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Erschienen in: Current Hematologic Malignancy Reports 2/2019

26.02.2019 | Acute Lymphocytic Leukemias (K Ballen and M Keng, Section Editors)

Hematopoietic Stem Cell Transplantation in Pediatric Acute Lymphoblastic Leukemia

verfasst von: Pietro Merli, Mattia Algeri, Francesca Del Bufalo, Franco Locatelli

Erschienen in: Current Hematologic Malignancy Reports | Ausgabe 2/2019

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Abstract

Purpose of Review

The remarkable improvement in the prognosis of children with acute lymphoblastic leukemia (ALL) has been mainly achieved through the administration of risk-adapted therapy, including allogeneic hematopoietic stem cell transplantation (HSCT). This paper reviews the current indications to HSCT in ALL children, as well as the type of donor and conditioning regimens commonly used. Finally, it will focus on future challenges in immunotherapy.

Recent Findings

As our comprehension of disease-specific risk factors improves, indications to HSCT continue to evolve. Future studies will answer the year-old question on the best conditioning regimen to be used in this setting, while a recent randomized controlled study fixed the optimal anti-thymocyte globulin dose in unrelated donor HSCT.

Summary

HSCT, the oldest immunotherapy used in clinical practice, still represents the gold standard consolidation treatment for a number of pediatric patients with high-risk/relapsed ALL. New immunotherapies hold the promise of further improving outcomes in this setting.
Literatur
8.
Zurück zum Zitat • Borowitz MJ, Devidas M, Hunger SP, Bowman WP, Carroll AJ, Carroll WL, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children’s Oncology Group study. Blood. 2008;111(12):5477–85. https://doi.org/10.1182/blood-2008-01-132837 First demonstration that end-induction MRD appears to predict disease relapse and long-term outcome in a multivariate analysis. CrossRefPubMedPubMedCentral • Borowitz MJ, Devidas M, Hunger SP, Bowman WP, Carroll AJ, Carroll WL, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children’s Oncology Group study. Blood. 2008;111(12):5477–85. https://​doi.​org/​10.​1182/​blood-2008-01-132837 First demonstration that end-induction MRD appears to predict disease relapse and long-term outcome in a multivariate analysis. CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat • Conter V, Bartram CR, Valsecchi MG, Schrauder A, Panzer-Grumayer R, Moricke A, et al. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood. 2010;115(16):3206–14. https://doi.org/10.1182/blood-2009-10-248146 Demonstration that PCR-MRD at the end of consolidation therapy is the major determinant of relapse risk. CrossRefPubMed • Conter V, Bartram CR, Valsecchi MG, Schrauder A, Panzer-Grumayer R, Moricke A, et al. Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood. 2010;115(16):3206–14. https://​doi.​org/​10.​1182/​blood-2009-10-248146 Demonstration that PCR-MRD at the end of consolidation therapy is the major determinant of relapse risk. CrossRefPubMed
14.
Zurück zum Zitat McNeer J, Meenakshi D, Dai Y, Carroll AJ, Heerema NA, Gastier-Foster JM, et al. Hematopoietic stem cell transplantation does not improve the poor outcome of children with Hypodiploid Acute Lymphoblastic Leukemia: A report from Children's Oncology Group. J Clin Oncol. 2019. Epub ahead of print. McNeer J, Meenakshi D, Dai Y, Carroll AJ, Heerema NA, Gastier-Foster JM, et al. Hematopoietic stem cell transplantation does not improve the poor outcome of children with Hypodiploid Acute Lymphoblastic Leukemia: A report from Children's Oncology Group. J Clin Oncol. 2019. Epub ahead of print.
