Factors affecting the outcome of stem cell transplantation from unrelated donors for childhood acute lymphoblastic leukemia in third remission

Between July 1990 and March 2002, 35 consecutive children with ALL in third complete remission (CR3) underwent stem cell transplantation (SCT) from unrelated donors (UD). All patients received CAMPATH-1M 5-20 mg daily for 5 days. Grafts were T-cell depleted in 30 patients, 29 by CAMPATH antibodies and one by CD34 selection. Median follow-up was 3.8 years (0.3-9.3). Event-free survival (EFS) at 3 years was 35% (SE 8%); relapse rate and transplant-related mortality (TRM) at 3 years was 42 and 23%. Short first complete remission (CR1) <2.5 years was associated with lower EFS (P=0.001), higher TRM (P=0.019) and higher relapse rate (P=0.023). Short second complete remission (CR2) <2.5 years was associated with lower EFS (P=0.003) and higher TRM (0.009). Higher relapse rate and lower EFS were associated with isolated first extramedullary relapse (P=0.019, 0.012). There was no significant difference in outcome between mismatched unrelated donor stem cell transplantation (MMUD-SCT) and matched unrelated donor stem cell transplantation (UD-SCT). We conclude that UD-SCT is an effective treatment of ALL in CR3. The outcome remains limited by TRM and a high relapse rate. Short duration of CR1 and of CR2 and extramedullary site at first relapse are particularly adverse. MMUD should also be considered in high-risk patients, since the outcome of MMUD appears similar to MUD.