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Biomedical subjects

J Blatt

Publications and source records attributed to J Blatt.

107 records · Page 6Linked to original sources
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IGF1 and leukemia.

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Animals↗
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Leukemia in a child with a history of medulloblastoma.

Leukemia of mixed lineage, was diagnosed in a 6.5-year-old boy with a history of medulloblastoma, 38 months after his initial cancer diagnosis. Therapy had included craniospinal radiation and nitrosourea-based chemotherapy. In addition, onset of leukemia was preceded by therapy with recombinant growth hormone for short stature. Although rare, leukemia is a treatment-related complication for patients with past brain tumors whose follow-up should therefore include surveillance with complete blood counts.

Brain Neoplasms↗
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Relapse in acute lymphoblastic leukemia as a function of white blood cell and absolute neutrophil counts during maintenance chemotherapy.

Several reports document an inverse correlation between bioavailability of maintenance chemotherapeutic agents and the likelihood of relapse in childhood. White blood cell counts (WBC) and absolute neutrophil counts (ANC) are easily ascertainable parameters which might be expected to reflect plasma levels of chemotherapy. To determine whether WBC and ANC predict outcome of children with acute lymphoblastic leukemia (ALL), we did a multivariate analysis of means of these values during maintenance therapy in patients with ALL treated on a single protocol. Of the 52 patients, 15 (29%) relapsed. For those still disease-free, minimum time of follow-up is 7-8/12 years. During the first year of maintenance therapy, mean WBC (x 10(3)/mm3) in the relapsed and nonrelapsed groups were 4.5 +/- 0.9 and 3.9 +/- 0.7, respectively (p = 0.03); mean ANC (x 10(3)/mm3) were 3.0 +/- 0.9 and 2.5 +/- 0.6 (p = 0.05). However, the range of values was large with considerable overlap between the two groups. There was no obvious difference in distribution of values when confounding prognostic features were adjusted for in the analysis. No significant differences were seen between WBC or ANC during the second year of therapy. Larger numbers of patients will be needed to ascertain whether specific guidelines for dosage modifications can be made on the basis of serial WBC. Future pharmacokinetic studies should look at possible correlations with mean WBC and ANC.

Antineoplastic Combined Chemotherapy Protocols↗
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Idiopathic hypereosinophilic syndrome terminating in acute lymphoblastic leukemia.

Idiopathic hypereosinophilic syndrome (IHES) is a heterogeneous group of disorders characterized by multisystem dysfunction and persistent, extreme eosinophilia of unknown cause. We describe a 9-1/2-year-old boy whose course included several unusual clinical features and terminated 2 years after diagnosis in acute lymphoblastic leukemia (ALL). Serial studies suggest that leukemia was not present earlier in his course. We speculate that this child may have had an evolving lymphoproliferative syndrome with a terminal blast crisis to which the eosinophilia was a nonmalignant leukemoid reaction.

Antigens, Differentiation↗
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Impact of gender on the natural history of neuroblastoma.

To study of the possible impact of gender on the natural history of neuroblastoma, the medical records of 136 consecutive children with that diagnosis treated at the Children's Hospital of Pittsburgh from 1975 to 1992 were reviewed. An attempt was made to investigate the association between sex and age at diagnosis, primary tumor site, stage, and histology. Although overall male:female ratio was only 1.3:1, in the group of 17 patients who were older than six years at diagnosis the incidence was 2.0:1. Primary tumor site also could be stratified on the basis of sex, with twofold more adrenal tumors occurring in boys than in girls (P = 0.012). Based on retrospective data, there was no clear association between sex and stage or extent of histologic differentiation. Because these observations cannot readily be explained on the basis of male predominance in the population at large or on uneven referral patterns, they deserve further examination in larger series, such as those of cooperative groups.

Cell Differentiation↗
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Pilot study of cardiac function after treatment of childhood Wilms' tumor with doxorubicin.

