Identification of Prognostic Factors Predicting the Outcome of Reduced Intensity Allogeneic Stem Cell Transplantation in Mantle Cell Lymphoma. An Analysis from the Lymphoma Working Party of the EBMT

Abstract

Mantle cell lymphoma (MCL) is a disease associated with a poor prognosis characterised by inevitable relapse following both conventional chemotherapy and autologous stem cell transplantation (SCT). The role of reduced intensity allogeneic stem cell transplantation (RIST) in MCL remains controversial. We have conducted a retrospective study of RIST in MCL as reported to the EBMT registry in an attempt to define factors predicting the outcome of this procedure. Between 1998 and 2006 279 patients with MCL received a RIST with 210 procedures performed after the year 2001. 219 (78%) were male and the median age at transplant was 55 years (range 30–71). At diagnosis 97% had stage IV disease and 39% had B symptoms. Patients had received a median of 3 lines (range 1–9) of prior therapy and 119 (43%) had undergone a previous autologous SCT. The median time from diagnosis to transplant was 30 months (range 3–161). The disease status at transplant was; complete remission 124, partial remission 95, refractory disease 32 and untested relapse 17. The performance status at transplant was poor in 15 patients. Conditioning for RIST was achieved with fludarabine+alkylating agent in 66%, fludarabine+TBI in 13%, and a variety of other reduced intensity regimens in 20%. Transplants were performed from 193 matched family donors, 60 matched unrelated donors and 22 mismatched donors who provided peripheral blood stem cells in 252 cases and bone marrow in 26. T cell depletion with either CAMPATH or ATG was performed in 85 transplants. 274 patients were evaluable for engraftment of whom 272 engrafted with 4 secondary graft failures. Acute graft versus host disease (GVHD) developed in 149 patients (grade I 45, grade II 52, grade III/IV 50, unknown extent 2). Of 214 patients at risk 30 developed limited chronic GVHD and 58 extensive chronic GVHD. There were 91 transplant related deaths with infection and GVHD accounting for 51 of these deaths. The resulting 100 day, 1 year and 3 year non-relapse mortality rates were 13, 32 and 41% respectively. NRM was associated with poor PS at transplant (RR=3.7 p=0.001) and transplantation prior to 2002 (RR= 1.7 p=0.02) but age, prior transplantation and donor relationship had no significant impact. Sixty one patients relapsed at a median time of 7 months (range 1–50 months) post transplant. The cumulative incidence of relapse at 1 years and 4 years was 19% and 31% respectively. Disease relapse was associated with refractory disease at transplant (RR=4.5 p<0.001), T cell depletion of the graft (RR= 4.2 p<0.001) and the use of fludarabine+low dose TBI conditioning (RR=2.7 p=0.03). The Kaplan-Meier estimate of the PFS at 1 and 3 years was 49% and 29% respectively. PFS was significantly worse for patients with refractory disease (RR=2.2, p<0.001), poor PS (RR2.6, p=0.005) or those transplanted prior to 2002 (RR=1.5, p=0.03). The overall survival at 1 and 3 years was 60% and 43% respectively and was lower in patients with refractory disease (RR 2.3, p<0.001), poor PS (RR 2.3 p=0.01) and those transplanted before 2002 (RR 1.7 p=0.005). In summary the outcome of RIST in MCL has improved in recent years although NRM remains a substantial problem. Survival was significantly worse for patients with a poor performance status or refractory disease at transplant. The type of reduced intensity conditioning regimen employed and the use of T cell depletion may also have a significant impact upon the incidence of relapse after these procedures.