Central nervous system relapse of acute promyelocytic leukemia

To the Editor: We read with interest the article by Chow and Feusner [1] as well as the letter by Kaspers et al. [2] and response from Feusner and Chow [3] regarding isolated central nervous system (CNS) relapse of acute promyelocytic leukemia (APL) in children. They found a total incidence of CNS relapse of 6/431 (1.39%), and in good risk patients an incidence of truly isolated CNS relapse of 2/218 (0.92%). We would like to comment on our patient who developed an isolated relapse of his APL, with a CNS myelocytic sarcoma, which quickly developed into a marrow relapse as well. Our patient initially presented at the age of 6 with fever, abdominal pain, and splenomegaly. A complete blood count revealed a white cell count (WBC) of 35 10/L. His bone marrow aspirate (BMA) showed 96% blasts with M3 morphology and cytogenetics were positive for t(15;17) by fluorescent in situ hybridization. The WBC peaked at 60 10/L and the patient was treated according to the POG/CALGB 9710 protocol using ATRA, daunorubicin, cytarbine, methotrexate and 6-mercaptopurine. The patient did not have a diagnostic lumbar puncture (LP) due to his coagulopathy but an LP done 20 days into therapy was negative as were all LPs done during and at the end of therapy. His end of therapy and 3 months off therapy BMA were morphologically normal and negative for t(15:17) by PCR. At 6 months off therapy the patient described two recent episodes of left sided weakness/ numbness lasting 15 min. An MRI showed a 1.7 cm 0.9 cm 0.9 cm meningeal-based soft tissue tumor as well as nodular leptomeningeal enhancement (Fig. 1). His bone marrow aspirate was morphologically normal but PCR was positive for t(15;17). His CSF showed 227 white cells of which 91% were blasts of M3 morphology. He was treated with intrathecal triple chemotherapy and while awaiting arsenic therapy, he developed circulating blasts. A bone marrow done 17 days after the first marrow, showed 70% blasts of M3 morphology. He received therapy with arsenic and ATRA followed by cytarabine and a stem cell transplant. His CSF did not clear after five doses of intrathecal chemotherapy, so he received an additional two doses of intrathecal chemotherapy as well as craniospinal irradiation. APL has a very low incidence of isolated CNS relapse of 1.39% in all patients [1]. As well, there are only limited reports of myelocytic sarcomas occurring in APL [4–11], with only one report of a myelocytic sarcoma within the CNS [4], and only two reports involving children [7,11]. Our patient presented with an isolated CNS relapse associated with a CNS myelocytic sarcoma with evidence of molecular relapse in the marrow that quickly progressed to a morphologic relapse in the marrow. Although rare to have an isolated CNS relapse of APL, it must be considered for any patient with a history of APL who presents with any neurologic symptoms. Donna L. Johnston, MD* Karen Mandel, MD Children’s Hospital of Eastern Ontario Division of Hematology/Oncology Ottawa, Ontario, Canada