Biomedical subjects

J M Boyett

Publications and source records attributed to J M Boyett.

At least 19 recordsLinked to original sources

PubMed2003

Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements.

To assess the clinical heterogeneity among patients with acute lymphoblastic leukemia (ALL) and various 11q23 abnormalities, we analyzed data on 497 infants, children and young adults treated between 1983 and 1995 by 11 cooperative groups and single institutions. The substantial sample size allowed separate analyses according to age younger or older than 12 months for the various cytogenetic subsets. Infants with t(4;11) ALL had an especially dismal prognosis when their disease was characterized by a poor early response to prednisone (P=0.0005 for overall comparison; 5-year event-free survival (EFS), 0 vs 23+/-+/-12% s.e. for those with good response), or age less than 3 months (P=0.0003, 5-year EFS, 5+/-+/-5% vs 23.4+/-+/-4% for those over 3 months). A poor prednisone response also appeared to confer a worse outcome for older children with t(4;11) ALL. Hematopoietic stem cell transplantation failed to improve outcome in either age group. Among patients with t(11;19) ALL, those with a T-lineage immunophenotype, who were all over 1 year of age, had a better outcome than patients over 1 year of age with B-lineage ALL (overall comparison, P=0.065; 5-year EFS, 88+/-+/-13 vs 46+/-14%). In the heterogeneous subgroup with del(11)(q23), National Cancer Institute-Rome risk criteria based on age and leukocyte count had prognostic significance (P=0.04 for overall comparison; 5-year EFS, 64+/-+/-8% (high risk) vs 83+/-+/-6% (standard risk)). This study illustrates the marked clinical heterogeneity among and within subgroups of infants or older children with ALL and specific 11q23 abnormalities, and identifies patients at particularly high risk of failure who may benefit from innovative therapy.

Adolescent↗

PubMed2001

Intellectual outcome after reduced-dose radiation therapy plus adjuvant chemotherapy for medulloblastoma: a Children's Cancer Group study.

PURPOSE: To investigate the intellectual outcomes of children with medulloblastomas/primitive neuroectodermal tumors (MB/PNET) treated with reduced-dose craniospinal radiotherapy (RT) plus adjuvant chemotherapy. PATIENTS AND METHODS: Forty-three children with average-risk posterior fossa MB/PNETs underwent longitudinal intelligence testing. All had been treated with a reduced-dose craniospinal RT regimen (23.4 Gy to the neuraxis, 32.4-Gy boost to the posterior fossa) and adjuvant chemotherapy. RESULTS: The estimated rate of change from baseline was significant for Full Scale Intelligence Quotient (FSIQ), Verbal IQ (VIQ), and Nonverbal IQ (NVIQ) (P <.001 for all three outcomes). The rate of change was estimated to be -4.3 FSIQ points per year, -4.2 VIQ points per year, and -4.0 NVIQ points per year. Females were more subject to VIQ decline than were males (P =.008), and young children (< 7 years of age) were more negatively affected than were older children, with a significant decline in NVIQ (P =.016). Finally, patients with higher baseline evaluations suffered greater declines in IQ than did those with lower baseline scores. CONCLUSION: This study represents the largest series of patients with average-risk MB/PNETs treated with a combination of reduced-dose RT and adjuvant chemotherapy whose intellectual development has been followed prospectively. Intellectual loss was substantial but suggestive of some degree of intellectual preservation compared with effects associated with conventional RT doses. However, this conclusion remains provisional, pending further research.

Adolescent↗

PubMed2001

Growth hormone replacement therapy in children with medulloblastoma: use and effect on tumor control.

