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Biomedical subjects

D H Mahoney

Publications and source records attributed to D H Mahoney.

At least 37 records · Page 2Linked to original sources
PubMed1996

Mixed neuronal-glial tumors (gangliogliomas) in children.

Mixed tumors account for about 10% of the childhood central nervous system tumors. Studies of the most common tumor, the ganglioglioma, in patients of all ages suggest that optimal therapy is total gross resection. There are few studies on these tumors in children. In our institution between 1984 and 1993, 28 children with gangliogliomas (4 of which were anaplastic) and 4 children with dysembryoplastic neuroepithelial tumors were treated and followed. Fourteen had local subarachnoid involvement. Total gross resection was usually curative, regardless of histology. Subarachnoid involvement was not indicative of a poorer prognosis.

Adolescent↗
PubMed1996

High-dose melphalan and cyclophosphamide with autologous bone marrow rescue for recurrent/progressive malignant brain tumors in children: a pilot pediatric oncology group study.

PURPOSE: To determine the maximum-tolerated dose of cyclophosphamide (CTX) when administered sequentially with melphalan 60 mg/m2/d for 3 days, followed by autologous bone marrow rescue (ABMR), in children with recurrent or progressive malignant brain tumors, and to make preliminary observations on efficacy. PATIENTS AND METHODS: Nineteen patients between the ages of 2 and 21 years were enrolled and 18 were assessable for effects of therapy. CTX was administered to seven patients at 750 mg/m2/d for 4 days, to five patients at 975 mg/m2/d, to three patients at 1,200 mg/m2/d, and to three patients at 1,500 mg/m2/d. All patients received ABMR. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was used in 15 patients. Toxicity, response to therapy, time to progression, and survival and monitored. RESULTS: The median time to a granulocyte count more than 500/dL was 19 days (range, 11 to 39), and for a platelet count more than 50,000/dL was 33 days (range, 16 to 60). Four heavily pretreated patients (22%) died of transplant-related complications. No dose-limiting, non-hematologic toxicities were defined for the study. Seven of 18 patients (39%) had a complete response (CR) or a partial response (PR). These included four patients with medulloblastoma (CR and three PRs), two with germinomas (two CRs), and one with ependymoma (one CR). The estimated 1-year survival rate was 39% (SE 12%). CONCLUSION: CTX, at a maximum total dose of 6,000 mg/m2, administered sequentially with melphalan and followed by ABMR was tolerable in children with recurrent brain tumors who had not been heavily pretreated. Responses were seen in patients with medulloblastoma and germinomas. Further trials in children with chemosensitive tumors, with minimal residual disease, are planned.

Adolescent↗
PubMed1995

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↗
PubMed1995

Lymphoid malignancies following Kawasaki disease.

Kawasaki disease is a childhood multisystem vasculitic syndrome of unknown etiology. Associated immunological dysregulation is consistently observed and may be pathogenic in the known cardiac and noncardiac complications of the disease. Despite the well-known association between acquired immunodeficiency states and neoplasia, there are no reports of cancer accompanying or following the onset of this disease. We report here two children who were diagnosed with lymphoid malignancies shortly following the diagnosis of Kawasaki disease, suggesting an association between the two entities.

Child↗
PubMed1995

Study of the molecular defects in pyruvate kinase deficient patients affected by nonspherocytic hemolytic anemia.

We have examined DNA from fifteen unrelated pyruvate kinase deficient patients with hereditary nonspherocytic hemolytic anemia (HNSHA) for the molecular alterations responsible for the enzyme deficiency. All but 3 of the 30 putative mutations were identified. Fourteen different mutations were found. Nine were missense mutations: 320 T-->C, 823 G-->C, 1276 C-->T, 1378 G-->A, 1484 C-->T, 1529 G-->A, 1654 G-->A, 1675 C-->G; three were nonsense mutations: 603 G-->A, 721 G-->T, 1501 C-->T; one was an insertion at 1574 GGG-->GGGG and the other a three nucleotide in-frame deletion 391-392-393 ATC. Eight of these mutations have not been previously described. We also investigated all of the patients for the C/A polymorphism at nt 1705 and the microsatellite ATT repeat in intron 11. All of the mutations that had previously been reported by us (391-393del, 721T, 1484T, 1529A) were found in the context of the same haplotype as the earlier cases, supporting the concept that each may have a single origin.

Anemia, Hemolytic, Congenital Nonspherocytic↗
PubMed1994

Molecular epidemiology of coagulase-negative Staphylococcus blood isolates from neonates with persistent bacteremia and children with central venous catheter infections.

