nach oben

Indian Journal of Hematology and Blood Transfusion

Erschienen in:

23.01.2019 | Review Article

Allogeneic Hematopoietic Stem Cell Transplantation for Myeloma: Time for an Obituary or Not Just Yet!

verfasst von: Sarita Rani Jaiswal, Suparno Chakrabarti

Erschienen in: Indian Journal of Hematology and Blood Transfusion | Ausgabe 3/2019

Einloggen, um Zugang zu erhalten

Abstract

The management of myeloma has evolved dramatically in the last two decades. High dose melphalan and autologous hematopoietic stem cell transplantation (HSCT) marked the beginning of this journey. This was followed by an explosion of novel agents which were approved for management of myeloma. Allogeneic HSCT which was deemed as the only curative option was largely abhorred due to high transplant-related mortality (TRM) until the advent of reduced intensity conditioning (RIC). An approach of tandem autologous and RIC-allogeneic transplantations has showed the best promise for cure for this condition, particularly for those with high-risk cytogenetics. Yet, allogeneic HSCT seems to have fallen out of favor due to the projected high TRM and late relapses, even though the alternatives do not offer a cure, but merely prolong survival. Offering an allogeneic HSCT as a final resort in unlikely to yield gratifying results. At the same time, allogeneic HSCT needs to evolve in a disease-specific manner to address the relevant concerns regarding TRM and relapse. With the introduction of effective GVHD prophylaxis in the form of post-transplantation cyclophosphamide, transplantation from a haploidentical family donor has become a reality. The challenge lies in segregating graft-vs-myeloma effect from a graft-versus-host effect. We discuss the pro-survival and anti-apoptotic pathways via CD28-CD86 interactions which confer survival advantages to myeloma cells and the possibility of disruption of this pathway in the context of haploidentical transplantation through the use of CTLA4Ig without incurring T cell alloreactivity.

Harousseau JL, Attal M, Divine M, Marit G, Leblond V, Stoppa AM et al (1995) Autologous stem cell transplantation after first remission induction treatment in multiple myeloma: a report of the French Registry on autologous transplantation in multiple myeloma. Blood 85(11):3077–3085PubMed

Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P et al (1999) Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 341(21):1565–1571. https://doi.org/10.1056/NEJM199911183412102 CrossRefPubMed

Kumar S (2017) Emerging options in multiple myeloma: targeted, immune, and epigenetic therapies. Hematol Am Soc Hematol Edu Program 2017(1):518–524. https://doi.org/10.1182/asheducation-2017.1.518 CrossRef

Harousseau JL, Attal M (2017) How I treat first relapse of myeloma. Blood 130(8):963–973. https://doi.org/10.1182/blood-2017-03-726703 CrossRefPubMed

Bjorkstrand BB, Ljungman P, Svensson H, Hermans J, Alegre A, Apperley J et al (1996) Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: a retrospective case-matched study from the European Group for Blood and Marrow Transplantation. Blood 88(12):4711–4718PubMed

Gahrton G, Tura S, Ljungman P, Blade J, Brandt L, Cavo M et al (1995) Prognostic factors in allogeneic bone marrow transplantation for multiple myeloma. J Clin Oncol 13(6):1312–1322. https://doi.org/10.1200/JCO.1995.13.6.1312 CrossRefPubMed

Hari P (2017) Recent advances in understanding multiple myeloma. Hematol Oncol Stem Cell Ther 10(4):267–271. https://doi.org/10.1016/j.hemonc.2017.05.005 CrossRefPubMed

Chakrabarti S, Buyck HC (2007) Reduced-intensity transplantation in the treatment of haematological malignancies: current status and future-prospects. Curr Stem Cell Res Ther 2(2):163–188CrossRefPubMed

Karlin L, Arnulf B, Chevret S, Ades L, Robin M, De Latour RP et al (2011) Tandem autologous non-myeloablative allogeneic transplantation in patients with multiple myeloma relapsing after a first high dose therapy. Bone Marrow Transplant 46(2):250–256. https://doi.org/10.1038/bmt.2010.90 CrossRefPubMed

10.

