Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Non-relapse cytopenias following allogeneic stem cell transplantation, a case based review

Bone Marrow Transplantation volume 57, pages 1489–1499 (2022)Cite this article

Subjects

Abstract

The development of non-relapse cytopenias (NRC) is a relatively common occurrence post allogeneic stem cell transplant (alloSCT). Whilst there have been attempts to classify post alloSCT cytopenias by transplantation groups, ambiguity of definitions in prior publications compounded by a lack of availability of high-quality evidence, provide challenges to clinicians attempting to manage these complex patients. In this review we describe 3 cases of NRC, (1) Graft Failure with graft rejection representing cytopenias with minimal donor chimerism (2) Poor Graft Function representing cytopenias with complete donor chimerism and (3) Cytopenias with mixed donor chimerism. This case-based review will evaluate the currently available evidence regarding the pathophysiology of each entity as well as the evidence for current therapies with the aim of providing guidance to clinicians managing these complex patients.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Classification for Non-relapse Cytopenias following alloSCT based on level of donor chimerism.
Fig. 2: Blood counts (left y axis) and Chimerism (right y axis) for all cases presented.

Similar content being viewed by others

References

  1. Valcárcel D, Sureda A. Graft failure. In: Carreras E, Dufour C, Mohty M, Kröger N, editors. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies. Cham (CH): Springer Copyright 2019, EBMT and the Author(s). 2019. p. 307-13.

  2. Kharfan-Dabaja MA, Kumar A, Ayala E, Aljurf M, Nishihori T, Marsh R, et al. Standardizing definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism in allogeneic hematopoietic cell transplantation: a report on behalf of the american society for transplantation and cellular therapy. Transplant Cell Ther, Off Publ Am Soc Transplant Cell Ther. 2021;27:642–9.

    CAS  Google Scholar 

  3. Olsson RF, Logan BR, Chaudhury S, Zhu X, Akpek G, Bolwell BJ, et al. Primary graft failure after myeloablative allogeneic hematopoietic cell transplantation for hematologic malignancies. Leukemia. 2015;29:1754–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Morrison SJ, Scadden DT. The bone marrow niche for haematopoietic stem cells. Nature. 2014;505:327–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kokkaliaris KD, Scadden DT. Cell interactions in the bone marrow microenvironment affecting myeloid malignancies. Blood Adv. 2020;4:3795–803.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Fisher DAC, Fowles JS, Zhou A, Oh ST. Inflammatory pathophysiology as a contributor to myeloproliferative neoplasms. Front Immunol. 2021;12. https://doi.org/10.3389/fimmu.2021.683401.

  7. Xingmin F, Phillip S, Colin OW, Leigh S, Olga N, Courtney P, et al. Cytokine signature profiles in acquired aplastic anemia and myelodysplastic syndromes. Haematologica. 2011;96:602–6.

    Article  Google Scholar 

  8. Olsson R, Remberger M, Schaffer M, Berggren DM, Svahn BM, Mattsson J, et al. Graft failure in the modern era of allogeneic hematopoietic SCT. Bone Marrow Transpl. 2013;48:537–43.

    Article  CAS  Google Scholar 

  9. Park JH, Lee JH, Lee JH, Park HS, Choi EJ, Kang YA, et al. Incidence, management, and prognosis of graft failure and autologous reconstitution after allogeneic hematopoietic stem cell transplantation. J Korean Med Sci. 2021;36:e151.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kernan NA, Flomenberg N, Dupont B, O’Reilly RJ. Graft rejection in recipients of T-cell-depleted HLA-nonidentical marrow transplants for leukemia. Identification of host-derived antidonor allocytotoxic T lymphocytes. Transplantation. 1987;43:842–7.

    Article  CAS  PubMed  Google Scholar 

  11. Nakamura H, Gress RE. Graft rejection by cytolytic T cells. Specificity of the effector mechanism in the rejection of allogeneic marrow. Transplantation. 1990;49:453–8.

    Article  CAS  PubMed  Google Scholar 

  12. Voogt PJ, Fibbe WE, Marijt WA, Goulmy E, Veenhof WF, Hamilton M, et al. Rejection of bone-marrow graft by recipient-derived cytotoxic T lymphocytes against minor histocompatibility antigens. Lancet. 1990;335:131–4.