Multilocus enzyme electrophoresis was used to genetically characterize sequential isolates of coagulase-negative staphylococci (CONS) from 3 neonates with persistent bacteremia and organisms cultured from several sites in 23 children with presumed catheter-related sepsis (CRS). For 2 of 3 neonates and 21 (91%) of 23 of the patients with presumed CRS, the same CONS clone was isolated from multiple consecutive blood cultures (mean, 7.3 isolates; range, 3-19). For the 23 children with presumed CRS, 7 (30%) had catheter hub (CH) and 7 (30%) had catheter exist site (CES) cultures positive for CONS; cultures from 3 of these patients (from both CH and CES) grew CONS. Genetic analysis of isolates recovered from the CH and peripheral and central venous catheter blood cultures of all 7 patients revealed clonal identity of the strain grown from all sites. In contrast, only 4 (57%) of 7 of the CONS isolates from the CES were the same clone as that isolated from the blood. These data suggest that repetitive isolation of CONS during the course of CRS is due to ongoing bacteremia, not culture contamination with distinct CONS isolates. The results also are consistent with the hypothesis that the CH is a more likely site of initial colonization by CONS than the exist site in patients with CRS.

Bacteremia↗
PubMed1994

Phase II investigational window using carboplatin, iproplatin, ifosfamide, and epirubicin in children with untreated disseminated neuroblastoma: a Pediatric Oncology Group study.

PURPOSE: Children less than 1 year of age with metastatic neuroblastoma NB are at high risk of death. The need to identify new and effective chemotherapy agents is clear. A study was conducted by the Pediatric Oncology Group (POG) to determine the efficacy and safety of administering two courses of a single phase II agent before conventional treatment as a means to evaluate new agents in this setting. PATIENTS AND METHODS: One hundred seventy-three eligible patients more than 1 year of age with disseminated neuroblastoma received two courses of one of the following: ifosfamide (IFOS) 2 g/m2/d for 4 days intravenously (IV) plus mesna; carboplatin (CARB) 560 mg/m2 i.v. over 1 hour; iproplatin (CHIP) 325 mg/m2 IV over 2 hours; or epirubicin (EPIR) 90 mg/m2 i.v. push. Following evaluation for response and toxicity, eligible patients were randomized to receive either cisplatin 90 mg/m2 i.v. on day 1, etoposide 200 mg/m2 i.v. on day 3, cyclophosphamide 150 mg/m2/d orally on days 7 to 13, doxorubicin 35 mg/m2 i.v. on day 14 (CECA), or cisplatin 40 mg/m2 IV on days 1 to 5 and etoposide 200 mg/m2 i.v. on days 2 to 4 alternating at 3-week intervals with cyclophosphamide 150 mg/m2/d orally on days 1 to 7 and doxorubicin 35 mg/m2 IV on day 8 (HDP/VP/CA). An additional 86 patients were randomized to receive either CECA or HDP/VP/CA without initial phase II therapy. RESULTS: After phase II therapy, only 20% of patients experienced grade 3/4 hematopoietic toxicity. No toxic deaths occurred. Objective response rates (partial responses [PRs] plus minor responses [MRs]) following IFOS, CARB, CHIP, and EPIR were 70%, 77%, 67%, and 26%, respectively. Following phase III treatment, there was no statistically significant difference in rates of complete response (CR)/PR or progressive disease (PD), or in time to PD of patients who participated in the phase II window versus those who received only CECA or HDP/VP/CA. CONCLUSION: IFOS, CARB, and CHIP are efficacious in neuroblastoma, are well tolerated, and should be incorporated into primary treatment regimens. Combination regimens using these agents may be possible, since most repeat courses were given within 2 weeks. Administering phase II therapy to untreated patients with high-risk tumors provides a unique and sensitive method to assess new agents without compromising patient outcome.

Adolescent↗
PubMed1993

Intensive alternating drug pairs for treatment of high-risk childhood acute lymphoblastic leukemia. A Pediatric Oncology Group pilot study.

