Hematopoietic Cell Transplantation as Therapy for Pediatric Patients with Isolated CNS Relapse.

Treatment options for pediatric patients with isolated central nervous system (CNS) relapse of acute lymphoblastic leukemia (ALL) include intensive chemotherapy followed by craniospinal irradiation and hematopoietic stem cell transplantation (HSCT). However, there is little information regarding outcomes of HSCT in this situation. At the University of Minnesota 15 patients <18 years of age underwent allogeneic HSCT for ALL with isolated CNS relapses between 1990 and 2004. Leukemic subtypes included B cell (7), pre-B cell (6), T cell (1), and ALL NOS (1). All patients were in remission at the time of transplantation; 9 patients were in CR2, 5 patients were in CR3, and 1 patient was in CR5. Median duration of CR1 in all patients was 21.9 months (range 8.5–57.7) with median time from diagnosis of ALL to CNS relapse 23.4 months (range 8.9–127.7) in all patients. For patients transplanted in CR2, the median duration of 1st CR was 16.2 months (range 8.5–30.1). For all patients, transplantation was performed following a relapse limited to the CNS. Stem cell sources were related in 8 cases (5 HLA-matched marrow, 2 mismatched marrow, 1 matched cord blood) and unrelated in 7 (3 mismatched URD marrow, 2 5/6 matched cord blood, 2 4/6 matched cord blood). Preparative regimens included total body irradiation (TBI) and cyclophosphamide (Cy) for 12 patients, and Cy, TBI, VP16 for 3 patients. Grade II-IV GvHD occurred in 7 patients (47%; 95% CI 21–72) and grade III-IV in 3 patients (20%; 95% CI 0–40) by day 100. All patients were alive 1 year following transplantation. With a median follow-up of 7 years (range 1 to 19.4), the estimated 5 year survival is 78% (95% CI 51–100%). Of the 2 patients that died, 1 transplanted in CR2 died of relapse, while another transplanted in CR2 died of ARDS. Both were recipients of related donor grafts. These data demonstrate hematopoietic stem cell transplantation is a viable therapeutic option for pediatric patients with isolated CNS relapse, and suggests that a larger multi-institutional analysis should be undertaken.