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Stem cell transplantation

Bone marrow versus mobilized peripheral blood stem cell graft in T-cell-replete haploidentical transplantation in acute lymphoblastic leukemia

Leukemia volume 34, pages 2766–2775 (2020)Cite this article

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Abstract

The ideal stem cell graft source remains unknown in haploidentical haematopietic cell transplantation (haplo-HCT) with posttransplantation cyclophosphamide (PTCy). This study compared outcomes of bone marrow (BM) versus peripheral blood (PB) stem cell graft for haplo-HCT in acute lymphoblastic leukemia (ALL). A total of 314 patients with ALL (BM—157; PB—157) were included in this study. The cumulative incidence of engraftment at day 30 was higher in the PB group compared with BM (93% vs. 88%, p < 0.01). The incidences of acute graft-versus-host disease (GVHD) and chronic GVHD were not significantly different between the study cohorts. In the multivariate analysis, there were tendencies toward a higher incidence of grade II–IV acute GVHD (hazard ratio (HR) = 1.52, p = 0.07), chronic GVHD (HR = 1.58, p = 0.05), and nonrelapse mortality (NRM) (HR = 1.66, p = 0.06) in patients receiving PB versus BM graft, respectively. The use of PB grafts was associated with lower leukemia-free survival (LFS) (HR = 1.43, p = 0.05), overall survival (OS) (HR = 1.59, p = 0.02), and GVHD-free, relapse-free survival (GRFS) (HR = 1.42, p = 0.03) compared with BM grafts. There was no difference in relapse incidence (HR = 1.23, p = 0.41) between the study groups. In conclusion, use of BM graft results in better survival after haplo-HCT with PTCy in patients with ALL, compared with PB stem cell graft.

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Fig. 1: Transplant outcomes of bone marrow versus peripheral blood transplantation using haploidentical donors in patients with acute lymphoblastic leukemia.
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Please contact the EBMT for the original data used for this study (www.ebmt.org).

References

  1. Enrico M, Francesco S, Francesco L. Treatment of adult patients with relapsed/refractory B-cell Philadelphia-negative acute lymphoblastic. Leuk Clin Hematol Int. 2019;1:85–93.

    Google Scholar 

  2. Elad J. Relapse and resistance to CAR-T cells and blinatumomab in hematologic malignancies. Clin Hematol Int. 2019;1:79–84.

    Article  Google Scholar 

  3. Passweg JR, Baldomero H, Bader P, Bonini C, Cesaro S, Dreger P, et al. Hematopoietic stem cell transplantation in Europe 2014: more than 40,000 transplants annually. Bone Marrow Transplant. 2016;51:786–92.

    Article  CAS  Google Scholar 

  4. Kanakry CG, Fuchs EJ, Luznik L. Modern approaches to HLA-haploidentical blood or marrow transplantation. Nat Rev Clin Oncol. 2016;13:10–24.

    Article  CAS  Google Scholar 

  5. Ciurea SO, Zhang MJ, Bacigalupo AA, Bashey A, Appelbaum FR, Aljitawi OS, et al. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. Blood. 2015;126:1033–40.

    Article  CAS  Google Scholar 

  6. Bashey A, Zhang X, Jackson K, Brown S, Ridgeway M, Solh M, et al. 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. 2016;22:125–33.

    Article  CAS  Google Scholar 

  7. McCurdy SR, Kasamon YL, Kanakry CG, Bolanos-Meade J, Tsai HL, Showel MM, et al. Comparable composite endpoints after HLA-matched and HLA-haploidentical transplantation with post-transplantation cyclophosphamide. Haematologica. 2017;102:391–400.

    Article  CAS  Google Scholar 

  8. Solomon SR, Sizemore CA, Zhang X, Brown S, Holland HK, Morris LE, et al. Impact of donor type on outcome after allogeneic hematopoietic cell transplantation for acute leukemia. Biol Blood Marrow Transplant. 2016;22:1816–22.

    Article  Google Scholar 

  9. Shem-Tov N, Peczynski C, Labopin M, Itala-Remes M, Blaise D, Labussiere-Wallet H, et al. Haploidentical vs. unrelated allogeneic stem cell transplantation for acute lymphoblastic leukemia in first complete remission: on behalf of the ALWP of the EBMT. Leukemia. 2020;34:283–92.

