Non Myeloablative Transplant in Patients with Indolent Non-Hodgkin’s Lymphoma (NHL): Results of Two Prospectives Multicenter Trials.

Myeloablative transplant has been investigated in poor prognosis indolent lymphoma; although recurrence rate is low it is associated with high mortality; the use of non-myeloablative conditioning regimens could reduce TRM maintaining the GVH effect.

Up to February 2004, 40 patients with indolent NHL(87% Folicular lymphoma(FL) 5% a lymphocytic well differenciate lymphoma (WDLL) 5% Waldenström Macroglobulinemia(WM) and 3% a Marginal Lymphoma(MZL) have been registered in two prospective multicenter trials;Conditioning regimen consisted of Fludarabine 150 mg and Melphalan 70–140 mg. GVHD prophylaxis consisted of CSA plus short-course MTX. All patients received filgrastim-stimulated peripheral blood stem cells from a HLA related identical donor.Median age at transplant was 50 years (34–67) and 15(40%) had received a previous autologous transplant. At transplant, 5 patients (13%) were in CR1 (after several lines of chemotherapy), 9 (22%) in >CR1, 16 (40%) in PR, 1(2%) had stable disease (after 3 chemotherapy lines) and 9(23%) progressive disease. All patients engrafted. Acute GVHD developed in 22 patients (55%) (18 patients grade II–IV). Chronic GVHD developed in 22 out of 27 patients at risk (81%), being extensive in 13; Disease was evaluated at day +100 and at that moment 22 patients(58%) were in CR, 3 (8%) in PR, two (5%) had stable disease and 11 patients (27%) have died. With a median follow up of 30 months (range: 10–56 months), 24 patients (60%) are alive disease free, 16 (39%) have died, 14 of them (35%) due to transplant toxicity and 2 patients (5%) due to progression. Overall Survival (OS) and Event Free Survival (EFS) are 60 and 58 % respectively. Analysing variables which influence on OS and EFS, patients ≥55 years have a OS significantly shorter than patients < 55 years old (22% vs 66%; p:0,01). Moreover, patients who develop chronic GVHD have an OS and EFS significantly better than those which do not develop it (OS: 89,7 vs 57%; p=0,02 (HR: 9,3-IC95% (2,08–41,5); EFS: 89 vs 42%; p=0,002 (HR: 11,08-IC95% (2,49–49,28)). In conclusion, our results demonstrates the efficacy of non-myeloablative transplant in indolent NHL with a very low relapse rate, indicating the important role of chronic GVHD in the control of the disease; however, mortality rate is still high, mainly in patients ≥55 years