Evaluation of left ventricular function in asymptomatic children about to undergo anthracycline-based chemotherapy for acute leukemia: an outcome study.

BACKGROUND: Cardiac toxicity is a well-recognized potential complication of anthracycline use. Children treated with anthracyclines undergo several cardiac screening procedures before therapy, but the usefulness of these pretherapy cardiac studies has never been evaluated. The authors examined whether induction chemotherapy in patients with high-risk acute lymphoblastic leukemia (ALL) was altered based on a pretherapy left ventricular shortening fraction (SF). PATIENTS AND METHODS: Medical records of 134 children registered on treatment protocols of the Pediatric Oncology Group for high-risk B-precursor and T-cell ALL between 1987 and 1998 were reviewed. Demographic information consisting of age at diagnosis, sex, and past cardiac history was collected, as were the results of all echocardiographic evaluations for SF and actions taken based on these evaluations. The outcome measured was whether any changes were made in induction therapy based on initial SF. In addition, secondary SF results obtained at the cumulative anthracycline dose range of 90 to 150 mg/m2 were studied to determine whether modifications of future chemotherapy were made after this limited exposure. RESULTS: Three of 128 children (2.3%) without a previous cardiac history had an initial SF on their pretherapy echocardiogram that prompted additional evaluation but no change in therapy. A secondary analysis of SF in 85 children who completed anthracycline doses of 90 to 150 mg/m2 was performed. There were three (3.5%) with abnormal study results who were evaluated further. Again, no changes were made in the anthracycline doses based on these findings. No cardiac dysfunction occurred among these six patients during later follow-up. CONCLUSIONS: In the absence of a previous cardiac history or signs and symptoms or cardiac disease, pretherapy evaluation of left ventricular function may not be indicated in children about to undergo anthracycline-based treatment of acute leukemia. The timing of initiation of cardiac evaluation remains unclear, but these results suggest that even at a cumulative dose of 90 to 150 mg/m2, studies to determine left ventricular function do not yield data sufficient to warrant a change in the clinical management of these patients.

Design and analysis of epidemiological studies of excess cancer among children exposed to Chernobyl radionuclides.

Within the last decade, a substantial amount of attention has been devoted to etiological research on the association between exposure to fallout radionuclides from the Chernobyl accident and radiation-induced late effects (cancer) among children. A majority of the studies completed to date have been of the descriptive type, which only correlate average population exposure with average rate of cancer incidence as a function of calendar period. Since individual dosimetry is not performed in descriptive studies, it is unclear whether exposure precedes the development of cancer and a final decision cannot be made regarding the association between radiation exposure and cancer. This paper reviews the background epidemiology and outlines an analytical study design that is needed to clarify the unclear association between Chernobyl fallout exposure and childhood cancer. We discuss the essential elements of an analytical case-control design such as genetic predisposition, vital statistics, sample size and power determinations, ascertainment of cases and controls, and phenomenological dose modeling to establish individual doses. Examples such as cytogenetic biodosimetry, medical radiation dosimetry, and cytogenetic characterization of leukemia to minimize exposure and diagnostic misclassification are provided. We recommend the analytical methods described in this paper for studying the role of Chernobyl radionuclides and development of childhood cancer.

Chest infections and syndromes in sickle cell disease of childhood.

Sickle cell lung disease occurs in all of the more common sickle hemoglobinopathies. Of the acute pulmonary diseases, acute chest syndrome (ACS) is most common. The risk of recurrence after one episode of ACS ranges from 20% to 80%. Repeated episodes of ACS contribute to the development of earlier and potentially rapid pulmonary deterioration particularly in young adults. ACS is the second most common cause for hospital admission and has been reported to be responsible for 25% of sickle cell deaths. The exact etiology of ACS may be unclear and is often caused by the interaction of a number of factors. Although infection is most likely in the young child, infarction and thromboembolism are the more likely causes in older patients. Outcome is dependent on immediate recognition and rapid institution of therapy. Maintenance of adequate oxygenation treatment of possible underlying infection, and adequate hemoglobin delivery are essential. Simple or exchange transfusion is vital to improve hemoglobin delivery and decrease hemoglobin S concentration. Caution is advised when administering drugs such as morphine for pain control because of risk of exacerbation of pulmonary symptomatology.

Renal venous thrombosis complicating acute myeloid leukemia with hyperleukocytosis.

