Graft Source: Marrow or Peripheral Blood with Posttransplant Cyclophosphamide—What Matters?

Chapter
Part of the Advances and Controversies in Hematopoietic Transplantation and Cell Therapy book series (ACHTCT)

Abstract

The choice of bone marrow (BM) or G-CSF-mobilized peripheral blood (PB) as the source of CD34+ cells for transplantation from HLA-haploidentical, related donors is controversial. Short of a randomized clinical trial comparing these two graft sources (which is highly unlikely), it has been necessary to compare multicenter or single-center phase II data retrospectively using either of these two graft sources in the setting of ablative or non-myeloablative conditioning or by comparing registry data. This chapter will review the data and will discuss whether BM or PB as the source of graft for haploidentical transplantation using PTCy makes any difference in the transplant outcomes of engraftment/hematopoietic recovery, acute and chronic GvHD, NRM, relapse, or survival.

Keywords

G-CSF Graft Haploidentical transplant Posttransplant cyclophosphamide Bone marrow Peripheral blood Harvest GvHD 

References

  1. 1.
    Anasetti A, Logan BR, Lee SJ, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med. 2012;367:1487–96.CrossRefGoogle Scholar
  2. 2.
    Lee SJ, Kim HT, Ho VT, et al. Quality of life associated with acute and chronic graft-versus-host disease. Bone Marrow Transplant. 2006;38:305–10.CrossRefGoogle Scholar
  3. 3.
    El-Jawahri A, Pidala J, Inamoto Y, et al. Impact of age on quality of life, functional status and survival in patients with chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2014;20:1341–8.CrossRefGoogle Scholar
  4. 4.
    Stem Cell Trialists’ Collaborative Group. Allogeneic peripheral blood stem cell compared with bone marrow transplantation in the management of hematologic malignancies: An individual patient data meta-analysis of nine randomized trials. J Clin Oncol. 2005;23:5074–87.CrossRefGoogle Scholar
  5. 5.
    Shulman HM, Sullivan KM, Weiden PL, 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.CrossRefGoogle Scholar
  6. 6.
    https://bethematchclinical.org/Transplant-Therapy-and-Donor-Matching/Cell-Sources/. Accessed 25 April 2016.Google Scholar
  7. 7.
    Eapen M, Logan BR, Horowitz M, et al. Bone marrow or peripheral blood for reduced-intensity conditioning unrelated donor transplantation. J Clin Oncol. 2015;33:364–9.CrossRefGoogle Scholar
  8. 8.
    Anthias C, Shaw BE, Kiefer DM, et al. Significant improvements in the practice patterns of adult related donor care in US transplantation centers. Biol Blood Marrow Transplant. 2016;22:520–7.CrossRefGoogle Scholar
  9. 9.
    Pulsipher MA, Chitphakdithai P, Logan BR, et al. Acute toxicities of unrelated bone marrow versus peripheral blood stem cell donation: results of a prospective trial from the National Marrow Donor Program. Blood. 2013;121:197–206.CrossRefGoogle Scholar
  10. 10.
    Pulsipher MA, Chitphakdithai O, Logan BR, et al. Lower risk for serious adverse events and no increased risk for cancer after PBSC vs BM donation. Blood. 2014;123:3655–63.CrossRefGoogle Scholar
  11. 11.
    D’Orsogna LJ, Roelen DL, Doxiadis II, et al. TCR cross-reactivity and allorecognition: new insights into the immunogenetics of allorecognition. Immunogenetics. 2012;64:77–85.CrossRefGoogle Scholar
  12. 12.
    Powles RL, Morgenstern GR, Kay HE, et al. Mismatched family donors for bone-marrow transplantation as treatment for acute leukemia. Lancet. 1983;19:612–5.CrossRefGoogle Scholar
  13. 13.
    Pg B, Clift RA, Mickelson EM, et al. Marrow transplantation from related donors other than HLA-identical siblings. N Engl J Med. 1985;313:765–71.CrossRefGoogle Scholar
  14. 14.
    Aversa F, Terenzi A, Tabilio A, et al. Full haplotype-mismatched hematopoietic stem cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol. 2005;23:3447–54.CrossRefGoogle Scholar
  15. 15.
