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.

  • Original Article
  • Published:

Post-Transplant Events

Delayed platelet recovery after allogeneic transplantation: a predictor of increased treatment-related mortality and poorer survival

Bone Marrow Transplantation volume 46, pages 981–986 (2011)Cite this article

Subjects

Abstract

Delayed platelet recovery (DPR) is common after allo-SCT. Insufficient data on risk factors and association with OS and TRM are available. We conducted a retrospective analysis of all allografts at the University of Minnesota between 2000 and 2005 to characterize the frequency of DPR (platelets <50 000/μL by day 60), risk factors and related complications. A total of 850 patients with hematological malignancies and benign disorders were included. Myeloablative (MA) conditioning was used in 65% of the patients and 45% received umbilical cord blood (UCB) grafts. The 60-day cumulative incidence of platelet recovery was 40% in UCB, 57% in unrelated donor (URD) and 74% in sibling donor. Multivariate analysis confirmed that the variables associated with DPR were MA (versus reduced intensity) conditioning, graft source other than sibling donor, ABO major mismatch, recipient CMV-positive serostatus, the presence of grade II–IV acute GVHD and slower neutrophil recovery. These data demonstrate that DPR is frequent after allogeneic hematopoietic cell transplantation, especially after UCB. DPR is a significant independent risk factor for increased TRM and poorer OS along with HLA-mismatched URD, but not UCB, grade II–IV acute GVHD, old age and advanced disease stage.

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

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Yamazaki R, Kuwana M, Mori T, Okazaki Y, Kawakami Y, Ikeda Y et al. Prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation: associations with impaired platelet production and increased platelet turnover. Bone Marrow Transplant 2006; 38: 377–384.

    Article  CAS  Google Scholar 

  2. Nash RA, Gooley T, Davis C, Appelbaum FR . The problem of thrombocytopenia after hematopoietic stem cell transplantation. Oncologist 1996; 1: 371–380.

    CAS  PubMed  Google Scholar 

  3. Koreth J, Schlenk R, Kopecky KJ, Honda S, Sierra J, Djulbegovic BJ et al. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. JAMA 2009; 301: 2349–2361.

    Article  CAS  Google Scholar 

  4. Rowe JM . Optimal management of adults with ALL. Br J Haematol 2009; 144: 468–483.

    Article  Google Scholar 

  5. Bosticardo M, Marangoni F, Aiuti A, Villa A, Grazia Roncarolo M . Recent advances in understanding the pathophysiology of Wiskott-Aldrich syndrome. Blood 2009; 113: 6288–6295.

    Article  CAS  Google Scholar 

  6. Sullivan KM, Parkman R, Walters MC . Bone marrow transplantation for non-malignant disease. Hematol Am Soc Hematol Educ Program 2000, 319–338.

    Article  Google Scholar 

  7. Filipovich A . Hematopoietic cell transplantation for correction of primary immunodeficiencies. Bone Marrow Transplant 2008; 42 (Suppl 1): S49–S52.

    Article  Google Scholar 

  8. Bernstein SH, Nademanee AP, Vose JM, Tricot G, Fay JW, Negrin RS et al. A multicenter study of platelet recovery and utilization in patients after myeloablative therapy and hematopoietic stem cell transplantation. Blood 1998; 91: 3509–3517.

    CAS  PubMed  Google Scholar 

  9. Sierra J, Storer B, Hansen JA, Bjerke JW, Martin PJ, Petersdorf EW et al. Transplantation of marrow cells from unrelated donors for treatment of high-risk acute leukemia: the effect of leukemic burden, donor HLA-matching, and marrow cell dose. Blood 1997; 89: 4226–4235.

    CAS  Google Scholar 

  10. Verdonck LF, de Gast GC, van Heugten HG, Nieuwenhuis HK, Dekker AW . Cytomegalovirus infection causes delayed platelet recovery after bone marrow transplantation. Blood 1991; 78: 844–848.

    CAS  PubMed  Google Scholar 

  11. Dominietto A, Raiola AM, van Lint MT, Lamparelli T, Gualandi F, Berisso G et al. Factors influencing haematological recovery after allogeneic haemopoietic stem cell transplants: graft-versus-host disease, donor type, cytomegalovirus infections and cell dose. Br J Haematol 2001; 112: 219–227.

    Article  CAS  Google Scholar 

  12. Ninan MJ, Flowers CR, Roback JD, Arellano ML, Waller EK . Posttransplant thrombopoiesis predicts survival in patients undergoing autologous hematopoietic progenitor cell transplantation. Biol Blood Marrow Transplant 2007; 13: 895–904.

    Article  Google Scholar 

  13. Lin DY . Non-parametric inference for cumulative incidence functions in competing risks studies. Stat Med 1997; 16: 901–910.

    Article  CAS  Google Scholar 

  14. Kaplan E, Meier P . Nonparametric estimation from incomplete observations. J Amer Statist Assn 1958; 53: 457–481.

    Article  Google Scholar 

  15. Fine J, Gray R . A proportional hazards model for the subdistribution of a competing risk. J Amer Statist Assn 1999; 94: 496–497.

    Article  Google Scholar 

  16. Cox D . Regression models and life-tables. J Roy Statist Soc 1972; 34: 187–220.

    Google Scholar 

  17. Snedecor G, Cochran W . Statistical Methods, 8th edn. Iowa State University Press: Ames, IA, 1989.

    Google Scholar 

  18. Bensinger WI, Clift R, Martin P, Appelbaum FR, Demirer T, Gooley T et al. Allogeneic peripheral blood stem cell transplantation in patients with advanced hematologic malignancies: a retrospective comparison with marrow transplantation. Blood 1996; 88: 2794–2800.

