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Biomedical subjects

D H Berry

Publications and source records attributed to D H Berry.

At least 37 records · Page 2Linked to original sources

Comparison of maintenance treatment regimens for first central nervous system relapse in children with acute lymphocytic leukemia. A Pediatric Oncology Group study.

Eighty-seven children with central nervous system (CNS) leukemia were randomized to receive either induction intrathecal chemotherapy (ITC) and cranial irradiation (CRT) plus maintenance ITC, or induction ITC and craniospinal irradiation (CSpRT) with no maintenance ITC. ITC consisted of six weekly injections of methotrexate, hydrocortisone, and arabinosylcytosine. Also, intensification of systemic induction and maintenance chemotherapy was given. CRT + ITC was given as CRT, 2400 rad in 12 fractions followed by ITC maintenance bimonthly for 2 years. Craniospinal irradiation consisted of CRT + 1400 rad in ten fractions to the spine. Randomization was stratified according to whether CNS leukemia occurred at initial diagnosis of acute lymphocytic leukemia (ALL) (Stratum I, 15 patients), during first bone marrow (BM) remission (Stratum II, 49 patients), simultaneous with first BM relapse (Stratum III, 12 patients), or during second BM remission (Stratum IV, 11 patients). The median follow-up for patients who remain at risk is 15 + months. Eight children (seven on CRT + ITC, one on CSpRT) developed presumed therapy related encephalopathy. In Stratum II, 16 of 29 (55%) patients receiving CRT + ITC experienced adverse events: 3 deaths during continuous complete remission (CCR) and 13 relapses (2 CNS, 1 CNS + BM, 1 BM + testes, and 2 testes) as compared with only 5 relapses in 20 (25%) patients on CSpRT (1 CNS, 1 CNS + BM, 1 BM, and 2 testes). The children on both regimens were comparable for sex, race, age at initial ALL diagnosis, time from ALL diagnosis to first episode of CNS leukemia, systemic therapy both before and after CNS relapse, and number of blasts in the spinal fluid at diagnosis of CNS leukemia. The conclusion is that children with isolated CNS leukemia can achieve prolonged survival with aggressive therapy, and that CSpRT is possibly less toxic and more likely than is CRT + ITC to prevent subsequent BM and testicular relapse (P less than 0.02), but not subsequent CNS relapse (P = 0.7). A possible systemic therapy effect of spinal irradiation is postulated to explain the superiority of CSpRT.

Antineoplastic Combined Chemotherapy Protocols↗

Spurious elevated platelet counts associated with bacteremia.

Spuriously elevated automated platelet counts secondary to in vivo bacteremia have not been reported previously. Two patients are described with blood cultures positive for Escherichia coli and Klebsiella pneumoniae, respectively, and bacteria present on peripheral blood smear. Those bacteria caused falsely elevated platelet counts to be generated by the Ortho ELT-8. These cases illustrate an unusual artifact and demonstrate that spurious counts can be generated by laser optical blood cell counters.

Adult↗

Acute cytoreduction techniques in the early treatment of hyperleukocytosis associated with childhood hematologic malignancies.

Early and effective cytoreduction for high peripheral white blood cell counts in pediatric patients with acute leukemia may be helpful in preventing complications secondary to hyperviscosity. It also may be a useful adjunct to systemic chemotherapy. As an alternative to automated apheresis for this purpose, manual exchange transfusion is efficacious and does not require hemapheresis instrumentation and disposables and the related special staff. Two patients, a neonate with acute myeloblastic leukemia and a white blood cell count of 422.2 k/microliter as well as a 2 1/2-year-old with an admission diagnosis of acute promyelocytic leukemia and a white blood cell count of 617.4 k/microliter, underwent manual exchange hemotherapy for acute cytoreduction. The procedures were tolerated well, and significant leukocyte removal was achieved, with the respective leukocyte reductions being 81.1 and 68.7%. The techniques available for pediatric cytoreduction are compared, with emphasis on their efficiency and safety and appropriateness for very small children.

Acute Disease↗

Conversion to resectability by intra-arterial infusion chemotherapy after failure of systemic chemotherapy.

