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Post-transplant cyclophosphamide combined with anti-thymocyte globulin for graft-vs-host disease prophylaxis improves survival and lowers non-relapse mortality in older patients undergoing allogeneic hematopoietic cell transplantation

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Abstract

Graft-versus-host disease (GVHD) represents a major contributor to morbidity and mortality in recipients of allogeneic hematopoietic cell transplants (HCT). Several strategies exist for GVHD prophylaxis and include post-transplant cyclophosphamide (PTCY) and anti-thymocyte globulin (ATG). While several groups have described the use of PTCY in younger patients, there is a paucity of data about the efficacy of PTCY in older individuals, particularly when combined with ATG. We investigated the effect of PTCY and ATG combination on transplant outcomes in older patients at Princess Margaret Cancer Centre, Toronto, Canada. Compared to those patients who received other forms of GVHD prophylaxis, individuals who received ATG-PTCY combination had higher 2-year overall survival (OS), 57% (95% confidence interval, 44–69) vs 37% (26–49), P = 0.02; higher 2-year graft-vs-host– and relapse-free survival (GRFS), 27% (17–39) vs 12% (6–21), P = 0.01; lower 2-year non-relapse mortality (NRM), 21% (12–32) vs 45% (33–56), P = 1.00 × 10−3; lower 100-day incidence of grade 2–4 acute GVHD (aGVHD), 11% (5–21) vs 28% (18–39), P = 0.02; and lower 100-day incidence of grade 3–4 aGVHD, 0% vs 7% (3–15), P = 0.02 without an increase in the 2-year cumulative incidence of relapse (CIR), 31% (20–43) vs 21% (12–32), P = 0.14. Therefore, in older HCT recipients, use of PTCY combined with ATG is associated with improved OS, lower NRM, decreased risk of aGVHD, and improved GRFS without a significant increase in relapse risk. Therefore, the PTCY with ATG combination represents an effective strategy for GVHD prophylaxis in older allogeneic HCT recipients.

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References

  1. Lee SJ (2016) Classification systems for chronic graft-versus-host disease. Blood 129:30–37. https://doi.org/10.1182/blood-2016-07-686642

    Article  PubMed  CAS  Google Scholar 

  2. Zeiser R, Blazar BR (2017) Acute graft-versus-host disease - biologic process, prevention, and therapy. New Engl J Med 377:2167–2179. https://doi.org/10.1056/nejmra1609337

    Article  PubMed  CAS  Google Scholar 

  3. Jagasia MH, Greinix HT, Arora M et al (2014) National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biology Blood Marrow Transplant J Am Soc Blood Marrow Transplant 21:389–401.e1. https://doi.org/10.1016/j.bbmt.2014.12.001

    Article  Google Scholar 

  4. MacDonald KP, Betts BC, Couriel D (2018) Emerging therapeutics for the control of chronic graft-versus-host disease. Biol Blood Marrow Tr 24:19–26. https://doi.org/10.1016/j.bbmt.2017.10.006

    Article  Google Scholar 

  5. Sarantopoulos S, Cardones AR, Llivan K (2019) How I treat refractory chronic graft-versus-host disease. Blood 133:1191–1200. https://doi.org/10.1182/blood-2018-04-785899

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Ghalie R et al (1988) Cyclosporine and graft-versus-host disease after bone marrow transplantation. New Engl J Med 319:1607–1608. https://doi.org/10.1056/nejm198812153192414

    Article  Google Scholar 

  7. Bianchi M, Heim D, Lengerke C et al (2018) Cyclosporine levels > 195 μg/L on day 10 post-transplant was associated with significantly reduced acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. Ann Hematol 98:971–977. https://doi.org/10.1007/s00277-018-3577-1

    Article  PubMed  CAS  Google Scholar 

  8. Chhabra S, Liu Y, Hemmer MT et al (2018) Comparative analysis of calcineurin inhibitor-based methotrexate and mycophenolate mofetil-containing regimens for prevention of graft-versus-host disease after reduced-intensity conditioning allogeneic transplantation. Biology Blood Marrow Transplant J Am Soc Blood Marrow Transplant 25:73–85. https://doi.org/10.1016/j.bbmt.2018.08.018