PURPOSE: Progress has been made in the treatment of medulloblastoma, the most common childhood malignant brain tumor: However, many long-term survivors will have posttherapy growth hormone insufficiency with resultant linear growth retardation. Growth hormone replacement therapy (GHRT) may significantly improve growth, but there is often reluctance to initiate GHRT because of concerns of an increased likelihood of tumor relapse. PATIENTS AND METHODS: This study retrospectively reviewed the use of GHRT for survivors of medulloblastoma in 11 neuro-oncology centers in North America who received initial treatment for disease between 1980 and 1993 to determine its impact on disease control. A Landmark analysis was used to evaluate the relative risk of relapse in surviving patients. RESULTS: Five hundred forty-five consecutive patients less than 15 years of age at diagnosis were identified. Six-year progression-free survival (mean +/- SD) was 40% +/- 5% in children less than 3 years of age at diagnosis compared with 59% +/- 3% for older patients. Older patients with total or near-total resections (P = .003) and localized disease at diagnosis (P < .0001) had the highest likelihood of survival. One hundred seventy patients (33% +/- 3% of the cohort) received GHRT. GHRT use varied widely among institutions, ranging from 5% to 73%. GHRT was begun a mean of 3.9 years after diagnosis, later in children younger than 3 years at diagnosis (5.4 years). By Landmark analyses, for those surviving 2, 3, and 5 years after diagnosis, there was no evidence that GHRT increased the rate of disease relapse. CONCLUSION: This large retrospective review demonstrates that GHRT is underutilized in survivors of medulloblastoma and is used relatively late in the course of the illness. GHRT is not associated with an increased likelihood of disease relapse.

Adolescent↗

PubMed2001

Somatostatin-immunoreactive interneurons contribute to lateral inhibitory circuits in the dentate gyrus of control and epileptic rats.

Lateral inhibition, a feature of neuronal circuitry that enhances signaling specificity, has been demonstrated in the rat dentate gyrus. However, neither the underlying neuronal circuits, nor the ways in which these circuits are altered in temporal lobe epilepsy, are completely understood. This study examines the potential contribution of one class of inhibitory interneurons to lateral inhibitory circuits in the dentate gyrus of both control and epileptic rats. The retrograde tracer wheat germ ag-glutinin-apo-horse radish peroxidase-gold (WGA-apo-HRP-gold) was injected into the septal dentate gyrus. Neurons double-labeled for glutamic acid decarboxylase (GAD) and the retrograde tracer are concentrated in the hilus and may contribute to lateral inhibition. Neurons double-labeled for somatostatin and the retrograde tracer account for at least 28% of GAD-positive neurons with axon projections appropriate for generating lateral inhibition in control rats. Despite an overall loss of somatostatin-expressing cells in epileptic animals, the number of somatostatin-positive interneurons with axon projections appropriate for generating lateral inhibition is similar to that seen in controls. These findings suggest that somatostatinergic interneurons participate in lateral inhibitory circuits in the dentate gyrus of both control and epileptic rats, and that surviving somatostatinergic interneurons might sprout new axon collaterals in epileptic animals.

Animals↗

PubMed2001

Bone mineral decrements in survivors of childhood acute lymphoblastic leukemia: frequency of occurrence and risk factors for their development.

We assessed the clinical and treatment factors that predispose survivors of childhood acute lymphoblastic leukemia (ALL) to low bone mineral density (BMD). Using quantitative computed tomography, we determined the frequency of low BMD (defined as >1.645 standard deviations (SD) below the mean) in leukemia survivors treated with multiagent chemotherapy including prednisone and antimetabolite. All participants had completed therapy at least 4 years earlier, remained in continuous complete remission, and had no second malignancies. We statistically correlated BMD results with patient characteristics and treatment histories. Among 141 survivors (median age, 15.9 years; median time after diagnosis, 11.5 years), median BMD z score was -0.78 SD (range, -3.23 to 3.61 SDs). Thirty participants (21%; 95% confidence interval, 15% to 29%) had abnormally low BMD, a proportion significantly (P < 0.0001) greater than the expected 5% in normal populations. Risk factors for BMD decrements included male sex (P = 0.038), Caucasian race (P < 0.0001), and cranial irradiation (P= 0.0087). BMD inversely correlated with cranial irradiation dose. BMD z scores of patients who received higher doses of antimetabolites were lower than those of other patients. Childhood ALL survivors are at risk to have low BMD, especially males, Caucasians, and those who received cranial irradiation.

Adolescent↗

PubMed2000

Traumatic lumbar puncture at diagnosis adversely affects outcome in childhood acute lymphoblastic leukemia.