    Article  CAS  Google Scholar 

  10. Piemontese S, Ciceri F, Labopin M, Arcese W, Kyrcz-Krzemien S, Santarone S, et al. A comparison between allogeneic stem cell transplantation from unmanipulated haploidentical and unrelated donors in acute leukemia. J Hematol Oncol. 2017;10:24.

    Article  Google Scholar 

  11. Versluis J, Labopin M, Ruggeri A, Socie G, Wu D, Volin L, et al. Alternative donors for allogeneic hematopoietic stem cell transplantation in poor-risk AML in CR1. Blood Adv. 2017;1:477–85.

    Article  CAS  Google Scholar 

  12. O’Donnell PV, Luznik L, Jones RJ, Vogelsang GB, Leffell MS, Phelps M, et al. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2002;8:377–86.

    Article  Google Scholar 

  13. Luznik L, O’Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14:641–50.

    Article  CAS  Google Scholar 

  14. Bacigalupo A, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, et al. Unmanipulated haploidentical bone marrow transplantation and post-transplant cyclophosphamide for hematologic malignanices following a myeloablative conditioning: an update. Bone Marrow Transplant. 2015;50:S37–9.

    Article  CAS  Google Scholar 

  15. Sugita J, Kagaya Y, Miyamoto T, Shibasaki Y, Nagafuji K, Ota S, et al. Myeloablative and reduced-intensity conditioning in HLA-haploidentical peripheral blood stem cell transplantation using post-transplant cyclophosphamide. Bone Marrow Transplant. 2019;54:432–41.

    Article  CAS  Google Scholar 

  16. Maria Queralt S, Arjun Datt L, Wilson L, Zeyad A-S, David L, Dennis K, et al. Safety and efficacy of haploidentical peripheral blood stem cell transplantation for myeloid malignancies using post-transplantation cyclophosphamide and anti-thymocyte globulin as graft-versus-host disease prophylaxis. Clin Hematol Int. 2019;1:105–13.

    Google Scholar 

  17. Bashey A, Zhang MJ, McCurdy SR, St Martin A, Argall T, Anasetti C, et al. Mobilized peripheral blood stem cells versus unstimulated bone marrow as a graft source for T-cell-replete haploidentical donor transplantation using post-transplant cyclophosphamide. J Clin Oncol. 2017;35:3002–9.

    Article  CAS  Google Scholar 

  18. O’Donnell PV, Eapen M, Horowitz MM, Logan BR, DiGilio A, Brunstein C, et al. Comparable outcomes with marrow or peripheral blood as stem cell sources for hematopoietic cell transplantation from haploidentical donors after non-ablative conditioning: a matched-pair analysis. Bone Marrow Transplant. 2016;51:1599–601.

    Article  Google Scholar 

  19. Castagna L, Crocchiolo R, Furst S, Bramanti S, El Cheikh J, Sarina B, et al. Bone marrow compared with peripheral blood stem cells for haploidentical transplantation with a nonmyeloablative conditioning regimen and post-transplantation cyclophosphamide. Biol Blood Marrow Transplant. 2014;20:724–9.

    Article  Google Scholar 

  20. Bradstock K, Bilmon I, Kwan J, Blyth E, Micklethwaite K, Huang G, et al. Influence of stem cell source on outcomes of allogeneic reduced-intensity conditioning therapy transplants using haploidentical related donors. Biol Blood Marrow Transplant. 2015;21:1641–5.

    Article  Google Scholar 

  21. Ruggeri A, Labopin M, Bacigalupo A, Gulbas Z, Koc Y, Blaise D, et al. Bone marrow versus mobilized peripheral blood stem cells in haploidentical transplants using posttransplantation cyclophosphamide. Cancer. 2018;124:1428–37.

    Article  CAS  Google Scholar 

  22. Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15:1628–33.

    Article  Google Scholar 

  23. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825–8.

    CAS  PubMed  Google Scholar 

  24. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69:204–17.

    Article  CAS  Google Scholar 

  25. Ruggeri A, Labopin M, Ciceri F, Mohty M, Nagler A. Definition of GvHD-free, relapse-free survival for registry-based studies: an ALWP-EBMT analysis on patients with AML in remission. Bone Marrow Transplant. 2016;51:610–1.