    Article  CAS  Google Scholar 

  9. de Kort EA, de Lil HS, Bremmers ME et al (2019) Cyclosporine a trough concentrations are associated with acute GvHD after non-myeloablative allogeneic hematopoietic cell transplantation. PLoS One 14:e0213913. https://doi.org/10.1371/journal.pone.0213913

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Deeg H, Storb R, Thomas E et al (1985) Cyclosporine as prophylaxis for graft-versus-host disease: a randomized study in patients undergoing marrow transplantation for acute nonlymphoblastic leukemia. Blood 65:1325–1334. https://doi.org/10.1182/blood.v65.6.1325.bloodjournal6561325

    Article  PubMed  CAS  Google Scholar 

  11. Stocker N, Duléry R, Battipaglia G et al (2019) Impact of cyclosporine a concentration on acute graft-vs-host disease incidence after haploidentical hematopoietic cell transplantation. Eur J Haematol 103:10–17. https://doi.org/10.1111/ejh.13233

    Article  PubMed  CAS  Google Scholar 

  12. Bolaños-Meade J, Reshef R, Fraser R et al (2019) Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of graft-versus-host disease with haemopoietic cell transplantation with reduced-intensity conditioning: a randomised phase 2 trial with a non-randomised contemporaneous control group (BMT CTN 1203). Lancet Haematol 6:e132–e143. https://doi.org/10.1016/s2352-3026(18)30221-7

    Article  PubMed  PubMed Central  Google Scholar 

  13. Fay J, Wingard J, Antin J et al (1996) FK506 (Tacrolimus) monotherapy for prevention of graft-versus-host disease after histocompatible sibling allogenic bone marrow transplantation. Blood 87:3514–3519. https://doi.org/10.1182/blood.v87.8.3514.bloodjournal8783514

    Article  PubMed  CAS  Google Scholar 

  14. Nash R, Etzioni R, Storb R et al (1995) Tacrolimus (FK506) alone or in combination with methotrexate or methylprednisolone for the prevention of acute graft-versus-host disease after marrow transplantation from HLA-matched siblings: a single-center study. Blood 85:3746–3753. https://doi.org/10.1182/blood.v85.12.3746.bloodjournal85123746

    Article  PubMed  CAS  Google Scholar 

  15. Shah M, Liba R, Rondon G et al (2018) Pilot study using post-transplant cyclophosphamide (PTCy), tacrolimus and mycophenolate GVHD prophylaxis for older patients receiving 10/10 HLA-matched unrelated donor hematopoietic stem cell transplantation. Bone Marrow Transplant 54:601–606. https://doi.org/10.1038/s41409-018-0367-2

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  16. Salhotra A, Mei M, Stiller T et al (2018) Outcomes of patients with recurrent and refractory lymphoma undergoing allogeneic hematopoietic cell transplantation with BEAM conditioning and sirolimus- and tacrolimus-based GVHD prophylaxis. Biology Blood Marrow Transplant J Am Soc Blood Marrow Transplant 25:287–292. https://doi.org/10.1016/j.bbmt.2018.09.009

    Article  CAS  Google Scholar 

  17. Antin JH, Kim HT, Cutler C et al (2003) Sirolimus, tacrolimus, and low-dose methotrexate for graft-versus-host disease prophylaxis in mismatched related donor or unrelated donor transplantation. Blood 102:1601–1605. https://doi.org/10.1182/blood-2003-02-0489

    Article  PubMed  CAS  Google Scholar 

  18. Benito AI, Furlong T, Martin PJ et al (2001) Sirolimus (rapamycin) for the treatment of steroid-refractory acute graft-versus-host disease. Transplantation 72:1924–1929. https://doi.org/10.1097/00007890-200112270-00010

