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Biomedical subjects

W A Bleyer

Publications and source records attributed to W A Bleyer.

At least 19 recordsLinked to original sources
PubMed1991

Lymphomatous presentation of childhood acute lymphoblastic leukemia. A subgroup at high risk of early treatment failure.

Multivariate analyses of the clinical course of 1537 children with acute lymphoblastic leukemia (ALL) identified a subgroup which experienced short remission duration and a high incidence of extramedullary relapse. The patients differed from other ALL patients by the presence at diagnosis of two or more of a constellation of clinical and laboratory features: organomegaly or mass disease, E-rosette positivity, hemoglobin level greater than 10 g/dl, leukocyte count greater than 50,000/microliters, male predominance, and older age. This type of presentation of ALL is referred to as the "lymphoma syndrome" (LS) since such patients exhibit a pattern of several clinical and laboratory features which were observed repeatedly but in differing combinations, and some of which clinically resemble lymphoma. A subsequent database from 2231 patients was analyzed. Patients with a mediastinal mass, massive splenomegaly, or massive adenopathy, alone or in combination, had a worse outcome when the patient also had either leukocytosis, E-rosette-positive lymphoblasts, or a normal or near normal hemoglobin (Hb) level at diagnosis. Similarly, the above three laboratory features alone or in combination did not predict less than 40% disease-free survival (DFS) unless they were accompanied by at least one of the clinical features of mass disease. When at least one clinical feature and at least one laboratory feature were present, the overall DFS was 36% 6 years after diagnosis versus 64% for all other patients. The association of these features with poor prognosis remained significant after adjusting for the level of leukocyte count at diagnosis, age at diagnosis, and sex of the patients. Patients with this recurrent syndrome of features do not represent a homogeneous biologic entity but they constitute a subgroup of patients with ALL having a high risk of treatment failure using current therapies, including failure to achieve remission, early relapse, and increased frequency of relapse in extramedullary sites. They deserve early recognition at diagnosis and selection of treatment strategies appropriate for very high risk ALL.

Adolescent↗
PubMed1991

Association of delivered drug dose and outcome for children with acute lymphoblastic leukemia and unfavorable presenting features.

Dose and dose intensity are believed critical for attaining a maximal therapeutic effect in drug-responsive tumor systems. Childhood acute lymphoblastic leukemia may be an example of such a drug-responsive system as it is cured with current chemotherapy in a majority of cases. Between August 1981 and May 1983, the Childrens Cancer Study Group enrolled 209 children with ALL and unfavorable presenting features in CCG-193P, a trial based on the Berlin Frankfurt Munster 76/79 regimen. The cumulative delivered dose of each medication was recorded prospectively. Patients who completed the intensive portion of therapy in continuous complete remission were ranked by the percentage of protocol required drug delivered from the initiation of therapy to that date. No association was found between delivery of any single drug and subsequent disease-free survival. However, when patients were ranked by the sum of the percentages of protocol vincristine, l-asparaginase, and anthracycline delivered, children in the approximate middle and lower tertiles were 3 and 5 times more likely to have had a subsequent relapse than were those in the upper tertile (P = 0.025, test for trend). Delivery of the full protocol prescribed dose of these agents may have been critical, but corroboration is certainly needed. Only prospective trials can determine if children with acute lymphoblastic leukemia and unfavorable presenting features might benefit from greater use of vincristine, l-asparaginase, and/or anthracycline.

Adolescent↗
PubMed1991

Intellectual function in long-term survivors of childhood acute lymphoblastic leukemia: protective effect of pre-irradiation methotrexate? A Childrens Cancer Study Group study.

Having demonstrated in a laboratory model that the neurotoxicity of CNS irradiation can be ameliorated with pre-irradiation methotrexate, we retrospectively compared two methods of CNS prophylaxis in childhood acute lymphoblastic leukemia which differed only in the timing of intrathecal methotrexate and radiotherapy. The results of standard IQ tests conducted 2-11 years after 24 Gy of cranial radiotherapy were obtained in 72 patients, of whom 27 had pre-irradiation methotrexate and 45 did not (control group). The two groups were otherwise comparable. In girls, the full-, performance-, and verbal-scale IQ scores were consistently higher in the pre-irradiation methotrexate group than in the corresponding control group (P less than 0.025). Among girls less than 5 years of age when irradiated, the mean IQ scores were 25-29 points higher after pre-irradiation methotrexate than after the control treatment (P less than 0.0007). These results suggest that pre-irradiation methotrexate may help prevent CNS radiotoxicity in children, and that the benefit is dependent on patient age and gender.

Asparaginase↗
PubMed1991

The effect of age on the latency of radiation myelopathy.