    Article  CAS  PubMed  Google Scholar 

  13. Masouridi-Levrat S, Simonetta F, Chalandon Y. Immunological basis of bone marrow failure after allogeneic hematopoietic stem cell transplantation. Front Immunol. 2016;7. https://doi.org/10.3389/fimmu.2016.00362.

  14. Jiang Z, Adams GB, Hanash AM, Scadden DT, Levy RB. The contribution of cytotoxic and noncytotoxic function by donor T-cells that support engraftment after allogeneic bone marrow transplantation. Biol Blood Marrow Transpl. 2002;8:588–96.

    Article  Google Scholar 

  15. Hanash AM, Levy RB. Donor CD4+CD25+ T cells promote engraftment and tolerance following MHC-mismatched hematopoietic cell transplantation. Blood. 2005;105:1828–36.

    Article  CAS  PubMed  Google Scholar 

  16. Ciurea SO, de Lima M, Cano P, Korbling M, Giralt S, Shpall EJ, et al. High risk of graft failure in patients with anti-HLA antibodies undergoing haploidentical stem-cell transplantation. Transplantation. 2009;88:1019–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ciurea SO, Thall PF, Wang X, Wang SA, Hu Y, Cano P, et al. Donor-specific anti-HLA Abs and graft failure in matched unrelated donor hematopoietic stem cell transplantation. Blood. 2011;118:5957–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Cutler C, Kim HT, Sun L, Sese D, Glotzbecker B, Armand P, et al. Donor-specific anti-HLA antibodies predict outcome in double umbilical cord blood transplantation. Blood. 2011;118:6691–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yoshihara S, Maruya E, Taniguchi K, Kaida K, Kato R, Inoue T, et al. Risk and prevention of graft failure in patients with preexisting donor-specific HLA antibodies undergoing unmanipulated haploidentical SCT. Bone Marrow Transpl. 2012;47:508–15.

    Article  CAS  Google Scholar 

  20. Xie Y, Parekh J, Tang Z, Wu D, Wu X. Donor-specific antibodies and primary graft failure in allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis. Transpl Cell Ther. 2021;27:687.e1–7.

    Article  CAS  Google Scholar 

  21. Ciurea SO, Thall PF, Milton DR, Barnes TH, Kongtim P, Carmazzi Y, et al. Complement-binding donor-specific anti-HLA antibodies and risk of primary graft failure in hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2015;21:1392–8.

    Article  CAS  Google Scholar 

  22. Guardiola P, Kuentz M, Garban F, Blaise D, Reiffers J, Attal M, et al. Second early allogeneic stem cell transplantations for graft failure in acute leukaemia, chronic myeloid leukaemia and aplastic anaemia. French Society of Bone Marrow Transplantation. Br J Haematol. 2000;111:292–302.

    CAS  PubMed  Google Scholar 

  23. Chewning JH, Castro-Malaspina H, Jakubowski A, Kernan NA, Papadopoulos EB, Small TN, et al. Fludarabine-based conditioning secures engraftment of second hematopoietic stem cell allografts (HSCT) in the treatment of initial graft failure. Biol Blood Marrow Transpl. 2007;13:1313–23.

    Article  CAS  Google Scholar 

  24. Lund TC, Liegel J, Bejanyan N, Orchard PJ, Cao Q, Tolar J, et al. Second allogeneic hematopoietic cell transplantation for graft failure: poor outcomes for neutropenic graft failure. Am J Hematol. 2015;90:892–6.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Harada K, Fuji S, Seo S, Kanda J, Ueki T, Kimura F, et al. Comparison of the outcomes after haploidentical and cord blood salvage transplantations for graft failure following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2020;55:1784–95.

    Article  CAS  PubMed  Google Scholar 

  26. Kongtim P, Bittencourt M, Srour SA, Ramdial J, Rondon G, Chen J, et al. Haploidentical transplants for patients with graft failure after the first allograft. Am J Hematol. 2020;95:E267–9.