    Article  PubMed  CAS  Google Scholar 

  19. Carpenter PA, Logan BR, Lee SJ et al (2018) A phase II/III randomized, multicenter trial of prednisone/sirolimus versus prednisone/ sirolimus/calcineurin inhibitor for the treatment of chronic graft- versus -host disease: BMT CTN 0801. Haematologica 103:1915–1924. https://doi.org/10.3324/haematol.2018.195123

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Kim T, DeVeaux M, Stahl M et al (2018) Long-term follow-up of a single institution pilot study of sirolimus, tacrolimus, and short course methotrexate for graft versus host disease prophylaxis in mismatched unrelated donor allogeneic stem cell transplantation. Ann Hematol 98:237–240. https://doi.org/10.1007/s00277-018-3427-1

    Article  PubMed  Google Scholar 

  21. Adachi Y, Ozeki K, Ukai S et al (2019) Optimal dosage of methotrexate for GVHD prophylaxis in umbilical cord blood transplantation. Int J Hematol 109:440–450. https://doi.org/10.1007/s12185-019-02598-x

    Article  PubMed  CAS  Google Scholar 

  22. Filipovich A, Krawczak C, Kersey J et al (1985) Graft-versus-host disease prophylaxis with anti-T-cell monoclonal antibody OKT3, prednisone and methotrexate in allogeneic bone-marrow transplantation. Brit J Haematol 60:143–152. https://doi.org/10.1111/j.1365-2141.1985.tb07395.x

    Article  CAS  Google Scholar 

  23. Lazarus H, Coccia P, Herzig R et al (1984) Incidence of acute graft-versus-host disease with and without methotrexate prophylaxis in allogeneic bone marrow transplant patients. Blood 64:215–220. https://doi.org/10.1182/blood.v64.1.215.215

    Article  PubMed  CAS  Google Scholar 

  24. Kawashima N, Iida M, Suzuki R et al (2019) Prophylaxis and treatment with mycophenolate mofetil in children with graft-versus-host disease undergoing allogeneic hematopoietic stem cell transplantation: a nationwide survey in Japan. Int J Hematol 109:491–498. https://doi.org/10.1007/s12185-019-02601-5

    Article  PubMed  CAS  Google Scholar 

  25. Ruutu T, Volin L, Parkkali T et al (2000) Cyclosporine, methotrexate, and methylprednisolone compared with cyclosporine and methotrexate for the prevention of graft-versus-host disease in bone marrow transplantation from HLA-identical sibling donor: a prospective randomized study. Blood 96:2391–2398. https://doi.org/10.1182/blood.v96.7.2391

    Article  PubMed  CAS  Google Scholar 

  26. Delgado J, Pillai N, Benjamin R et al (2008) The effect of in vivo T cell depletion with alemtuzumab on reduced-intensity allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia. Biology Blood Marrow Transplant J Am Soc Blood Marrow Transplant 14:1288–1297. https://doi.org/10.1016/j.bbmt.2008.09.001

    Article  CAS  Google Scholar 

  27. Hamad N, Bel R, Messner HA et al (2014) Outcomes of hematopoietic cell transplantation in adult patients with acquired aplastic anemia using intermediate-dose alemtuzumab-based conditioning. Biol Blood Marrow Tr 20:1722–1728. https://doi.org/10.1016/j.bbmt.2014.06.033

    Article  CAS  Google Scholar 

  28. Ho AY, Pagliuca A, Kenyon M et al (2004) Reduced-intensity allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myeloid leukemia with multilineage dysplasia using fludarabine, busulphan, and alemtuzumab (FBC) conditioning. Blood 104:1616–1623. https://doi.org/10.1182/blood-2003-12-4207

    Article  PubMed  CAS  Google Scholar 

  29. Potter VT, Krishnamurthy P, Barber LD et al (2013) Long-term outcomes of alemtuzumab-based reduced-intensity conditioned hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myelogenous leukemia secondary to myelodysplastic syndrome. Biology Blood Marrow Transplant J Am Soc Blood Marrow Transplant 20:111–117. https://doi.org/10.1016/j.bbmt.2013.10.021

