, 130(3), 285–296.PubMedPubMedCentral Gomes-Silva, D., Srinivasan, M., Sharma, S., Lee, C. M., Wagner, D. L., Davis, T. H., Rouce, R. H., Bao, G., Brenner, M. K., & Mamonkin, M. (2017). CD7-edited T cells expressing a CD7-specific CAR for the therapy of T-cell malignancies. Blood, 130(3), 285–296.PubMedPubMedCentral
114.
Zurück zum Zitat Png, Y. T., Vinanica, N., Kamiya, T., Shimasaki, N., Coustan-Smith, E., & Campana, D. (2017). Blockade of CD7 expression in T cells for effective chimeric antigen receptor targeting of T-cell malignancies. Blood Advances, 1(25), 2348–2360.PubMedPubMedCentral Png, Y. T., Vinanica, N., Kamiya, T., Shimasaki, N., Coustan-Smith, E., & Campana, D. (2017). Blockade of CD7 expression in T cells for effective chimeric antigen receptor targeting of T-cell malignancies. Blood Advances, 1(25), 2348–2360.PubMedPubMedCentral
115.
Zurück zum Zitat Qasim, W., Zhan, H., Samarasinghe, S., Adams, S., Amrolia, P., Stafford, S., et al. (2017). Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells. Science Translational Medicine, 9(374), eaaj2013.PubMed Qasim, W., Zhan, H., Samarasinghe, S., Adams, S., Amrolia, P., Stafford, S., et al. (2017). Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells. Science Translational Medicine, 9(374), eaaj2013.PubMed
116.
Zurück zum Zitat Kantarjian, H., Ravandi, F., Short, N. J., Huang, X., Jain, N., Sasaki, K., Daver, N., Pemmaraju, N., Khoury, J. D., Jorgensen, J., Alvarado, Y., Konopleva, M., Garcia-Manero, G., Kadia, T., Yilmaz, M., Bortakhur, G., Burger, J., Kornblau, S., Wierda, W., DiNardo, C., Ferrajoli, A., Jacob, J., Garris, R., O’Brien, S., & Jabbour, E. (2018). Inotuzumab ozogamicin in combination with low-intensity chemotherapy for older patients with Philadelphia chromosome–negative acute lymphoblastic leukaemia: a single-arm, phase 2 study. The Lancet Oncology, 19(2), 240–248.PubMed Kantarjian, H., Ravandi, F., Short, N. J., Huang, X., Jain, N., Sasaki, K., Daver, N., Pemmaraju, N., Khoury, J. D., Jorgensen, J., Alvarado, Y., Konopleva, M., Garcia-Manero, G., Kadia, T., Yilmaz, M., Bortakhur, G., Burger, J., Kornblau, S., Wierda, W., DiNardo, C., Ferrajoli, A., Jacob, J., Garris, R., O’Brien, S., & Jabbour, E. (2018). Inotuzumab ozogamicin in combination with low-intensity chemotherapy for older patients with Philadelphia chromosome–negative acute lymphoblastic leukaemia: a single-arm, phase 2 study. The Lancet Oncology, 19(2), 240–248.PubMed
117.
Zurück zum Zitat Chiaretti, S., Bassan, R., Vitale, A., Elia, L., Piciocchi, A., Ferrara, F., et al. (2019). A dasatinib-blinatumomab combination for the front-line treatment of adult Ph+ ALL patients. Preliminary results of the GIMEMA LAL2116 D-ALBA trial; on behalf of Gimema Acute Leukemia Working Party. HemaSphere, 3, 746. Chiaretti, S., Bassan, R., Vitale, A., Elia, L., Piciocchi, A., Ferrara, F., et al. (2019). A dasatinib-blinatumomab combination for the front-line treatment of adult Ph+ ALL patients. Preliminary results of the GIMEMA LAL2116 D-ALBA trial; on behalf of Gimema Acute Leukemia Working Party. HemaSphere, 3, 746.
Metadaten
Titel
Immunotherapy in pediatric acute lymphoblastic leukemia
verfasst von
Hiroto Inaba
Ching-Hon Pui
Publikationsdatum
06.12.2019
Verlag
Springer US
Erschienen in
Cancer and Metastasis Reviews / Ausgabe 4/2019
Print ISSN: 0167-7659
Elektronische ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-019-09834-0

Weitere Artikel der Ausgabe 4/2019

Cancer and Metastasis Reviews 4/2019 Zur Ausgabe

Announcement

Biographies

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

15% bedauern gewählte Blasenkrebs-Therapie

29.05.2024 Urothelkarzinom Nachrichten

Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

28.05.2024 Nebenwirkungen der Krebstherapie Nachrichten

Kardiotoxische Nebenwirkungen einer Therapie mit Immuncheckpointhemmern mögen selten sein – wenn sie aber auftreten, wird es für Patienten oft lebensgefährlich. Voruntersuchung und Monitoring sind daher obligat.

Costims – das nächste heiße Ding in der Krebstherapie?

28.05.2024 Onkologische Immuntherapie Nachrichten

„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.