  27. Prata PH, Resche-Rigon M, Blaise D, Socié G, Rohrlich P-S, Milpied N, et al. Outcomes of salvage haploidentical transplant with post-transplant cyclophosphamide for rescuing graft failure patients: a report on behalf of the francophone society of bone marrow transplantation and cellular therapy. Biol Blood Marrow Transplant. 2019;25:1798–802.

    Article  PubMed  Google Scholar 

  28. Giammarco S, Raiola AM, Di Grazia C, Bregante S, Gualandi F, Varaldo R, et al. Second haploidentical stem cell transplantation for primary graft failure. Bone Marrow Transplant. 2021;56:1291–6.

    Article  CAS  PubMed  Google Scholar 

  29. Park JA, Koh KN, Choi ES, Jang S, Kwon SW, Park CJ, et al. Successful rescue of early graft failure in pediatric patients using T-cell-depleted haploidentical hematopoietic SCT. Bone Marrow Transplant. 2014;49:270–5.

    Article  CAS  PubMed  Google Scholar 

  30. Tang BL, Zhu XY, Zheng CC, Liu HL, Geng LQ, Wang XB, et al. Successful early unmanipulated haploidentical transplantation with reduced-intensity conditioning for primary graft failure after cord blood transplantation in hematologic malignancy patients. Bone Marrow Transpl. 2015;50:248–52.

    Article  CAS  Google Scholar 

  31. Sun Y-Q, Wang Y, Wang F-R, Yan C-H, Cheng Y-F, Chen Y-H, et al. Graft failure in patients with hematological malignancies: a successful salvage with a second transplantation from a different haploidentical donor. Front Med. 2021;8. https://doi.org/10.3389/fmed.2021.604085.

  32. Yoshihara S, Ikegame K, Taniguchi K, Kaida K, Kim EH, Nakata J, et al. Salvage haploidentical transplantation for graft failure using reduced-intensity conditioning. Bone Marrow Transpl. 2012;47:369–73.

    Article  CAS  Google Scholar 

  33. Harada K, Kimura SI, Fuji S, Najima Y, Yakushijin K, Uchida N, et al. Prognostic factors in salvage transplantation for graft failure following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transpl. 2021;56:2183–93.

    Article  CAS  Google Scholar 

  34. Prabahran AA, Koldej R, Chee L, Ritchie DS. Clinical features, pathophysiology and therapy of poor graft function post allogeneic stem cell transplantation. Blood Advances. 2022;6:1947–59.

  35. Bonifazi F, Barbato F, Ravaioli F, Sessa M, Defrancesco I, Arpinati M, et al. Diagnosis and treatment of VOD/SOS after allogeneic hematopoietic stem cell transplantation. Front Immunol. 2020;11:489.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Shi MM, Kong Y, Song Y, Sun YQ, Wang Y, Zhang XH, et al. Atorvastatin enhances endothelial cell function in posttransplant poor graft function. Blood. 2016;128:2988–99.

    Article  CAS  PubMed  Google Scholar 

  37. Alchalby H, Yunus DR, Zabelina T, Ayuk F, Kroger N. Incidence and risk factors of poor graft function after allogeneic stem cell transplantation for myelofibrosis. Bone Marrow Transpl. 2016;51:1223–7.

    Article  CAS  Google Scholar 

  38. Prabahran A, Koldej R, Chee L, Wong E, Ritchie D. Evaluation of risk factors for and subsequent mortality from poor graft function (PGF) post allogeneic stem cell transplantation. Leuk Lymphoma. 2021;62:1482–9.

    Article  CAS  PubMed  Google Scholar 

  39. Alvarado LJ, Huntsman HD, Cheng H, Townsley DM, Winkler T, Feng X, et al. Eltrombopag maintains human hematopoietic stem and progenitor cells under inflammatory conditions mediated by IFN-γ. Blood. 2019;133:2043–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Shono Y, Ueha S, Wang Y, Abe J, Kurachi M, Matsuno Y, et al. Bone marrow graft-versus-host disease: early destruction of hematopoietic niche after MHC-mismatched hematopoietic stem cell transplantation. Blood. 2010;115:5401–11.

    Article  CAS  PubMed  Google Scholar 

  41. Zhao H-Y, Lyu Z-S, Duan C-W, Song Y, Han T-T, Mo X-D, et al. An unbalanced monocyte macrophage polarization in the bone marrow microenvironment of patients with poor graft function after allogeneic haematopoietic stem cell transplantation. Br J Haematol. 2018;182:679–92.

