Composite GRFS and CRFS Outcomes After Adult Alternative Donor HCT.

PURPOSE There is no consensus on the best choice of an alternative donor (umbilical cord blood [UCB], haploidentical, one-antigen mismatched [7/8]-bone marrow [BM], or 7/8-peripheral blood [PB]) for hematopoietic cell transplantation (HCT) for patients lacking an HLA-matched related or unrelated donor. METHODS We report composite end points of graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) and chronic GVHD (cGVHD)-free relapse-free survival (CRFS) in 2,198 patients who underwent UCB (n = 838), haploidentical (n = 159), 7/8-BM (n = 241), or 7/8-PB (n = 960) HCT. All groups were divided by myeloablative conditioning (MAC) intensity or reduced intensity conditioning (RIC), except haploidentical group in which most received RIC. To account for multiple testing, P < .0071 in multivariable analysis and P < .00025 in direct pairwise comparisons were considered statistically significant. RESULTS In multivariable analysis, haploidentical group had the best GRFS, CRFS, and overall survival (OS). In the direct pairwise comparison of other groups, among those who received MAC, there was no difference in GRFS or CRFS among UCB, 7/8-BM, and 7/8-PB with serotherapy (alemtuzumab or antithymocyte globulin) groups. In contrast, the 7/8-PB without serotherapy group had significantly inferior GRFS, higher cGVHD, and a trend toward worse CRFS (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.69; P = .002) than the 7/8-BM group and higher cGVHD and trend toward inferior CRFS (HR, 1.36; 95% CI, 1.14 to 1.63; P = .0006) than the UCB group. Among patients with RIC, all groups had significantly inferior GRFS and CRFS compared with the haploidentical group. CONCLUSION Recognizing the limitations of a registry retrospective analysis and the possibility of center selection bias in choosing donors, our data support the use of UCB, 7/8-BM, or 7/8-PB (with serotherapy) grafts for patients undergoing MAC HCT and haploidentical grafts for patients undergoing RIC HCT. The haploidentical group had the best GRFS, CRFS, and OS of all groups.

[1]  S. Fathizadeh,et al.  Shaping Cartilage Grafts. , 2022, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[2]  M. Pasquini,et al.  T-Replete Haploidentical Cell Transplantation Using Post-Transplant Cyclophosphamide for Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome: Effect of Transplant Conditioning Regimen Intensity on Outcomes , 2018, Blood.

[3]  M. Perales,et al.  Blood and Marrow Transplant Clinical Trials Network Report on the Development of Novel Endpoints and Selection of Promising Approaches for Graft-versus-Host Disease Prevention Trials. , 2018, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[4]  C. Martínez,et al.  Single Antigen-Mismatched Unrelated Hematopoietic Stem Cell Transplantation Using High-Dose Post-Transplantation Cyclophosphamide Is a Suitable Alternative for Patients Lacking HLA-Matched Donors. , 2018, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[5]  Georg Heinze,et al.  Weighted Cox Regression Using the R Package coxphw , 2018 .

[6]  M. Labopin,et al.  Bone marrow versus mobilized peripheral blood stem cells in haploidentical transplants using posttransplantation cyclophosphamide , 2018, Cancer.

[7]  G. Hill,et al.  Mismatched unrelated donor allogeneic stem cell transplant for high risk haematological malignancy: A single centre experience , 2017, Blood Cancer Journal.

[8]  Shannon R. McCurdy,et al.  Mobilized Peripheral Blood Stem Cells Versus Unstimulated Bone Marrow As a Graft Source for T-Cell-Replete Haploidentical Donor Transplantation Using Post-Transplant Cyclophosphamide. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  E. Leifer,et al.  Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  D. Niederwieser,et al.  Increased age-associated mortality risk in HLA-mismatched hematopoietic stem cell transplantation , 2017, Haematologica.

[11]  K. Rezvani,et al.  Results of a 2‐arm, phase 2 clinical trial using post‐transplantation cyclophosphamide for the prevention of graft‐versus‐host disease in haploidentical donor and mismatched unrelated donor hematopoietic stem cell transplantation , 2016, Cancer.

[12]  F. Appelbaum,et al.  Cord-Blood Transplantation in Patients with Minimal Residual Disease. , 2016, The New England journal of medicine.