    Article  CAS  Google Scholar 

  26. Abraham SK, Arnon N, Bipin S. Summary of scientific and statistical methods, study endpoints and definitions for observational and registry-based studies in hematopoietic cell transplantation. Clin Hematol Int. 2019;2:2–4.

    Google Scholar 

  27. Andersen PK, Klein JP, Zhang MJ. Testing for centre effects in multi-centre survival studies: a Monte Carlo comparison of fixed and random effects tests. Stat Med. 1999;18:1489–500.

    Article  CAS  Google Scholar 

  28. Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med. 2012;367:1487–96.

    Article  CAS  Google Scholar 

  29. Savani BN, Labopin M, Blaise D, Niederwieser D, Ciceri F, Ganser A, et al. Peripheral blood stem cell graft compared to bone marrow after reduced intensity conditioning regimens for acute leukemia: a report from the ALWP of the EBMT. Haematologica. 2016;101:256–62.

    Article  CAS  Google Scholar 

  30. Eapen M, Logan BR, Horowitz MM, Zhong X, Perales MA, Lee SJ, et al. Bone marrow or peripheral blood for reduced-intensity conditioning unrelated donor transplantation. J Clin Oncol. 2015;33:364–9.

    Article  Google Scholar 

  31. Castagna L, Bramanti S, Devillier R, Sarina B, Crocchiolo R, Furst S, et al. Haploidentical transplantation with post-infusion cyclophosphamide in advanced Hodgkin lymphoma. Bone Marrow Transplant. 2017;52:683–8.

    Article  CAS  Google Scholar 

  32. Yu X, Liu L, Xie Z, Dong C, Zhao L, Zhang J, et al. Bone marrow versus peripheral blood as a graft source for haploidentical donor transplantation in adults using post-transplant cyclophosphamide—a systematic review and meta-analysis. Crit Rev Oncol Hematol. 2019;133:120–8.

    Article  Google Scholar 

  33. Wachsmuth LP, Patterson MT, Eckhaus MA, Venzon DJ, Gress RE, Kanakry CG. Post-transplantation cyclophosphamide prevents graft-versus-host disease by inducing alloreactive T cell dysfunction and suppression. J Clin Investig. 2019;129:2357–73.

    Article  Google Scholar 

  34. Ganguly S, Ross DB, Panoskaltsis-Mortari A, Kanakry CG, Blazar BR, Levy RB, et al. Donor CD4+ Foxp3+ regulatory T cells are necessary for posttransplantation cyclophosphamide-mediated protection against GVHD in mice. Blood. 2014;124:2131–41.

    Article  CAS  Google Scholar 

  35. Zhao XY, Wang YT, Mo XD, Zhao XS, Wang YZ, Chang YJ, et al. Higher frequency of regulatory T cells in granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts compared with G-CSF-primed peripheral blood grafts. J Transl Med. 2015;13:145.

    Article  Google Scholar 

  36. Ding L, Zhu H, Yang Y, Yan HM, Zhang HH, Han DM, et al. The absolute number of regulatory T cells in unmanipulated peripheral blood grafts predicts the occurrence of acute graft-versus-host disease post haplo-identical hematopoietic stem cell transplantation. Leuk Res. 2017;56:13–20.

    Article  CAS  Google Scholar 

  37. Copsel S, Wolf D, Komanduri KV, Levy RB. The promise of CD4(+)FoxP3(+) regulatory T-cell manipulation in vivo: applications for allogeneic hematopoietic stem cell transplantation. Haematologica. 2019;104:1309–21.

    Article  CAS  Google Scholar 

  38. Deotare U, Atenafu EG, Loach D, Michelis FV, Kim DD, Thyagu S, et al. Reduction of severe acute graft-versus-host disease using a combination of pre transplant anti-thymocyte globulin and post-transplant cyclophosphamide in matched unrelated donor transplantation. Bone Marrow Transplant. 2018;53:361–5.

    Article  CAS  Google Scholar 

  39. Law AD, Salas MQ, Lam W, Michelis FV, Thyagu S, Kim DDH, et al. Reduced-intensity conditioning and dual T lymphocyte suppression with antithymocyte globulin and post-transplant cyclophosphamide as graft-versus-host disease prophylaxis in haploidentical hematopoietic stem cell transplants for hematological malignancies. Biol Blood Marrow Transplant. 2018;24:2259–64.