15.
Zurück zum Zitat Biondi A, Cimino G, Pieters R, Pui CH. Biological and therapeutic aspects of infant leukemia. Blood. 2000;96(1):24–33.PubMed Biondi A, Cimino G, Pieters R, Pui CH. Biological and therapeutic aspects of infant leukemia. Blood. 2000;96(1):24–33.PubMed
18.
Zurück zum Zitat Dreyer ZE, Dinndorf PA, Camitta B, Sather H, La MK, Devidas M, et al. Analysis of the role of hematopoietic stem-cell transplantation in infants with acute lymphoblastic leukemia in first remission and MLL gene rearrangements: a report from the Children’s Oncology Group. J Clin Oncol. 2011;29(2):214–22. https://doi.org/10.1200/JCO.2009.26.8938.CrossRefPubMed Dreyer ZE, Dinndorf PA, Camitta B, Sather H, La MK, Devidas M, et al. Analysis of the role of hematopoietic stem-cell transplantation in infants with acute lymphoblastic leukemia in first remission and MLL gene rearrangements: a report from the Children’s Oncology Group. J Clin Oncol. 2011;29(2):214–22. https://​doi.​org/​10.​1200/​JCO.​2009.​26.​8938.CrossRefPubMed
19.
Zurück zum Zitat • Mann G, Attarbaschi A, Schrappe M, De Lorenzo P, Peters C, Hann I, et al. Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)-rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study. Blood. 2010;116(15):2644–50. https://doi.org/10.1182/blood-2010-03-273532 Demonstration that HSCT in CR1 is superior to chemotherapy in infant MLL+ ALL carrying additional poor prognostic factors. CrossRefPubMed • Mann G, Attarbaschi A, Schrappe M, De Lorenzo P, Peters C, Hann I, et al. Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)-rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study. Blood. 2010;116(15):2644–50. https://​doi.​org/​10.​1182/​blood-2010-03-273532 Demonstration that HSCT in CR1 is superior to chemotherapy in infant MLL+ ALL carrying additional poor prognostic factors. CrossRefPubMed
20.
Zurück zum Zitat Heerema NA, Carroll AJ, Devidas M, Loh ML, Borowitz MJ, Gastier-Foster JM, et al. Intrachromosomal amplification of chromosome 21 is associated with inferior outcomes in children with acute lymphoblastic leukemia treated in contemporary standard-risk children’s oncology group studies: a report from the children’s oncology group. J Clin Oncol. 2013;31(27):3397–402. https://doi.org/10.1200/JCO.2013.49.1308.CrossRefPubMedPubMedCentral Heerema NA, Carroll AJ, Devidas M, Loh ML, Borowitz MJ, Gastier-Foster JM, et al. Intrachromosomal amplification of chromosome 21 is associated with inferior outcomes in children with acute lymphoblastic leukemia treated in contemporary standard-risk children’s oncology group studies: a report from the children’s oncology group. J Clin Oncol. 2013;31(27):3397–402. https://​doi.​org/​10.​1200/​JCO.​2013.​49.​1308.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Moorman AV, Robinson H, Schwab C, Richards SM, Hancock J, Mitchell CD, et al. Risk-directed treatment intensification significantly reduces the risk of relapse among children and adolescents with acute lymphoblastic leukemia and intrachromosomal amplification of chromosome 21: a comparison of the MRC ALL97/99 and UKALL2003 trials. J Clin Oncol. 2013;31(27):3389–96. https://doi.org/10.1200/JCO.2013.48.9377.CrossRefPubMed Moorman AV, Robinson H, Schwab C, Richards SM, Hancock J, Mitchell CD, et al. Risk-directed treatment intensification significantly reduces the risk of relapse among children and adolescents with acute lymphoblastic leukemia and intrachromosomal amplification of chromosome 21: a comparison of the MRC ALL97/99 and UKALL2003 trials. J Clin Oncol. 2013;31(27):3389–96. https://​doi.​org/​10.​1200/​JCO.​2013.​48.​9377.CrossRefPubMed
26.
