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Biomedical subjects

D J Ganick

Publications and source records attributed to D J Ganick.

At least 19 recordsLinked to original sources

Repetitive low dose oral methotrexate and intravenous mercaptopurine treatment for patients with lower risk B-lineage acute lymphoblastic leukemia. A Pediatric Oncology Group pilot study.

BACKGROUND: This trial evaluated the toxicity and preliminary efficacy of a repeated oral low dose (LD) methotrexate schedule with intravenous mercaptopurine infusions as intensification therapy for children with lower risk B-lineage acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS. From December 1986 to January 1991, 96 children with newly diagnosed, lower risk ALL were enrolled. Vincristine, L-asparaginase, and prednisone were used for remission induction. Age-based methotrexate was administered intrathecally (IT) for central nervous system (CNS) prophylaxis. An outpatient-based intensification treatment included LD methotrexate 30 mg/M2 every 6 hours for 5 doses, followed by intravenous mercaptopurine 1000 mg/M2 for 6 hours every 2 weeks for 12 courses. Leucovorin rescue was administered 48 hours after methotrexate treatment was begun. Maintenance therapy included standard daily oral mercaptopurine, weekly intramuscular methotrexate, and IT methotrexate every 12 weeks, for 2 years. RESULTS: All patients had disease remission. Thirty-two patients relapsed; there were 17 isolated bone marrow relapses, 10 isolated CNS relapses, 2 isolated testicular relapses, 1 marrow plus CNS relapse, 1 marrow plus testicular relapse, and 1 CNS plus testicular relapse. Event free survival (EFS) at 4 years was 66% (standard error, 7%) by Kaplan-Meier analysis. Complications associated with LD methotrexate/mercaptopurine courses were few and resulted in hospital readmissions in 2.4% of courses. Two patients were unable to comply with the oral LD methotrexate schedule and received intravenous methotrexate. Three patients were unable to complete scheduled maintenance because of hepatic or hematopoietic dysfunction. CONCLUSIONS: Low dose methotrexate/mercaptopurine can be administered safely on an outpatient basis to children with lower risk B-lineage ALL. However, there was a higher than expected incidence of bone marrow and CNS relapse. The reasons for this outcome were not completely clear but raise the possibility that LD methotrexate therapy may be less effective in preventing relapse than are higher dose, parenteral methotrexate regimens.

Administration, Oral

Severe hematologic toxicity of valproic acid. A report of four patients.

Four patients with severe cerebral palsy, mental retardation, and seizures who were treated with valproic acid showed a broad spectrum of hematologic toxicity, which included thrombocytopenia, macrocytic red cells with or without anemia, and the Pelger-Huet anomaly in the segmented neutrophils, along with elevated vitamin B12 levels, normal serum folic acid levels, and elevated fetal hemoglobin values (two cases). Bone marrow findings in all four patients were abnormal, suggestive of a myelodysplastic syndrome. These hematologic findings have not been previously reported and are important for monitoring a patient on valproic acid therapy. The Pelger-Huet anomaly may be mistaken for an elevated band count, the macrocytic anemia appears not to be secondary to a vitamin B12 or folate deficiency, and the thrombocytopenia may be sensitive to drug dosage. The bone marrow changes appear to be a drug-related myelodysplastic phenomenon.

Adolescent

Clinical utility of fine needle aspiration in the diagnosis and management of neuroblastoma.

Eleven fine needle aspiration (FNA) biopsies were performed in five children with neuroblastoma, including one patient with peripheral neuroectodermal tumor of the thoracopulmonary region (Askin tumor). Cytologic features in conjunction with immunocytochemistry and electron microscopy on the aspirated material enabled us to make a primary diagnosis in four of the five patients and diagnose local recurrence and metastatic disease in three patients. There were no false-positive or false-negative cytologic diagnoses; therefore, diagnostic accuracy was 100%. FNA is an extremely useful technique for the primary diagnosis and management of neuroblastoma and excludes other small cell malignancies of children. The results of this study and literature review demonstrate that FNA cytology coupled with ancillary techniques of immunocytochemistry and electron microscopy is a rapid, safe, minimally invasive procedure which can aid in the diagnosis and management of patients with neuroblastoma without resorting to more aggressive diagnostic procedures in selective cases.