    Bertaina A, Merli P, Rutella S, et al. HLA-haploidentical stem cell transplantation after removal of αβ+ T and B cells in children with nonmalignant disorders. Blood. 2014;124:822–6.CrossRefGoogle Scholar
  16. 16.
    Lang P, Feuchtinger T, Teltschik H-M, et al. Improved immune recovery after transplantation of TCRαβ/CD19-depleted allografts from haploidentical donors in pediatric patients. Bone Marrow Transplant. 2015;50:S6–10.CrossRefGoogle Scholar
  17. 17.
    Martelli MF, Di Ianni M, Ruggeri L, et al. HLA-haploidentical transplantation with regulatory and conventional T-cell adoptive immunotherapy prevents acute leukemia relapse. Blood. 2014;124:638–44.CrossRefGoogle Scholar
  18. 18.
    Huang X-J, Liu D-H, Liu K-Y, et al. Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies. Bone Marrow Transplant. 2006;38:291–7.CrossRefGoogle Scholar
  19. 19.
    Wang Y, Liu D-H, Liu K-Y, et al. Long-term follow-up of haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of leukemia. Cancer. 2013;119:978–85.CrossRefGoogle Scholar
  20. 20.
    Di Bartolomeo P, Santoarone S, De A, et al. Haploidentical, unmanipulated, G-CSF-primed bone marrow transplantation for patients with high-risk hematologic malignancies. Blood. 2013;121:849–57.CrossRefGoogle Scholar
  21. 21.
    O’Donnell PV, Luznik L, Jones RJ, et al. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2002;8:377–86.CrossRefGoogle Scholar
  22. 22.
    Luznik L, O’Donnell PV, Symons HJ, 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.CrossRefGoogle Scholar
  23. 23.
    McCurdy SR, Kanakry JA, Showel MM, et al. Risk-stratified outcomes of nonmyeloablative HLA-haploidentical BMT with high-dose posttransplantation cyclophosphamide. Blood. 2015;125:3024–31.CrossRefGoogle Scholar
  24. 24.
    Raiola AM, Dominietto A, Ghiso A, et al. Unmanipulated haploidentical bone marrow transplantation and post-transplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning. Biol Blood Marrow Transplant. 2013;19:117–22.CrossRefGoogle Scholar
  25. 25.
    Bacigalupo A, Dominietto A, Ghiso A, et al. Unmanipulated haploidentical bone marrow transplantation and post-transplant cyclophosphamide for hematologic malignancies following a myeloablative conditioning: an update. Bone Marrow Transplant. 2015;50:S37–9.CrossRefGoogle Scholar
  26. 26.
    Raj K, Pagliuca A, Bradstock K, et al. Peripheral blood hematopoietic stem cells for transplantation of hematological diseases from related, haploidentical donors after reduced-intensity conditioning. Biol Blood Marrow Transplant. 2014;20:881–903.CrossRefGoogle Scholar
  27. 27.
    Castagna L, Crocchiolo R, Furst S, 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.CrossRefGoogle Scholar
  28. 28.
    Bhamidipati PK, Di Persio JF, Stokerl-Goldstein K, et al. Haploidentical transplantation using G-CSF-mobilized T-cell replete PBSCs and post-transplantation CY after nonmyeloablative conditioning is safe and is associated with favorable outcomes. Bone Marrow Transplant. 2014;49:1124–6.CrossRefGoogle Scholar
  29. 29.
    Bradstock K, Bilmon I, Kwan J, et al. Influence of stem cell source on outcomes of allogeneic reduced-intensity conditioning therapy transplant using haploidentical related donors. Biol Blood Marrow Transplant. 2015;21:1641–5.CrossRefGoogle Scholar
  30. 30.
    Bashey A, Zhang X, Sizemore CA, et al. T-cell-replete HLA-haploidentical hematopoietic transplantation for hematologic malignancies using post-transplantation cyclophosphamide results in outcomes equivalent to those contemporaneous HLA-matched related and unrelated donor transplantation. J Clin Oncol. 2013;31:1310–6.CrossRefGoogle Scholar
  31. 31.
    Grosso D, Carabasi M, Filicko-O’Hara J, et al. A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase ½ trial performed with optimized T-cell dosing. Blood. 2011;118:4732–9.CrossRefGoogle Scholar
  32. 32.
    Gaballa S, Palmisiano N, Alpdogan O, et al. A two-step haploidentical versus a two-step matched related allogeneic myeloablative peripheral blood stem cell transplantation. Biol Blood Marrow Transplant. 2016;22:141–8.CrossRefGoogle Scholar
  33. 33.