A 17 cm hepatoblastoma was unresectable at initial exploration. Multiagent chemotherapy (ADR, CTX, VCR, 5FU, BLEO) incurred minimal response at 5 months. Infuse-A-Ports were placed in each hepatic artery and FUDR infused intermittently but there was no response at 6 weeks. Adriamycin and vincristine were then begun via the Infuse-A-Port, with prompt regression of the tumor mass. The intra-arterial course was continued 3 months. Repeat arteriography showed vascular distortion but exploration revealed no gross tumor. A persistent alpha-feto-protein elevation prompted repeat arteriography 4 months afterward. A 3 cm calcific tumor was removed via an extended left lobectomy. Selective hepatic arterial infusion appeared to potentiate chemotherapy after systemic chemotherapy had failed to produce sufficient cytoreduction to allow safe surgical excision. The intra-arterial chemotherapy for unresectable hepatoblastoma warrants further investigation.

Antineoplastic Agents↗

Clinical oncology assistantship program for medical students.

The Clinical Oncology Assistantship Program has been offered to approximately 16 sophomore medical students each year at the University of Arkansas for Medical Sciences since 1975. This is an elective, 10-week program given during the summer recess. In the first week of the program, core lectures are given by a multidisciplinary team of cancer educators affiliated with the University of Arkansas. Following this, students spend nine weeks rotating through medical, surgical, and pediatric oncology services of the University of Arkansas for Medical Sciences. In addition, they spend several hours during the program participating in self-directed learning activities at the university's Cancer Teaching Center. The program has been well received by the students, and each year all of the available positions have been filled. Responses on a follow-up questionnaire sent in July 1983 to past participants showed that they continued to rate the program highly. Moreover, 78 percent of the respondents felt the program had influenced positively their attitude toward cancer patients.

Arkansas↗

Primary intracranial immunoblastic lymphoma in infancy.

Primary intracranial lymphoma is uncommon in any age group, but it is especially rare in childhood. This report describes a previously healthy, 14-month-old female infant who developed a primary intracranial immunoblastic (probable B-cell) lymphoma which remained confined to the central nervous system until the time of death, 23 months after diagnosis. She appears to be the youngest patient with documentation of such a diagnosis by light and electron microscopy and by histochemical and immunoperoxidase studies. An immunological investigation was negative. Significant maternal and paternal family histories of malignancy suggest that a genetic predisposition, combined with postzygotic events such as viral infection, may be responsible for this familial cluster of tumors, and for this patient's unusual presentation.

Brain Neoplasms↗

Combination chemotherapy with vincristine (NSC-67574), procarbazine (NSC-77213), prednisone (NSC-10023) with or without nitrogen mustard (NSC-762)(MOPP vs OPP) in children with recurrent brain tumors.

Seventy-three patients under 18 years of age with a recurrent central nervous system tumor were randomized to receive combination chemotherapy with MOPP or OPP. Patients were stratified according to the tumor type into four major disease categories: (1) medulloblastoma, (2) astrocytoma and other glioma, (3) ependymoma, and (4) miscellaneous tumors to provide equal distribution of patients for each treatment within each disease category. Evaluation of response was based on computerized brain scan findings. Thirty-five patients received MOPP and 38 received OPP treatment. There were three complete and six partial remissions among patients receiving MOPP and one complete and five partial remissions among patients receiving OPP. In addition, six patients on MOPP had stable disease for seven to 21 months. Only two patients on OPP had stable disease(6 and 36 months). Most of responses in both treatment regimens occurred in patients with medulloblastoma and astrocytoma. Median duration of remission was nine months for the MOPP and 11 months for the OPP. Two patients on MOPP regimen had fatal myelosuppression. Although the more toxic MOPP regimen produced more responses than OPP in children, differences in the duration of response or survival were not statistically significant (P = .79 and P = .84, respectively).

Adolescent↗

Impact of the timing of triple intrathecal therapy on remission induction in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study.