    Article  CAS  Google Scholar 

  30. Brodsky R, Luznik L, Bolaños-Meade J et al (2008) Reduced intensity HLA-haploidentical BMT with post transplantation cyclophosphamide in nonmalignant hematologic diseases. Bone Marrow Transplant 42:523–527. https://doi.org/10.1038/bmt.2008.203

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Kanakry CG, O’Donnell PV, Furlong T et al (2014) 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 Off J Am Soc Clin Oncol 32:3497–3505. https://doi.org/10.1200/jco.2013.54.0625

    Article  CAS  Google Scholar 

  32. Pagliardini T, Castagna L, Harbi S et al (2019) Thiotepa, fludarabine and busulfan conditioning regimen before t-cell replete haploidentical transplantation with post-transplant cyclophosphamide for acute myeloid leukemia: a bicentric experience of 100 patients. Biology Blood Marrow Transplant J Am Soc Blood Marrow Transplant 25:1803–1809. https://doi.org/10.1016/j.bbmt.2019.05.014

    Article  CAS  Google Scholar 

  33. Bashey A, Zhang M-J, McCurdy SR et al (2017) 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 35. https://doi.org/10.1200/jco.2017.72.8428

  34. Vine S (2017) Haploidentical hematopoietic cell transplantation using post-transplantation cyclophosphamide: does graft source matter? J Clin Oncol Off J Am Soc Clin Oncol 35:2984–2986. https://doi.org/10.1200/jco.2017.73.7775

    Article  Google Scholar 

  35. Bashey A, Zhang X, Sizemore CA et al (2013) T-cell–replete HLA-haploidentical hematopoietic transplantation for hematologic malignancies using post-transplantation cyclophosphamide results in outcomes equivalent to those of contemporaneous HLA-matched related and unrelated donor transplantation. J Clin Oncol 31:1310–1316. https://doi.org/10.1200/jco.2012.44.3523

    Article  PubMed  CAS  Google Scholar 

  36. Kasamon YL, Bolaños-Meade J, Prince GT et al (2015) Outcomes of nonmyeloablative HLA-haploidentical blood or marrow transplantation with high-dose post-transplantation cyclophosphamide in older adults. J Clin Oncol Off J Am Soc Clin Oncol 33:3152–3161. https://doi.org/10.1200/jco.2014.60.4777

    Article  CAS  Google Scholar 

  37. Martínez C, Gayoso J, Canals C et al (2017) Post-transplantation cyclophosphamide-based haploidentical transplantation as alternative to matched sibling or unrelated donor transplantation for Hodgkin lymphoma: a registry study of the lymphoma working Party of the European Society for blood and marrow transplantation. J Clin Oncol 35. https://doi.org/10.1200/jco.2017.72.6869

  38. Rimondo A, Crocchiolo R, El-Cheikh J et al (2016) The calcineurin inhibitor and the intensity of the conditioning regimen may affect the occurrence of polyomavirus-associated hemorrhagic cystitis after haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide. Bone Marrow Transplant 52:135–137. https://doi.org/10.1038/bmt.2016.193

    Article  PubMed  CAS  Google Scholar 

  39. Carnevale-Schianca F, Caravelli D, Gallo S et al (2017) Post-transplant cyclophosphamide and tacrolimus–mycophenolate mofetil combination prevents graft-versus-host disease in allogeneic peripheral blood hematopoietic cell transplantation from HLA-matched donors. Biol Blood Marrow Tr 23:459–466. https://doi.org/10.1016/j.bbmt.2016.12.636

    Article  CAS  Google Scholar 

  40. Moiseev IS, Pirogova OV, Alyanski AL et al (2016) Graft-versus-host disease prophylaxis in unrelated peripheral blood stem cell transplantation with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Biol Blood Marrow Tr 22:1037–1042. https://doi.org/10.1016/j.bbmt.2016.03.004

    Article  CAS  Google Scholar 

  41. Cieri N, Greco R, Crucitti L et al (2015) Post-transplantation cyclophosphamide and sirolimus after haploidentical hematopoietic stem cell transplantation using a treosulfan-based myeloablative conditioning and peripheral blood stem cells. Biology Blood Marrow Transplant J Am Soc Blood Marrow Transplant 21:1506–1514. https://doi.org/10.1016/j.bbmt.2015.04.025

