Outcomes of Nonmyeloablative HLA-Haploidentical Blood or Marrow Transplantation With High-Dose Post-Transplantation Cyclophosphamide in Older Adults

J Clin Oncol. 2015 Oct 1;33(28):3152-61. doi: 10.1200/JCO.2014.60.4777. Epub 2015 Aug 10.

Abstract

Purpose: Recent advances in nonmyeloablative (NMA), related HLA-haploidentical blood or marrow transplantation (haplo-BMT) have expanded the donor pool. This study evaluated the effect of age on NMA haplo-BMT outcomes in patients age 50 to 75 years.

Patients and methods: A retrospective analysis was performed of 271 consecutive patients with hematologic malignancies, age 50 to 75 years, who received NMA, T-cell-replete haplo-BMT with high-dose post-transplantation cyclophosphamide.

Results: The median age was 61 years, with 115 patients (42%) age 50 to 59, 129 (48%) age 60 to 69, and 27 (10%) age 70 to 75 years. Overall, 84% of patients had intermediate- or high-/very high-risk disease. The 6-month probabilities of grade 3 or 4 acute graft-versus-host disease (GVHD) and nonrelapse mortality (NRM) were 3% and 8%, respectively. Patients in their 50s, 60s, and 70s had 6-month NRM probabilities of 8%, 9%, and 7%, respectively (P=.20). With a median follow-up of 4 years, corresponding 3-year progression-free survival probabilities were 39%, 35%, and 33% (P=.65), and corresponding 3-year overall survival probabilities were 48%, 45%, and 44% (P=.66). Three-year progression-free survival probabilities were 40% in acute myeloid leukemia (n=65), 39% in aggressive non-Hodgkin lymphoma (n=83), and 37% in indolent or mantle-cell lymphoma (n=65). Older patient age was associated with a significantly higher risk of grade 2 to 4 acute GVHD but not grade 3 to 4 acute or chronic GVHD. No statistically significant associations were found between older age (relative to age 50 to 59 years or as a continuous variable) and NRM, relapse, or survival.

Conclusion: NMA haplo-BMT with post-transplantation cyclophosphamide has encouraging safety and survival outcomes in patients age 50 to 75 years. In patients otherwise fit for BMT, the results support consideration of this approach despite advanced age.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage*
  • Antineoplastic Agents, Alkylating / adverse effects
  • Bone Marrow Transplantation* / adverse effects
  • Bone Marrow Transplantation* / mortality
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / administration & dosage*
  • Cyclophosphamide / adverse effects
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease / diagnosis
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / mortality
  • HLA Antigens / genetics*
  • HLA Antigens / immunology
  • Haplotypes*
  • Hematologic Neoplasms / diagnosis
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / mortality
  • Hematologic Neoplasms / therapy*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Patient Selection
  • Proportional Hazards Models
  • Recurrence
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Tissue Donors*
  • Transplantation Conditioning*
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Alkylating
  • HLA Antigens
  • Cyclophosphamide