    CAS  PubMed  Google Scholar 

  19. Couban S, Simpson DR, Barnett MJ, Bredeson C, Hubesch L, Howson-Jan K et al. A randomized multicenter comparison of bone marrow and peripheral blood in recipients of matched sibling allogeneic transplants for myeloid malignancies. Blood 2002; 100: 1525–1531.

    Article  CAS  Google Scholar 

  20. Frassoni F, Podesta M, Maccario R, Giorgiani G, Rossi G, Zecca M et al. Cord blood transplantation provides better reconstitution of hematopoietic reservoir compared with bone marrow transplantation. Blood 2003; 102: 1138–1141.

    Article  CAS  Google Scholar 

  21. Laughlin MJ, Eapen M, Rubinstein P, Wagner JE, Zhang MJ, Champlin RE et al. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 2004; 351: 2265–2275.

    Article  CAS  Google Scholar 

  22. Eapen M, Rubinstein P, Zhang MJ, Stevens C, Kurtzberg J, Scaradavou A et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet 2007; 369: 1947–1954.

    Article  Google Scholar 

  23. Ooi J, Takahashi S, Tomonari A, Tsukada N, Konuma T, Kato S et al. Unrelated cord blood transplantation after myeloablative conditioning in adults with acute myelogenous leukemia. Biol Blood Marrow Transplant 2008; 14: 1341–1347.

    Article  CAS  Google Scholar 

  24. Ooi J, Takahashi S, Tomonari A, Tsukada N, Konuma T, Kato S et al. Unrelated cord blood transplantation after myeloablative conditioning in adults with ALL. Bone Marrow Transplant 2009; 43: 455–459.

    Article  CAS  Google Scholar 

  25. Brunstein CG, Barker JN, Weisdorf DJ, DeFor TE, Miller JS, Blazar BR et al. Umbilical cord blood transplantation after nonmyeloablative conditioning: impact on transplantation outcomes in 110 adults with hematologic disease. Blood 2007; 110: 3064–3070.

    Article  CAS  Google Scholar 

  26. Verneris MR, Brunstein CG, Barker J, MacMillan ML, DeFor T, McKenna DH et al. Relapse risk after umbilical cord blood transplantation: enhanced graft-versus-leukemia effect in recipients of 2 units. Blood 2009; 114: 4293–4299.

    Article  CAS  Google Scholar 

  27. Flynn CM, Hirsch B, Defor T, Barker JN, Miller JS, Wagner JE et al. Reduced intensity compared with high dose conditioning for allotransplantation in acute myeloid leukemia and myelodysplastic syndrome: a comparative clinical analysis. Am J Hematol 2007; 82: 867–872.

    Article  Google Scholar 

  28. Tomonari A, Takahashi S, Ooi J, Tsukada N, Konuma T, Kobayashi T et al. Impact of ABO incompatibility on engraftment and transfusion requirement after unrelated cord blood transplantation: a single institute experience in Japan. Bone Marrow Transplant 2007; 40: 523–528.

    Article  CAS  Google Scholar 

  29. First LR, Smith BR, Lipton J, Nathan DG, Parkman R, Rappeport JM . Isolated thrombocytopenia after allogeneic bone marrow transplantation: existence of transient and chronic thrombocytopenic syndromes. Blood 1985; 65: 368–374.

    CAS  PubMed  Google Scholar 

  30. Anasetti C, Rybka W, Sullivan KM, Banaji M, Slichter SJ . Graft-v-host disease is associated with autoimmune-like thrombocytopenia. Blood 1989; 73: 1054–1058.

    CAS  PubMed  Google Scholar 

  31. Narimatsu H, Miyakoshi S, Yamaguchi T, Kami M, Matsumura T, Yuji K et al. Chronic graft-versus-host disease following umbilical cord blood transplantation: retrospective survey involving 1072 patients in Japan. Blood 2008; 112: 2579–2582.

    Article  CAS  Google Scholar 

  32. Przepiorka D, Anderlini P, Saliba R, Cleary K, Mehra R, Khouri I et al. Chronic graft-versus-host disease after allogeneic blood stem cell transplantation. Blood 2001; 98: 1695–1700.

    Article  CAS  Google Scholar 

  33. Prebet T, Ladaique P, Ferrando M, Chabannon C, Faucher C, De Lavallade H et al. Platelet recovery and transfusion needs after reduced intensity conditioning allogeneic peripheral blood stem cell transplantation. Exp Hematol 2010; 38: 55–60.

    Article  CAS  Google Scholar 

  34. Heldal D, Tjonnfjord G, Brinch L, Albrechtsen D, Egeland T, Steen R et al. A randomised study of allogeneic transplantation with stem cells from blood or bone marrow. Bone Marrow Transplant 2000; 25: 1129–1136.

    Article  CAS  Google Scholar 

  35. Mielcarek M, Martin PJ, Leisenring W, Flowers ME, Maloney DG, Sandmaier BM et al. Graft-versus-host disease after non-myeloablative versus conventional hematopoietic stem cell transplantation. Blood 2003; 102: 756–762.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN, USA

    P Ramírez, C G Brunstein, B Miller, T DeFor & D Weisdorf

Authors
  1. P Ramírez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C G Brunstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T DeFor
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D Weisdorf
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D Weisdorf.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ramírez, P., Brunstein, C., Miller, B. et al. Delayed platelet recovery after allogeneic transplantation: a predictor of increased treatment-related mortality and poorer survival. Bone Marrow Transplant 46, 981–986 (2011). https://doi.org/10.1038/bmt.2010.218

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2010.218

Keywords

This article is cited by

Search

Advanced search

Quick links