Allogeneic hematopoietic cell transplantation (alloHCT) is the only potentially curative treatment option for patients with high-risk relapsed or refractory lymphoma, but the lack of a human leukocyte antigen (HLA)-matched sibling donor (MSD) and delays in identifying matched unrelated donors (URDs) remain challenges to using fully matched alloHCT.
In an analysis of data from the Center for International Blood and Marrow Transplant Research, investigators, led by Nilanjan Ghosh, MD, PhD, from the Levine Cancer Institute and the Carolinas Healthcare System in Charlotte, North Carolina, compared survival outcomes between patients who received alloHCT from haploidentical related donors (haplo-HCT) or from MSD donors (MSD-HCT).
The results of the observational database study, published in the Journal of Clinical Oncology, demonstrate that overall survival (OS) rates were comparable regardless of donor source. Patients undergoing haplo-HCT, however, had a substantially lower risk of chronic graft-versus-host disease (GVHD).
"This large analysis shows comparable outcomes between MSD transplantation versus transplants from half-matched related donors," Mehdi Hamadani, MD, the study's corresponding author, told ASH Clinical News. "Considering near universal availability of at least half-matched family donors (parents, siblings, children, etc.), donor unavailability should no longer be considered a major barrier for alloHCT."
The researchers evaluated data from 987 patients with Hodgkin lymphoma and non-Hodgkin lymphoma undergoing their first reduced-intensity or non-myeloablative conditioning alloHCT between 2008 and 2013: 180 undergoing haplo-HCT and 807 undergoing MSD-HCT.
Haplo-HCT patients received GVHD prophylaxis with post-transplant cyclophosphamide (PT-Cy) with or without a calcineurin inhibitor and mycophenolate. MSD-HCT patients received calcineurin inhibitor-based prophylaxis. Haplo-HCT patients also received conditioning with fludarabine and 200 cGy total body irradiation (TBI); MSD-HCT patients received fludarabine plus an alkylator and/or 200 cGy TBI.
Baseline characteristics were similar for both cohorts, however, the haplo-HCT group had a greater proportion of patients â‰¥60 years (35% vs. 24%; p<0.001), African-American patients (15% vs. 4%; p<0.001), and those with a Karnofsky performance score â‰¥90 (79% vs. 68%; p<0.001).
The median follow-up for surviving patients was three years.
OS (the study's primary endpoint) was similar between both cohorts (61% [95% CI 54-69] for haplo-HCT vs. 62% [95% CI 59-66] for MRD-HCT; p=0.82). Most patients achieved neutrophil recovery at 28 days: 95 percent in the haplo-HCT group and 97 percent in the MSD-HCT group (p=0.31). More patients in the MSD-HCT group achieved platelet recovery at day 28 (91 percent vs. 63 percent; p<0.001), but the numbers were similar at day 100 (96% vs. 94%; p=0.33).
"The delay in platelet recovery in the haplo-HCT cohort is likely due to the application of PT-Cy," the authors wrote.
Both groups had a similar incidence of grade 2-4 acute GVHD at day 100 (27% for haplo-HCT patients vs. 25% for MSD-HCT patients; p=0.84), while the cumulative incidence of chronic GVHD at one year was significantly lower in haplo-HCT patients (12% vs. 45%; p<0.001). Multivariate analysis confirmed the long-term benefit of haplo-HCT for reducing the risk of chronic GVHD (RR = 0.21; 95% CI 0.14-0.31). See the TABLE for GVHD outcomes.
At three-year follow-up, the cumulative incidence of disease progression and/or relapse was 37 percent in the haplo-HCT cohort and 40 percent in the MSD-HCT cohort (p=0.51). Rates of one-year non-relapse mortality were also similar in each cohort (10% for haplo-HCT vs. 9% for MSD-HCT; p=0.57).
After a median follow-up of three years, the progression-free survival (PFS) was not significantly different between the haplo-HCT and MSD-HCT groups (48% for each; p=0.96).
The most common cause of death in the haplo-HCT and MSD-HCT cohorts was recurrent/progressive lymphoma (47% [n=34] vs. 52% [n=151]). GVHD was the cause of death in 13 patients in the MSD cohort (5%) and one death in the haploidentical cohort.
"These findings are paradigm shifting in the sense that this is the first study – to our knowledge – that shows outcomes following an alternative donor source, approaching those following matched sibling transplantation, generally considered the best donor source for allogeneic transplant," Dr. Hamadani told ASH Clinical News. "[However], the results of our study warrant confirmation in prospective, randomized, controlled trials."
Additional analyses are in development in collaboration with the European Group for Blood and Marrow Transplantation to validate these results in a larger international patient cohort.
The study is limited by its observational registry design and patients' treatment included different interventions that could have been influenced by treating centers' or physicians' preferences. In addition, the study did not evaluate quality of life or other patient-reported outcomes, which are important to the impact of chronic GVHD on long-term survivorship. This should be studied in a prospective setting, according to the authors.
Ghosh N, Karmali R, Rocha V, et al. Reduced-intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors: A Center for International Blood and Marrow Transplant research analysis. J Clin Oncol. 2016 June 27. [Epub ahead of print]