Allogeneic Stem Cell Transplantation Following Reduced Intensity Conditioning Regimen for Treatment of Refractory Leukemia

Objective To evaluate the efficacy of allogeneic stem cell transplantation (allo-HSCT) following reduced intensity conditioning (RIC) regimen in the treatment of relapsed and refractory leukemia.

Methods Fourteen patients with acute myeloid leukemia, eleven patients with acute lymphocyte leukemia and two patients with chronic myeloid leukemia blast phase received allo-HSCT following RIC regimen consisting of fludarabine and small or moderate dose total body irradiation (TBI). Patients received mobilized peripheral stem cell from HLA matched siblings (n=11), at least 5/6 matched unrelated donor (n=10) or haploidentical related donor (n=6). All patients were in advanced disease before transplantation. Graft versus host disease (GVHD) prophylaxis program consist of cyclosporin A plus mycophenolate mofetil or short-term methotrexate, or these three drugs combination; CD25 monoclone antibody and ATG were also used in patients with unrelated or haploidentical donors.

Results Sustained engraftment was attained in 22 patients, the median time to ANC >0.5×10⁹/L was 13 days (range: 11~17days), and the median time to BPC > 50×10⁹/L was 19 days (range: 12~42days). Detected by short tandem repeat (STR)-PCR, complete donor chimerism was comfirmed in 20 patients with a median of 14days (range: 7~70 days). With a median follow-up of 9 months (range, 1~44months), the incidences of acute GVHD and chronic GVHD were 50% (11/22) and 41.2% (8/17) respectively. The transplant related mortality was 25.9% (7/27), mainly from graft failure (n=4), intracranial hemorrhage (n=1), acute GVHD (n=1), and severe infection(n=1). At the time of last follow up, ten patients relapsed, eleven patients were alive and leukemia free. Probabilities of overall survival for AML and ALL patients were (51.9±13.4)% and (32.7±15.0)% at 2 years, respectively. It seems that AML patients had a better outcome than ALL patients, but there was no significant difference (289).

Conclusion Allogeneic stem cell transplantation following fludarabine and TBI based RIC regimen could be used in the treatment of relapsed and refractory leukemia with well tolerance and low transplant related mortality from which patients may be benefit.