    Article  CAS  Google Scholar 

  42. Greco R, Lorentino F, Morelli M et al (2016) Posttransplantation cyclophosphamide and sirolimus for prevention of GVHD after HLA-matched PBSC transplantation. Blood 128:1528–1531. https://doi.org/10.1182/blood-2016-06-723205

    Article  PubMed  CAS  Google Scholar 

  43. Jaiswal S, Chatterjee S, Mukherjee S et al (2015) Pre-transplant sirolimus might improve the outcome of haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide for patients with severe aplastic anemia. Bone Marrow Transplant 50:873–875. https://doi.org/10.1038/bmt.2015.50

    Article  PubMed  CAS  Google Scholar 

  44. Jaiswal S, Bhakuni P, Zaman 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 43–44:54–59. https://doi.org/10.1016/j.trim.2017.07.004

    Article  PubMed  CAS  Google Scholar 

  45. Solomon SR, Sanacore M, Zhang X et al (2014) Calcineurin inhibitor--free graft-versus-host disease prophylaxis with post-transplantation cyclophosphamide and brief-course sirolimus following reduced-intensity peripheral blood stem cell transplantation. Biology Blood Marrow Transplant J Am Soc Blood Marrow Transplant 20:1828–1834. https://doi.org/10.1016/j.bbmt.2014.07.020

    Article  CAS  Google Scholar 

  46. Deotare U, Atenafu EG, Loach D et al (2017) 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 53:361–365. https://doi.org/10.1038/s41409-017-0053-9

    Article  PubMed  CAS  Google Scholar 

  47. Law A, Salas M, Lam W et al (2018) Reduced intensity conditioning and dual T-lymphocyte suppression with anti-thymocyte globulin and post-transplant cyclophosphamide as graft versus host disease prophylaxis in haploidentical stem cell transplants for hematological malignancies. Biology Blood Marrow Transplant J Am Soc Blood Marrow Transplant 24:2259–2264. https://doi.org/10.1016/j.bbmt.2018.07.008

    Article  Google Scholar 

  48. Prem S, Atenafu EG, Al-Shaibani Z et al (2019) Low rates of acute and chronic GVHD with ATG and PTCy in matched and mismatched unrelated donor peripheral blood stem cell transplants. Eur J Haematol 102:486–493. https://doi.org/10.1111/ejh.13230

    Article  PubMed  CAS  Google Scholar 

  49. Wang Y, Wu D-P, Liu Q-F et al (2019) Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients. J Hematol Oncol 12:88. https://doi.org/10.1186/s13045-019-0781-y

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Lazaryan A, Weisdorf DJ, DeFor T et al (2015) Risk factors for acute and chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation with umbilical cord blood and matched sibling donors. Biology Blood Marrow Transplant J Am Soc Blood Marrow Transplant 22:134–140. https://doi.org/10.1016/j.bbmt.2015.09.008

    Article  Google Scholar 

  51. Kyriakou C, Boumendil A, Finel H et al (2018) The impact of advanced patient age on mortality after allogeneic hematopoietic cell transplantation for non-Hodgkin lymphoma: a retrospective study by the European Society for Blood and Marrow Transplantation Lymphoma Working Party. Biology Blood Marrow Transplant J Am Soc Blood Marrow Transplant 25:86–93. https://doi.org/10.1016/j.bbmt.2018.08.025

    Article  Google Scholar 

  52. Sorror ML (2013) How I assess comorbidities before hematopoietic cell transplantation. Blood 121:2854–2863. https://doi.org/10.1182/blood-2012-09-455063

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Ruggeri A, Sun Y, Labopin M et al (2016) Post-transplant cyclophosphamide versus anti-thymocyte globulin as graft- versus -host disease prophylaxis in haploidentical transplant. Haematologica 102:401–410. https://doi.org/10.3324/haematol.2016.151779