Five weekly doses of triple intrathecal (IT) chemotherapy (methotrexate, hydrocortisone, cytosine arabinoside) starting on day 1 of treatment were added to systemic induction therapy in a regimen (Arm 3) that was compared to three other regimens (Arms 1, 2, and 4) in which central nervous system (CNS) prophylaxis was initiated after complete marrow remission (CR) was attained. The CR rate for Arm 3 was only 83% as compared to 91-92% for other Arms. The lower CR rate was the result of a significantly higher death rate during induction for patients receiving early CNS prophylaxis (10.6 vs 0.9-3.5%). These differences were only observed in high risk patients as defined in the study. The early death rate was especially high (30%) in Arm 3 for children who were less than 2 years of age. Infection was the primary cause of morbidity and mortality. Severe infection following the initiation of induction therapy was found in 16.7% of patients on Arm 3 vs 1.8-6% on other regimens. Immediate triple IT chemoprophylaxis during induction therapy of acute lymphoblastic leukemia as used in this study appears to be associated with increased susceptibility to infection and this form of CNS prophylaxis has increased hazards of morbidity and mortality in infants and other high risk patients.

Age Factors↗

Growth in children with acute lymphocytic leukemia: a Pediatric Oncology Group study.

We have studied 127 children from 5 participating institutions as to the effect of acute lymphoblastic leukemia (ALL) or the therapy used in the treatment of ALL on growth, growth hormone concentrations, and somatomedin activity. The study (SWOG No. 7581) was initiated in December 1975 and was closed to new entry in September 1979 and to data collection in February 1981. Heights, weights, and blood samples for growth hormone and somatomedin activity were obtained at the time of initial diagnosis and at intervals during the 55 months of observation. The percentage of boys less than 4 years of age below the 50th percentile is significantly greater than the expected 50% for both initial and final height (P less than 0.01). Girls less than 4 years appeared to have significantly different percentile height distribution from the normal for their final height measurement (P less than 0.05) but not for their initial height measurement. No other significant differences in the percentile height distribution were found. When growth rate, since time of diagnosis of ALL, is compared to the expected growth of normal children of the same age by linear regression analysis, there is a difference in the slope of the lines. Children with ALL are significantly shorter. The mean initial growth hormone and somatomedin concentration, 6.2 ng/ml and 1.3 micrograms/ml, respectively, vs mean remission growth hormone and somatomedin of 2.5 ng/ml and 1.1 micrograms/ml, respectively, were different. This was significant at P less than 0.01. The slope of the computed regression lines for multiple analysis of growth hormone and somatomedin were negative for more than 60% of the patients when compared to the initial concentration. These data suggest that a significant number of the children less than 4 years of age are short prior to the onset of therapy, and this persists throughout the course of their disease. Second, there is a reduction in growth rate during intensive therapy or the first year of the disease, with a normal growth rate thereafter. Third, growth hormone and somatomedin concentrations appear to be higher at the time of onset of the disease and decrease while on therapy.

Adolescent↗

Detection of G6PD and pyruvate kinase deficiencies in reticulocytosis by reference to erythrocyte creatine.

Erythrocyte activities of G6PD and PK, referenced to creatine content, are presented as a means to detect enzyme deficiencies despite the presence of variable proportions of young erythrocytes in the assayed cell population. Lysate enzyme activities, creatine and hemoglobin concentrations, and whole blood reticulocyte counts were determined on 110 samples from 87 patients with a variety of anemias, including two pyruvate kinase deficient, three G6PD deficient, and four proven G6PD heterozygotes. Highest correlations were obtained between log of G6PD activity/g hemoglobin and lysate creatine, and between PK activity/g hemoglobin and lysate creatine. Ninety-five percent limits for this population are presented for creatine concentrations to 28 mg/dl, corresponding to 20% reticulocyte count. In addition to providing reference intervals appropriate to the suspect patient population, the data afford greater confidence in detecting partial enzyme deficiencies concomitant with other hemolytic processes, such as hemoglobinopathies.

Creatine↗

Comparison of prednisolone, vincristine, methotrexate and 6-mercaptopurine vs. 6-mercaptopurine and prednisone maintenance therapy in childhood acute leukemia: a Southwest Oncology Group Study.

The study was designed to compare the relapse rate and toxicity of intermittent prednisone, oncovin (vincristine), methotrexate, and 6-mercaptopurine (POMP) vs. 6-mercaptopurine daily and a prednisone pulse every three months (PIP) for maintenance therapy in acute leukemia. Children with acute lymphoblastic, acute undifferentiated, or acute stem-cell leukemia were stratified on the basis of initial leukocyte count and age, then randomly assigned to POMP or PIP maintenance therapy. All patients received cranial irradiation and intrathecal chemotherapy. Of the 67 patients receiving POMP maintenance, 20(30%) remain in continuous remission. The median length of continuous remission achieved with POMP therapy was 49 weeks. Of 80 patients receiving PIP maintenance, 25(31%) remain in remission. The median length of continuous remission for PIP was 62 weeks. Of the possible prognostic factors evaluated, the only significant factor was the prognostic grouping base in age and initial leukocyte regimen was associated with a higher incidence of toxic reactions, frequently causing therapy interruption. The results for both regimens as studied are inferior to those for 6-mercaptopurine methotrexate maintenance regimens as reported by others.