[13]  M. Robin,et al.  Improved graft-versus-host disease-free, relapse-free survival associated with bone marrow as the stem cell source in adults , 2016, Haematologica.

[14]  E. Shpall,et al.  Post‐transplantation cyclophosphamide versus conventional graft‐versus‐host disease prophylaxis in mismatched unrelated donor haematopoietic cell transplantation , 2016, British journal of haematology.

[15]  A. Gennery,et al.  Hematopoietic stem cell transplantation in Europe 2014: more than 40 000 transplants annually , 2016, Bone Marrow Transplantation.

[16]  K. Rezvani,et al.  Better allele-level matching improves transplant-related mortality after double cord blood transplantation , 2015, Haematologica.

[17]  J. Sierra,et al.  Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia , 2015, Leukemia.

[18]  M. MacMillan,et al.  Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. , 2015, Blood.

[19]  Medhat Askar,et al.  Nonpermissive HLA-DPB1 mismatch increases mortality after myeloablative unrelated allogeneic hematopoietic cell transplantation. , 2014, Blood.

[20]  Loren Gragert,et al.  HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. , 2014, The New England journal of medicine.

[21]  M. Horowitz,et al.  Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation. , 2014, Blood.

[22]  D. Weisdorf,et al.  Alternative donor transplantation for older patients with acute myeloid leukemia in first complete remission: a center for international blood and marrow transplant research-eurocord analysis. , 2014, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[23]  J. Klein,et al.  Impact of allele-level HLA matching on outcomes after myeloablative single unit umbilical cord blood transplantation for hematologic malignancy. , 2014, Blood.

[24]  J. Klein,et al.  Effect of donor-recipient HLA matching at HLA A, B, C, and DRB1 on outcomes after umbilical-cord blood transplantation for leukaemia and myelodysplastic syndrome: a retrospective analysis. , 2011, The Lancet. Oncology.

[25]  J. Wingard,et al.  Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. , 2011, Blood.

[26]  J. Wagner,et al.  Effect of graft source on unrelated donor haemopoietic stem-cell transplantation in adults with acute leukaemia: a retrospective analysis. , 2010, The Lancet. Oncology.

[27]  B. Sandmaier,et al.  Defining the intensity of conditioning regimens: working definitions. , 2009, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[28]  M. Schemper,et al.  The estimation of average hazard ratios by weighted Cox regression , 2009, Statistics in medicine.

[29]  K. Kawa,et al.  Disease-specific analyses of unrelated cord blood transplantation compared with unrelated bone marrow transplantation in adult patients with acute leukemia. , 2009, Blood.

[30]  M. Remberger,et al.  Outcome of haematopoietic stem cell transplantation in patients transplanted with matched unrelated donors vs allele-mismatched donors: a single centre study. , 2008, Tissue antigens.

[31]  Harriet Noreen,et al.  High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. , 2007, Blood.

[32]  Xu Zhang,et al.  A SAS macro for estimation of direct adjusted survival curves based on a stratified Cox regression model , 2007, Comput. Methods Programs Biomed..

[33]  S. Asano,et al.  Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell transplants from related donors in adult patients with hematologic malignancies after myeloablative conditioning regimen. , 2007, Blood.

[34]  Daniel Wolff,et al.  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. , 2005, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[35]  P. Bartolomeo,et al.  Outcomes of Unrelated Cord Blood and Haploidentical Stem Cell Transplantation in Adults with Acute Leukaemia. , 2005 .

[36]  M. Sorror,et al.  Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. , 2005, Blood.

[37]  M. Labopin,et al.  Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. , 2004, The New England journal of medicine.

[38]  J. Wagner,et al.  Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. , 2004, The New England journal of medicine.

[39]  John P Klein,et al.  Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. , 2002, Blood.

[40]  E D Thomas,et al.  1994 Consensus Conference on Acute GVHD Grading. , 1995, Bone marrow transplantation.

[41]  K. Sullivan,et al.  Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. , 1980, The American journal of medicine.

[42]  J. Wagner,et al.  Matching at Human Leukocyte Antigen-C Improved the Outcomes after Double Umbilical Cord Blood Transplantation for Recipients of Two to Four of Six Human Leukocyte Antigen-Matched Grafts. , 2017, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[43]  Mei-Jie Zhang,et al.  SAS macros for estimation of direct adjusted cumulative incidence curves under proportional subdistribution hazards models , 2011, Comput. Methods Programs Biomed..