    Article  PubMed  Google Scholar 

  54. Kanda Y (2012) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48:452–458. https://doi.org/10.1038/bmt.2012.244

    Article  PubMed  PubMed Central  Google Scholar 

  55. Ashizawa M, Akahoshi Y, Nakano H et al (2014) A combination of fludarabine, half-dose cyclophosphamide, and anti-thymocyte globulin is an effective conditioning regimen before allogeneic stem cell transplantation for aplastic anemia. Int J Hematol 99:311–317. https://doi.org/10.1007/s12185-014-1501-6

    Article  PubMed  CAS  Google Scholar 

  56. Pasic I, Da’na W, Lam W et al (2019) Influence of FLT3-ITD and NPM1 status on allogeneic hematopoietic cell transplant outcomes in patients with cytogenetically normal AML. Eur J Haematol 102:368–374. https://doi.org/10.1111/ejh.13216

    Article  PubMed  CAS  Google Scholar 

  57. Bashey ZA, Zhang X, Brown S et al (2018) Comparison of outcomes following transplantation with T-replete HLA-haploidentical donors using post-transplant cyclophosphamide to matched related and unrelated donors for patients with AML and MDS aged 60 years or older. Bone Marrow Transplant 53:756–763. https://doi.org/10.1038/s41409-018-0126-4

    Article  PubMed  CAS  Google Scholar 

  58. Blaise D, Fürst S, Crocchiolo R et al (2015) Haploidentical T cell-replete transplantation with post-transplantation cyclophosphamide for patients in or above the sixth decade of age compared with allogeneic hematopoietic stem cell transplantation from an human leukocyte antigen-matched related or unrelated donor. Biology Blood Marrow Transplant J Am Soc Blood Marrow Transplant 22:119–124. https://doi.org/10.1016/j.bbmt.2015.08.029

    Article  Google Scholar 

  59. Pagliardini T, Harbi S, Fürst S et al (2018) Post-transplantation cyclophosphamide-based haploidentical versus Atg-based unrelated donor allogeneic stem cell transplantation for patients younger than 60 years with hematological malignancies: a single-center experience of 209 patients. Bone Marrow Transplant 54:1067–1076. https://doi.org/10.1038/s41409-018-0387-y

    Article  PubMed  CAS  Google Scholar 

  60. Chemnitz J, von Lilienfeld-Toal M, Holtick U et al (2011) Intermediate intensity conditioning regimen containing FLAMSA, treosulfan, cyclophosphamide, and ATG for allogeneic stem cell transplantation in elderly patients with relapsed or high-risk acute myeloid leukemia. Ann Hematol 91:47–55. https://doi.org/10.1007/s00277-011-1253-9

    Article  PubMed  CAS  Google Scholar 

  61. Devillier R, Granata A, Fürst S et al (2016) Low incidence of chronic GVHD after HLA-haploidentical peripheral blood stem cell transplantation with post-transplantation cyclophosphamide in older patients. Brit J Haematol 176:132–135. https://doi.org/10.1111/bjh.13923

    Article  CAS  Google Scholar 

  62. Slade M, DiPersio JF, Westervelt P et al (2017) Haploidentical hematopoietic cell transplant with post-transplant cyclophosphamide and peripheral blood stem cell grafts in older adults with acute myeloid leukemia or Myelodysplastic syndrome. Biol Blood Marrow Tr 23:1736–1743. https://doi.org/10.1016/j.bbmt.2017.06.019

    Article  CAS  Google Scholar 

  63. Yang J, Jiang J, Cai Y et al (2018) Low-dose anti-thymocyte globulin plus low-dose posttransplant cyclophosphamide as graft-versus-host disease prophylaxis in haploidentical peripheral blood stem cell transplantation combined with unrelated cord blood for patients with hematologic malignancies: a prospective, phase II study. Bone Marrow Transplant 54:1049–1057. https://doi.org/10.1038/s41409-018-0382-3

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Beelen D, Trenschel R, Stelljes M et al (2019) Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MC-FludT.14/L): a randomised, non-inferiority, phase 3 trial. Lancet Haematol 7:e28–e39. https://doi.org/10.1016/s2352-3026(19)30157-7