    Article  CAS  PubMed  Google Scholar 

  42. Kong Y, Wang Y-T, Cao X-N, Song Y, Chen Y-H, Sun Y-Q, et al. Aberrant T cell responses in the bone marrow microenvironment of patients with poor graft function after allogeneic hematopoietic stem cell transplantation. J Transl Med. 2017;15:57.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Mahat U, Rotz SJ, Hanna R. Use of thrombopoietin receptor agonists in prolonged thrombocytopenia after hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2020;26:e65–73.

    Article  CAS  Google Scholar 

  44. Larocca A, Piaggio G, Podesta M, Pitto A, Bruno B, Di Grazia C, et al. Boost of CD34+-selected peripheral blood cells without further conditioning in patients with poor graft function following allogeneic stem cell transplantation. Haematologica. 2006;91:935–40.

    PubMed  Google Scholar 

  45. Ghobadi A, Fiala MA, Ramsingh G, Gao F, Abboud CN, Stockerl-Goldstein K, et al. Fresh or cryopreserved CD34(+)-selected mobilized peripheral blood stem and progenitor cells for the treatment of poor graft function after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transpl. 2017;23:1072–7.

    Article  CAS  Google Scholar 

  46. Klyuchnikov E, El-Cheikh J, Sputtek A, Lioznov M, Calmels B, Furst S, et al. CD34(+)-selected stem cell boost without further conditioning for poor graft function after allogeneic stem cell transplantation in patients with hematological malignancies. Biol Blood Marrow Transpl. 2014;20:382–6.

    Article  CAS  Google Scholar 

  47. Mainardi C, Ebinger M, Enkel S, Feuchtinger T, Teltschik HM, Eyrich M, et al. CD34(+) selected stem cell boosts can improve poor graft function after paediatric allogeneic stem cell transplantation. Br J Haematol. 2018;180:90–9.

    Article  CAS  PubMed  Google Scholar 

  48. Mohty R, Brissot E, Battipaglia G, Ruggeri A, Sestili S, Mediavilla C, et al. CD34(+)-selected stem cell “Boost” for poor graft function after allogeneic hematopoietic stem cell transplantation. Curr Res Transl Med. 2019;67:112–4.

  49. Stasia A, Ghiso A, Galaverna F, Raiola AM, Gualandi F, Luchetti S, et al. CD34 selected cells for the treatment of poor graft function after allogeneic stem cell transplantation. Biol Blood Marrow Transpl. 2014;20:1440–3.

    Article  CAS  Google Scholar 

  50. Jiang S, Penack O, Terzer T, Schult D, Majer-Lauterbach J, Radujkovic A, et al. Predicting sinusoidal obstruction syndrome after allogeneic stem cell transplantation with the EASIX biomarker panel. Haematologica. 2021;106:446–53.

    Article  CAS  PubMed  Google Scholar 

  51. Kong Y, Chang YJ, Wang YZ, Chen YH, Han W, Wang Y, et al. Association of an impaired bone marrow microenvironment with secondary poor graft function after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2013;19:1465–73.

    Article  Google Scholar 

  52. Kong Y, Song Y, Hu Y, Shi MM, Wang YT, Wang Y, et al. Increased reactive oxygen species and exhaustion of quiescent CD34-positive bone marrow cells may contribute to poor graft function after allotransplants. Oncotarget. 2016;7:30892–906.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Kong Y, Wang Y, Zhang Y-Y, Shi M-M, Mo X-D, Sun Y-Q, et al. Prophylactic oral NAC reduced poor hematopoietic reconstitution by improving endothelial cells after haploidentical transplantation. Blood Adv. 2019;3:1303–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Marty FM, Ljungman P, Chemaly RF, Maertens J, Dadwal SS, Duarte RF, et al. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation. N. Engl J Med. 2017;377:2433–44.

    Article  CAS  PubMed  Google Scholar 

  55. Blyth E, Clancy L, Simms R, Ma CK, Burgess J, Deo S, et al. Donor-derived CMV-specific T cells reduce the requirement for CMV-directed pharmacotherapy after allogeneic stem cell transplantation. Blood. 2013;121:3745–58.