Bjorkstrand B, Iacobelli S, Hegenbart U, Gruber A, Greinix H, Volin L et al (2011) Tandem autologous/reduced-intensity conditioning allogeneic stem-cell transplantation versus autologous transplantation in myeloma: long-term follow-up. J Clin Oncol 29(22):3016–3022. https://doi.org/10.1200/JCO.2010.32.7312 CrossRefPubMed

11.

Palumbo A, Attal M, Roussel M (2011) Shifts in the therapeutic paradigm for patients newly diagnosed with multiple myeloma: maintenance therapy and overall survival. Clin Cancer Res 17(6):1253–1263. https://doi.org/10.1158/1078-0432.CCR-10-1925 CrossRefPubMed

12.

Rajkumar SV (2011) Multiple myeloma: 2011 update on diagnosis, risk-stratification, and management. Am J Hematol 86(1):57–65. https://doi.org/10.1002/ajh.21913 CrossRefPubMed

13.

Rajkumar SV (2016) Myeloma today: Disease definitions and treatment advances. Am J Hematol. 91(1):90–100. https://doi.org/10.1002/ajh.24236 CrossRefPubMedPubMedCentral

14.

Palumbo A, Cavallo F, Gay F, Di Raimondo F, Ben Yehuda D, Petrucci MT et al (2014) Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med 371(10):895–905. https://doi.org/10.1056/NEJMoa1402888 CrossRefPubMed

15.

Hari P, Pasquini MC, Vesole DH (2006) Cure of multiple myeloma – more hype, less reality. Bone Marrow Transplant 37(1):1–18. https://doi.org/10.1038/sj.bmt.1705194 CrossRefPubMed

16.

Hari P, Reece DE, Randhawa J, Flomenberg N, Howard DS, Badros AZ et al (2018) Final outcomes of escalated melphalan 280 mg/m(2) with amifostine cytoprotection followed autologous hematopoietic stem cell transplantation for multiple myeloma: high CR and VGPR rates do not translate into improved survival. Bone Marrow Transplant. https://doi.org/10.1038/s41409-018-0261-y CrossRefPubMed

17.

Breitkreutz I, Becker N, Benner A, Kosely F, Heining C, Hillengass J et al (2016) Dose-intensified bendamustine followed by autologous peripheral blood stem cell support in relapsed and refractory multiple myeloma with impaired bone marrow function. Hematol Oncol 34(4):200–207. https://doi.org/10.1002/hon.2199 CrossRefPubMed

18.

Roussel M, Moreau P, Huynh A, Mary JY, Danho C, Caillot D et al (2010) Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM). Blood 115(1):32–37. https://doi.org/10.1182/blood-2009-06-229658 CrossRefPubMed

19.

Byun JM, Lee J, Shin SJ, Kang M, Yoon SS, Koh Y (2018) Busulfan plus melphalan versus high-dose melphalan as conditioning regimens in autologous stem cell transplantation for newly diagnosed multiple myeloma. Blood Res 53(2):105–109. https://doi.org/10.5045/br.2018.53.2.105 CrossRefPubMedPubMedCentral

20.

Moreau P (2017) How I treat myeloma with new agents. Blood 130(13):1507–1513. https://doi.org/10.1182/blood-2017-05-743203 CrossRefPubMed

21.

Auner HW, Szydlo R, van Biezen A, Iacobelli S, Gahrton G, Milpied N et al (2013) Reduced intensity-conditioned allogeneic stem cell transplantation for multiple myeloma relapsing or progressing after autologous transplantation: a study by the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 48(11):1395–1400. https://doi.org/10.1038/bmt.2013.73 CrossRefPubMed

22.

