The risks of central nervous system relapse and leukoencephalopathy in patients receiving marrow transplants for acute leukemia

Abstract

Abstract The records of 415 patients who received allogeneic marrow transplants for acute leukemia were reviewed to assess the risk of central nervous system (CNS) relapse and leukoencephalopathy after marrow transplantation. The Kaplan-Meier estimates of the probability of CNS relapse posttransplant were 13% for patients with acute lymphoblastic leukemia (ALL) and 2% for patients with acute nonlymphoblastic leukemia (ANL). Previous CNS disease was significantly correlated with an increased risk of CNS relapse in patients transplanted for ALL but not for ANL. In contrast, bone marrow involvement with leukemia at the time of transplant was associated with an increased risk of CNS relapse in patients with ANL but not in patients with ALL. Seventy-one patients with ALL did not receive posttransplant intrathecal methotrexate (IT- MTX) and 127 did. The probability of CNS relapse in these two groups was 38% and 7%, respectively (P less than .02). This protective benefit from IT-MTX was present in patients both with and without a history of CNS involvement or marrow involvement at the time of transplant. In patients with ANL, 116 patients did not receive posttransplant IT-MTX and 101 patients did, but no protection from CNS relapse was observed from IT-MTX irrespective of a patient's previous CNS history or marrow status at the time of transplant. Leukoencephalopathy was seen exclusively in patients who had received radiation and/or intrathecal chemotherapy to the CNS before preparation for marrow transplantation and posttransplant IT-MTX. In such patients the risk of leukoencephalopathy was 7%. From our data, it appears that posttransplant IT-MTX is a significant benefit for ALL patients in preventing CNS relapse after marrow transplantation. A similar benefit from posttransplant IT-MTX for ANL patients cannot be established from this study. In both groups, increasing total CNS therapy was associated with an increasing risk of leukoencephalopathy.