    Article  CAS  PubMed  Google Scholar 

  56. John TD, Friend B, Yassine K, Sasa G, Bhar S, Salem B, et al. Matched related hematopoietic cell transplant for sickle cell disease with alemtuzumab: the Texas Children’s Hospital experience. Bone Marrow Transpl. 2021;56:2797–803.

    Article  CAS  Google Scholar 

  57. Burney C, Wadhera K, Breslin P, Pearce R, Wells M, Alajangi R, et al. BEAM-campath allogeneic stem cell transplant for patients with relapsed/refractory lymphoma: high incidence of long-term mixed donor-recipient chimerism and the response to donor lymphocyte infusions. Biol Blood Marrow Transpl. 2020;26:2271–8.

    Article  CAS  Google Scholar 

  58. Xu ZL, Cheng YF, Zhang YY, Mo XD, Han TT, Wang FR, et al. The incidence, clinical outcome, and protective factors of mixed chimerism following hematopoietic stem cell transplantation for severe aplastic anemia. Clin Transpl. 2021;35:e14160.

    Article  CAS  Google Scholar 

  59. Chen H, Li XY, Zhan LP, Fang JP, Huang K, Li Y, et al. Prediction, management, and prognosis of mixed chimerism after hematopoietic stem cell transplantation in transfusion-dependent pediatric thalassemia patients. Pediatr Transpl. 2020;24:e13876.

    Article  CAS  Google Scholar 

  60. Faraci M, Bagnasco F, Leoni M, Giardino S, Terranova P, Subissi L, et al. Evaluation of chimerism dynamics after allogeneic hematopoietic stem cell transplantation in children with nonmalignant diseases. Biol Blood Marrow Transpl. 2018;24:1088–93.

    Article  Google Scholar 

  61. Marsh RA, Rao MB, Gefen A, Bellman D, Mehta PA, Khandelwal P, et al. Experience with alemtuzumab, fludarabine, and melphalan reduced-intensity conditioning hematopoietic cell transplantation in patients with nonmalignant diseases reveals good outcomes and that the risk of mixed chimerism depends on underlying disease, stem cell source, and alemtuzumab regimen. Biol Blood Marrow Transpl. 2015;21:1460–70.

    Article  CAS  Google Scholar 

  62. Kinsella FAM, Zuo J, Inman CF, Pearce H, Maggs L, Eldershaw SE, et al. Mixed chimerism established by hematopoietic stem cell transplantation is maintained by host and donor T regulatory cells. Blood Adv. 2019;3:734–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Lejman M, Zawitkowska J, Zaucha-Prażmo A, Cienkusz M, Mroczkowska A, Kowalczyk J, et al. Influence of mixed chimerism on outcome in children with anaemia after haematopoietic stem cell transplantation. Vivo. 2019;33:2051–7.

    Article  CAS  Google Scholar 

  64. Stikvoort A, Sundin M, Uzunel M, Gertow J, Sundberg B, Schaffer M, et al. Long-term stable mixed chimerism after hematopoietic stem cell transplantation in patients with non-malignant disease, shall we be tolerant? PLoS One. 2016;11:e0154737.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Bernaudin F, Dalle JH, Bories D, de Latour RP, Robin M, Bertrand Y, et al. Long-term event-free survival, chimerism and fertility outcomes in 234 patients with sickle-cell anemia younger than 30 years after myeloablative conditioning and matched-sibling transplantation in France. Haematologica. 2020;105:91–101.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Bhat DK, Olkhanud PB, Gangaplara A, Seifuddin F, Pirooznia M, Biancotto A, et al. Early myeloid derived suppressor cells (eMDSCs) are associated with high donor myeloid chimerism following haploidentical HSCT for sickle cell disease. Front Immunol. 2021;12. https://doi.org/10.3389/fimmu.2021.757279.

  67. Shaw A, Passweg JR, De La Fuente J, Bajwa R, Stein J, Al-Zaben A, et al. Relapse of aplastic anemia with majority donor chimerism (Donor-Type Aplasia) occurring late after bone marrow transplantation. Biol Blood Marrow Transpl. 2020;26:480–5.