Kane RC, Farrell AT, Sridhara R, Pazdur R (2006) United States Food and Drug Administration approval summary: bortezomib for the treatment of progressive multiple myeloma after one prior therapy. Clin Cancer Res 12(10):2955–2960. https://doi.org/10.1158/1078-0432.CCR-06-0170 CrossRefPubMed

23.

Pulte ED, Dmytrijuk A, Nie L, Goldberg KB, McKee AE, Farrell AT et al (2018) FDA Approval Summary: Lenalidomide as Maintenance Therapy After Autologous Stem Cell Transplant in Newly Diagnosed Multiple Myeloma. Oncologist 23(6):734–739. https://doi.org/10.1634/theoncologist.2017-0440 CrossRefPubMedPubMedCentral

24.

Baz RC, Martin TG 3rd, Lin HY, Zhao X, Shain KH, Cho HJ et al (2016) Randomized multicenter phase 2 study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma. Blood 127(21):2561–2568. https://doi.org/10.1182/blood-2015-11-682518 CrossRefPubMed

25.

Yin X, Tang L, Fan F, Jiang Q, Sun C, Hu Y (2018) Allogeneic stem-cell transplantation for multiple myeloma: a systematic review and meta-analysis from 2007 to 2017. Cancer Cell Int 18:62. https://doi.org/10.1186/s12935-018-0553-8 CrossRefPubMedPubMedCentral

26.

Collins RH Jr, Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R et al (1997) Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol 15(2):433–444CrossRefPubMed

27.

Zeidan AM, Forde PM, Symons H, Chen A, Smith BD, Pratz K et al (2014) HLA-haploidentical donor lymphocyte infusions for patients with relapsed hematologic malignancies after related HLA-haploidentical bone marrow transplantation. Biol Blood Marrow Transplant 20(3):314–318. https://doi.org/10.1016/j.bbmt.2013.11.020 CrossRefPubMed

28.

Yanamandra U, Khattry N, Kumar S, Raje N, Jain A, Jagannath S et al (2017) Consensus in the Management of Multiple Myeloma in India at Myeloma State of the Art 2016 Conference. Indian J Hematol Blood Transfus 33(1):15–21. https://doi.org/10.1007/s12288-016-0773-9 CrossRefPubMedPubMedCentral

29.

Chakrabarti S (2002) Critical factors in optimizing graft-versus-leukemia effect for relapsed leukemias. J Clin Oncol 20(11):2756. https://doi.org/10.1200/JCO.2002.20.11.2756 CrossRefPubMed

30.

Malek E, El-Jurdi N, Kroger N, de Lima M (2017) Allograft for Myeloma: Examining Pieces of the Jigsaw Puzzle. Front Oncol 7:287. https://doi.org/10.3389/fonc.2017.00287 CrossRefPubMedPubMedCentral

31.

Kolb HJ (2008) Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood 112(12):4371–4383. https://doi.org/10.1182/blood-2008-03-077974 CrossRefPubMed

32.

Schmid C, Labopin M, Nagler A, Bornhauser M, Finke J, Fassas A et al (2007) Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia Working Party. J Clin Oncol 25(31):4938–4945. https://doi.org/10.1200/JCO.2007.11.6053 CrossRefPubMed

33.

Soiffer RJ (2008) Donor lymphocyte infusions for acute myeloid leukaemia. Best Pract Res Clin Haematol 21(3):455–466. https://doi.org/10.1016/j.beha.2008.07.009 CrossRefPubMed

34.

Bashey A, Solomon SR (2014) T-cell replete haploidentical donor transplantation using post-transplant CY: an emerging standard-of-care option for patients who lack an HLA-identical sibling donor. Bone Marrow Transplant 49(8):999–1008. https://doi.org/10.1038/bmt.2014.62 CrossRefPubMed

35.