BACKGROUND: To prevent drug resistance, the authors designed a protocol that featured early intensive rotating drug pairs as part of the therapy for acute lymphoblastic leukemia (ALL). METHODS: After prednisone, vincristine, asparaginase, and daunorubicin induction, 12 intensive treatments (ABACABACABAC) were given in 30 weeks: A--intermediate-dose methotrexate (IDMTX) plus intermediate-dose mercaptopurine (MP); B--cytosine arabinoside (AC) plus daunorubicin (DNR); C--AC plus teniposide (VM-26). Triple intrathecal chemotherapy (AC, MTX, and hydrocortisone) was given for central nervous system (CNS) prophylaxis. Continuation therapy consisted of weekly MTX and daily MP until 2.5 years of continuous complete remission had been achieved. RESULTS: Seventy-four children (age range, 1-19 years) at high risk of relapse were treated. Of 55 with B-lineage (early pre-B, pre-B) ALL, 24 have failed (2 induction failures, 2 deaths from infection, and 20 relapses). The event-free survival (EFS) rate at 4 years was 55.5% (standard error [SE] +/- 7.7%). Of 19 patients with T-cell ALL, 12 have failed (2 induction failures and 10 relapses). The EFS rate at 4 years was 32.6% (SE +/- 26.8%). Toxicities were significantly more common after AC and DNR or AC and VM-26 than IDMTX and MP. There were no toxicity-related deaths during intensive treatments. CONCLUSION: Early intensive rotating therapy is tolerable and warrants consideration for additional trials of patients with high-risk, B-lineage ALL.

Administration, Oral↗
PubMed1993

Hodgkin's disease associated with central pontine myelinolysis.

We describe a 12-year-old black male who presented with cervical lymphadenopathy, hepatosplenomegaly of 3 months duration, and ataxia and incoordination of recent onset. Hodgkin's disease, stage IVB, was diagnosed. An MRI of the head demonstrated a nonenhancing, well-defined pontine lesion. The pontine lesion and the associated neurologic symptoms were consistent with central pontine myelinolysis. Treatment of Hodgkin's disease resulted in complete remission and complete disappearance of the pontine abnormality.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Chronic neutropenia of childhood: frequent association with parvovirus infection and correlations with bone marrow culture studies.

Children with neutropenia of more than 3 months duration often have evidence of immune-mediated destruction of mature neutrophils and variable abnormalities of myeloid precursors in their bone marrow. These patients often have anti-neutrophil antibodies which persist for several months. To further investigate the aetiology of neutropenia in such patients, bone marrow cells were evaluated for the presence of common viruses. Fifteen of 19 patients tested had evidence for parvovirus infection by PCR amplification of bone marrow DNA with parvovirus specific primers. Of these 15, six also had serologic evidence of parvovirus infection. Anti-neutrophil antibodies were identified in nine of 12 patients with parvovirus infection. Bone marrow culture studies done on six patients revealed varying degrees of myeloid and erythroid inhibition by patient plasma. These studies indicate that parvovirus may be a common cause of immune-mediated neutropenia in children.

Autoantibodies↗
PubMed1992

Soft-tissue sarcomas other than rhabdomyosarcoma in children.

Forty-seven children with nonrhabdomyosarcomatous soft-tissue sarcomas (NRSTS) were treated by the Hematology-Oncology Service at Texas Children's Hospital, Houston, Texas, between 1958 and 1990. The male:female ratio was 1:1, and the median age was 11 years (3 weeks-16 years). A preexisting condition was found in 9/47 (19%) patients including neurofibromatosis (3), Down's syndrome (1), spina bifida (1), congenital facial asymmetry (1), giant pigmented nevus (1), juvenile onset diabetes mellitus (1), and acquired immune deficiency syndrome (1). The site of primary tumor was head and neck (3), trunk (33), and extremities (11). Twenty-four patients (51%) have survived free of disease with a median follow-up of 5 years (4 months-22 years). No patient whose disease recurred achieved a second remission. Of the 19 patients with group I disease, 16 (84%) survived free of disease. Wide excision of the primary tumor, with no microscopic residual disease, was associated with the greatest chance of disease-free survival.

Adolescent↗
PubMed1992

Therapy-related myelodysplastic syndrome in children with medulloblastoma following MOPP chemotherapy.

Between 1978 and 1988, 20 children with medulloblastoma (MB) of the brain were treated postoperatively with MOPP (nitrogen mustard, vincristine, prednisone, and procarbazine). All but one received post-operative radiation prior to MOPP. Eight of 20 patients remained in continuous complete remission from MB, two of whom eventually developed myelodysplastic syndrome (MDS). Following resection of MB at age 12 months, one patient was treated with 24 courses of MOPP over 2 years without radiation therapy. She developed pancytopenia, and MDS was diagnosed 19 months after the completion of MOPP. Analysis of unstimulated bone marrow (BM) chromosomes showed structural abnormalities involving chromosomes 7, 10, 17, and 21. Eight months later, MDS evolved into acute myeloid leukemia. The second patient was diagnosed with MB at age 7 years and received postoperative craniospinal radiation followed by 12 courses of MOPP over one year. Five months after completion of MOPP, she developed MDS with monosomy 7 on chromosome analysis of bone marrow cells. Therapy-related MDS may be a complication of MOPP chemotherapy for MB in young children.

Adolescent↗