Cardiomyopathy in children with Down syndrome treated for acute myeloid leukemia: a report from the Children's Oncology Group Study POG 9421.

PURPOSE: To determine the outcomes, with particular attention to toxicity, of children with Down syndrome (DS) and acute myeloid leukemia (AML) treated on Pediatric Oncology Group (POG) protocol 9421. PATIENTS AND METHODS: Children with DS and newly diagnosed AML (n = 57) were prospectively enrolled onto the standard-therapy arm of POG 9421 and were administered five cycles of chemotherapy, which included daunorubicin 135 mg/m(2) and mitoxantrone 80 mg/m(2). Outcomes and toxicity were evaluated prospectively and were compared with the non-DS-AML cohort (n = 565). A retrospective chart review was performed to identify adverse cardiac events. RESULTS: In the DS-AML group, 54 patients (94.7%) entered remission. One experienced induction failure and two died. Of the 54 who entered remission, three relapsed and six died as a result of other causes. The remission induction rate was similar in the non-DS-French-American-British (FAB) M7 (91.7%) and non-DS-non-M7 (89.3%) groups. The 5-year overall survival was significantly better in the DS-AML group (78.6%) than in the non-DS-M7 (36.3%) or the non-DS-non-M7 (51.8%) groups (P < .001). No age-related difference in 5-year, event-free survival was seen between patients younger than 2 years (75.8%) and those aged 2 to 4 years (78.3%). Symptomatic cardiomyopathy developed in 10 patients (17.5%) with DS-AML during or soon after completion of treatment; three died as a result of congestive heart failure. CONCLUSION: The POG 9421 treatment regimen was highly effective in both remission induction and disease-free survival for patients with DS-AML. However, there was a high incidence of cardiomyopathy, which supports current strategies for dose reduction of anthracyclines in this patient population.

Translocation-positive acute myeloid leukemia associated with valproic acid therapy.

Valproic acid is an effective anti-epileptic medication often used for long-term control of seizure disorders that has been implicated in hematological toxicities, including rare reports of myelodysplasia and acute leukemia. Here, we report a case of valproic acid-related leukemia-like syndrome with a t(8;16) chromosomal translocation. After discontinuing valproic acid, the hematological findings completely resolved.

A prospective study of the natural history of transient leukemia (TL) in neonates with Down syndrome (DS): Children's Oncology Group (COG) study POG-9481.

A unique transient leukemia (TL) has been described in newborns with Down syndrome (DS; or trisomy 21 mosaics). This leukemia has a high incidence of spontaneous remission; however, early death and subsequent development of acute megakaryoblastic leukemia (AMKL) have been reported. We prospectively evaluated 48 infants with DS and TL to determine the natural history and biologic characteristics of this disease, identify the clinical characteristics associated with early death or subsequent leukemia, and assess the incidence of subsequent leukemia. Blast cells associated with TL in DS infants exhibited FAB M(7) morphology and phenotype. Most infants (74%) had trisomy 21 (or mosaicism) as the only cytogenetic abnormality in the blast cells. Most children were able to spontaneously clear peripheral blasts (89%), normalize blood counts (74%), and maintain a complete remission (64%). Early death occurred in 17% of infants and was significantly correlated with higher white blood cell count at diagnosis (P < .001), increased bilirubin and liver enzymes (P < .005), and a failure to normalize the blood count (P = .001). Recurrence of leukemia occurred in 19% of infants at a mean of 20 months. Development of leukemia was significantly correlated with karyotypic abnormalities in addition to trisomy 21 (P = .037). Ongoing collaborative clinical studies are needed to determine the optimal role of chemotherapy for infants at risk for increased mortality or disease recurrence and to further the knowledge of the unique biologic features of this TL.

Transient leukemia in newborns with Down syndrome.

