Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide Using Non–First-Degree Related Donors

Abstract

Outcomes of nonmyeloablative (NMA) haploidentical (haplo) blood or marrow transplant (BMT) with post-transplantation cyclophosphamide (PTCy) using non-first-degree relatives are unknown. We evaluated 33 consecutive adult patients (median age, 56 years) with hematologic malignancies who underwent NMA haplo T cell-replete BMT with PTCy at Johns Hopkins using second- or third-degree related donors. Donors consisted of 10 nieces (30%), 9 nephews (27%), 7 first cousins (21%), 5 grandchildren (15%), and 2 uncles (6%). Thirty-one patients (94%) reached full donor chimerism by day 60. The estimated cumulative incidence (CuI) of grades II to IV acute graft-versus-host disease (aGVHD) at day 180 was 24% (90% confidence interval [CI], 9% to 38%). Only 1 patient experienced grades III to IV aGVHD. At 1 year the CuI of chronic GVHD was 10% (90% CI, 0% to 21%). The CuI of nonrelapse mortality at 1 year was 5% (90% CI, 0% to 14%). At 1 year the probability of relapse was 31% (90% CI, 12% to 49%), progression-free survival 64% (90% CI, 48% to 86%), and overall survival 95% (90% CI, 87% to 100%). The 1-year probability of GVHD-free, relapse-free survival was 57% (90% CI, 41% to 79%). NMA haplo BMT with PTCy from non-first-degree relatives is an acceptably safe and effective alternative donor platform, with results similar to those seen with first-degree relatives.

Effect of increased dose of total body irradiation on graft failure associated with HLA-haploidentical transplantation in patients with severe haemoglobinopathies: a prospective clinical trial

“…All the donors were related haploidentical family members, and included 7 (41%) siblings, 5 (29%) mothers, 4 fathers (24%), and 1 aunt (6%). (21) Engraftment.…”

BSHI guideline: HLA matching and donor selection for haematopoietic progenitor cell transplantation

“…For the majority of paediatric patients, the donor will either be the patient's mother or father. For adult patients, this choice is often impracticable and siblings and children are usually considered, with second degree‐related donors also possible (Elmariah et al., 2018). Preferred donor characteristics, which vary depending on the transplant protocol (T‐cell deplete or T‐cell replete), have been reviewed and published in the European Society for Blood and Marrow Transplant (EBMT) consensus recommendations (Ciurea et al., 2020).…”

HLA-haploidentical stem cell transplantation using posttransplant cyclophosphamide

“…Younger donor age (≤ 40 years) may be a predictor for improved survival in older patients with AML and MDS receiving PTCy-haploSCT [11]. PTCy-haploBMT from non-first-degree relatives results is similar to those seen with first-degree relatives [12]. The impact of donor versus recipient killer cell immunoglobulin-like receptor (KIR)ligand mismatch in PTCy-haploSCT is still controversial [13][14][15][16].…”