Bashey A, Zhang X, Jackson K, Brown S, Ridgeway M, Solh M et al (2015) Comparison of Outcomes of Hematopoietic Cell Transplants from T-Replete Haploidentical Donors Using Post-Transplantation Cyclophosphamide with 10 of 10 HLA-A, -B, -C, -DRB1, and -DQB1 Allele-Matched Unrelated Donors and HLA-Identical Sibling Donors: A Multivariable Analysis Including Disease Risk Index. Biol Blood Marrow Transplant. https://doi.org/10.1016/j.bbmt.2015.09.002 CrossRefPubMedPubMedCentral

36.

Raiola AM, Dominietto A, Di GC, Lamparelli T, Gualandi F, Ibatici A et al (2014) Unmanipulated haploidentical transplants compared with other alternative donors and matched sibling grafts. Biol Blood Marrow Transplant 20(10):1573–1579. https://doi.org/10.1016/j.bbmt.2014.05.029 CrossRefPubMed

37.

McCurdy SR, Kanakry JA, Showel MM, Tsai HL, Bolanos-Meade J, Rosner GL et al (2015) Risk-stratified outcomes of nonmyeloablative HLA-haploidentical BMT with high-dose posttransplantation cyclophosphamide. Blood 125(19):3024–3031. https://doi.org/10.1182/blood-2015-01-623991 CrossRefPubMedPubMedCentral

38.

Jaiswal SR, Zaman S, Chakrabarti A, Sen S, Mukherjee S, Bhargava S et al (2016) Improved Outcome of Refractory/Relapsed Acute Myeloid Leukemia after Post-Transplantation Cyclophosphamide-Based Haploidentical Transplantation with Myeloablative Conditioning and Early Prophylactic Granulocyte Colony-Stimulating Factor-Mobilized Donor Lymphocyte Infusions. Biol Blood Marrow Transplant 22(10):1867–1873. https://doi.org/10.1016/j.bbmt.2016.07.016 CrossRefPubMed

39.

Kanakry CG, Ganguly S, Zahurak M, Bolanos-Meade J, Thoburn C, Perkins B et al (2013) Aldehyde dehydrogenase expression drives human regulatory T cell resistance to posttransplantation cyclophosphamide. Sci Transl Med 5(211):211. https://doi.org/10.1126/scitranslmed.3006960 CrossRef

40.

Jaiswal SR, Zaman S, Nedunchezhian M, Chakrabarti A, Bhakuni P, Ahmed M et al (2017) CD56-enriched donor cell infusion after post-transplantation cyclophosphamide for haploidentical transplantation of advanced myeloid malignancies is associated with prompt reconstitution of mature natural killer cells and regulatory T cells with reduced incidence of acute graft versus host disease: A pilot study. Cytotherapy 19(4):531–542. https://doi.org/10.1016/j.jcyt.2016.12.006 CrossRefPubMed

41.

Najafian N, Sayegh MH (2000) CTLA4-Ig: a novel immunosuppressive agent. Expert Opin Investig Drugs 9(9):2147–2157. https://doi.org/10.1517/13543784.9.9.2147 CrossRefPubMed

42.

Jaiswal SR, Bhakuni P, Zaman S, Bansal S, Bharadwaj P, Bhargava S et al (2017) T cell costimulation blockade promotes transplantation tolerance in combination with sirolimus and post-transplantation cyclophosphamide for haploidentical transplantation in children with severe aplastic anemia. Transpl Immunol. https://doi.org/10.1016/j.trim.2017.07.004 CrossRefPubMed

43.

Chen Y, Fukuda T, Thakar MS, Kornblit BT, Storer BE, Santos EB et al (2011) Immunomodulatory effects induced by cytotoxic T lymphocyte antigen 4 immunoglobulin with donor peripheral blood mononuclear cell infusion in canine major histocompatibility complex-haplo-identical non-myeloablative hematopoietic cell transplantation. Cytotherapy 13(10):1269–1280. https://doi.org/10.3109/14653249.2011.586997 CrossRefPubMedPubMedCentral

44.