    Article  Google Scholar 

  40. Wang Y, Wu DP, Liu QF, Xu LP, Liu KY, Zhang XH, et al. Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients. J Hematol Oncol. 2019;12:88.

    Article  Google Scholar 

  41. R Core Team. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2017. https://www.R-project.org/.

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Acknowledgements

We sincerely thank the centers of the EBMT and national registries for contributing patient information and data collection.

Author information

Author notes

  1. These authors contributed equally: Arnon Nagler, Bhagirathbhai Dholaria

Authors and Affiliations

  1. Division of Hematology, Chaim Sheba Medical Center, Tel Aviv University, Tel Hashomer, Israel

    Arnon Nagler

  2. EBMT ALWP Office, Saint Antoine Hospital, Paris, France

    Arnon Nagler & Mohamad Mohty

  3. Department of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN, USA

    Bhagirathbhai Dholaria & Bipin N. Savani

  4. Department of Haematology and EBMT Paris Study Office/CEREST-TC, Saint Antoine Hospital, Paris, France

    Myriam Labopin

  5. Hematology and Transplant Center, IRCCS Ospedale Policlinico San Martino, Genova, Italy

    Emanuele Angelucci

  6. Medicana International, Istanbul, Turkey

    Yener Koc

  7. Hematopoietic SCT Unit, Florence Nightingale Sisli Hospital, Istanbul, Turkey

    Mutlu Arat

  8. Ospedale San Gerardo, Clinica Ematologica dell’Universita Milano-Biocca, Monza, Italy

    Pietro Pioltelli

  9. Divisione di Ematologia, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome, Italy

    Simona Sica

  10. Bone Marrow Transplantation Department, Anadolu Medical Center Hospital, Kocaeli, Turkey

    Zafer Gülbas

  11. Klinikum Grosshadern, Med. Klinik III, Munich, Germany

    Johanna Tischer

  12. BMT Unit, Clinica Ematologica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Paolo Bernasconi

  13. Department of Haematology, Hammersmith Hospital, Imperial College, London, UK

    Jiri Pavlu

  14. Dept. of Hematology-BMT, Hospital St. Louis, Paris, France

    Gerard Socié

  15. Programme de Transplantation&Therapie Cellulaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli Calmettes, Marseille, France

    Didier Blaise

  16. Dept. of Hematology and BMT, Ospedale S. Camillo-Forlanini, Rome, Italy

    Luigi Rigacci

  17. Grande Ospedale Metropolitano Bianchi Melacrino Morelli, Centro Unico Trapianti A. Neri, Alberto Neri, Bianchi-Melacrino-Morelli, Reggio Calabri, Italy

    Massimo Martino

  18. Department of Hematology, Hospital GU Gregorio Marañon, Instituto de Investigación Sanitaria Gregorio Marañon’ Universidad Complutense Medicina, Madrid, Spain

    Jose Luis Diez-Martin

  19. Dept.of Internal Medicine, University of Zagreb, School of Medicine, Zagreb, Croatia

    Zinaida Perić

  20. Department of Bone Marrow Transplantation and Oncohematology, Maria Sklodowska-Curie Institute—Oncology Center, Gliwice Branch, Gliwice, Poland

    Sebastian Giebel

  21. Service d’Hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, AP-HP, Sorbonne University, and INSERM UMRs 938, Paris, France

    Mohamad Mohty

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  1. Arnon Nagler
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Contributions

AN, MM, and ML contributed to the conception and design of the study; BD, AN, ML, and MM contributed to the writing of the paper; all authors critically reviewed the paper and approved the final version.

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Correspondence to Bhagirathbhai Dholaria.

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The authors declare that they have no conflict of interest.

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All required data for the current survey were collected according to EBMT guidelines. The scientific boards of the ALWP of the EBMT approved the study.

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All patients gave informed consent to use their personal information for research purposes. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.

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Nagler, A., Dholaria, B., Labopin, M. et al. Bone marrow versus mobilized peripheral blood stem cell graft in T-cell-replete haploidentical transplantation in acute lymphoblastic leukemia. Leukemia 34, 2766–2775 (2020). https://doi.org/10.1038/s41375-020-0850-9

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