Fludarabine and Busuphan (Flu-Bu) as Reduced Intensity-Conditioning (RIC) Regimen in HLA-Identical Sibling Allogeneic Hematopoietic Stem Transplantation (Allo-SCT) for Myeloid Malignancies. Results of a Prospective Multicenter Study.

Allo-SCT is the only curative treatment in many myeloid malignancies. The reduction of non-relapse mortality (NRM) achieved with RIC regimens has allowed high risk patients to undergo an Allo-SCT. In this study we show the results achieved with Flu-Bu conditioning as RIC Allo-SCT. In this prospective, multicenter study we included all 107 consecutive patients who underwent an RIC HLA-identical sibling Allo-SCT in 6 Spanish hospitals between November 1997 and April 2006. Conditioning consisted of fludarabine 30 mg/m² since day -9 to -5 and busulphan 1 mg/kg/6 hours since day -4 to -2 (total dose 8–10 mg/kg). Graft versus host disease (GVHD) prophylaxis consisted of cyclosporine A (CyA) (from day -1 until at least day +90) and methotrexate (MTX) (days +1, +3 and +6) or mycophenolate mofetil (MMF) (since day +1 until at least day +28). MTX and MMF were used in combination with CyA in two consecutive cohorts (1997–2003 and 2004–2006, respectively) There were 38 (35%) women, median age 58 years (range 21–70 years). There were 58 (54%) acute myeloid leukemia, 35 (33%) myelodisplastic syndrome, 8 (7%) chronic myeloid leukemia and 6 (6%) other chronic myeloprolipherative syndrome. Twenty six (23%) patients were in advanced phase (Refractory disease, partial remission or more than 2^nd complete remission). Median time to achieve more than 0.5×10⁹/l neutrophils and more than 20×10⁹/l platelets was 16 (7–29) and 12 (0–59) days respectively. Median follow up for survivors was 43.3 (3–69) months. Four year overall (OS) and disease free survival (DFS) were 47% (95% C.I 42–52%) and 46% (95% C.I 41–51%) respectively. Thirty-seven patients relapsed at median of 4.5 (0.7–45) months. The risk of relapse at 4 years was 45% (95% C.I 39–51%). The development of chronic GVHD was associated with lower relapse rate and higher DFS (29% vs 69%, P<0.001) and (70% vs 23%; P<0.001) respectively. Twenty-five patients died as consequence of NRM at median of 5.4 (0.3–21.4) months, the cumulative incidence (Cum Inc) of NRM at 100 days and 1 year was 7% (95% C.I 4–15%) and 19% (95% C.I 13–28%). Forty-three (39%) patients developed acute GVHD at a median of 58 (13–173), 30 (27%) patients grade 2–4, for a Cum Inc of acute GVHD of 50% (95% CI 40–62%). Fifty nine (71%) of 83 evaluable patients developed chronic GVHD (41 extensive) at a median of 128 (61–831) days. The Cum Inc of chronic GVHD was 66% (95% CI 56–77%). In conclusion Flu-Bu RIC conditioning offers a curative option for myeloid neoplasias with an acceptable TRM. The development of chronic GVHD was associated with lower relapse rate and better DFS. Relapse is still the most important cause of treatment failure and new strategies are needed to improve the relapse rate.