    Article  Google Scholar 

  68. Breuer S, Preuner S, Fritsch G, Daxberger H, Koenig M, Poetschger U, et al. Early recipient chimerism testing in the T- and NK-cell lineages for risk assessment of graft rejection in pediatric patients undergoing allogeneic stem cell transplantation. Leukemia. 2012;26:509–19.

    Article  CAS  PubMed  Google Scholar 

  69. Zhang Y, Li Y, Wu L, Zhou M, Wang C, Mo W, et al. Mixed chimerism after allogeneic hematopoietic stem cell transplantation for severe aplastic anemia. Hematology. 2021;26:435–43.

    Article  CAS  PubMed  Google Scholar 

  70. M. Cuadrado M, Richard MS, Mike W, Nishil P, Hanna R, Jude D, et al. Predictors of recovery following allogeneic CD34+-selected cell infusion without conditioning to correct poor graft function. Haematologica. 2019;105:2639–46.

    Article  Google Scholar 

  71. Ren RR, Ma LM, Xie YX, Tian WW, Wang T. Effect of donor lymphocyte infusion from two types of donors on mixed chimerism with secondary graft failure after allogeneic hematopoietic stem cell transplantation. Transpl Cell Ther. 2022;28:152.e1–7.

    Article  Google Scholar 

  72. Au WY, Chan EC, Lie AK, Liang R, Leung AY, Ma SK, et al. Poor engraftment after allogeneic bone marrow transplantation: role of chimerism analysis in treatment and outcome. Ann Hematol. 2003;82:410–5.

    Article  CAS  PubMed  Google Scholar 

  73. Rondón G, Saliba RM, Khouri I, Giralt S, Chan K, Jabbour E, et al. Long-term follow-up of patients who experienced graft failure postallogeneic progenitor cell transplantation. Results of a single institution analysis. Biol Blood Marrow Transpl. 2008;14:859–66.

    Article  Google Scholar 

  74. Passweg JR, Zhang MJ, Rocha V, Kan F, Champlin RE, Isola LM, et al. Donor characteristics affecting graft failure, graft-versus-host disease, and survival after unrelated donor transplantation with reduced-intensity conditioning for hematologic malignancies. Biol Blood Marrow Transpl. 2011;17:1869–73.

    Article  Google Scholar 

  75. Ferra C, Sanz J, Diaz-Perez MA, Morgades M, Gayoso J, Cabrera JR, et al. Outcome of graft failure after allogeneic stem cell transplant: study of 89 patients. Leuk Lymphoma. 2015;56:656–62.

    Article  PubMed  Google Scholar 

  76. Cluzeau T, Lambert J, Raus N, Dessaux K, Absi L, Delbos F, et al. Risk factors and outcome of graft failure after HLA matched and mismatched unrelated donor hematopoietic stem cell transplantation: a study on behalf of SFGM-TC and SFHI. Bone Marrow Transpl. 2016;51:687–91.

    Article  CAS  Google Scholar 

  77. Xiao Y, Song J, Jiang Z, Li Y, Gao Y, Xu W, et al. Risk-factor analysis of poor graft function after allogeneic hematopoietic stem cell transplantation. Int J Med Sci. 2014;11:652–7.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Sun YQ, He GL, Chang YJ, Xu LP, Zhang XH, Han W, et al. The incidence, risk factors, and outcomes of primary poor graft function after unmanipulated haploidentical stem cell transplantation. Ann Hematol. 2015;94:1699–705.

    Article  CAS  PubMed  Google Scholar 

  79. Zhao Y, Gao F, Shi J, Luo Y, Tan Y, Lai X, et al. Incidence, risk factors, and outcomes of primary poor graft function after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2019;25:1898–907.

    Article  Google Scholar 

  80. Reich-Slotky R, Al-Mulla N, Hafez R, Segovia-Gomez J, Goel R, Mayer S, et al. Poor graft function after T cell-depleted allogeneic hematopoietic stem cell transplant. Leuk Lymphoma. 2020;61:2894–9.

  81. Prabahran A, Koldej R, Chee L, Wong E, Ritchie D. Evaluation of risk factors for and subsequent mortality from poor graft function (PGF) post allogeneic stem cell transplantation. Leuk Lymphoma. 2021;62:1482–9.