Children with Down syndrome (DS) have a 10- to 20-fold increased risk of developing leukemia, particularly acute megakaryocytic leukemia. Newborns with DS or trisomy 21 mosaicism may exhibit a particularly unique form of leukemia that historically has been associated with a high rate of spontaneous remission. This transient leukemia (TL) has been shown to be a clonal proliferation of blast cells exhibiting megakaryocytic features. Its true incidence remains to be determined. At presentation, many infants are clinically well with only an incidental finding of abnormal blood counts and circulating blasts in the peripheral blood. However, in approximately 20% of cases, the disease is severe and life-threatening, manifesting as hydrops faetalis, multiple effusions, and liver or multi-organ system failure resulting in death. Of those children who enter a spontaneous remission, 13-33% have been found to develop subsequent acute megakaryoblastic leukemia, usually within the first 3 years of life, which if left untreated is fatal. This unique TL of the DS newborn has been the subject of recent clinical cooperative group trials as well as many biological and genetic research efforts. We summarize here the known clinical, biological, and cytogenetic features of TL associated with DS.

2-Deoxy-2-[18F]fluoro-D-glucose positron emission tomography uptake in systemic lupus erythematosus-associated adenopathy.

Systemic lupus erythematosus (SLE) and lymphoma are disease entities that often have similar presenting signs and symptoms that can complicate or delay definitive diagnosis. 2-Deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography (FDG-PET) has become a valuable tool in the diagnosis, staging, and evaluation of response to therapy in lymphoma patients. However, its utility in patients with SLE has been limited to the central nervous system. Significant FDG uptake has not been previously reported in lymphadenopathy associated with SLE. The case presented is an example of histologically proven benign adenopathy in a 16-year-old female with SLE that was hypermetabolic on FDG-PET imaging. It highlights the importance of recognizing that widespread inflammatory adenopathy in SLE can mimic the pattern of FDG uptake seen with lymphoma at PET imaging.

Continuous lidocaine infusion for the relief of refractory malignant pain in a terminally ill pediatric cancer patient.

Despite aggressive pain management with opiates, debilitating pain still occurs in a subset of children with terminal cancer. A 5-year-old girl with metastatic retinoblastoma, profound opiate tolerance, and refractory pain was treated. Continuous lidocaine infusion was initiated at a dose of 35 microg/kg per minute and increased over 4 days to 50 microg/kg per minute, at which point the patient was discharged for continued end-of-life comfort care. The patient had excellent pain relief without the associated lethargy of high-dose opiates. No complicating neuroexcitatory symptoms or cardiac conduction abnormalities were experienced. Intravenous lidocaine may be an effective alternative to opioids in the treatment of refractory malignant pain in the pediatric patient with terminal cancer.

Incidence and treatment of potentially lethal diseases in transient leukemia of Down syndrome: Pediatric Oncology Group Study.

Transient leukemia (TL or transient myeloproliferative disorder) occurs in approximately 10% of newborn infants with Down syndrome. The disorder is characterized by the presence of megakaryoblasts in the peripheral blood; most cases resolve spontaneously within the first 3 months of life, and the child is well thereafter. However, there are cases in which a severe, potentially lethal form of disease develops, manifesting as hepatic fibrosis or cardiopulmonary failure. Hitherto, the incidence of these severe forms of the disease has not been reported. A prospective study of TL was conducted by the Pediatric Oncology Group (POG Study 9481) in which 48 children with TL were identified. Life-threatening disease occurred in nine patients (19%); seven had hepatic fibrosis and two had cardiopulmonary failure. Five children died of the disease within the first 3 months of life, none of whom received antileukemic therapy. One patient died on day 31 after receiving minimal therapy within 1 day of death. Three children received low-dose cytosine arabinoside (Ara-C) (0.4-1.5 mg/kg every 12 hours for 5 or 7 days). In all these patients, the disease resolved. It is concluded that potentially lethal disease is relatively common in TL, and the available evidence suggests that these diseases are responsive to low-dose Ara-C therapy.