Pediatric Patients with Extramedullary Leukemia Involving the Central Nervous System Have a Superior Outcome.

Purpose: Extramedullary leukemia (EML), formally known as chloroma, is discrete collections of leukemia cells outside of the bone marrow. EML is often seen within the central nervous system (CNS) and these are often treated in a similar fashion as leukemia cells within the cerebral spinal fluid (CSF). We previously demonstrated that the presence of leukemia cells within the CSF (CNS leukemia) does not affect overall survival. We sought to determine the outcome of patients with central nervous system EML and compare these patients with those with CNS disease and non CNS EML.

Methods: Patients enrolled on Children’s Cancer Group protocols 2861, 2891, 2941 and 2961 being treated for de novo acute myeloid leukemia (AML) with intensive timing chemotherapy were classified for the presence of CNS disease as CNS1 (<5 wbc in the CSF without blasts), CNS2 (<5 wbc in the CSF with blasts), or CNS3 (≥ 5 wbc in the CSF with blasts), as well as EML in the CNS (eg orbit, brain, etc) or non-CNS EML (eg skin, lung, etc). These patient’s outcomes were then analyzed.

Results: A total of 1459 patients treated with intensive timing chemotherapy were analyzed in this study. At diagnosis, 1113 (76%) were CNS1, 143 (13%) CNS2, 154 (11%) CNS3, 48 (3%) had CNS EML, 57 (4%) had a non-CNS EML, and only 6 patients (0.4%) with CNS EML had CNS3 status. Patients with CNS EML had a significantly higher overall survival from study entry compared to patients with non-CNS EML (83% vs 38%, p<0.001), and compared to CNS3 patients (83% vs 50%, p<0.001). The patients with CNS EML also had a significantly higher event free survival compared to patients with non-CNS EML (65% vs 34%, p<0.001), and compared to CNS3 patients (65% vs 34%, p<0.001). There was no significant difference in relapse risk, bone marrow relapse, isolated CNS relapse, or EML relapse comparing patients with CNS EML and non-CNS EML. CNS EML patients had a significantly lower relapse risk compared to CNS3 patients (29% vs 49%, p=0.025). There was not a significant difference in bone marrow relapse, isolated CNS relapse, or EML relapse comparing these 2 groups of patients.

Conclusion: Patients with extramedullary leukemia involving the CNS had a significantly better survival than patients with non-CNS EML or patients with CNS leukemia at diagnosis. This should reassure clinicians caring for these often challenging patients.