Reduced Intensity vs Myeloablative Conditioning for HLA Matched Sibling Transplantation in Follicular Lymphoma.

Abstract

Several new reduced intensity conditioning regimens are being investigated for allogeneic transplantation. To evaluate their effects in follicular lymphoma, we studied outcome of HLA-identical sibling transplants in 205 recipients reported to the CIBMTR between 1997 and 2002. Only patients without prior allogeneic or autologous transplantation were included. Twenty-seven patients (13%) had follicular large cell (grade III) lymphoma; the remaining had grade I or II disease. 27% had chemotherapy-resistant disease and 32% had poor performance status prior to transplantation. Conditioning regimens were categorized as myeloablative (ABLAT; n=120) or reduced intensity (RIC; n=85). ABLAT was defined as total body irradiation (TBI) containing regimens with single fraction of ≥500 cGy, fractionated doses of ≥ 800 cGy, busulfan doses >9 mg/kg or melphalan doses >150 mg/m2. We defined RIC as TBI doses <500 cGy, busulfan doses <9 mg/kg, melphalan doses of ≤150 mg/m2 and fludarabine regimens without busulfan or melphalan. 70% of ABLAT was TBI based; 24% was busulfan-cyclophosphamide. Melphalan based regimens were used in 23% of RIC, reduced dose busulfan in 21%, fludarabine-cyclophosphamide in 41% and low dose TBI in 7%. RIC constituted fewer than 10% of transplants reported in 1997, about 50% in 2000 and 80% in 2002. Median recipient age was 45 y (28–70y) for ABLAT vs. 50 y (27–67y) for RIC (p<0.001). Median time from diagnosis to transplant was 24 mo for ABLAT vs. 34 mo for RIC (p=0.001). PBSC was used for 65% of ABLAT but 92% of RIC (p<0.001). GVHD prophylaxis included a calcineurin antagonist in all patients, but was combined with MTX in 86% of ABLAT compared to 54% of RIC (p<0.001). Median follow-up of survivors was 49 mo for ABLAT vs. 36 mo for RIC (p=0.004). In univariate analysis, there were no differences in acute or chronic GVHD, treatment-related mortality (TRM), progression-free survival (PFS) or overall survival (OS) between the two groups. The median hospital stay was slightly shorter for RIC vs. ABLAT (25 vs. 28 days, p=0.05), and there was a trend toward an increased risk of disease recurrence after RIC (p=0.09). Forty ABLAT recipients and 30 RIC recipients have died. Eleven of 40 deaths with ABLAT transplant vs 2 of 30 with RIC were attributed to organ failure (p=0.03); 5 and 4 deaths, respectively, were attributed to GVHD (p=NS), and 8 and 11 deaths, respectively, to relapse (p=NS). In multivariate analysis, performance score and chemotherapy sensitivity were independently associated with TRM, OS and PFS, but conditioning regimen was not. There was a trend for increased risk of recurrence after RIC (RR=1.91; p=0.09). In summary, RIC is now, by far, the most common approach for allotransplantation in follicular lymphoma. In this analysis, TRM, GVHD, OS and PFS after RIC are similar to ABLAT.OutcomesABLAT (%)RIC (%)P-value30 day mortality8 (3–13)6 (2–12)0.64100 day mortality19 (13–27)15 (8–24)0.46Acute GVHD @ 100 days, grades (2–4)37 (28–46)40 (30–51)0.62Chronic GVHD @ 1 year44 (34–53)53 (42–64)0.20TRM @ 1 year23 (16–31)20 (12–29)0.57TRM @ 3 years25 (18–24)24 (16–24)0.83Progression/Relapse @ 1 year8 (4–14)17 (9–25)0.09Progression/Relapse @ 3 years9 (5–15)21 (13–31)0.03PFS @ 1 year68 (60–76)63 (53–73)0.47PFS @ 3 years65 (56–74)55 (44–66)0.14OS @ 1 year72 (64–80)72 (62–81)0.90OS @ 3 years70 (61–77)64 (53–74)0.40