Zurück zum Zitat Einsiedel HG, von Stackelberg A, Hartmann R, Fengler R, Schrappe M, Janka-Schaub G, et al. Long-term outcome in children with relapsed ALL by risk-stratified salvage therapy: results of trial acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Munster Group 87. J Clin Oncol. 2005;23(31):7942–50. https://doi.org/10.1200/JCO.2005.01.1031.CrossRefPubMed Einsiedel HG, von Stackelberg A, Hartmann R, Fengler R, Schrappe M, Janka-Schaub G, et al. Long-term outcome in children with relapsed ALL by risk-stratified salvage therapy: results of trial acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Munster Group 87. J Clin Oncol. 2005;23(31):7942–50. https://​doi.​org/​10.​1200/​JCO.​2005.​01.​1031.CrossRefPubMed
27.
Zurück zum Zitat Lawson SE, Harrison G, Richards S, Oakhill A, Stevens R, Eden OB, et al. The UK experience in treating relapsed childhood acute lymphoblastic leukaemia: a report on the medical research council UKALLR1 study. Br J Haematol. 2000;108(3):531–43.CrossRefPubMed Lawson SE, Harrison G, Richards S, Oakhill A, Stevens R, Eden OB, et al. The UK experience in treating relapsed childhood acute lymphoblastic leukaemia: a report on the medical research council UKALLR1 study. Br J Haematol. 2000;108(3):531–43.CrossRefPubMed
33.
36.
38.
Zurück zum Zitat • Peters C, Schrappe M, von Stackelberg A, Schrauder A, Bader P, Ebell W, et al. Stem-cell transplantation in children with acute lymphoblastic leukemia: a prospective international multicenter trial comparing sibling donors with matched unrelated donors-the ALL-SCT-BFM-2003 trial. J Clin Oncol. 2015;33(11):1265–74. https://doi.org/10.1200/JCO.2014.58.9747 The first prospective study to compare HSCT from unrelated donors and matched family donors in well-defined cohorts of children with high-risk ALL. CrossRefPubMed • Peters C, Schrappe M, von Stackelberg A, Schrauder A, Bader P, Ebell W, et al. Stem-cell transplantation in children with acute lymphoblastic leukemia: a prospective international multicenter trial comparing sibling donors with matched unrelated donors-the ALL-SCT-BFM-2003 trial. J Clin Oncol. 2015;33(11):1265–74. https://​doi.​org/​10.​1200/​JCO.​2014.​58.​9747 The first prospective study to compare HSCT from unrelated donors and matched family donors in well-defined cohorts of children with high-risk ALL. CrossRefPubMed
40.
Zurück zum Zitat • Locatelli F, Merli P, Pagliara D, Li Pira G, Falco M, Pende D, et al. Outcome of children with acute leukemia given HLA-haploidentical HSCT after alphabeta T-cell and B-cell depletion. Blood. 2017;130(5):677–85. https://doi.org/10.1182/blood-2017-04-779769 A large single-center study on TCRαβ-depleted haploidentical HSCT demonstrating similar outcomes when haploidentical, unrelated and matched-family donors were used. CrossRefPubMed • Locatelli F, Merli P, Pagliara D, Li Pira G, Falco M, Pende D, et al. Outcome of children with acute leukemia given HLA-haploidentical HSCT after alphabeta T-cell and B-cell depletion. Blood. 2017;130(5):677–85. https://​doi.​org/​10.​1182/​blood-2017-04-779769 A large single-center study on TCRαβ-depleted haploidentical HSCT demonstrating similar outcomes when haploidentical, unrelated and matched-family donors were used. CrossRefPubMed
45.
Zurück zum Zitat Berger M, Lanino E, Cesaro S, Zecca M, Vassallo E, Faraci M, et al. Feasibility and outcome of haploidentical hematopoietic stem cell transplantation with post-transplant high-dose cyclophosphamide for children and adolescents with hematologic malignancies: an AIEOP-GITMO retrospective multicenter study. Biol Blood Marrow Transplant. 2016;22(5):902–9. https://doi.org/10.1016/j.bbmt.2016.02.002.CrossRefPubMed Berger M, Lanino E, Cesaro S, Zecca M, Vassallo E, Faraci M, et al. Feasibility and outcome of haploidentical hematopoietic stem cell transplantation with post-transplant high-dose cyclophosphamide for children and adolescents with hematologic malignancies: an AIEOP-GITMO retrospective multicenter study. Biol Blood Marrow Transplant. 2016;22(5):902–9. https://​doi.​org/​10.​1016/​j.​bbmt.​2016.​02.​002.CrossRefPubMed
