Multiple intracranial tumors in Philadelphia chromosome-positive acute lymphoblastic leukemia

Abstract

A three-year-old female presented with prolonged fever and petechiae. Her initial complete blood workup showed a white blood cell (WBC) count of 159 9 10/L with 92 % lymphoblasts, hemoglobin of 9.3 g/dL, and a platelet count of 22 9 10/L. Marked elevations of C-reactive protein (CRP) and lactate dehydrogenase were identified. The immunophenotype of the blast cells was CD10, CD19, HLA-DR, smIg, and smIg j=k , which is compatible with a diagnosis of precursor B cell lymphoblastic leukemia (pre-B ALL). CD66c expression was also detected, so we confirmed the bcr/abl rearrangement by fluorescence in situ hybridization analysis, and used transcriptase-polymerase chain reaction analysis to detect the minor bcr/abl fusion gene transcript. Given these results, the patient was diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL). By conventional cytogenetic analysis of bone marrow and peripheral blood cells at the onset, abnormalities of 9pq and 22q were suggested, but the complete karyotype of this case could not be confirmed at the time; however, the karyotype was later revealed at her first relapse to be 46, XX, dup(1)(q25q32), add(1)(q32), del(3)(q2?), der(9)t(9;22)(q34;q11)del(9)(p13), del(14)(13). As she presented with severe hyperleukocytosis, she received intravenous hyperhydration and prednisone at low doses for the purpose of cytoreduction until the beginning of remission induction therapy. A broad-spectrum antibacterial agent and fluconazole were also administered intravenously against her suspected systemic infection. However, her blood culture was negative, and her serum b-D glucan was not elevated. Whole-body computed tomography (CT) imaging was performed and high-density multiple intracranial tumors were detected (Fig. 1a–c) despite the absence of focal neurological symptoms or meningeal irritation. However, an analysis of her cerebrospinal fluid (CSF) showed no nucleated cells, and normal protein (18 mg/dL) and glucose (69 mg/dL) levels. The CRP level became negative at 3 days before starting induction chemotherapy, so both the antibacterial agent and fluconazole were stopped. During the period of myelosuppression after starting induction therapy, she remained afebrile with no elevation of CRP. Head CT scans at 16 days and 30 days after induction therapy, showed the intracranial masses to be markedly reduced compared with those on her head CT scans before induction therapy (Fig. 2a–c). Her intracranial tumors completely disappeared after two cycles of chemotherapy and never recurred. Unfortunately, she died from refractory leukemia, although she received allogeneic cord blood transplantation twice. At first, the intracranial lesions were suspected to be multiple brain abscesses or cerebral hemorrhage. If either were the case, rapid regression of intracranial lesions such as those observed in the present case would not be expected to occur. Moreover, several patients with acute leukemia who developed multiple intracranial hemorrhages associated with hyperleukocytosis have been reported. In such patients, severe neurological symptoms are commonly N. Hatakeyama (&) T. Hori M. Yamamoto N. Inazawa K. Igarashi H. Tsutsumi N. Suzuki Department of Pediatrics, Sapporo Medical University School of Medicine, South-1, West-16 Chuo-ku, Sapporo, Hokkaido 060-8543, Japan e-mail: nhatake@sapmed.ac.jp