Age Factors↗

Quality of survival in histiocytosis X: a Southwest Oncology Group study.

Sixty children survived for five years after the diagnosis of histiocytosis X. Serious disabilities were seen in 50% of children whose disease involved soft tissue and bone. Late deaths from pulmonary failure were associated with opportunistic infections in two cases. Future treatment approaches must weigh the risks of therapy-related complications against the probability of significant disability if the disease continues for many years.

Adolescent↗

Intensive chemotherapy for metastatic neuroblastoma: a Southwest Oncology Group study.

Thirty-three children with Evans stage IV neuroblastoma were treated with an intensive chemotherapy regimen reported by Helson to be highly effective. The purpose of the study was to determine whether the toxic regimen was manageable by different investigators and to increase the sample of patients. Remission induction therapy consisted of courses repeated every four weeks: Cyclophosphamide (CTX) 80 mg/kg IV, with IV fluids, and furosemide on days 1 and 2; vincristine (VCR) 0.03 mg/kg IV 12 hours after cyclophosphamide; trifluoro-methyl-2-deoxyridine (F3TdR) 45 mg/kg IV push, and papaverine (PAP) 45 mg/kg (12-hour infusion) under cardiac monitoring on days 3 and 4. Initially during maintenance, courses of therapy were reduced to two days. Because this was found to be ineffective therapy, the courses were extended to four days. Some of the patients who achieved response were removed from the protocol and placed on different maintenance therapy. Seventeen of 21 children newly diagnosed and 6/12 children previously treated for metastatic neuroblastoma achieved partial or complete remission. Eight of 16 newly diagnosed patients achieving response are still alive, six without evidence of disease for periods of time ranging from 20 to 41 months. The median of the administered drug dosages was 100% of the recommended dosages. Seventy percent of the 229 courses given were initiated at correct interval. Therapy had to be delayed on the others because of toxicity. The value of the four-drug combination is limited because of side effects related to myelosuppression which resulted in severe complications and frequent hospitalizations.

Adolescent↗

Serial studies of serum dopamine-B-hydroxylase and urinary vanillylmandelic and homovanillic acids in neuroblastoma.

Recent reports have suggested that elevations of serum dopamine-B-hydroxylase (DBH) activity may correlate with diagnosis in neuroblastoma patients excreting vanillylmandelic acid (VMA). We have serially studied serum DBH and urinary homovanillic acid (HVA) and VMA excretion during the disease course of five patients with neuroblastoma. DBH activities did not indicate clinical course, therapies, or prognosis. Dilution studies revealed an age-related alteration in DBH effectors and they suggest that these may be different in neuroblastoma.

Child↗

Long-term survival in childhood acute leukemia: "late" relapses.

The "late" relapse patterns of childhood acute leukemia were studied in 83 children in their first continuous complete remission for more than three years prior to randomization for stopping therapy (40 patients) or continuing therapy (43 patients) for a total of six years. Twenty of 83 (22.9%) have relapsed: Ten in the bone marrow, one in the central nervous system, and nine in the testes. The testes relapse rate of 41.1% (7/17) in males discontinuing therapy at three years was much higher than that of 8.7% (2/23) in males continuing therapy. This difference is significant at P = 0.01 (Wilcoxon test).

Bone Neoplasms↗

Repeated use of L-asparaginase in multi-drug therapy of childhood leukemia.

The capacity of 1-asparaginase in two separate schedules (consecutive and intermittent), along with vincristine and prednisone to produce multiple responses, was evaluated in previously treated children with acute leukemia in relapse. The response rates varied inversely with previous 1-asparaginase exposure. A history of prior resistance to prednisone and vincristine appeared to reduce the response rate. Hypersensitivity reactions occurred in 14%.

Acute Disease↗