46.
Zurück zum Zitat Hong KT, Kang HJ, Choi JY, Hong CR, Cheon JE, Park JD, et al. Favorable outcome of post-transplantation cyclophosphamide haploidentical peripheral blood stem cell transplantation with targeted busulfan-based myeloablative conditioning using intensive pharmacokinetic monitoring in pediatric patients. Biol Blood Marrow Transplant. 2018;24(11):2239–44. https://doi.org/10.1016/j.bbmt.2018.06.034.CrossRefPubMed Hong KT, Kang HJ, Choi JY, Hong CR, Cheon JE, Park JD, et al. Favorable outcome of post-transplantation cyclophosphamide haploidentical peripheral blood stem cell transplantation with targeted busulfan-based myeloablative conditioning using intensive pharmacokinetic monitoring in pediatric patients. Biol Blood Marrow Transplant. 2018;24(11):2239–44. https://​doi.​org/​10.​1016/​j.​bbmt.​2018.​06.​034.CrossRefPubMed
47.
Zurück zum Zitat Rocha V, Cornish J, Sievers EL, Filipovich A, Locatelli F, Peters C, et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood. 2001;97(10):2962–71.CrossRefPubMed Rocha V, Cornish J, Sievers EL, Filipovich A, Locatelli F, Peters C, et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood. 2001;97(10):2962–71.CrossRefPubMed
52.
54.
Zurück zum Zitat Kato M, Ishida H, Koh K, Inagaki J, Kato K, Goto H, et al. Comparison of chemotherapeutic agents as a myeloablative conditioning with total body irradiation for pediatric acute lymphoblastic leukemia: a study from the pediatric ALL working group of the Japan Society for Hematopoietic Cell Transplantation. Pediatr Blood Cancer. 2015;62(10):1844–50. https://doi.org/10.1002/pbc.25602.CrossRefPubMed Kato M, Ishida H, Koh K, Inagaki J, Kato K, Goto H, et al. Comparison of chemotherapeutic agents as a myeloablative conditioning with total body irradiation for pediatric acute lymphoblastic leukemia: a study from the pediatric ALL working group of the Japan Society for Hematopoietic Cell Transplantation. Pediatr Blood Cancer. 2015;62(10):1844–50. https://​doi.​org/​10.​1002/​pbc.​25602.CrossRefPubMed
55.
Zurück zum Zitat Zecca M, Pession A, Messina C, Bonetti F, Favre C, Prete A, et al. Total body irradiation, thiotepa, and cyclophosphamide as a conditioning regimen for children with acute lymphoblastic leukemia in first or second remission undergoing bone marrow transplantation with HLA-identical siblings. J Clin Oncol. 1999;17(6):1838–46. https://doi.org/10.1200/JCO.1999.17.6.1838.CrossRefPubMed Zecca M, Pession A, Messina C, Bonetti F, Favre C, Prete A, et al. Total body irradiation, thiotepa, and cyclophosphamide as a conditioning regimen for children with acute lymphoblastic leukemia in first or second remission undergoing bone marrow transplantation with HLA-identical siblings. J Clin Oncol. 1999;17(6):1838–46. https://​doi.​org/​10.​1200/​JCO.​1999.​17.​6.​1838.CrossRefPubMed
56.
Zurück zum Zitat Blume KG, Forman SJ, O’Donnell MR, Doroshow JH, Krance RA, Nademanee AP, et al. Total body irradiation and high-dose etoposide: a new preparatory regimen for bone marrow transplantation in patients with advanced hematologic malignancies. Blood. 1987;69(4):1015–20.PubMed Blume KG, Forman SJ, O’Donnell MR, Doroshow JH, Krance RA, Nademanee AP, et al. Total body irradiation and high-dose etoposide: a new preparatory regimen for bone marrow transplantation in patients with advanced hematologic malignancies. Blood. 1987;69(4):1015–20.PubMed
