Unrelated Donor Hematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukemia in First Complete Remission.

Allogeneic hematopoietic stem cell transplantation (Allo-SCT) has a better anti-leukemic effect than conventional chemotherapy or autologous hematopoietic stem cell transplantation (Auto-SCT) for acute lymphoblastic leukemia (ALL). Large prospective studies on adult ALL showed Allo-SCT would be able to improve disease free survival, and Allo-SCT is currently recommended for patients in first complete remission (CR1), although the role of Allo-SCT for standard-risk ALL patients in CR1 remains controversial. Unrelated donor hematopoietic stem cell transplantation (URD-SCT), considered with higher transplant-related mortality (TRM), is usually not offered to patients in CR1, however, it appears promising now. Over the past few years, improved results of URD-SCT with lower TRM have been reported, reflecting improvements in donor/recipient matching, GVHD prophylaxis, and supportive care. Until now, there were 37 patients with ALL in CR1 received unrelated donor transplantation in our bone marrow transplantation center between July 1999 and April 2007. Philadelphia chromosome occurred in 7 (18.9%) patients at diagnosis. The median age of all patients was 21 years (range 8∼48 years). HLA high-resolution typing was used for donor-recipient matching with 18 cases of HLA-matched and 19 cases of HLA 1–2 alleles mismatched. Graft with a median number of total nucleated cells was 3.43×10⁸/kg (range 2.24∼9.38×10⁸/kg), including CD34+ cells 4.58×10⁶/kg (range 0.96∼9.21×10⁶/kg) and CFU-GM 2.96×10⁵/kg (range 2.15∼6.25×10⁵/kg). All of the patients were received Bu/Cy2 regimen as conditioning with busulfan 16mg/kg plus cyclophosphamide 120mg/kg. Mycophenolate mofetil combined with CsA and short course MTX were performed to prevent aGVHD and 3 patients received additional anti-CD25 monoclonal antibody. The median time to achieve ANC >0.5×10⁹/L was 15 days (range 12∼22 days), platelets >20×10⁹/L was 21 days (range 8∼32 days), and all 37 patients achieved sustained engraftment by the analysis of cytogenetics and STR-DNA. MMF+CsA+MTX could be used as an effective and safe prophylaxis regimen for aGVHD, and incidence of aGVHD was 72.97%, aGVHD of grade I-II observed in 22 (59.46%) patients and the severe aGVHD of grade III-IV observed in 5 (13.51%) patients. The incidence of cGVHD was 58.82%. Early TRM was 8.11% at 100 days after transplant. With a median follow-up of 9.8 months (range 1.0∼79.5 months), clinical relapse were detected in 6 (16.22%) patients and 22 (59.46%) patients achieved disease free survival. By Kaplan-Meier method, the accumulative probability of 3-year overall survival was 59.26±9.18%, and overall survival of Ph(+) ALL was 71.43±17.07%. A strong anti-leukemia effect of GVHD might occur in URD-SCT for ALL, and the 3-year overall surviva was 70.16±11.78% vs 45.00±16.60% in patients with I-II aGVHD or without aGVHD (p=0.0085), which was 76.74±12.52% vs 34.62±14.40% in patients with or without cGVHD (p=0.0015). 4 of 5 patients who developed severe aGVHD died. In our experience of unrelated donor transplantation for ALL in CR1, I-II aGVHD and cGVHD are favorable factors for overall survival, and Bu/Cy2 conditioning regimen could be safely used in the URD-SCT for ALL. Allo-SCT, represents a curative option for ALL, show a significantly increased disease free survival in standard risk or high risk patients in CR1. Unrelated donor transplantation with a greater GVL effect, appears promising for ALL in CR1.