Reduced Intensity vs Myeloablative Conditioning for HLA Matched Sibling Transplantation in Follicular Lymphoma.
Authors: Van Besien Koen , Carreras Jeanette , Zhang Mei-Jie , Vose Julie , Lazarus Hillard , Bredeson Christopher , Hari Parameswaran 
Published: April 2020

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 &gt;9 mg/kg or melphalan doses &gt;150 mg/m2. We defined RIC as TBI doses &lt;500 cGy, busulfan doses &lt;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&lt;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&lt;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&lt;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.

Outcomes ABLAT (%) RIC (%) P-value 30 day mortality 8 (3–13) 6 (2–12) 0.64 100 day mortality 19 (13–27) 15 (8–24) 0.46 Acute GVHD @ 100 days, grades (2–4) 37 (28–46) 40 (30–51) 0.62 Chronic GVHD @ 1 year 44 (34–53) 53 (42–64) 0.20 TRM @ 1 year 23 (16–31) 20 (12–29) 0.57 TRM @ 3 years 25 (18–24) 24 (16–24) 0.83 Progression/Relapse @ 1 year 8 (4–14) 17 (9–25) 0.09 Progression/Relapse @ 3 years 9 (5–15) 21 (13–31) 0.03 PFS @ 1 year 68 (60–76) 63 (53–73) 0.47 PFS @ 3 years 65 (56–74) 55 (44–66) 0.14 OS @ 1 year 72 (64–80) 72 (62–81) 0.90 OS @ 3 years 70 (61–77) 64 (53–74) 0.40