57.
Zurück zum Zitat Snyder DS, Chao NJ, Amylon MD, Taguchi J, Long GD, Negrin RS, et al. Fractionated total body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 99 patients with acute leukemia in first complete remission. Blood. 1993;82(9):2920–8.PubMed Snyder DS, Chao NJ, Amylon MD, Taguchi J, Long GD, Negrin RS, et al. Fractionated total body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 99 patients with acute leukemia in first complete remission. Blood. 1993;82(9):2920–8.PubMed
58.
Zurück zum Zitat Marks DI, Forman SJ, Blume KG, Perez WS, Weisdorf DJ, Keating A, et al. A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission. Biol Blood Marrow Transplant. 2006;12(4):438–53. https://doi.org/10.1016/j.bbmt.2005.12.029.CrossRefPubMed Marks DI, Forman SJ, Blume KG, Perez WS, Weisdorf DJ, Keating A, et al. A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission. Biol Blood Marrow Transplant. 2006;12(4):438–53. https://​doi.​org/​10.​1016/​j.​bbmt.​2005.​12.​029.CrossRefPubMed
59.
Zurück zum Zitat Giorgiani G, Bozzola M, Locatelli F, Picco P, Zecca M, Cisternino M, et al. Role of busulfan and total body irradiation on growth of prepubertal children receiving bone marrow transplantation and results of treatment with recombinant human growth hormone. Blood. 1995;86(2):825–31.PubMed Giorgiani G, Bozzola M, Locatelli F, Picco P, Zecca M, Cisternino M, et al. Role of busulfan and total body irradiation on growth of prepubertal children receiving bone marrow transplantation and results of treatment with recombinant human growth hormone. Blood. 1995;86(2):825–31.PubMed
61.
Zurück zum Zitat Bunin N, Aplenc R, Kamani N, Shaw K, Cnaan A, Simms S. Randomized trial of busulfan vs total body irradiation containing conditioning regimens for children with acute lymphoblastic leukemia: a Pediatric Blood and Marrow Transplant Consortium study. Bone Marrow Transplant. 2003;32(6):543–8. https://doi.org/10.1038/sj.bmt.1704198.CrossRefPubMed Bunin N, Aplenc R, Kamani N, Shaw K, Cnaan A, Simms S. Randomized trial of busulfan vs total body irradiation containing conditioning regimens for children with acute lymphoblastic leukemia: a Pediatric Blood and Marrow Transplant Consortium study. Bone Marrow Transplant. 2003;32(6):543–8. https://​doi.​org/​10.​1038/​sj.​bmt.​1704198.CrossRefPubMed
62.
64.
Zurück zum Zitat Soiffer RJ, Kim HT, McGuirk J, Horwitz ME, Johnston L, Patnaik MM, et al. Prospective, randomized, double-blind, phase III clinical trial of anti-T-lymphocyte globulin to assess impact on chronic graft-versus-host disease-free survival in patients undergoing HLA-matched unrelated Myeloablative hematopoietic cell transplantation. J Clin Oncol. 2017;35(36):4003–11. https://doi.org/10.1200/JCO.2017.75.8177.CrossRefPubMedPubMedCentral Soiffer RJ, Kim HT, McGuirk J, Horwitz ME, Johnston L, Patnaik MM, et al. Prospective, randomized, double-blind, phase III clinical trial of anti-T-lymphocyte globulin to assess impact on chronic graft-versus-host disease-free survival in patients undergoing HLA-matched unrelated Myeloablative hematopoietic cell transplantation. J Clin Oncol. 2017;35(36):4003–11. https://​doi.​org/​10.​1200/​JCO.​2017.​75.​8177.CrossRefPubMedPubMedCentral
65.
