ABSTRACT
Donor-lymphocyte infusion (DLI) for relapse following haploidentical hematopoietic cell transplantation (haploHCT) with post-transplant cyclophosphamide (PTCy) has been described in recipients of bone marrow grafts, but not recipients of G-CSF mobilized peripheral blood (PB) grafts. We retrospectively identified patients who underwent DLI following PB-haploHCT with PTCy for relapse, or loss of chimerism (LOC). Twelve patients (57%) received DLI for hematologic relapse/persistent disease, seven (33%) for extramedullary relapse and two (10%) for LOC. Sixteen (76%) received chemotherapy prior to DLI, which did not correlate with response. The most common first dose was 1 × 106 CD3+ cells/kg. Two patients developed grade I aGvHD post DLI, one had grade II and two had grade III. One developed mild skin cGvHD 1361 days post DLI. Pre-DLI aGvHD predicted post-DLI aGvHD (P=0.025). Six patients achieved CR after DLI for overt relapse, one achieved full donor chimerism after LOC. Patients with LOC or EM relapse had superior relapse-free survival following DLI (P=0.029). DLI following PB-haploHCT with PTCy is a viable salvage therapy for overt relapse or LOC without a substantial increase in GvHD, and donor lymphocytes may be collected simultaneously with graft collection to facilitate availability in patients at high risk of relapse.
Subject(s)
Cyclophosphamide/therapeutic use , Lymphocyte Transfusion , Peripheral Blood Stem Cell Transplantation/methods , Salvage Therapy/methods , Aged , Disease-Free Survival , Graft vs Host Disease/etiology , Hematologic Neoplasms/therapy , Humans , Middle Aged , Retrospective Studies , Tissue Donors , Transplantation, Haploidentical , Treatment OutcomeSubject(s)
HLA Antigens , Hematologic Neoplasms , Isoantibodies/blood , Peripheral Blood Stem Cell Transplantation , Unrelated Donors , Adolescent , Adult , Aged , Allografts , Child , Disease-Free Survival , Female , Hematologic Neoplasms/blood , Hematologic Neoplasms/mortality , Hematologic Neoplasms/therapy , Humans , Male , Middle Aged , Retrospective Studies , Survival RateSubject(s)
Granulocyte Colony-Stimulating Factor/administration & dosage , Hematologic Neoplasms/mortality , Hematologic Neoplasms/therapy , Lymphocyte Depletion , Peripheral Blood Stem Cell Transplantation , Peripheral Blood Stem Cells , Adolescent , Adult , Aged , Allografts , Disease-Free Survival , Female , Hematologic Neoplasms/pathology , Humans , Male , Middle Aged , Survival RateABSTRACT
In recent years, the use of haploidentical donors for hematopoietic cell transplantation has expanded rapidly. Approximately 50% of patients requiring hematopoietic cell transplant lack a traditional donor. The use of HLA haploidentical-related donors is attractive due to nearly universal availability of this graft source. We summarize the current and future need for haploidentical donors and detail the rise of post-transplant cyclophosphamide as the dominant haploidentical approach. Further, we examine ongoing controversies in the field of haploidentical transplant, including conditioning regimens and graft source. Finally, we review the evidence available from preliminary comparative studies and discuss future direction of research.
Subject(s)
Cyclophosphamide/therapeutic use , Hematopoietic Stem Cell Transplantation , Tissue Donors , Transplantation Conditioning , Allografts , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cell Transplantation/trends , Histocompatibility Testing/methods , Humans , Transplantation Conditioning/methods , Transplantation Conditioning/trendsABSTRACT
Post-transplant cyclophosphamide (PT-Cy) is the backbone of GvHD prophylaxis following haploidentical hematopoietic cell transplantation (haplo-HCT). PT-Cy has also been used in matched related (MRD) and unrelated (MUD) settings. It is not known whether outcomes are similar between haplo-HCT and MRD/MUD HCT when PT-Cy is used. We performed a retrospective analysis of 83 patients with AML who underwent HCT (using PT-Cy-based GvHD prophylaxis) from MRD, MUD or haploidentical donors. The groups were similar in baseline characteristics with the exception of older age in the MRD/MUD group (P=0.012). In multivariate analysis, the effect of donor type (MRD/MUD vs haploidentical) on transplant outcomes was not significant in any of the models except for faster neutrophil recovery after MRD/MUD transplants (hazard ratio: 2.21; 95% confidence interval: 1.31-3.72, P=0.002). In conclusion, we showed similar outcomes in MRD/MUD vs haploidentical HCT (except slower count recovery following haplo-HCT) when PT-Cy is used for GvHD prophylaxis. Although slower count recovery following haplo-HCT (compared with MRD/MUD transplants without PT-Cy) has been attributed to using PT-Cy, our results suggest that HLA disparity is the primary cause of this difference. Furthermore, our analysis supports PT-Cy as a viable option for GvHD prophylaxis after MRD/MUD transplants.
Subject(s)
Cyclophosphamide/administration & dosage , Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation/methods , Leukemia, Myeloid, Acute/therapy , Adolescent , Adult , Aged , Blood Donors , Female , Graft Survival , Haplotypes , Hematopoietic Stem Cell Transplantation/adverse effects , Histocompatibility , Humans , Leukemia, Myeloid, Acute/complications , Male , Middle Aged , Premedication , Retrospective Studies , Treatment Outcome , Young AdultSubject(s)
Histocompatibility , Peripheral Blood Stem Cell Transplantation/methods , Transplantation, Haploidentical/methods , Adult , Aged , Female , HLA Antigens/analysis , Humans , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Peripheral Blood Stem Cell Transplantation/mortality , Retrospective Studies , Survival Analysis , T-Lymphocytes , Transplantation, Haploidentical/mortality , Young AdultSubject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Adult , Aged , Humans , NetherlandsSubject(s)
Granulocyte Colony-Stimulating Factor/administration & dosage , Hematologic Neoplasms , Hematopoietic Stem Cell Mobilization , Lymphocyte Depletion , Peripheral Blood Stem Cell Transplantation , Transplantation Conditioning , Adult , Aged , Allografts , Disease-Free Survival , Female , Follow-Up Studies , Hematologic Neoplasms/mortality , Hematologic Neoplasms/therapy , Humans , Male , Middle Aged , Survival Rate , Time FactorsABSTRACT
Recent advances in allogeneic hematopoietic cell transplant (allo-HCT) have led to an increasing use of alternative donors, including banked umbilical cord blood (UCB). Despite these advances, acute GVHD (aGVHD) and chronic GVHD (cGVHD) continue to be the leading causes of early and late transplant-related mortality. ABO-mismatch has been frequently reported as a risk factor for GVHD, however, data in the UCB recipients are limited. We hypothesized that as the lymphocytes in the cord blood are thought to be naive, they will therefore be less likely to mediate GVHD. Therefore, we analyzed the impact of ABO-mismatch on aGVHD and cGVHD in recipients of single and double UCB-HCT. In both univariate and multivariate analyses, presence of ABO-mismatch did not have an impact on aGVHD or cGVHD. Whereas ABO-compatible donors are preferred in recipients of URD-HCT, ABO compatibility generally need not be considered in recipients of UCB-HCT.