PURPOSE: Leukemic hyperleukocytosis may cause organ- or life-threatening complications. Patients at highest risk appear to be those with acute myeloid leukemia (AML). Blast cell aggregation and thrombus formation in the microvasculature most commonly involves the central nervous system and the pulmonary circulation. We describe a child with AML and renal venous thrombosis (RVT), a previously unreported complication of hyperleukocytosis. PATIENTS AND METHODS: A 17-month-old boy had a white blood cell count of 103 X 10(9) cells/L and RVT (hematuria, arterial systolic hypertension, unilateral nephromegaly, poor renal venous blood flow) at diagnosis of acute myelomonocytic leukemia (AML, FAB M4). CONCLUSION: This case emphasizes the danger of hyperleukocytosis in AML and demonstrates that there may be other organ system dysfunction in addition to the well-described central nervous system and pulmonary complications. Renal venous thrombosis should be considered in the patient with leukemic hyperleukocytosis, hematuria, arterial hypertension, and appropriate radiographic findings. Aggressive cytoreductive measures should be pursued in such cases.

Atypical cytogenic aberrations in two childhood peripheral primitive neuroectodermal tumors.

Atypical cytogenetic abnormalities were detected in peripheral primitive neuroectodermal tumors (PPNET) of the extremity in two children. One had an osseous tumor with a balanced reciprocal translocation, t(5;9)(q22;q32), and had a complete response to therapy. The other had a non-osseous tumor with an interstitial deletion, del(18)(q12.2q21.2), was resistant to combination therapy, and at autopsy had evidence of possible clonal evolution with the karyotype 46,XX der(8)t(8;8)(p11.2;q13), inv(16)(p13.2q12),del(18)(q12.2q21.2). Neither tumor demonstrated the t(11;22)(q24;q12) typically found in Ewing's sarcoma and PPNET, suggesting heterogeneity of the cytogenetic aberrations seen in this rare childhood malignancy.

Isolated bone relapse during hematologic remission in childhood acute lymphoblastic leukemia: report of a metatarsal relapse and review of the literature.

An 11-year-old boy with prior bone marrow and testicular relapses of his acute lymphoblastic leukemia (ALL) developed an isolated metatarsal bone relapse during complete hematologic remission 10 months after completion of chemotherapy. Although there was no radiographic or histologic evidence of additional occult leukemia, the polymerase chain reaction (PCR) technique detected a leukemic clone in both his bone marrow and metatarsal. A literature survey revealed only 10 reported cases of isolated bone relapse occurring during complete bone marrow remission in childhood ALL. Most of these patients had prior bone marrow or extramedullary relapses. The majority experienced subsequent relapses after their isolated bone recurrence. We report a case of isolated bone recurrence, review all previously reported cases, and suggest that PCR elucidation of clonal disease may provide a better understanding of these extremely rare extramedullary events.

Hodgkin's disease associated with central pontine myelinolysis.

We describe a 12-year-old black male who presented with cervical lymphadenopathy, hepatosplenomegaly of 3 months duration, and ataxia and incoordination of recent onset. Hodgkin's disease, stage IVB, was diagnosed. An MRI of the head demonstrated a nonenhancing, well-defined pontine lesion. The pontine lesion and the associated neurologic symptoms were consistent with central pontine myelinolysis. Treatment of Hodgkin's disease resulted in complete remission and complete disappearance of the pontine abnormality.

Infection-associated hemophagocytic syndrome. Evidence for Epstein-Barr virus gene expression.

Autopsy specimens from a patient with infection-associated hemophagocytic syndrome (IAHS) were evaluated for the presence of Epstein-Barr virus DNA and RNA using in situ hybridization. Frozen sections of liver, lymph node, and spleen were probed with EBV Bam HI-H & W, gamma interferon, and SP-65 plasmid DNA as a negative control probe. Hybridization patterns before and after treatment with ribonuclease A were examined. Both EBV probes produced diffuse hybridization throughout the tissues; in addition, there were some foci of extremely heavy concentrations of silver granules. A gamma interferon probe showed evidence of hybridization, but the overall intensity was not as great as with EBV probes. Pretreatment with ribonuclease A dramatically decreased hybridization in all tissues to EBV probes, but hybridization with SP-65 was unaffected. The elimination of EBV hybridization with ribonuclease A pretreatment provides the first evidence of EBV gene expression in an IAHS patient.