Zurück zum Zitat •• Locatelli F, Bernardo ME, Bertaina A, Rognoni C, Comoli P, Rovelli A, et al. Efficacy of two different doses of rabbit anti-T-lymphocyte globulin to prevent graft-versus-host disease in children with haematological malignancies transplanted from an unrelated donor: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(8):1126–36. https://doi.org/10.1016/S1470-2045(17)30417-5 Multicenter randomized-controlled study demonstrating that a lower dose of ATLG determines a better outcome as compared to the use of an higher dose. This was due to a lower incidence of infectious complications, while the incidence of acute and chronic GvHD, as well as that of recurrence of the original disease was not significantly affected. CrossRefPubMed •• Locatelli F, Bernardo ME, Bertaina A, Rognoni C, Comoli P, Rovelli A, et al. Efficacy of two different doses of rabbit anti-T-lymphocyte globulin to prevent graft-versus-host disease in children with haematological malignancies transplanted from an unrelated donor: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(8):1126–36. https://​doi.​org/​10.​1016/​S1470-2045(17)30417-5 Multicenter randomized-controlled study demonstrating that a lower dose of ATLG determines a better outcome as compared to the use of an higher dose. This was due to a lower incidence of infectious complications, while the incidence of acute and chronic GvHD, as well as that of recurrence of the original disease was not significantly affected. CrossRefPubMed
74.
Zurück zum Zitat Ragab AH, Abdel-Mageed A, Shuster JJ, Frankel LS, Pullen J, van Eys J, et al. Clinical characteristics and treatment outcome of children with acute lymphocytic leukemia and Down’s syndrome. A Pediatric Oncology Group study. Cancer. 1991;67(4):1057–63.CrossRefPubMed Ragab AH, Abdel-Mageed A, Shuster JJ, Frankel LS, Pullen J, van Eys J, et al. Clinical characteristics and treatment outcome of children with acute lymphocytic leukemia and Down’s syndrome. A Pediatric Oncology Group study. Cancer. 1991;67(4):1057–63.CrossRefPubMed
75.
Zurück zum Zitat Rubin CM, Mick R, Johnson FL. Bone marrow transplantation for the treatment of haematological disorders in Down’s syndrome: toxicity and outcome. Bone Marrow Transplant. 1996;18(3):533–40.PubMed Rubin CM, Mick R, Johnson FL. Bone marrow transplantation for the treatment of haematological disorders in Down’s syndrome: toxicity and outcome. Bone Marrow Transplant. 1996;18(3):533–40.PubMed
77.
Zurück zum Zitat Meissner B, Borkhardt A, Dilloo D, Fuchs D, Friedrich W, Handgretinger R, et al. Relapse, not regimen-related toxicity, was the major cause of treatment failure in 11 children with Down syndrome undergoing haematopoietic stem cell transplantation for acute leukaemia. Bone Marrow Transplant. 2007;40(10):945–9. https://doi.org/10.1038/sj.bmt.1705844.CrossRefPubMed Meissner B, Borkhardt A, Dilloo D, Fuchs D, Friedrich W, Handgretinger R, et al. Relapse, not regimen-related toxicity, was the major cause of treatment failure in 11 children with Down syndrome undergoing haematopoietic stem cell transplantation for acute leukaemia. Bone Marrow Transplant. 2007;40(10):945–9. https://​doi.​org/​10.​1038/​sj.​bmt.​1705844.CrossRefPubMed
82.
Zurück zum Zitat Rives S, Estella J, Gomez P, Lopez-Duarte M, de Miguel PG, Verdeguer A, et al. Intermediate dose of imatinib in combination with chemotherapy followed by allogeneic stem cell transplantation improves early outcome in paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL): results of the Spanish Cooperative Group SHOP studies ALL-94, ALL-99 and ALL-2005. Br J Haematol. 2011;154(5):600–11. https://doi.org/10.1111/j.1365-2141.2011.08783.x.CrossRefPubMed Rives S, Estella J, Gomez P, Lopez-Duarte M, de Miguel PG, Verdeguer A, et al. Intermediate dose of imatinib in combination with chemotherapy followed by allogeneic stem cell transplantation improves early outcome in paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL): results of the Spanish Cooperative Group SHOP studies ALL-94, ALL-99 and ALL-2005. Br J Haematol. 2011;154(5):600–11. https://​doi.​org/​10.​1111/​j.​1365-2141.​2011.​08783.​x.CrossRefPubMed