    Solomon SR, Sizemore CA, Sanacore M, et al. Haploidentical transplantation using T cell replete peripheral blood stem cells and myeloablative conditioning in patients with high-risk hematologic malignancies who lack conventional donors is well tolerated and produces excellent relapse-free survival: results of a prospective phase II trial. Biol Blood Marrow Transplant. 2012;18:1859–66.CrossRefGoogle Scholar
  34. 34.
    Solomon SR, Sizemore CA, Sanacore M, et al. Total body irradiation-based myeloablative haploidentical stem cell transplantation is a safe and effective alternative to unrelated donor transplantation in patients without matched sibling donors. Biol Blood Marrow Transplant. 2015;21:1299–307.CrossRefGoogle Scholar
  35. 35.
    O’Donnell PV, Eapen M, Horowitz M, et al. Comparable survival outcomes with marrow or peripheral blood as stem cell sources for hematopoietic transplantation from haploidentical donors after reduced-intensity conditioning: a matched pair analysis. Bone Marrow Transplant. 2016;51:1599–601.CrossRefGoogle Scholar
  36. 36.
    Brunstein CG, Fuchs EJ, Carter SL, et al. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood. 2011;118:282–8.CrossRefGoogle Scholar
  37. 37.
    Eapen M, O’Donnell P, Brunstein C, et al. Mismatched related and unrelated donors for allogeneic hematopoietic cell transplantation for adults with hematologic malignancies. Biol Blood Marrow Transplant. 2014;20:1485–92.CrossRefGoogle Scholar
  38. 38.
    Armand P, Haesook TK, Logan BR, et al. Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation. Blood. 2014;123:3664–71.CrossRefGoogle Scholar
  39. 39.
    Bashey A, Zhang M-J, McCurdy SR, et al. Mobilized peripheral blood stem cells versus unstimulated bone marrow as graft source for T-replete haploidentical donor transplantation using post-transplant cyclophosphamide. J Clin Oncol. 2017;35:3002–9.CrossRefGoogle Scholar
  40. 40.
    Ruggeri A, Labopin M, Bacigalupo A, et al. Use of bone marrow or peripheral blood stem cell grafts in non-T-depleted haploidentical transplants using post-transplant cyclophosphamide, an ALWP-EBMT analysis. Blood. 2016;128:1165. AbstractCrossRefGoogle Scholar
  41. 41.
    Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11:945–56.CrossRefGoogle Scholar
  42. 42.
    Storb R, Gyurkocza B, Storer B, et al. Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation. J Clin Oncol. 2013;31:1530–8.CrossRefGoogle Scholar
  43. 43.
    Flowers MED, Inamoto Y, Carpenter P, et al. Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood. 2011;117:3214–9.CrossRefGoogle Scholar
  44. 44.
    Luznik L, Bolanos-Meade J, Zahurak M, et al. High-dose cyclophosphamide as single agent, short course prophylaxis of graft-versus-host disease. Blood. 2010;115:3224–30.CrossRefGoogle Scholar
  45. 45.
    Kanakry CG, O’Donnell PV, Furlong T, et al. Multi-institutional study of post-transplantation cyclophosphamide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning. J Clin Oncol. 2014;32:3497–505.CrossRefGoogle Scholar
  46. 46.
    Bradstock KF, Bilmon I, Kwan J, et al. Single-agent high-dose cyclophosphamide for graft-versus-host disease prophylaxis in human leukocyte antigen-matched reduced intensity peripheral blood stem cell transplantation results in an unacceptably high rate of severe acute graft-versus-host disease. Biol Blood Marrow Transplant. 2015;21:941–4.CrossRefGoogle Scholar
  47. 47.
    Mielcarek M, Furlong T, O’Donnell PV, et al. Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation. Blood. 2016;127:1502–8.CrossRefGoogle Scholar
  48. 48.
    Moiseev IS, Pirogova OV, Alyanski AL, et al. Graft-versus-host disease prophylaxis in unrelated peripheral blood stem cell transplantation with post-transplantation cyclophosphamide, tacrolimus and mycophenolate mofetil. Biol Blood Marrow Transplant. 2016;22:1037–42.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Massachusetts General Hospital Cancer CenterBostonUSA

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