The role of allogeneic stem cell transplantation in the management of aggressive non-Hodgkin's lymphoma (NHL) remains to be established. Autologous stem cell transplantation (SCT) remains the standard salvage therapy for patients with diffuse large B cell lymphoma failing first line therapy although patients relapsing early after Rituximab based immunochemotherapy have a poor outcome. For patients with aggressive T cell lymphomas the role of consolidation or salvage transplant strategies also remains controversial. Reduced intensity allogeneic transplants have been employed in these diseases with variable success. In the United Kingdom the more intensive BEAM conditioning regimen has been employed prior to allogeneic stem cell transplantation in lymphoproliferative diseases. We report here the outcome of BEAM-CAMPATH conditioning prior to allogeneic stem cell transplantation for aggressive NHL as reported to the British Bone Marrow Registry.
We retrospectively identified all patients reported to the BSBMT registry as having undergone an allogeneic stem cell transplant following BEAM-CAMPATH conditioning for aggressive non-Hodgkin's lymphomas. All patients received conditioning with BEAM (BCNU 300mg/m2, etoposide 800mg/m2, cytarabine 1600mg/m2, melphalan 140mg/m2) and CAMPATH-1H 10mg days -6 to -2. Cyclosporin A was administered for 90 days post transplant. Six transplant centres contributed data to this study.
46 patients (27 male, 19 female) with a median age of 45 (range 17–59) at diagnosis with DLBCL (29), Burkitt's lymphoma (1) or T cell lymphoma (PTCL NOS 14, anaplastic large cell lymphoma 3, angioimmunoblastic lymphoma 1) were identified. 37 patients had stage III/IV disease at diagnosis and 56% of patients had a high or high-intermediate International Prognostic Score. They had received a median of 3 lines of prior therapy (range 1–5), 11 of 29 patients with B cell lymphomas had received Rituximab prior to transplant and 4 patients had received a prior autologous stem cell transplant. The median time from diagnosis to transplant was 11 months (range 3 months–13 years) and 22 patients had received the transplant in first response. At transplant 34 patients had chemosenstive disease and 11 patients had chemorefractory disease. Transplants from 32 siblings and 14 volunteer unrelated donors were performed using peripheral blood stem cells in 42 patients. 3 patients received a mismatched transplant. The Performance Status (PS) at transplant was good (KPS>80) in 40 of 46 patients. All patients engrafted with a median time to neutrophil recovery of 14 days (range 11–27). At last follow up 20 patients are alive with 17 in complete remission. 5 patients have died from non-relapse causes (infection 3, GVHD 1, respiratory failure 1) and 21 died following relapse of lymphoma. Acute GVHD grades II-IV developed in 7 patients and chronic GVHD in 13 (7 limited, 6 extensive) of 37 patients surviving beyond 100 days. The cumulative incidence (CI) of non-relapse mortality (NRM) was 7% at 100 days and 11% at 3 and 5 years post transplant. NRM was significantly worse for those with a poor PS, use of a VUD, prior autologous SCT and more lines of prior therapy. The relapse risk at 1 and 5 years was 51% and 53% respectively and was associated with use of a sibling donor. Disease status at transplant had no impact on the relapse rate. The progression free survival (PFS) was 41% and 36% at 1 and 5 years respectively with a trend to a higher PFS in patients under 45 years. The overall survival (OS) was 54% t 1 year and 42% at 5 years with a significantly better OS in CMV low risk transplants.
BEAM-CAMPATH conditioning prior to allogeneic SCT is well tolerated in patients with aggressive NHL although there remains a significant relapse rate following this therapy. A significant minority of patients achieve durable disease free survival. The role of BEAM-CAMPATH allogeneic stem cell transplantation in these diseases warrants further investigation.
No relevant conflicts of interest to declare.
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