Acute lymphoblastic leukemia with the (8;14)(q24;q32) translocation and FAB L3 morphology associated with a B-precursor immunophenotype: the Pediatric Oncology Group experience.

Five pediatric patients are described with acute lymphoblastic leukemia (ALL) who at presentation had clinical findings suggestive of B cell ALL and lymphoblasts with FAB L3 morphology and the characteristic t(8;14)(q24;q32). However, the leukemia cells of all five patients failed to express surface immunoglobulin (sIg) and kappa or lambda light chains. Based on initial immunophenotyping results consistent with B-precursor ALL, four of these cases were initially treated with conventional ALL chemotherapy. These four patients were switched to B cell ALL treatment protocols once cytogenetic results became available revealing the 8;14 translocation. The fifth case was treated with B cell ALL therapy from the outset. Four of the five patients are in complete remission at 64, 36, 29 and 13 months from diagnosis. One patient relapsed and died 6 months after initial presentation. These five unusual cases with clinical B cell ALL, the t(8;14), and FAB L3 morphology, but negative sIg, demonstrate the importance of careful and multidisciplinary evaluation of leukemic cells with morphology, cytochemistry, immunophenotyping and cytogenetic analysis. Future identification of patients with this profile will allow us to expand our knowledge regarding prognostic significance and optimal treatment for this rare subgroup of patients.

Preradiation chemotherapy in advanced medulloblastoma. A Pediatric Oncology Group pilot study.

BACKGROUND: Children diagnosed with medulloblastoma whose tumor involves the brain stem or has spread through the cerebrospinal fluid pathways to other areas of the brain or spinal cord have a poor prognosis despite therapy with surgery, craniospinal irradiation (CSI), and chemotherapy. Preradiation chemotherapy may improve the outlook for these patients. METHODS: To further study the role and feasibility of preradiation chemotherapy, children between the ages of 4 and 21 years diagnosed with advanced medulloblastoma and measurable disease were enrolled in the Pediatric Oncology Group 8695 study. Patients were treated with a 9-week course of vincristine, cisplatin, and cyclophosphamide followed by CSI. Imaging films were reviewed centrally for eligibility and response to chemotherapy. Toxicity to chemotherapy and radiation as well as delays and modifications in subsequent CSI were recorded. RESULTS: Thirteen of 30 fully evaluable patients achieved complete or partial response (43%) to chemotherapy. Toxicity was mostly fever and neutropenia after cyclophosphamide, which is predictable and tolerable. Radiation therapy was delivered in full doses and volumes in most patients but was delayed in its start in most patients. Central review of films revealed frequent use of different imaging modalities at baseline and after therapy, making accurate assessment of tumor response difficult. CONCLUSION: Preradiation chemotherapy with vincristine, cisplatin, and cyclophosphamide is active in patients with advanced medulloblastoma but should be modified to minimize the risk of progressive disease while on therapy and to avoid delays in starting radiation therapy. Consistent use of the same neuroimaging modality is essential in documenting response.

Rapidly progressive myelomonocytic leukemia (juvenile CML).

A rare type of rapidly fatal childhood leukemia, generally called juvenile chronic myelogenous leukemia, is characterized by absence of the Philadelphia chromosome and a predominantly monocytic proliferation, among other features. Unlike Philadelphia chromosome positive chronic myelogenous leukemia, this disease is neither chronic nor principally a disorder of granulocytic cell lines. A case is presented, with several clinical and laboratory parameters useful in establishing the correct diagnosis, and a change in terminology to "rapidly progressive juvenile myelomonocytic leukemia" is proposed.

Cardiomyopathy in a child with hypereosinophilic syndrome.

A 9-year-old boy presented with increasing fatigue, anorexia, weight loss, fever, and absolute eosinophilia (48,000/microL). Pulmonary infiltrates occurred 3 months later. A murmur of mitral regurgitation was heard 5 months after onset of illness, and heart failure soon followed. Despite corticosteroid therapy the eosinophilia persisted intermittently until 1 month before death. The patient died within 9 months of the onset of illness. At necropsy there was cardiomegaly with subendocardial fibrosis in the right and left ventricles. Thrombi were present in the left ventricular apex and behind the posterior mitral leaflet. The findings in 12 previously reported pediatric cases are reviewed. The etiopathogenesis of the hypereosinophilic syndrome is discussed: half of the cases in children are associated with leukemia.

Second malignancy in acute lymphocytic leukemia. Review of 33 cases.

Improved survival in childhood cancer resulting from advances in therapy is frequently associated with long-term morbidity, including the potential for second malignancy. In a review of the literature in the English language, we found 33 cases of acute lymphocytic leukemia (ALL) followed by a second neoplasm. Second tumors in this group of patients with ALL include seven cases of histiocytic medullary reticulosis, four cases of Hodgkin's disease, nine cases of acute myelocytic leukemia, four cases of chronic myelocytic leukemia, and nine cases of solid tumors. The appearance of subsequent malignancies may be related to a combination of therapy-induced immunosuppression, a direct carcinogenic effect resulting from therapy, and/or constitutional factors. Physicians should be alert to the possibility of subsequent malignant neoplasms in survivors of cancer.

Anthracycline cardiomyopathy in children: report of two cases.

Two children with leukemia are presented, each demonstrating an unusual aspect of anthracycline-induced cardiomyopathy. In the first patient (a 7-month-old female with acute monocytic leukemia) extremely young age and previous chemotherapy with a podophyllotoxin derivative, VP-16, may have prediposed the patient to fatal congestive heart failure at a total Daunorubicin dose of only 225 mg/m2. In the second patient, a delay of 4 1/2 years was not sufficient in preventing congestive heart failure resulting from the administration of additional anthracycline chemotherapy. We conclude that extremely young age and, possibly, prior therapy with VP-16 may be addition risk factors in the development of anthracycline cardiomyopathy. Also, we suggest that once an anthracycline agent has reached a toxic threshold for the myocardium, the heart may always be at risk to injury from additional Adriamycin or Daunorubicin therapy.

Hepatoma in a child with methotrexate-induced hepatic fibrosis.

During autopsy, an 11-year-old girl with acute lymphocytic leukemia was found to have hepatic fibrosis with a 2.5-cm nodule of hepatocarcinoma. For 5 1/2 of the six years of treatment, chemotherapy consisted of daily orally administered methotrexate with monthly doses of vincristine sulfate and prednisone. The cumulative dose of methotrexate was 2.5 g. To our knowledge, this report constitutes the first association of hepatoma with methotrexate-induced hepatic fibrosis. A careful follow-up of patients receiving methotrexate for malignant neoplasms is urged; caution is suggested in the prolonged use of methotrexate when treating benign disease.