Dataset Information

Bone Marrow versus Peripheral Blood Grafts for Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide.

ABSTRACT: In the coronavirus disease 19 (COVID-19) pandemic era, the number of haploidentical hematopoietic cell transplantations (HCTs) with peripheral blood (PB) grafts increased significantly compared with HCTs with bone marrow (BM) grafts, which may be associated with adverse outcomes. We compared outcomes of HCT in BM graft and PB graft recipients age ≥18 years with hematologic malignancies who underwent T cell- replete haploidentical HCT and received graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Among the 264 patients, 180 (68%) received a BM graft and 84 (32%) received a PB graft. The median patient age was 50 years in both groups. The majority (n = 199; 75%) received reduced-intensity conditioning. The rate of acute leukemia or myelodysplastic syndrome was higher in the BM graft recipients compared with the PB graft recipients (85% [n = 152] versus 55% [n = 46]; P < .01). The median times to neutrophil and platelet engraftment and the incidence of grade II-IV and grade III-IV acute GVHD (aGVHD) were comparable in the 2 groups. Among the patients with grade II-IV aGVHD, the rate of steroid-refractory aGVHD was 9% (95% confidence interval [CI], 5% to 18%) in the BM group versus 32% (95% CI, 19% to 54%) in the PB group (hazard ratio [HR], 3.7, 95% CI, 1.5 to 9.3; P = .006). At 1 year post-HCT, the rate of chronic GVHD (cGVHD) was 8% (95% CI, 4% to 13%) in the BM group versus 22% (95% CI, 14% to 36%) in the PB group (HR, 3.0; 95% CI, 1.4-6.6; P = .005), and the rate of systemic therapy-requiring cGVHD was 2.5% (95% CI, 1% to 7%) versus 14% (95% CI, 7% to 27%), respectively (HR, 5.6; 95% CI, 1.7 to 18; P = .004). The PB group had a significantly higher risk of bacterial and viral infections, with no appreciable advantage in the duration of hospitalization, immune reconstitution, relapse, nonrelapse mortality, or survival. Our data suggest a benefit of the use of BM grafts over PB grafts for haplo-HCT.

SUBMITTER: Mehta RS

PROVIDER: S-EPMC8504778 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Bone Marrow versus Peripheral Blood Grafts for Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide.

Mehta Rohtesh S RS Saliba Rima M RM Alsfeld Leonard C LC Jorgensen Jeffrey L JL Wang Sa A SA Anderlini Paolo P Al-Atrash Gheath G Bashir Qaiser Q Ciurea Stefan O SO Hosing Chitra M CM Im Jin S JS Kebriaei Partow P Khouri Issa I Marin David D Nieto Yago Y Olson Amanda A Oran Betul B Popat Uday R UR Qazilbash Muzaffar H MH Ramdial Jeremy J Rondon Gabriela G Saini Neeraj N Srour Samer A SA Rezvani Katayoun K Shpall Elizabeth J EJ Champlin Richard E RE Alousi Amin M AM

Transplantation and cellular therapy 20210916 12

In the coronavirus disease 19 (COVID-19) pandemic era, the number of haploidentical hematopoietic cell transplantations (HCTs) with peripheral blood (PB) grafts increased significantly compared with HCTs with bone marrow (BM) grafts, which may be associated with adverse outcomes. We compared outcomes of HCT in BM graft and PB graft recipients age ≥18 years with hematologic malignancies who underwent T cell- replete haploidentical HCT and received graft-versus-host disease (GVHD) prophylaxis with ...[more]

