Outcomes after HLA-Matched Sibling Transplants or Chemotherapy in Children with Acute Lymphoblastic Leukemia in Second Remission: A Collaborative Study of the Children’s Oncology Group (COG) and the Center for International Blood and Marrow Transplant Research (CIBMTR).

The best treatment for children with B-precursor acute lymphoblastic leukemia (ALL) in second remission after a marrow relapse is controversial. To address this question, we compared outcomes in 192 patients enrolled on COG chemotherapy trials 9110 (n=109), 9310 (n=59) and 9411 (n=29) and 189 HLA-matched sibling transplant recipients reported to the CIBMTR. Patients received treatment between 1991 and 1997. Patients with isolated extra-medullary relapse were excluded. Median follow-up was 103 (range 34–159) and 101 (16–160) months after chemotherapy and transplantation, respectively. Groups were similar with respect to sex, leukemia sub-type, leukocyte count at diagnosis and duration of first remission. Chemotherapy recipients were younger at diagnosis (5 vs. 8 years) and less likely to have combined marrow and extra-medullary site relapse (12% vs. 30%). To adjust for time-to transplant bias, we used left-truncated Cox regression models to examine treatment outcomes. The relative efficacy of chemotherapy and transplantation depended on the duration of first clinical remission and transplant conditioning regimen as shown in the Table below. Comparing children with early relapse (<36 months from diagnosis) the 5-year probabilities of leukemia-free survival (LFS) were 23%, 44% and 8% after chemotherapy alone, transplantation with a total body radiation (TBI)-containing regimen and a non-TBI regimen, respectively. In contrast to these findings, relapse and treatment failure were similar after transplantation with a TBI-containing regimen or chemotherapy after a late relapse (≥36 months from diagnosis). The 5-year probabilities of LFS were 61% and 60% after chemotherapy alone and a TBI-containing regimen, respectively and significantly lower at 30% after a non-TBI regimen. These data support HLA-matched related donor transplantation using a TBI-containing regimen in second remission for patients with ALL and early relapse.