    Article  PubMed  Google Scholar 

  65. Negrin RS (2015) Graft-versus-host disease versus graft-versus-leukemia. Hematology 2015:225–230. https://doi.org/10.1182/asheducation-2015.1.225

    Article  PubMed  Google Scholar 

  66. Kröger N, Zabelina T, Krüger W et al (2002) In vivo T cell depletion with pretransplant anti-thymocyte globulin reduces graft-versus-host disease without increasing relapse in good risk myeloid leukemia patients after stem cell transplantation from matched related donors. Bone Marrow Transplant 29:683–689. https://doi.org/10.1038/sj.bmt.1703530

    Article  PubMed  Google Scholar 

  67. Portier D, Sabo R, Roberts C et al (2012) Anti-thymocyte globulin for conditioning in matched unrelated donor hematopoietic cell transplantation provides comparable outcomes to matched related donor recipients. Bone Marrow Transplant 47:1513–1519. https://doi.org/10.1038/bmt.2012.81

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Giebel S, Labopin M, Czerw T et al (2019) Impact of anti-thymocyte globulin on results of allogeneic peripheral blood stem cell transplantation for patients with Philadelphia-positive acute lymphoblastic leukaemia: an analysis by the acute leukemia working party of the EBMT. Eur J Cancer 106:212–219. https://doi.org/10.1016/j.ejca.2018.11.003

    Article  PubMed  CAS  Google Scholar 

  69. Ratanatharathorn V, Deol A, Ayash L et al (2014) Low-dose antithymocyte globulin enhanced the efficacy of tacrolimus and mycophenolate for GVHD prophylaxis in recipients of unrelated SCT. Bone Marrow Transplant 50:106–112. https://doi.org/10.1038/bmt.2014.203

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Bashey A, Zhang X, Jackson K 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. Biology Blood Marrow Transplant J Am Soc Blood Marrow Transplant 22:125–133. https://doi.org/10.1016/j.bbmt.2015.09.002

    Article  CAS  Google Scholar 

  71. How J, Slade M, Vu K et al (2017) T cell–replete peripheral blood Haploidentical hematopoietic cell transplantation with post-transplantation cyclophosphamide results in outcomes similar to transplantation from traditionally matched donors in active disease acute myeloid leukemia. Biol Blood Marrow Tr 23:648–653. https://doi.org/10.1016/j.bbmt.2017.01.068

    Article  Google Scholar 

  72. Mariotti J, Devillier R, Bramanti S et al (2017) T cell-replete haploidentical transplantation with post-transplantation cyclophosphamide for Hodgkin lymphoma relapsed after autologous transplantation: reduced incidence of relapse and of chronic graft-versus-host disease compared with HLA-identical related donors. Biology Blood Marrow Transplant J Am Soc Blood Marrow Transplant 24:627–632. https://doi.org/10.1016/j.bbmt.2017.11.030

    Article  CAS  Google Scholar 

  73. Mehta RS, Liba R, Chen J et al (2016) Post-transplantation cyclophosphamide versus conventional graft-versus-host disease prophylaxis in mismatched unrelated donor haematopoietic cell transplantation. Brit J Haematol 173:444–455. https://doi.org/10.1111/bjh.13977

    Article  CAS  Google Scholar 

  74. Moiseev IS, Pirogova OV, Alyanski AL et al (2018) Risk-adapted GVHD prophylaxis with post-transplantation cyclophosphamide in adults after related, unrelated, and haploidentical transplantations. Eur J Haematol 100:395–402. https://doi.org/10.1111/ejh.13030

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Fotios V. Michelis.

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Pasic, I., Lipton, J.H., Kim, D.D. et al. Post-transplant cyclophosphamide combined with anti-thymocyte globulin for graft-vs-host disease prophylaxis improves survival and lowers non-relapse mortality in older patients undergoing allogeneic hematopoietic cell transplantation. Ann Hematol 99, 1377–1387 (2020). https://doi.org/10.1007/s00277-020-04033-2

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  • DOI: https://doi.org/10.1007/s00277-020-04033-2

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