Haploidentical vs haplo-cord transplant in adults under 60 years receiving fludarabine and melphalan conditioning

Blood Adv. 2019 Jun 25;3(12):1858-1867. doi: 10.1182/bloodadvances.2019000200.

Abstract

Haplo-identical transplant with posttransplant cyclophosphamide (haplo) and umbilical cord blood transplant supported by third-party CD34 cells (haplo-cord) are competing approaches to alternative donor transplant. We compared, in adults younger than age 60 years, the outcomes of 170 haplo at 1 institution with that of 137 haplo-cord at 2 other institutions. All received reduced intensity conditioning with fludarabine and melphalan ± total body irradiation. GVHD prophylaxis for haplo consisted of cyclophosphamide, tacrolimus, and mycophenolate, whereas haplo-cord received antithymocyte globulin, tacrolimus, and mycophenolate. Haplo transplant used mostly bone marrow, and peripheral blood stem cells were used in haplo-cord transplants. Haplo-cord were older and had more advanced disease. Haplo-cord hastened median time to neutrophil (11 vs 18 days, P = .001) and platelet recovery (22 vs 25 days, P = .03). At 4 years, overall survival (OS) was 50% for haplo-cord vs 49% for haplo. Progression-free survival (PFS) was 40% for haplo-cord vs 45% for haplo. In multivariate analysis, the disease risk index was significant for OS (hazard ratio, 1.8; 95% confidence interval, 1.48-2.17; P = .00) and PFS. Total body irradiation was associated with decreased recurrence and improved PFS, age >40 with increased nonrelapse mortality. The type of transplant had no effect on OS, PFS, relapse, or nonrelapse mortality. Cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) by day 100 was 16% after haplo-cord vs 33% after haplo (P < .0001), but grade 3-4 GVHD was similar. Chronic GVHD at 1 year was 4% after haplo-cord vs 16% after haplo (P < .0001). Haplo or haplo-cord results in similar and encouraging outcomes. Haplo-cord is associated with more rapid neutrophil and platelet recovery and lower acute and chronic GVHD. Institutional review board authorization for this retrospective study was obtained at each institution. Some patients participated in trials registered at www.clinicaltrials.gov as #NCT01810588 and NCT01050946.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adult
  • Bone Marrow Transplantation / methods
  • Cord Blood Stem Cell Transplantation / adverse effects*
  • Cord Blood Stem Cell Transplantation / methods
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / therapeutic use
  • Disease-Free Survival
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Graft vs Host Disease / drug therapy
  • Graft vs Host Disease / epidemiology
  • Graft vs Host Disease / prevention & control*
  • Haplotypes / drug effects
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / radiotherapy
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Melphalan / administration & dosage
  • Melphalan / therapeutic use
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / therapeutic use
  • Myeloablative Agonists / administration & dosage
  • Myeloablative Agonists / therapeutic use
  • Neutrophils / drug effects
  • Recovery of Function / drug effects
  • Retrospective Studies
  • Tacrolimus / administration & dosage
  • Tacrolimus / therapeutic use
  • Transplantation Conditioning / methods*
  • Transplantation Conditioning / statistics & numerical data
  • Transplantation, Homologous / statistics & numerical data*
  • Transplantation, Homologous / trends
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives
  • Vidarabine / therapeutic use
  • Whole-Body Irradiation / adverse effects
  • Whole-Body Irradiation / methods

Substances

  • Enzyme Inhibitors
  • Immunosuppressive Agents
  • Myeloablative Agonists
  • Cyclophosphamide
  • Vidarabine
  • Mycophenolic Acid
  • fludarabine
  • Melphalan
  • Tacrolimus

Associated data

  • ClinicalTrials.gov/NCT01810588
  • ClinicalTrials.gov/NCT01050946