Intrathecal Chemotherapy Post Hematopoietic Cell Transplantation for Prevention of Central Nervous System Relapse in Pediatric Acute Leukemia

Intrathecal (IT) chemotherapy can be given to patients with acute leukemia post hematopoietic stem cell transplant (HSCT) in an attempt to prevent relapse in the central nervous system (CNS). We performed a retrospective analysis of 166 patients with acute leukemia who underwent first HSCT at Memorial Sloan-Kettering Cancer Center between 1999 and 2013. Patients who were not eligible for post HSCT IT prophylaxis due to graft-versus-host disease or acute transplant related complications were excluded from the analysis. Indication for HSCT included acute lymphoblastic leukemia (ALL) (n=115), acute myeloid leukemia (n=45) or acute biphenotypic leukemia (n=6). The median age of patients was 10.7 years (range 0.6-27.5). Disease status at transplant included CR1 (38%), CR2 (44%) and not in remission (4%).  Donor grafts underwent ex vivo T cell depletion in 67% (110) of patients, and 71.6% (116) of patients received their graft from an unrelated donor. Conditioning therapy included TBI in 76% of cases. Patients with a history of CNS disease (36%) were included in this analysis; these patients received CNS radiation either  during induction therapy or as a boost prior HSCT. Monthly post-transplant IT prophylaxis was administered to 71% of patients, starting at 2 months post HSCT. Prophylaxis consisted of IT cytarabine +/- hydrocortisone, with patients with no prior CNS disease receiving 5 doses post HSCT and those with previous CNS disease receiving 11 doses. The rate of overall relapse at 2 years was 33.2% for the entire cohort, with a CNS relapse rate of 5.4%. The CNS relapse rate at 2 years for patients with ALL was 7.1%, and only 1 patient with AML developed CNS relapse. In subset analysis, patients with ALL who received IT prophylaxis post HSCT had a significantly lower rate of CNS relapse compared to those that did not (4.4% vs 17.3%, P = 0.04). Our study demonstrates that monthly IT prophylaxis with cytarabine +/- hydrocortisone post HSCT may be beneficial for patients with acute lymphoblastic leukemia in the prevention of CNS relapse.