Biopsy, Needle

Thoracic neuroblastoma presenting as a cystic hygroma.

A case of thoracic neuroblastoma with extension into the supraclavicular fossa is described. By physical examination and ultrasound the patient was thought to have a cystic hygroma with mediastinal extension. A 'cystic' neck mass may be the initial presentation of a mediastinal neuroblastoma.

Diagnosis, Differential

Wilms' tumor.

The clinical presentation and approach to the management of Wilms' tumor in children were reviewed. In addition, recent studies of chromosomal abnormalities in Wilms' tumor, histopathologic findings as they effect prognosis and design of treatment, controversial issues in therapy, and the long-term effects of treatment of this childhood tumor were discussed.

Child, Preschool

Initial laboratory evaluation of infants with 'presumed near-miss' sudden infant death syndrome.

We reviewed the cases of 201 infants hospitalized for "presumed near-miss" sudden infant death syndrome over a recent five-year period to determine the value of routine initial laboratory investigations in establishing diagnosis or altering therapy. A total of 1,278 measurements were performed on 163 patients aged 3 days to 6 months; 276 (22%) of the results were outside the normal limits for age. The most common abnormalities were hyperchloremia (58% of infants tested), hypermagnesemia (43%), hypobicarbonatemia (33%), and hyperkalemia (27%). There were no instances of polycythemia, hypochloremia, hypokalemia, hyperbicarbonatemia, or uremia. Only six (0.5%) of the abnormal values in four patients were useful in diagnosing or treating the apneic episodes. Infants with respiratory symptoms at the time of presentation had a statistically greater incidence of abnormal values than patients who were asymptomatic. Because of the low yield of useful information, we conclude that the use of a routine battery of laboratory investigations in the initial evaluation of infants with presumed near-miss sudden infant death syndrome should be questioned.

Electrolytes

Hematological changes in Down's syndrome.

The many hematological abnormalities observed in patients with Down's syndrome have intrigued hematologists for many years. This review summarizes recent studies concerning the hematological findings in newborn infants with Down's syndrome, the transient leukemoid/leukemia-like proliferative disorders in these infants, the increased incidence of leukemia and types of leukemia in patients with Down's syndrome, and immunological studies of these patients. In addition, studies concerning the significance of the extra genetic material in chromosome 21 found in patients with Down's syndrome are discussed. It appears that the extra genetic material in chromosome 21 confers a proliferative advantage to hematopoietic stem cells, and may make them more prone to further karyotypic changes leading to leukemia. Megakaryocytic proliferative disorders are more common in patients with Down's syndrome. The spectrum of myeloproliferative disorders including myelofibrosis, myeloid metaplasia, and megakaryoblastic leukemia is seen in these patients. Studies of the genetic loci on chromosome 21 have demonstrated loci for enzymes involved in purine biosyntheses. Further studies of specific loci on chromosome 21 may help explain the hematopoietic growth advantages found in the stem cells with an extra chromosome 21.

Chromosomes, Human, Pair 21

T-lymphoblasts with erythropoietic helper function in acute T-cell leukemia.

A patient with acute T-lymphoblastic leukemia was found to maintain a normal hemoglobin concentration both at presentation and preterminally several months later, despite a replaced bone marrow and over 80% circulating lymphoblasts on both occasions. Cell surface marker analysis demonstrated the T-lymphoblasts both at presentation and preterminally to belong to the T-helper subpopulation. In vitro culture studies demonstrated that the patient's T-lymphoblasts, as well as conditioned medium derived from these lymphoblasts, significantly stimulated normal bone marrow erythroid colony growth (CFU-E). These findings suggest that in this patient the preservation of erythropoiesis resulted from a helper effect exerted by his T-lymphoblasts.

Antineoplastic Combined Chemotherapy Protocols

Abdominal Hodgkin's disease in a child.

We describe a girl with Hodgkin's disease limited to the abdomen. She had severe hypochromic, microcytic anemia with increased iron deposition in the liver. Abdominal Hodgkin's disease should be considered in the differential diagnosis of a child with hypochromic anemia, systemic symptoms, and lack of peripheral adenopathy.

