Peripheral T-cell lymphoma (PTCL) is characterized by high rates of chemoresistance and relapse. The role of allogeneic (allo) BMT remains to be defined. Treatment-associated toxicities and donor availability remain key concerns. We reviewed the outcomes of 44 consecutive, related donor allo BMTs for PTCL performed at Johns Hopkins Hospital from 1994–2011. Nodal (n=23), extranodal (n=14), leukemic/disseminated (n=3), and cutaneous (n=4) histologies were represented. This was a poor-risk cohort, with 60% receiving > 2 prior chemotherapy regimens, 50% having history of chemorefractory disease, and 25% having active disease at BMT. Patients receiving reduced-intensity conditioning (RIC) were significantly older (median 59 years, range 24–70) than patients receiving myeloablative conditioning (MAC; median 46 years, range 18–64), p=0.01; median age at RIC/haplo BMT was 60. Thirty patients received post-transplantation cyclophosphamide (PT/Cy) as part of their GVHD prophylaxis, including all RIC/HLA-haploidentical (haplo) BMTs (n=18), all RIC/HLA-matched BMTs (n=6), 3 of the 4 myeloablative conditioning (MAC)/haplo BMTs, and 3 of the 16 MAC/HLA-matched BMTs (where PT/Cy was the sole GVHD prophylaxis). With 3.9 years median follow-up for survivors (range 0.5–13.7 years), the estimated 3-year progression-free survival (PFS) and overall survival (OS) were both 37% (95% confidence interval (CI) 24–56% and 24–57%). In older patients (> 60, n=14), the estimated 2-year PFS and OS were 38% (CI 13–63%) and 45% (CI 20–73%); in patients < 60 (n=30), 2-year PFS and OS were 41% (95% CI 24–59%) and 43% (95% CI 25–61%). On unadjusted analysis, there was a tendency towards superior PFS for allo BMT in first remission versus beyond first remission, with an estimated 3-year PFS of 53% (95% CI 34–82%) versus 23% (95% CI 10–51%), p=0.08. Of the 15 patients who remain alive in sustained remission, ten received allo BMT in first remission; represented among these ten are especially poor-risk histologies, including adult T-cell leukemia/lymphoma, hepatosplenic gamma-delta T-cell lymphoma, and subcutaneous panniculitis-like gamma-delta T-cell lymphoma. With a median time to relapse of 3.2 months (interquartile range 1.8–8.8 months), the estimated 3-year cumulative incidence of relapse was 46% after MAC, 56% after RIC, and 50% after RIC/haplo BMT by competing risk analysis. Estimated 1-year non-relapse mortality was 10% for MAC, 8% for RIC, and 11% for RIC/haplo BMT. On competing risk analysis, cumulative incidences of acute grade II-IV GVHD and chronic GVHD were 16% and 19%, with no differences between matched and haplo donors. On unadjusted analysis, patients with acute grade II-IV or chronic GVHD had a 17% probability of relapse, compared to 66% in patients without GVHD, p=0.02. Allo BMT affords long-term survival for a subset of PTCL patients. This RIC/haplo platform substantially expands allo BMT options to most patients with PTCL, including those who are older and unable to tolerate high-dose conditioning. Allo-BMT may be appropriate in first remission in select high-risk cases.
Symons:Busulfex: Research Funding.
Asterisk with author names denotes non-ASH members.