Kean LS, Hamby K, Koehn B, Lee E, Coley S, Stempora L et al (2006) NK cells mediate costimulation blockade-resistant rejection of allogeneic stem cells during nonmyeloablative transplantation. Am J Transplant. 6(2):292–304. https://doi.org/10.1111/j.1600-6143.2005.01172.x CrossRefPubMed

45.

Peng Y, Luo G, Zhou J, Wang X, Hu J, Cui Y et al (2013) CD86 is an activation receptor for NK cell cytotoxicity against tumor cells. PLoS ONE 8(12):e83913. https://doi.org/10.1371/journal.pone.0083913 CrossRefPubMedPubMedCentral

46.

Jaiswal SR, Bhakuni P, Zaman S, Chakrabarti S (2017) CTLA4Ig Primed Donor Lymphocyte Infusions (DLI): A Novel Approach to Natural Killer Cell Immunotherapy Following Haploidentical PBSC Transplantation for Advanced Hematological Malignancies. Blood 130(1):4468

47.

Murray ME, Gavile CM, Nair JR, Koorella C, Carlson LM, Buac D et al (2014) CD28-mediated pro-survival signaling induces chemotherapeutic resistance in multiple myeloma. Blood 123(24):3770–3779. https://doi.org/10.1182/blood-2013-10-530964 CrossRefPubMedPubMedCentral

48.

Nair JR, Carlson LM, Koorella C, Rozanski CH, Byrne GE, Bergsagel PL et al (2011) CD28 expressed on malignant plasma cells induces a prosurvival and immunosuppressive microenvironment. J Immunol 187(3):1243–1253. https://doi.org/10.4049/jimmunol.1100016 CrossRefPubMedPubMedCentral

49.

Besson L, Charrier E, Karlin L, Allatif O, Marcais A, Rouzaire P et al (2018) One-Year Follow-Up of Natural Killer Cell Activity in Multiple Myeloma Patients Treated With Adjuvant Lenalidomide Therapy. Front Immunol 9:704. https://doi.org/10.3389/fimmu.2018.00704 CrossRefPubMedPubMedCentral

50.

Hsu AK, Quach H, Tai T, Prince HM, Harrison SJ, Trapani JA et al (2011) The immunostimulatory effect of lenalidomide on NK-cell function is profoundly inhibited by concurrent dexamethasone therapy. Blood 117(5):1605–1613. https://doi.org/10.1182/blood-2010-04-278432 CrossRefPubMed

Titel: Allogeneic Hematopoietic Stem Cell Transplantation for Myeloma: Time for an Obituary or Not Just Yet!
verfasst von: Sarita Rani Jaiswal
Suparno Chakrabarti
Publikationsdatum: 23.01.2019
Verlag: Springer India
Erschienen in: Indian Journal of Hematology and Blood Transfusion / Ausgabe 3/2019
Print ISSN: 0971-4502
Elektronische ISSN: 0974-0449
DOI: https://doi.org/10.1007/s12288-019-01077-x

Neu im Fachgebiet Onkologie

25.04.2024 | Nierenkarzinom | Nachrichten

Springer Medizin

Allogeneic Hematopoietic Stem Cell Transplantation for Myeloma: Time for an Obituary or Not Just Yet!

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2019

Plasma Coagulation Tests for Detection of Antiphospholipid Antibodies: What’s Good, and What Might Be Improved?

Establishing Blood Group Genotyping to Resolve ABO Discrepancies in Iran

Detection of EBV DNA in Non-Hodgkin Lymphoma Patients in Bulgaria

Clinical Profile and Short Term Outcome of Adult Patients with Acute Myeloid Leukemia

Hemoglobin Titusville [α2 Codon 94 G>A]: A Rare Alpha Globin Chain Variant Causing Low Oxygen Saturation

Obituary: Professor Sir David John Weatherall GBE, MD, FRCP, FRS

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie