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
  • Published:

Interpreting outcome data in hematopoietic cell transplantation for leukemia: tackling common biases

Bone Marrow Transplantation volume 50, pages 324–333 (2015)Cite this article

Subjects

Abstract

Although patient outcomes after allogeneic hematopoietic cell transplantation (allo-HCT) have significantly improved in recent years, complications and associated mortality remain substantial. Although many transplants are performed worldwide, the number of patients enrolled prospectively into clinical trials is small. Patient and physician preferences often override treatment assignments in randomized transplant trials, biasing the common intention-to-treat analyses. Large retrospective and observational database studies are likely to detect the real effect of allo-HCT. However, they may be subject to immortal time and other biases derived from heterogeneity of allo-HCT indications and approaches and differences in referral or institutional policies affecting patient selection. Timing of the transplant procedure may be fundamental but studies commencing at start of transplant may neglect the influence of pretransplant therapies. Conversely, a prolonged lag period between the decision and execution of transplant may artificially ‘improve’ the outcome by ‘natural’ selection weeding out patients relapsing or dying before transplant. Finally, comparative nonrandomized transplantation trials often suffer from unbalanced assignment for therapy arms. We herein present common clinical dilemmas discussing proper application of available evidence in daily clinical practice. Pitfalls and caveats frequent in clinical studies of allo-SCT are highlighted to promote a balanced interpretation of available data.

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
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. 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  PubMed  PubMed Central  Google Scholar 

  2. Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood 2008; 111: 1827–1833.

    Article  CAS  PubMed  Google Scholar 

  3. Platzbecker U, Schetelig J, Finke J, Trenschel R, Scott BL, Kobbe G et al. Allogeneic hematopoietic cell transplantation in patients age 60–70 years with de novo high-risk myelodysplastic syndrome or secondary acute myelogenous leukemia: comparison with patients lacking donors who received azacitidine. Biol Blood Marrow Transplant 2012; 18: 1415–1421.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Gale RP, Lazarus HM . How helpful are meta-analyses in determining the best therapy of blood diseases? Acta Haematol 2011; 125: 91–101.

    Article  PubMed  Google Scholar 

  5. Gale RP, Eapen M, Logan B, Zhang MJ, Lazarus HM . Are there roles for observational database studies and structured quantification of expert opinion to answer therapy controversies in transplants? Bone Marrow Transplant 2009; 43: 435–446.

    Article  CAS  PubMed  Google Scholar 

  6. Majhail NS, Lazarus HM . Many are called but few are chosen: under-utilization of unrelated donor transplantation. Biol Blood Marrow Transplant 2013; 19: 1414–1415.

    Article  PubMed  Google Scholar 

  7. Lazarus HM, Litzow MR, Gale RP . Improving survival in acute myeloid leukemia: pick the best subjects? J Clin Oncol 2013; 31: 3854–3856.

    Article  PubMed  Google Scholar 

  8. Thomas X, Boiron JM, Huguet F, Dombret H, Bradstock K, Vey N et al. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol 2004; 22: 4075–4086.

    Article  CAS  PubMed  Google Scholar 

  9. Gale RP, Park RE, Dubois RW, Herzig GP, Hocking WG, Horowitz MM et al. Delphi-panel analysis of appropriateness of high-dose therapy and bone marrow transplants in adults with acute lymphoblastic leukemia in first remission. Leuk Res 1998; 22: 973–981.

    Article  CAS  PubMed  Google Scholar 

  10. Doney K, Gooley TA, Deeg HJ, Flowers ME, Storb R, Appelbaum FR . Allogeneic hematopoietic cell transplantation with full-intensity conditioning for adult acute lymphoblastic leukemia: results from a single center, 1998–2006. Biol Blood Marrow Transplant 2011; 17: 1187–1195.

    Article  PubMed  Google Scholar 

  11. Ram R, Gafter-Gvili A, Vidal L, Paul M, Ben-Bassat I, Shpilberg O et al. Management of adult patients with acute lymphoblastic leukemia in first complete remission: systematic review and meta-analysis. Cancer 2010; 116: 3447–3457.

    Article  PubMed  Google Scholar 

  12. Gupta V, Richards S, Rowe J . Allogeneic, but not autologous, hematopoietic cell transplantation improves survival only among younger adults with acute lymphoblastic leukemia in first remission: an individual patient data meta-analysis. Blood 2013; 121: 339–350.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Pidala J, Djulbegovic B, Anasetti C, Kharfan-Dabaja M, Kumar A . Allogeneic hematopoietic cell transplantation for adult acute lymphoblastic leukemia (ALL) in first complete remission. Cochrane Database Syst Rev 2011, CD008818.

  14. Burnett AK, Goldstone A, Hills RK, Milligan D, Prentice A, Yin J et al. Curability of patients with acute myeloid leukemia who did not undergo transplantation in first remission. J Clin Oncol 2013; 31: 1293–1301.

    Article  PubMed  Google Scholar 

  15. Hengeveld M, Suciu S, Karrasch M, Specchia G, Marie JP, Muus P et al. Intensive consolidation therapy compared with standard consolidation and maintenance therapy for adults with acute myeloid leukaemia aged between 46 and 60 years: final results of the randomized phase III study (AML 8B) of the European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups. Ann Hematol 2012; 91: 825–835.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sorror ML, Sandmaier BM, Storer BE, Maris MB, Baron F, Maloney DG et al. Comorbidity and disease status based risk stratification of outcomes among patients with acute myeloid leukemia or myelodysplasia receiving allogeneic hematopoietic cell transplantation. J Clin Oncol 2007; 25: 4246–4254.

    Article  PubMed  Google Scholar 

  17. Armand P, Gibson CJ, Cutler C, Ho VT, Koreth J, Alyea EP et al. A disease risk index for patients undergoing allogeneic stem cell transplantation. Blood 2012; 120: 905–913.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bokhari SW, Watson L, Nagra S, Cook M, Byrne JL, Craddock C et al. Role of HCT-comorbidity index, age and disease status at transplantation in predicting survival and non-relapse mortality in patients with myelodysplasia and leukemia undergoing reduced-intensity-conditioning hemopoeitic progenitor cell transplantation. Bone Marrow Transplant 2012; 47: 528–534.

    Article  CAS  PubMed  Google Scholar 

  19. Gratwohl A . The EBMT risk score. Bone Marrow Transplant 2012; 47: 749–756.

    Article  CAS  PubMed  Google Scholar 

  20. Gratwohl A, Stern M, Brand R, Apperley J, Baldomero H, de Witte T et al. Risk score for outcome after allogeneic hematopoietic stem cell transplantation: a retrospective analysis. Cancer 2009; 115: 4715–4726.

    Article  PubMed  Google Scholar 

  21. Forman SJ, Rowe JM . The myth of the second remission of acute leukemia in the adult. Blood 2013; 121: 1077–1082.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Tavernier E, Boiron JM, Huguet F, Bradstock K, Vey N, Kovacsovics T et al. Outcome of treatment after first relapse in adults with acute lymphoblastic leukemia initially treated by the LALA-94 trial. Leukemia 2007; 21: 1907–1914.

    Article  CAS  PubMed  Google Scholar 

  23. Gokbuget N, Stanze D, Beck J, Diedrich H, Horst HA, Huttmann A et al. Outcome of relapsed adult lymphoblastic leukemia depends on response to salvage chemotherapy, prognostic factors, and performance of stem cell transplantation. Blood 2012; 120: 2032–2041.

    Article  PubMed  Google Scholar 

  24. Oriol A, Vives S, Hernandez-Rivas JM, Tormo M, Heras I, Rivas C et al. Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group. Haematologica 2010; 95: 589–596.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Stelljes M, Krug U, Beelen DW, Braess J, Sauerland MC, Heinecke A et al. Allogeneic transplantation versus chemotherapy as postremission therapy for acute myeloid leukemia: a prospective matched pairs analysis. J Clin Oncol 2014; 32: 288–296.

    Article  PubMed  Google Scholar 

  26. Cornelissen JJ, Gratwohl A, Schlenk RF, Sierra J, Bornhauser M, Juliusson G et al. The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. Nat Rev Clin Oncol 2012; 9: 579–590.

    Article  CAS  PubMed  Google Scholar 

  27. Rowe JM . Interpreting data on transplant selection and outcome in adult acute lymphoblastic leukemia (ALL). Biol Blood Marrow Transplant 2011; 17: S76–S83.

    Article  PubMed  Google Scholar 

  28. Gamberi B, Bandini G, Visani G, Rosti G, Cenacchi A, Motta MR et al. Acute myeloid leukemia from diagnosis to bone marrow transplantation: experience from a single centre. Bone Marrow Transplant 1994; 14: 69–72.

    CAS  PubMed  Google Scholar 

  29. Berman E, Little C, Gee T, O'Reilly R, Clarkson B . Reasons that patients with acute myelogenous leukemia do not undergo allogeneic bone marrow transplantation. N Engl J Med 1992; 326: 156–160.

    Article  CAS  PubMed  Google Scholar 

  30. Cassileth PA, Harrington DP, Appelbaum FR, Lazarus HM, Rowe JM, Paietta E et al. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med 1998; 339: 1649–1656.

    Article  CAS  PubMed  Google Scholar 

  31. Kantarjian H, Ravandi F, O'Brien S, Cortes J, Faderl S, Garcia-Manero G et al. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood 2010; 116: 4422–4429.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Oran B, Weisdorf DJ . Survival for older patients with acute myeloid leukemia: a population-based study. Haematologica 2012; 97: 1916–1924.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Koreth J, Aldridge J, Kim HT, Alyea EP 3rd, Cutler C, Armand P et al. Reduced-intensity conditioning hematopoietic stem cell transplantation in patients over 60 years: hematologic malignancy outcomes are not impaired in advanced age. Biol Blood Marrow Transplant 2010; 16: 792–800.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kurosawa S, Yamaguchi T, Uchida N, Miyawaki S, Usuki K, Watanabe M et al. Comparison of allogeneic hematopoietic cell transplantation and chemotherapy in elderly patients with non-M3 acute myelogenous leukemia in first complete remission. Biol Blood Marrow Transplant 2011; 17: 401–411.

    Article  PubMed  Google Scholar 

  35. Kroger N, Zabelina T, de Wreede L, Berger J, Alchalby H, van Biezen A et al. Allogeneic stem cell transplantation for older advanced MDS patients: improved survival with young unrelated donor in comparison with HLA-identical siblings. Leukemia 2013; 27: 604–609.

    Article  CAS  PubMed  Google Scholar 

  36. Goldstone AH, Burnett AK, Wheatley K, Smith AG, Hutchinson RM, Clark RE . Attempts to improve treatment outcomes in acute myeloid leukemia (AML) in older patients: the results of the United Kingdom Medical Research Council AML11 trial. Blood 2001; 98: 1302–1311.

    Article  CAS  PubMed  Google Scholar 

  37. Bertz H, Lübbert M, Ohneberg K, Wäsch R, Zeiser R, Marks R et al. Allogeneic Stem Cell Transplantation—A Long-Term Curative Approach In Patients≥60 Years With Advanced Disease AML/MDS,—The Freiburg Experience Of 250 Consecutive Patients. Blood 2013; 122: 2135a.

    Article  Google Scholar 

  38. Abel GA, Kim HT, Armand P, Cutler CS, Antin JH, Koreth J et al. Age Does Not Predict Outcomes For Elderly Patients With Myelodysplastic Syndromes Undergoing Hematopoietic Stem Cell Transplantation With Reduced-Intensity Conditioning. Blood 2013; 122: 2147a.

    Article  Google Scholar 

  39. The CIBMTR Final 2013 Transplant Center-Specific Survival Report. Available at http://www.seattlecca.org/client/Final-2013-Transplant-Center-Specific-Survival-Report-12-27-2013.pdf.

  40. Pidala J, Craig BM, Lee SJ, Majhail N, Quinn G, Anasetti C . Practice variation in physician referral for allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 2013; 48: 63–67.

    Article  CAS  PubMed  Google Scholar 

  41. Kumar RR, Khair E, Paulson H, Szwajcer K, Seftel D, Rubinger M et al. Hematopoietic Stem Cell Transplantation (alloHSCT) is Underutilized in Myelodysplastic Syndrome (MDS): a Population-Based Canadian Province Experience. BIol Blood Marrow Transplant 2011; 17: S294.

    Article  Google Scholar 

  42. Kelaidi C, Stamatoullas A, Beyne-Rauzy O, Raffoux E, Quesnel B, Guerci A et al. Daily practice management of myelodysplastic syndromes in France: data from 907 patients in a one-week cross-sectional study by the Groupe Francophone des Myelodysplasies. Haematologica 2010; 95: 892–899.

    Article  PubMed  Google Scholar 

  43. Field T, Perkins J, Huang Y, Kharfan-Dabaja MA, Alsina M, Ayala E et al. 5-Azacitidine for myelodysplasia before allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 2010; 45: 255–260.

    Article  CAS  PubMed  Google Scholar 

  44. Gerds AT, Gooley TA, Estey EH, Appelbaum FR, Deeg HJ, Scott BL . Pretransplantation therapy with azacitidine vs induction chemotherapy and posttransplantation outcome in patients with MDS. Biol Blood Marrow Transplant 2012; 18: 1211–1218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Mahindra A, Bolwell B, Sobecks R, Rybicki L, Pohlman B, Dean R et al. Elevated pretransplant ferritin is associated with a lower incidence of chronic graft-versus-host disease and inferior survival after myeloablative allogeneic haematopoietic stem cell transplantation. Br J Haematol 2009; 146: 310–316.

    Article  CAS  PubMed  Google Scholar 

  46. Armand P, Kim HT, Cutler CS, Ho VT, Koreth J, Alyea EP et al. Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation. Blood 2007; 109: 4586–4588.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Giralt S, Estey E, Albitar M, van Besien K, Rondon G, Anderlini P et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 1997; 89: 4531–4536.

    CAS  PubMed  Google Scholar 

  48. Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 1998; 91: 756–763.

    CAS  PubMed  Google Scholar 

  49. Barrett AJ, Savani BN . Stem cell transplantation with reduced-intensity conditioning regimens: a review of ten years experience with new transplant concepts and new therapeutic agents. Leukemia 2006; 20: 1661–1672.

    Article  CAS  PubMed  Google Scholar 

  50. Giralt S, Logan B, Rizzo D, Zhang MJ, Ballen K, Emmanouilides C et al. Reduced-intensity conditioning for unrelated donor progenitor cell transplantation: long-term follow-up of the first 285 reported to the national marrow donor program. Biol Blood Marrow Transplant 2007; 13: 844–852.

    Article  PubMed  Google Scholar 

  51. Sayer HG, Kroger M, Beyer J, Kiehl M, Klein SA, Schaefer-Eckart K et al. Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia: disease status by marrow blasts is the strongest prognostic factor. Bone Marrow Transplant 2003; 31: 1089–1095.

    Article  CAS  PubMed  Google Scholar 

  52. Aoudjhane M, Labopin M, Gorin NC, Shimoni A, Ruutu T, Kolb HJ et al. Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective survey from the Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT). Leukemia 2005; 19: 2304–2312.

    Article  CAS  PubMed  Google Scholar 

  53. Shimoni A, Hardan I, Shem-Tov N, Yeshurun M, Yerushalmi R, Avigdor A et al. Allogeneic hematopoietic stem-cell transplantation in AML and MDS using myeloablative versus reduced-intensity conditioning: the role of dose intensity. Leukemia 2006; 20: 322–328.

    Article  CAS  PubMed  Google Scholar 

  54. de Lima M, Anagnostopoulos A, Munsell M, Shahjahan M, Ueno N, Ippoliti C et al. Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. Blood 2004; 104: 865–872.

    Article  CAS  PubMed  Google Scholar 

  55. Liu H, Stock W, Bishop MR . Expanded indications for allogeneic stem cell transplantation in patients with myeloid malignancies. Curr Opin Hematol 2013; 20: 115–122.

    Article  PubMed  Google Scholar 

  56. McClune BL, Weisdorf DJ, Pedersen TL, Tunes da Silva G, Tallman MS, Sierra J et al. Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome. J Clin Oncol 2010; 28: 1878–1887.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Ringden O, Labopin M, Ehninger G, Niederwieser D, Olsson R, Basara N et al. Reduced intensity conditioning compared with myeloablative conditioning using unrelated donor transplants in patients with acute myeloid leukemia. J Clin Oncol 2009; 27: 4570–4577.

    Article  PubMed  Google Scholar 

  58. Bornhauser M, Kienast J, Trenschel R, Burchert A, Hegenbart U, Stadler M et al. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol 2012; 13: 1035–1044.

    Article  PubMed  Google Scholar 

  59. A randomized, multi-center, phase iii study of allogeneic stem cell transplantation comparing regimen intensity in patients with myelodysplastic syndrome or acute myeloid leukemia. Available at http://www.cibmtr.org/Studies/ClinicalTrials/BMT_CTN/Protocols/Pages/0901.aspx.

  60. Schmitz N, Dreger P, Suttorp M, Rohwedder EB, Haferlach T, Loffler H et al. Primary transplantation of allogeneic peripheral blood progenitor cells mobilized by filgrastim (granulocyte colony-stimulating factor). Blood 1995; 85: 1666–1672.

    CAS  PubMed  Google Scholar 

  61. Bensinger WI, Weaver CH, Appelbaum FR, Rowley S, Demirer T, Sanders J et al. Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony-stimulating factor. Blood 1995; 85: 1655–1658.

    CAS  PubMed  Google Scholar 

  62. Blaise D, Kuentz M, Fortanier C, Bourhis JH, Milpied N, Sutton L et al. Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: a report from the Societe Francaise de Greffe de Moelle. J Clin Oncol 2000; 18: 537–546.

    Article  CAS  PubMed  Google Scholar 

  63. Powles R, Mehta J, Kulkarni S, Treleaven J, Millar B, Marsden J et al. Allogeneic blood and bone-marrow stem-cell transplantation in haematological malignant diseases: a randomised trial. Lancet 2000; 355: 1231–1237.

    Article  CAS  PubMed  Google Scholar 

  64. Bensinger WI, Martin PJ, Storer B, Clift R, Forman SJ, Negrin R et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N Engl J Med 2001; 344: 175–181.

    Article  CAS  PubMed  Google Scholar 

  65. Morton J, Hutchins C, Durrant S . Granulocyte-colony-stimulating factor (G-CSF)-primed allogeneic bone marrow: significantly less graft-versus-host disease and comparable engraftment to G-CSF-mobilized peripheral blood stem cells. Blood 2001; 98: 3186–3191.

    Article  CAS  PubMed  Google Scholar 

  66. 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  PubMed  Google Scholar 

  67. CIBMTR Newsletter. Available at http://www.cibmtr.org/ReferenceCenter/Newsletters/Documents/Newsletter_Dec2011.pdf2011.

  68. Friedrichs B, Tichelli A, Bacigalupo A, Russell NH, Ruutu T, Shapira MY et al. Long-term outcome and late effects in patients transplanted with mobilised blood or bone marrow: a randomised trial. Lancet Oncol 2010; 11: 331–338.

    Article  PubMed  Google Scholar 

  69. 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: 1487–1496.

    Article  CAS  PubMed  Google Scholar 

  70. Dini G, Valsecchi MG, Micalizzi C, Busca A, Balduzzi A, Arcese W et al. Impact of marrow unrelated donor search duration on outcome of children with acute lymphoblastic leukemia in second remission. Bone Marrow Transplant 2003; 32: 325–331.

    Article  CAS  PubMed  Google Scholar 

  71. Rowlings PA, Przepiorka D, Klein JP, Gale RP, Passweg JR, Henslee-Downey PJ et al. IBMTR Severity Index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade. Br J Haematol 1997; 97: 855–864.

    Article  CAS  PubMed  Google Scholar 

  72. Lee SJ, Klein JP, Barrett AJ, Ringden O, Antin JH, Cahn JY et al. Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. Blood 2002; 100: 406–414.

    Article  CAS  PubMed  Google Scholar 

  73. Ringden O, Pavletic SZ, Anasetti C, Barrett AJ, Wang T, Wang D et al. The graft-versus-leukemia effect using matched unrelated donors is not superior to HLA-identical siblings for hematopoietic stem cell transplantation. Blood 2009; 113: 3110–3118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Saber W, Opie S, Rizzo JD, Zhang MJ, Horowitz MM, Schriber J . Outcomes after matched unrelated donor versus identical sibling hematopoietic cell transplantation in adults with acute myelogenous leukemia. Blood 2012; 119: 3908–3916.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Alousi AM, Le-Rademacher J, Saliba RM, Appelbaum FR, Artz A, Benjamin J et al. Who is the better donor for older hematopoietic transplant recipients: an older-aged sibling or a young, matched unrelated volunteer? Blood 2013; 121: 2567–2573.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Peffault de Latour R, Brunstein CG, Porcher R, Chevallier P, Robin M, Warlick E et al. Similar overall survival using sibling, unrelated donor, and cord blood grafts after reduced-intensity conditioning for older patients with acute myelogenous leukemia. Biol Blood Marrow Transplant 2013; 19: 1355–1360.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel

    Y Ofran & J M Rowe

  2. Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel

    Y Ofran & J M Rowe

  3. Department of Medicine, University Hospitals Case Medical Center, Case Comprehensive Cancer Center, Cleveland, OH, USA

    H M Lazarus

  4. University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD, USA

    A P Rapoport

  5. Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel

    J M Rowe

Authors
  1. Y Ofran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H M Lazarus
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A P Rapoport
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J M Rowe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y Ofran.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ofran, Y., Lazarus, H., Rapoport, A. et al. Interpreting outcome data in hematopoietic cell transplantation for leukemia: tackling common biases. Bone Marrow Transplant 50, 324–333 (2015). https://doi.org/10.1038/bmt.2014.270

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2014.270

Search

Advanced search

Quick links