To assess the cardiotoxicity of moderate doses of anthracyclines and to control for possible contributions of other drugs, cardiac function in 12 patients 1 year 11 months to 9 years 4 months off treatment for Wilms' tumor whose therapy had included vincristine, dactinomycin, and the anthracycline doxorubicin (270 to 300 mg/m2 cumulative dose) was compared with that of 9 patients (controls) whose therapy had included vincristine and dactinomycin but not doxorubicin. The small numbers of patients studied suggest that a a medium of 6 years off therapy only small numbers of patients will have cardiac function values below age-related normal values. To confirm these results and to determine whether abnormalities are progressive or are clinically important, large cohorts of patients such as those available to the National Wilms' Tumor Study need to be studied.

Child↗
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Recognition of central nervous system metastases in children with metastatic primary extracranial neuroblastoma.

In children with primary extracranial neuroblastoma (NB), intrinsic central nervous system (CNS) metastases (brain parenchyma or leptomeninges) are thought to occur rarely. This study was done to evaluate our anecdotal experience, which suggested that CNS involvement is becoming more frequent. Reports of computed tomographic (CT) and magnetic resonance (MR) imaging scans, biopsies, cerebrospinal fluid (CSF) cytologies, and autopsies were reviewed for children with stage IV NB diagnosed in 1978-1993 and followed at the Children's Hospital of Pittsburgh. Of 43 children over the age of 1 year, CNS metastases were documented in 7 (16.2%). Six patients developed signs or symptoms best explained by the presence of CNS tumor and had radiographic and/or histologic evidence of parenchymal disease (cortical masses on CT and MR, n = 3; suprasellar mass on CT, n = 1; diffuse leptomeningeal carcinomatosis by MR and/or autopsy, n = 2). CSF cytologies were positive in the one patient so tested. An additional asymptomatic patient had extensive CNS involvement at autopsy. In two of these children, the CNS was the first or only site of recurrent disease. It is concluded that intrinsic CNS disease is not uncommon in children with NB over the age of 1 year and there has been a trend toward its increasing recognition in recent years. Whether this is a function of wider use of diagnostic tools or a true change in natural history over time with increased intensity of chemotherapy is not clear. A study that prospectively monitors children with advanced neuroblastoma, radiographically and with CSF cytologies (prior to treatment and at 6-monthly intervals), is under way and should help to better define the natural history in the context of current therapies.

Brain Neoplasms↗
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Tolerance to single-dose dactinomycin in combination chemotherapy for solid tumors.

We have reviewed our experience using single-dose dactinomycin (Act D). Twenty-nine patients with Ewing's sarcoma or rhabdomyosarcoma received 114 courses of Act D (2 mg/m2) in combination with vincristine, cyclophosphamide, or DTIC with or without radiotherapy. Side effects included nausea and vomiting (100% of the courses), severe thrombocytopenia (16%), granulocytopenia (18%), and mucositis (25%). In addition, skin reactions were observed in 74% of the courses following concomitant radiotherapy. These results were compared with those following 152 courses of combination chemotherapy which contained doxorubicin in place of Act D and which were administered to these same patients. It is concluded that single-bolus Act D is no more toxic, is at least as effective, and is more conveniently administered than the traditional divided daily dose of Act D.

Adolescent↗
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Deferoxamine in children with recurrent neuroblastoma.

We examined the short-term efficacy and toxicity of high doses of intravenous deferoxamine (DFO) in children with recurrent neuroblastoma. Ten children (3 2/12-20 years, median 6 5/12 years) had measurable recurrent disease following 1-3 prior treatment regimens. DFO (120-240 mg/kg/d) was planned as a continuous i.v. infusion for five days every other week. Serum ferritins at the start of this therapy ranged from 133-->5000 ng/ml (median 611 ng/ml). Of eight patients begun at a dose of 120-150 mg/kg/d, a single patient experienced visual disturbances which resolved after DFO was discontinued. Two patients begun at 240 mg/kg/d (with serum ferritins levels of 505 and 717 ng/ml) both experienced dose-limiting toxicity including lethargy, dizziness, blurred vision and leg cramps. Although decreases in serum ferritin levels of a least 10% were noted in 4 patients, there were no partial or complete response. DFO given at a dose of 150 mg/kg/d i.v. according to this schedule appears to be ineffective as a single agent against neuroblastoma. Starting doses of 240 mg/kg/d have unacceptable short-term toxicity.

Adolescent↗