  82. Kako S, Yamazaki H, Ohashi K, Ozawa Y, Ota S, Kanda Y, et al. Mixed chimerism and secondary graft failure in allogeneic hematopoietic stem cell transplantation for aplastic anemia. Biol Blood Marrow Transpl. 2020;26:445–50.

    Article  CAS  Google Scholar 

  83. Jabbour E, Rondon G, Anderlini P, Giralt SA, Couriel DR, Champlin RE, et al. Treatment of donor graft failure with nonmyeloablative conditioning of fludarabine, antithymocyte globulin and a second allogeneic hematopoietic transplantation. Bone Marrow Transpl. 2007;40:431–5.

    Article  CAS  Google Scholar 

  84. Schriber J, Agovi MA, Ho V, Ballen KK, Bacigalupo A, Lazarus HM, et al. Second unrelated donor hematopoietic cell transplantation for primary graft failure. Biol Blood Marrow Transpl. 2010;16:1099–106.

    Article  Google Scholar 

  85. Kanda J, Horwitz ME, Long GD, Gasparetto C, Sullivan KM, Chute JP, et al. Outcomes of a 1-day nonmyeloablative salvage regimen for patients with primary graft failure after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2012;47:700–5.

    Article  CAS  PubMed  Google Scholar 

  86. Fuji S, Nakamura F, Hatanaka K, Taniguchi S, Sato M, Mori S, et al. Peripheral blood as a preferable source of stem cells for salvage transplantation in patients with graft failure after cord blood transplantation: a retrospective analysis of the registry data of the Japanese Society for Hematopoietic Cell Transplantation. Biol Blood Marrow Transpl. 2012;18:1407–14.

    Article  Google Scholar 

  87. Onishi Y, Mori T, Kako S, Koh H, Uchida N, Kondo T, et al. Outcome of second transplantation using umbilical cord blood for graft failure after allogeneic hematopoietic stem cell transplantation for aplastic anemia. Biol Blood Marrow Transplant. 2017;23:2137–42.

    Article  PubMed  Google Scholar 

  88. Singh H, Nikiforow S, Li S, Ballen KK, Spitzer TR, Soiffer R, et al. Outcomes and management strategies for graft failure after umbilical cord blood transplantation. Am J Hematol. 2014;89:1097–101.

    Article  PubMed  Google Scholar 

  89. Subburaj D, Li AM, Rozmus J, Schultz KR. Successful rescue transplant for children with primary graft failure using early intervention with a single day preparative regimen and related haploidentical donor. Bone Marrow Transplant. 2021;56:2031–3.

    Article  PubMed  Google Scholar 

  90. Kliman D, Bilmon I, Kwan J, Blyth E, Micklethwaite K, Panicker S, et al. Rescue haploidentical peripheral blood stem cell transplantation for engraftment failure: a single-centre case series. Intern Med J. 2018;48:988–91.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Victorian State Government acting through the Victorian Cancer Agency and Maddie Riewoldt's Vision.

Author information

Authors and Affiliations

  1. Department, of Clinical Haematology, Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, Parkville, VIC, Australia

    Ashvind Prabahran, Lynette Chee, Jeff Szer & David Ritchie

  2. ACRF Translational Research Laboratory, Royal Melbourne Hospital, Parkville, VIC, Australia

    Ashvind Prabahran, Rachel Koldej, Lynette Chee & David Ritchie

  3. The University of Melbourne, Parkville, VIC, Australia

    Ashvind Prabahran, Rachel Koldej, Lynette Chee, Jeff Szer & David Ritchie

Authors
  1. Ashvind Prabahran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rachel Koldej
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lynette Chee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jeff Szer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David Ritchie
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AP drafted the manuscript JS, LC, and DR provided expert review of clinical literature relevant to the topic. RK provided expert review of scientific literature relevant to the topic.

Corresponding author

Correspondence to Ashvind Prabahran.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Prabahran, A., Koldej, R., Chee, L. et al. Non-relapse cytopenias following allogeneic stem cell transplantation, a case based review. Bone Marrow Transplant 57, 1489–1499 (2022). https://doi.org/10.1038/s41409-022-01761-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-022-01761-z

Search

Advanced search

Quick links