Work

276: Myeloablative Transplantation from Matched Siblings (MSD) using a Daily Intravenous Busulfan (Bu)/fludarabine (Flu) Regimen with Thymoglobulin (TG): Analysis Involving 200 Patients Indicates Low Transplant-related Mortality (TRM) in all but Older Patients with High-risk Disease

Year: 2008

Type: article

Abstract: We aimed to identify MSD transplant recipients given Flu/Bu and GVHD prophylaxis incorporating TG who may be at particular risk of TRM and perhaps merit some modification of the protocol. Between 1999 and 2005 200 patients (pts) aged 18–65 (median 46) received Flu 50 mg/m2 daily × 5 and IV Bu 3.2 mg/kg daily × 4. 46 had additional total body irradiation 200 cGy × 2. GVHD prophylaxis was CSA, methotrexate and TG (Genzyme) 4.5 mg/kg total dose. Cell source was mobilized blood cells in 172 and marrow in 28. At follow-up of survivors of 13–87 months (median 42) low-risk (LR, acute leukemia CR1/CR2, CML CP1) pts had projected 5 year TRM and overall survival (OS) of 4% and 76% for pts ≤45 years old (n = 54) vs 6% and 83% for those >45 (n = 31). For high-risk (HR) pts TRM was 6% vs 27% (18% at one year) (p = 0.04) and OS 64% vs 37% (p = 0.47) in younger (n = 40) and older (n = 75) pts respectively. To correct for imbalance in HR diagnoses we matched each of 17 younger HR pts with 2 older HR (OHR) pts by diagnosis and details of stage and thereafter for other risk factors. OS was 70% vs 37% (p = 0.02), TRM 0 vs 34% (p = 0.02) and relapse 63% (48% at 3 years) vs 46% at 5 years (p = ns) respectively. For a more robust analysis OHR pts were compared with the other 3 groups combined giving TRM of 27% vs 5% respectively (p = 0.002). Incidence of aGVHD grade II-IV, aGVHD grade III-IV and cGVHD was 23% vs 10% (p = 0.02), 4% vs 2% (p = ns) and 66% vs 41% (p = 0.001) respectively. Nine of 14 non-relapse deaths in the OHR group were related to GVHD or its treatment compared with 3 of 6 in all others (p value for GHVD related death = 0.01). Multivariate analysis of OS and DFS correcting for potentially confounding pretransplant factors idenitified only the HRO patients as having significantly increased risk (RR 3.32, CI 1.71–6.47, p < 0.0001 and RR 3.32, CI 1.71–6.43, p < 0.0001 respectively). We conclude that the effect of age on TRM is only apparent in HR pts and is not explained by heterogeneity in diagnoses. HRO pts experience more GVHD and more GVHD related death than others. TRM is no higher than reported with many non-myeloablative regimens, justification for our practice of treating all pts with the same regimen. Additional GVHD prophylaxis might help the HRO pts.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2007.12.286