Abdominal Neoplasms

Leukemia presenting as central nervous disease without bone marrow involvement.

A case of a nine-year-old boy who presented with central nervous system leukemia is described. This case was unusual because he presented without initial bone marrow involvement. Bone marrow involvement was documented 15 months after central nervous disease was diagnosed. Immunologic marker studies revealed that the spinal fluid blasts lacked definable B-cell, pre-B cell, T-cell, and pre-T cell surface markers. The marker studies helped to define the nature of the disease process.

Bone Marrow

Hodgkin's disease and non-Hodgkin's lymphoma in children and young adults: a clinicopathologic study of 127 cases.

One hundred twenty-seven cases of non-Hodgkin's lymphoma and Hodgkin's disease in children and young adults at the University of Wisconsin Hospital between 1969 and 1980 have been reviewed. Nodular sclerosing was the most frequent histologic type in patients with Hodgkin's disease. Malignant lymphoblastic lymphoma (MLLB) was the most common type of non-Hodgkin's lymphoma. The relationship of the histological pattern to age and sex as well as clinical behavior and survival are discussed.

Adolescent

Recategorizing childhood acute lymphoblastic leukemia with monoclonal antibodies to human T cells.

The lymphoblasts of three patients with childhood acute lymphoblastic leukemia (ALL) were analyzed for their immunologic surface markers. Blasts from two of these patients did not form rosettes with sheep erythrocytes and the third did so marginally, suggesting these patients had non-T-cell leukemia. These blasts were also tested with monoclonal antibodies that detect thymocyte differentiation markers, and all three patients were highly reactive with at least two of these reagents. We anticipate the availability of multiple standardized monoclonal reagents will necessitate a recategorization of ALL phenotypes. Some of these leukemic phenotypes may not correspond to normal stages of lymphoid differentiation. Therefore, we suggest that it may be inappropriate to attempt to identify and categorize leukemic cells by the pathways of normal differentiation.

Adolescent

Phlebotomy with iron therapy to correct the microcytic polycythemia of chronic hypoxia.

Patients with chronic hypoxia develop a physiologically appropriate "secondary" polycythemia that improves oxygen carrying capacity. Supplemental iron is often required to maintain this. In severe cases when hematocrit levels approach 70%, iron is withheld in order to avoid dangerously high hematocrit levels and the risks of vascular sludging due to "hyperviscosity." Some patients even require reduction of viscosity by exchange of their polycythemic blood for plasma when symptoms develop. Iron deficiency with microcytic polycythemia can then develop. Management of such patients is unclear. Continued blood withdrawal will worsen the iron deficiency; iron supplementation will increase the hematocrit level and the risks of hyperviscosity. The combination of frequent phlebotomy with oral iron therapy should improve iron stores while safely maintaining a stable hematocrit level in patients with microcytic polycythemia. This combination should also have multiple beneficial effects on tissue oxygen delivery and utilization. This approach has been discussed and used for a patient with microcytic polycythemia due to Eisenmenger syndrome. While on therapy the patient's clinical symptoms decreased, and his serum iron level, hematologic indices, and treadmill tolerance tests all improved.

Administration, Oral

Inability of intravenously injected monocellular suspensions of human bone marrow to establish in the nude mouse.

Mononuclear suspensions of normal and leukemic human bone marrow cells were injected into lethally irradiated nude mice. As judged by splenic focus assay, cells of human bone marrow suspensions were uniformly unable to establish colonies in the spleen, although comparably treated bone marrow cells from genetically unrealted mice readily produced such colonies. It thus appears that the nude mouse is able to prevent establishment of intravenously injected human bone marrow cells by means not involving T cell-dependent immunologic discrimination.

Animals

Acute bleomycin toxicity.

A case of acute pulmonary toxicity due to bleomycin leading to death in 60 hours is described in an 11-year-old male with Hodgkin's disease. This acute presentation in an immunologically comprised host caused consideration of etiologies other than drugs. Previous reports in the literature have not documented such an acute fatal course as a result of bleomycin toxicity.

Acute Disease