PMID: 34537419

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Project description:Identifying a suitable volunteer unrelated donor (UD) in South Africa is challenging due to the highly diverse ethnic groups and mixed-race populations in this region. Haploidentical hematopoietic cell transplantation (haploHCT) is thus an attractive procedure for patients with high-risk hematologic malignancies. This study was conducted to assess the safety and feasibility of haploHCT in South Africa. We retrospectively analyzed the outcome of 134 patients with hematologic malignancies who received unmanipulated haploHCT with post-transplantation cyclophosphamide at 2 high-volume HCT centers between 2014 and 2019. We assessed overall survival (OS), disease-free survival (DFS), nonrelapse mortality (NRM), relapse incidence (RI), and incidence of acute GVHD. The median recipient age was 44 years (range, 15 to 73 years) and the median donor age was 36 years (range, 9 to 68 years). Acute myelogenous leukemia or myelodysplastic syndrome (AML/MDS) and acute lymphoblastic leukemia (ALL) were the most common indications for haploHCT (61.2%). The European Society for Blood and Marrow Transplantation risk score was ≥5 in 44 patients (32.8%). Seventy-seven patients (57.4%) received a myeloablative conditioning regimen. The majority of patients received a sex-matched transplant (57.4%) and had peripheral blood stem cells (PBSCs) as the stem cell source (70.9%). Sixteen patients (11.9%) had an incongruent cytomegalovirus serostatus at transplantation. The median duration of follow-up was 10.8 months (range, 0.36 to 70.8 months). OS was 56% (95% confidence interval [CI], 47% to 64%) at 1 year and 37% (95% CI, 28% to 47%) at 3 years. DFS was 47% (95% CI, 38% to 55%) at 1 year and 32% (95% CI, 24% to 41%) at 3 years. The 100-day and 3-year cumulative incidence of NRM was 18% (95% CI, 11% to 25%) and 41% (95% CI, 32% to 50%), respectively, and the 1- and 3-year cumulative RI was 16% (95% CI, 11% to 24%) and 21% (95% CI, 14% to 29%), respectively. The 1-year OS was 55% (95% CI, 40% to 67%) for the patients with AML/MDS versus 41% (95% CI, 21% to 60%) for those with ALL. Forty-five patients (41.7%) developed acute GVHD by day +100; of these, 80% had grade I-II disease. Fifty patients (37.5%) developed cytomegalovirus infection that required therapy. On multivariable analysis, older donor age was an independent risk factor for lower DFS. RI was higher for diagnoses other than acute leukemia/MDS (relative risk [RR], 2.62; 95% CI, 1.12 to 6.15; P = .027), decreased for PBSC versus bone marrow (RR, 0.43; 95% CI, 0.19 to 0.95; P = .038) and decreased for offspring donors (RR, 0.25; 95% CI, 0.09 to 0.67; P = .006). These data support the feasibility of haploHCT and suggest that unmanipulated haploHCT using a younger parent or offspring donor is a viable option for adults in sub-Saharan Africa with acute leukemia and MDS who lack a suitable related or unrelated donor.

Project description:Recent studies have suggested that plasma-derived proteins may be potential biomarkers relevant for graft-versus-host disease and/or non-relapse mortality occurring after allogeneic blood or marrow transplantation. However, none of these putative biomarkers have been assessed in patients treated either with human leukocyte antigen-haploidentical blood or marrow transplantation or with post-transplantation cyclophosphamide, which has been repeatedly associated with low rates of severe acute graft-versus-host disease, chronic graft-versus-host disease, and non-relapse mortality. We explored whether seven of these plasma-derived proteins, as measured by enzyme-linked immunosorbent assays, were predictive of clinical outcomes in post-transplantation cyclophosphamide-treated patients using plasma samples collected at serial predetermined timepoints from patients treated on prospective clinical studies of human leukocyte antigen-haploidentical (n=58; clinicaltrials.gov Identifier: 00796562) or human leukocyte antigen-matched-related or -unrelated (n=100; clinicaltrials.gov Identifiers: 00134017 and 00809276) T-cell-replete bone marrow transplantation. Day 30 levels of interleukin-2 receptor α, tumor necrosis factor receptor 1, serum STimulation-2 (IL1RL1 gene product), and regenerating islet-derived 3-α all had high areas under the curve of 0.74-0.97 for predicting non-relapse mortality occurrence by 3 months post-transplant in both the human leukocyte antigen-matched and human leukocyte antigen-haploidentical cohorts. In both cohorts, all four of these proteins were also predictive of subsequent non-relapse mortality occurring by 6, 9, or 12 months post-transplant and were significantly associated with non-relapse mortality in univariable analyses. Furthermore, day 30 elevations of interleukin-2 receptor α were associated with grade II-IV and III-IV acute graft-versus-host disease occurring after day 30 in both cohorts. These data confirm that plasma-derived proteins previously assessed in other transplantation platforms appear to retain prognostic and predictive utility in patients treated with post-transplantation cyclophosphamide.

Dataset Information

Bone Marrow versus Peripheral Blood Grafts for Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide.

Publications

Bone Marrow versus Peripheral Blood Grafts for Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide.

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