Fludarabine, Melphalan and Low Dose Total Body Irradiation for Reduced Intensity Conditioning (RIC) Prior to Allogeneic Hematopoietic Cell Transplantation (AlloHCT)

Abstract 4570

RIC AlloHCT can provide a curative option for patients with hematologic diseases who are not candidates for myeloablative AlloHCT. However, this approach is limited by high relapse rates, especially with aggressive myeloid malignancies. We hypothesized that achieving greater cytoreduction by increasing conditioning intensity would increase the efficacy of a RIC regimen. Therefore, we utilized fludarabine (40 mg/m2/day × 4 days on days -5 to -2), melphalan 50 mg/m2 (day -2) and TBI (total of 400 cGy in 2 fractions on day -1) (FluMelTBI) in a pilot trial of RIC for hematologic disorders. Forty-nine patients who were not eligible for myeloablative transplantation accrued between March 2009 and June 2011. Tacrolimus (0.015 mg/kg oral every 12 hours, starting on day -1, titrated to 5–15 ng/ml), mycophenolate mofetil (1000 mg oral every 8 hours, starting on day -1) and methotrexate (2.5 mg/m² IV on days 1, 3 and 6) were used for Graft-versus-Host Disease (GvHD) prophylaxis in all patients. Patient and donor characteristics are presented in Table A. All 49 patients engrafted neutrophils at a median 16 days (range 10–39). One patient did not nadir platelets <20 × 10⁹/L; of the remaining 48 patients, two died before platelet recovery on days +14 and +50, while 46 achieved platelet recovery at a median 17 days (range, 11–73). At day +100 post-RIC AlloHCT, 71% were in CR, with 2 patients too early to evaluate. The transplant related mortality (TRM) was 10% at day +100 and 22% at 1 yr. The incidence of acute GvHD grade 2–4 was 49% and grade 3–4 was 23%. Chimerism data are presented in Table B. At a median follow-up of 364 days (range 17–821), the 1 yr OS and PFS are 58% (95% CI: 42–72%) and 50% (95% CI: 34–64%), respectively. Factors that were significantly related to lower OS were older age (p=0.02) and gender mismatch (p=0.03). In conclusion, FluMelTBI is a well-tolerated RIC regimen with low TRM, achieves early complete donor chimerism and a good early disease response. Longer follow-up is needed to determine long term survival and disease control.