The latent period to forelimb paresis following photon irradiation of the cervical spinal cord was evaluated in Sprague-Dawley rats ranging in age from 9 days to adulthood. The radiation was administered dorsally in single fractions, and in 15-day-old animals, to different lengths of the rostral cord and in doses ranging from 16 to 38 Gy. The duration of the latent period was found to be directly proportional to the age of the animal at the time of irradiation, and independent of radiation dose or the volume of the cervical cord which was irradiated. In the majority of paretic animals, the irradiated segment of the spinal cord demonstrated white matter necrosis. The results indicate that in the developing rat, the manifestations of radiation myelopathy are delayed by an interval determined in part by the age of the animal at the time of irradiation.

Age Factors↗
PubMed1991

Monthly pulses of vincristine and prednisone prevent bone marrow and testicular relapse in low-risk childhood acute lymphoblastic leukemia: a report of the CCG-161 study by the Childrens Cancer Study Group.

On study CCG-161 of the Childrens Cancer Study Group (CCSG), 631 children with acute lymphoblastic leukemia (ALL) at low risk for relapse were randomized to receive monthly pulses of vincristine-prednisone (VCR-PDN ) during maintenance therapy in addition to standard therapy with mercaptopurine (6MP) and methotrexate (MTX), and either cranial irradiation during consolidation or intrathecal (IT) MTX every 3 months during maintenance. All patients received six doses of IT MTX during induction and consolidation. With a minimum follow-up time of 4.25 years, 76.7% receiving VCR-PDN were in continuous complete remission at 5 years, in contrast to 63.9% receiving GMP-MTX alone (P = .002). The difference in relapse-free survival was due primarily to bone marrow relapse (P = .0008), and in boys also to testicular relapse (P = .003). Among the nonirradiated patients, the 5-year disease-free survival (DFS) was 79.4% for patients randomized to the VCR-PDN pulses, in contrast to 61.2% for the patients randomized to receive 6MP-MTX alone (P = .0002). Among the irradiated patients, the DFS was not significantly different. Of the four combinations of maintenance and CNS therapy studied, the highest DFS was achieved with VCR-PDN pulses and maintenance IT MTX.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Infants with medulloblastoma: a single institution review of survival.

Although the prognoses of children with medulloblastoma have improved dramatically over the last several decades, the reported survival for very young children with this tumor remains poor. We undertook a retrospective review of patients less than 36 months of age at the time of the diagnosis of a medulloblastoma who were treated at our institution during a 36-year period. Of 28 such patients, 10 patients are presently surviving without disease at a median of 150 months from diagnosis. The presence of a metastatic tumor at the time of diagnosis was identified as a significant indicator of a poor prognosis, and all completely staged patients without metastasis are surviving without a recurrence of disease. This report suggests that the survival of very young children with a medulloblastoma may not be as poor as has been previously reported, particularly if a disseminated tumor is not present at the time of diagnosis.

Cerebellar Neoplasms↗
PubMed1979

Intraventricular versus intralumbar methotrexate for central-nervous-system leukemia: prolonged remission with the Ommaya reservoir.

Ten children had recurrence of central-nervous-system (CNS) leukemia despite monthly injections of methotrexate into their lumbar cerebrospinal fluid. Each child was then reinduced into remission and maintained with intraventricular methotrexate administered via an Ommaya reservoir and the length of this remission was compared with the duration of the child's previous intralumbar-treated remission. Of eight evaluable patients, seven had longer CNS remissions with intraventricular therapy than with intralumbar therapy (P less than 0.02). The median CNS remission duration in all patients was 475 days with intraventricular and 286 days with intralumbar therapy (P less than 0.05). The rate of CNS relapse was reduced from 2.94 relapses per thousand days at risk during intralumbar therapy to 0.93 relapse per thousand days of intraventricular therapy. We conclude that intraventricular chemotherapy is significantly more effective against CNS leukemia than the same therapy given by lumbar puncture.

Adolescent↗
PubMed1979

Methotrexate-induced oral mucositis and salivary methotrexate concentrations.

We examined the plasma and saliva levels of methotrexate (MTX) achieved during the treatment and rescue periods of ten patients receiving 42-h MTX infusions followed by citrovorum rescue. Saliva MTX levels were generally 1%--2% of the simultaneous plasma levels. Four patients developed severe oral mucositis; three patients developed mild to moderate oral toxicity, and three others had no evidence of mucositis. MTX levels in the patients with severe mucositis were not higher and did not persist longer than the levels achieved in patients with mild or absent toxicity. Attempts at reducing the severity of oral mucositis with topical citrovorum mouthwashes or with atropine to suppress salivation were unsuccessful. MTX-induced oral mucositis is not related to salivary MTX concentrations, and the use of topical citrovorum therapy or the suppression of salivation does not appear to ameliorate this toxicity.

Humans↗
PubMed1979

Experimental approaches to the treatment of CNS leukemia.

Some of the current experimental approaches to the treatment of CNS leukemia are reviewed. While small animal models have provided a basic understanding of the pathophysiology of meningeal leukemia, large animal models, particularly the subhuman primate, allow a more detailed examination of the complex dynamics of CNS pharmacokinetics. Principles derived from these models have provided a rational basis for the development of new approaches to the treatment of meningeal leukemia in man.