86.
88.
Zurück zum Zitat Sasaki K, Jabbour EJ, Ravandi F, Short NJ, Thomas DA, Garcia-Manero G, et al. Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: a propensity score analysis. Cancer. 2016;122(23):3650–6. https://doi.org/10.1002/cncr.30231.CrossRefPubMed Sasaki K, Jabbour EJ, Ravandi F, Short NJ, Thomas DA, Garcia-Manero G, et al. Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: a propensity score analysis. Cancer. 2016;122(23):3650–6. https://​doi.​org/​10.​1002/​cncr.​30231.CrossRefPubMed
90.
Zurück zum Zitat •• von Stackelberg A, Locatelli F, Zugmaier G, Handgretinger R, Trippett TM, Rizzari C, et al. Phase I/phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. J Clin Oncol. 2016;34(36):4381–9. https://doi.org/10.1200/JCO.2016.67.3301 This study reports the results of a large phase I/phase II trial of blinatumomab in pediatric patients with relapsed/refractory ALL. CrossRef •• von Stackelberg A, Locatelli F, Zugmaier G, Handgretinger R, Trippett TM, Rizzari C, et al. Phase I/phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. J Clin Oncol. 2016;34(36):4381–9. https://​doi.​org/​10.​1200/​JCO.​2016.​67.​3301 This study reports the results of a large phase I/phase II trial of blinatumomab in pediatric patients with relapsed/refractory ALL. CrossRef
92.
Zurück zum Zitat •• Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in children and young adults with b-cell lymphoblastic leukemia. N Engl J Med. 2018;378(5):439–48. https://doi.org/10.1056/NEJMoa1709866 Large, updated, multicenter, phase II study proving the efficacy of tisagenlecleucel in pediatric and young adult patients with relapsed/refractory CD19+−ALL. CrossRefPubMedPubMedCentral •• Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in children and young adults with b-cell lymphoblastic leukemia. N Engl J Med. 2018;378(5):439–48. https://​doi.​org/​10.​1056/​NEJMoa1709866 Large, updated, multicenter, phase II study proving the efficacy of tisagenlecleucel in pediatric and young adult patients with relapsed/refractory CD19+−ALL. CrossRefPubMedPubMedCentral
94.
Zurück zum Zitat • Kansagra AJ, Frey NV, Bar M, Laetsch TW, Carpenter PA, Savani BN, et al. Clinical utilization of chimeric antigen receptors T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)—an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT). Biol Blood Marrow Transplant. 2018. https://doi.org/10.1016/j.bbmt.2018.12.068 A comprehensive expert opinion on the use of CD19 CAR T cells for ALL, including a commentary on the role of HSCT. • Kansagra AJ, Frey NV, Bar M, Laetsch TW, Carpenter PA, Savani BN, et al. Clinical utilization of chimeric antigen receptors T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)—an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT). Biol Blood Marrow Transplant. 2018. https://​doi.​org/​10.​1016/​j.​bbmt.​2018.​12.​068 A comprehensive expert opinion on the use of CD19 CAR T cells for ALL, including a commentary on the role of HSCT.
Metadaten
Titel
Hematopoietic Stem Cell Transplantation in Pediatric Acute Lymphoblastic Leukemia
verfasst von
Pietro Merli
Mattia Algeri
Francesca Del Bufalo
Franco Locatelli
Publikationsdatum
26.02.2019
Verlag
Springer US
Erschienen in
Current Hematologic Malignancy Reports / Ausgabe 2/2019
Print ISSN: 1558-8211
Elektronische ISSN: 1558-822X
DOI
https://doi.org/10.1007/s11899-019-00502-2

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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

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