Abstract
The optimal treatment for children with acute lymphoblastic leukemia (ALL) in second remission after an isolated central nervous system relapse is unknown. To address this question, we compared outcomes in 149 patients enrolled on Pediatric Oncology Group chemotherapy trials 9061 (n=79) and 9412 (n=70) and HLA-matched sibling transplant recipients (n=60) reported to the Center for International Blood and Marrow Transplant Research. Patients received treatment between 1990 and 2000. Median follow-up was 8 years and 9 years after chemotherapy and transplantation, respectively. Groups were similar with respect to sex and leukocyte count at diagnosis. Chemotherapy recipients were younger at diagnosis (5 vs. 7 years) and more likely to have had a longer duration of first remission (duration of first remission ≥18 months: 70% vs. 48%). All transplant recipients received bone marrow grafts and 83% received a total body irradiation containing preparatory regimen. The median time to transplantation after achieving a second remission was 2.5 months (range, <1 – 8). To adjust for time-to transplant bias, we used left-truncated Cox regression models to examine treatment outcomes. Risks of a subsequent leukemia relapse were similar in both treatment groups. As expected, risks of a subsequent leukemia relapse were significantly higher in older patients (11–17 years; relative risk [RR] 2.63, p=0.004) and those with a short duration of first remission (<18 months; RR 4.22, p<0.001) regardless of type of treatment. Relative to chemotherapy recipients, risks of treatment-related mortality (RR 4.29, p=0.001), treatment failure (RR 2.37, p=0.003) and overall mortality (RR 2.68, p=0.002) were significantly higher within the first 2 years after achieving a second remission in recipients of HLA-matched sibling transplants. Among transplant recipients who survived the first two years, subsequent mortality and treatment failure risks did not differ by treatment group. In both treatment groups, recurrent leukemia was the commonest cause of death (60% and 56% after chemotherapy and transplantation, respectively). The 8-year probabilities of leukemia-free survival (adjusted for age and duration of first remission) were 66% and 58% after chemotherapy and transplantation, respectively. These data support use of chemotherapy alone for patients with ALL and isolated central nervous system relapse who achieve a second remission regardless of duration of first remission.
Outcomes after HLA-matched sibling transplantation or chemotherapy in children with acute lymphoblastic leukemia in a second remission after an isolated central nervous system relapse: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research