Animals↗
PubMed1979

Phase II study of VM-26 in acute leukemia, neuroblastoma, and other refractory childhood malignancies: a report from the Children's Cancer Study Group.

VM-26, a semisynthetic podophyllotoxin, was tested for antitumor activity and clinical toxicity in 181 children. The drug was administered iv at weekly intervals, beginning at a dose of 130 mg/2/week. The dose was increased, as tolerated, after 3 and 6 weeks to 150 and 180 mg/m2/week, respectively. The only major toxicity was hematologic, with neutropenia predominating. Anaphylaxis occurred in one patient. The drug demonstrated significant activity in acute lymphocytic leukemia (four responses among 15 patients) and neuroblastoma (ten responses among 31 patients). Objective responses were also noted in one patient each with acute myelogenous leukemia, Hodgkin's disease, histiocytic lymphoma, Wilms' tumor, Ewing's sarcoma, undifferentiated carcinoma, and sacrococcygeal sarcoma. Further trials of VM-26 in these childhood malignancies are warranted.

Acute Disease↗
PubMed1979

Neurotoxicities of current leukemia therapy.

While major advances have been made in the treatment of acute leukemia, complications of therapy are significant. One of the most worisome complications is the neurotoxicity which is related to both central nervous system prophylaxis (cranial irradiatif neurotoxicity may be acute or delayed, and may range in severity from mild headaches ann of treatment-related neurotoxicity is important since this may permit amelioration of otherwise irreversible neurological sequelae in some patients. We review the clinical, phyh irradiation and chemotherapy, and offer recommendations for monitoring, evaluating and treating patients with potential or proven neurotoxicity.

Antineoplastic Agents↗
PubMed1978

Acute encephalopathy after initiation of cranial irradiation for meningeal leukaemia.

Five patients experienced severe encephalopathy within hours of receiving their initial dose of cranial irradiation for the treatment of central-nervous-system leukaemia. Neurological findings included cranial-nerve palsies, seizures, ataxia, depressed consciousness, increased intracranial pressure, and signs of herniation. Symptoms developed within 3-30 hours of the first radiation treatment of 50-200 rad. Each patient had also received one or more injections of intrathecal chemotherapy before encephalopathy developed. The aetiology of this syndrome is uncertain but may involve transient cerebral oedema and/or an altered blood-brain barrier produced by the combination of intrathecal chemotherapy and cranial irradiation.

Acute Disease↗
PubMed1978

The team approach to the management of pediatric cancer.

The last 20 years have witnessed remarkable improvements in the prognosis of children with many forms of malignant disease. The reasons for these improvements relate not only to the development of better drugs and more effective radiotherapy, but also to the multidisciplinary approach involving surgeon, chemotherapist, radiotherapist and immunotherapist in providing optimum treatment for the child with a particular cancer. In this paper, the changing role of the pediatric oncologist, surgeon and radiotherapist in improving the management of pediatric cancer is discussed.

Acute Disease↗
PubMed1978

The clinical pharmacology of methotrexate: new applications of an old drug.

Methotrexate is now used widely for the treatment of acute leukemia, non-Hodgkin's lymphoma, osteogenic sarcoma, choriocarcinoma, breast carcinoma, pulmonary and epidermoid carcinoma, and intrathecal chemotherapy. It is also useful in bone marrow transplantation, severe psoriasis, rheumatoid arthritis, dermatomyositis, Wegener's granulomatosis and sarcoidosis. The recent dramatic intensification of methotrexate therapy can be attributed in part to advances in our understanding of the clinical pharmacology of the folate antagonists, as well as to the combination of positive results and their effective dissemination to medical oncologists. The review summarizes the pharmacologic findings and illustrates how they are currently being applied to the treatment of malignant disease.

Absorption↗
PubMed1978

The Ommaya reservoir: newly recognized complications and recommendations for insertion and use.

Two of 27 patients treated with intraventricular chemotherapy via an Ommaya reservoir developed unusual life-threatening complications attributable to the reservoir. In one patient treated for meningeal Burkitt's lymphoma, the cause of death was a large mass of tumor cells growing around the cannula. Also the tip of the cannula was found in the contralateral cerebral peduncle. In the other patient, the tip of the cannula apparently perforated the ventricular wall postoperatively and migrated into the contralateral thalamus. In both cases evidence for methotrexate-associated leukoencephalopathy was present at autopsy. Based on the experience with these two patients, we offer specific recommendations for reservoir insertion and use.

Adult↗
PubMed1978

Transient, severe periventricular hypodensity after leukemic prophylaxis with cranial irradiation and intrathecal methotrexate.

Serial computed tomography (CT) demonstrated complete resolution of severe periventricular hypodensity occurring in a child after receiving prophylaxis for acute lymphocytic leukemia. The resolution of this encephalopathy suggests that early changes of subacute necrotizing leukoencephalopathy are reversible and CT is copable of detecting these early changes.

Acute Disease↗