Michael R. Wollman

Progressive varicella presenting with pain and minimal skin involvement in children with acute lymphoblastic leukemia.

PURPOSE Here we report the experience at the Childrens Hospital of Pittsburgh (CHP) with varicella zoster virus (VZV) in children with acute lymphoblastic leukemia (ALL). This record review was prompted by a patient with ALL who died suddenly of varicella hepatitis within 24 hours of presentation with a single skin lesion. METHODS We reviewed the medical records of children diagnosed with ALL at the CHP from January 1984 through December 1993, who subsequently developed VZV infection. RESULTS Of 294 patients aged 0 to 15 years, 41 (14%) were identified as having had 42 episodes of VZV infection. Twenty patients (49%) had received prophylaxis with varicella zoster immunoglobulin (VZIG), and all 39 patients in whom the diagnosis was made premortem were treated with acyclovir. Twenty-nine of the 42 cases (70%) had disease limited to the skin. Thirteen cases (30%) had extracutaneous involvement, and five of these episodes (12% of all cases) ended in death. Risk factors for progressive varicella included age greater than 6 years and intensive immunosuppressive therapy at the time of exposure. Six of eight patients with progressive varicella, including two who died, had received VZIG. The clinical presentation in 10 of 13 patients with progressive disease and in four of five patients who died was dominated by severe abdominal and/or back pain. In seven cases, these symptoms preceded the development of skin lesions by several days, and in six patients were associated with extensive involvement of the spleen by varicella, as demonstrated histopathologically by the presence of Howell-Jolly bodies on peripheral-blood smear or radiographically. No patient with uncomplicated varicella was reported to have had premonitory pain. CONCLUSION Recognition of these prodromes and suspicion of varicella even in the absence of skin lesions and even in children with a history of prior disease or VZIG administration should prompt early diagnostic and therapeutic measures.

Radiotherapy for cerebral metastases in children

Twelve children with cerebral metastases from non-lymphomatous primary tumors are reviewed. Eleven were treated with radiotherapy and four are alive without clinical or radiographic evidence of intracranial tumor 2-7 1/2 years later. Three of the four survivors are free of neurologic impairments. Eight patients died within two months of detection of cerebral metastases. There were no obvious differences between those patients who survived and those who did not, concerning the primary tumor, age at diagnosis, duration of symptoms or the interval from the primary to the cerebral metastases. All survivors are male.

Transient 7q- in association with megaloblastic anemia due to dietary folate and vitamin B12 deficiency.

Purpose: We describe a ease of acquired megaloblastic anemia in a 71/2-year-old while boy whose bone marrow showed unusual morphology and a nonrandom del(7q). Methods and Results: This patient was found to have megaloblastic anemia due to acquired folic acid and vitamin B12 deficiencies. Bone marrow examination exhibited unusual morphology, including intranuclear inclusions. Cytogenetic analysis revealed a nonrandom del(7q). a clonal abnormality usually associated with the myelodysplastic syndrome (MDS) or secondary acute myelogenous leukemia (AML). Specific treatment with both folic acid and vitamin B12 corrected the clinical as well as the marrow morphologic and cytogenetic abnormalities. Conclusions: Megaloblastic anemia causes abnormalities in DNA synthesis and repair that may result in unusual marrow findings, both morphologic and cytogenetic. Such findings must be interpreted with caution in view of total reversibility with specific vitamin therapy.

An abnormal clone with monosomy 7 and trisomy 21 in the bone marrow of a child with congenital agranulocytosis (Kostmann disease) treated with granulocyte colony-stimulating factor : evolution towards myelodysplastic syndrome and acute basophilic leukemia

Cytogenetic analysis of bone marrow cells revealed an abnormal clone with monosomy 7 and trisomy 21 in a 12-year-old child with Kostmann disease (KD). The patient presented with anemia, thrombocytopenia, and splenomegaly after 5 years of treatment with granulocyte colony-stimulating factor (G-CSF). The bone marrow morphology was consistent with the diagnosis of myelodysplastic syndrome (MDS). Administration of G-CSF was discontinued at this point. Bone marrow studies 2 and 5 months later showed persistence of both myelodysplasia and the abnormal clone with monosomy 7 and trisomy 21. Monosomy 7 was also confirmed by fluorescence in situ hybridization (FISH). After 2 months of follow-up, the patient presented with acute basophilic leukemia, a very rare variant of acute myeloid leukemia (AML), expressing the same bone marrow chromosome abnormalities as observed earlier. This is a rare case of KD with prolonged survival and a cytogenetically abnormal clone evolving to MDS and acute basophilic leukemia. The significance of monosomy 7 and trisomy 21 in KD treated with G-CSF is discussed.

Metoclopramide as an Antiemetic Agent in Pediatric Oncology Patients

Metoclopramide (MCP) was used as an antiemetic agent in 11 pediatric oncology patients during 22 courses of cancer therapy including cisplatin, doxorubicin, and other agents. Initial MCP regimens used 2 mg/kg/dose iv prior to and at 1.5, 3.5, 5.5, and 8.5 hours post-chemotherapy. Subsequent dose reduction to 1 mg/kg and addition of diphenhydramine to all regimens has been made to decrease adverse drug effects. Seven of 11 children reported subjective benefit, defined by comparison with previous antiemetic response, comfort, and willingness to continue MCP therapy. MCP effectively reduced the volume of emesis per 24-hour period as compared with volume of emesis recorded following other antiemetics, an observation that should be confirmed in controlled studies of efficacy. Acute dystonic reactions developed in five children, occurring most frequently in those who received 2 mg/kg/dose regimens or consecutive day dosing. These reactions were rapidly reversible with diphenhydramine, but limited patient acceptance of further MCP use.