The effect of traumatic lumbar puncture at the time of initial diagnostic workup on treatment outcome in children with newly diagnosed acute lymphoblastic leukemia (ALL) was investigated. The findings of the first 2 lumbar punctures performed on 546 patients with newly diagnosed ALL treated on 2 consecutive front-line studies (1984-1991) at St Jude Children's Research Hospital were retrospectively reviewed. Lumbar punctures were performed at the time of diagnosis and again for the instillation of first intrathecal chemotherapy. The event-free survival (EFS) experience for patients with 1 cerebrospinal fluid (CSF) sample contaminated with blast cells was worse than that for patients with no contaminated CSF samples (P =.026); that of patients with 2 consecutive contaminated CSF samples was particularly poor (5-year EFS = 46 +/- 9%). In a Cox multiple regression analysis, the strongest prognostic indicator was 2 consecutive contaminated CSF samples, with a hazard ratio of 2.39 (95% confidence interval, 1. 36-4.20). These data indicate that contamination of CSF with circulating leukemic blast cells during diagnostic lumbar puncture can adversely affect the treatment outcome of children with ALL and is an indication to intensify intrathecal therapy.

Adolescent↗

PubMed2000

Clinical importance of minimal residual disease in childhood acute lymphoblastic leukemia.

By using rapid flow cytometric techniques capable of detecting one leukemic cell in 10(4) normal cells, we prospectively studied minimal residual disease (MRD) in 195 children with newly diagnosed acute lymphoblastic leukemia (ALL) in clinical remission. Bone marrow aspirates (n = 629) were collected at the end of remission induction therapy and at 3 intervals thereafter. Detectable MRD (ie, > or = 0.01% leukemic mononuclear cells) at each time point was associated with a higher relapse rate (P < .001); patients with high levels of MRD at the end of the induction phase (> or = 1%) or at week 14 of continuation therapy (> or = 0.1%) had a particularly poor outcome. The predictive strength of MRD remained significant even after adjusting for adverse presenting features, excluding patients at very high or very low risk of relapse from the analysis, and considering levels of peripheral blood lymphoblasts at day 7 and day 10 of induction therapy. The incidence of relapse among patients with MRD at the end of the induction phase was 68% +/- 16% (SE) if they remained with MRD through week 14 of continuation therapy, compared with 7% +/- 7% if MRD became undetectable (P = .035). The persistence of MRD until week 32 was highly predictive of relapse (all 4 MRD(+) patients relapsed vs 2 of the 8 who converted to undetectable MRD status; P = .021). Sequential monitoring of MRD by the method described here provides highly significant, independent prognostic information in children with ALL. Recent improvements in this flow cytometric assay have made it applicable to more than 90% of all new patients. (Blood. 2000;96:2691-2696)

Adolescent↗

PubMed2000

Adverse effect of anticonvulsants on efficacy of chemotherapy for acute lymphoblastic leukaemia.

BACKGROUND: Many antileukaemic agents or their metabolites are inactivated by liver enzymes. Most anticonvulsant drugs induce drug-metabolising enzymes and thereby increase the clearance of anticancer agents. We investigated whether anticonvulsants compromise the efficacy of cancer chemotherapy. METHODS: We identified whom of 716 children treated consecutively for acute lymphoblastic leukaemia at a single academic hospital in the USA between 1984 and 1994 received treatment for 30 days or longer with anticonvulsants (phenytoin, phenobarbital, carbamazepine, or a combination) at the same time as antileukaemic therapy. Cox's proportional-hazards models were used to assess the prognostic significance of anticonvulsants on event-free survival and risk of haematological and central-nervous-system (CNS) relapse, with stratification for treatment protocol. FINDINGS: 40 (5.6%) of 716 patients received anticonvulsants. Use of these drugs was associated with age over 10 years (p=0.003), non-hyperdiploid leukaemia (p=0.031), and T-cell immunophenotype (p=0.022). After adjustment for age and ploidy, anticonvulsant therapy was significantly related to worse event-free survival (hazard ratio 2.67 [95% CI 1.50-4.76]; p=0.0009), haematological relapse (3.40 [1.69-6.88]; p=0.0006), and CNS relapse (2.90 [1.01-8.28]; p=0.047) among the 566 patients with B-lineage leukaemia. No such associations were seen among the 114 patients with T-cell leukaemia (p=0.61, 0.35, and 0.53, respectively). Faster clearance of teniposide (p=0.0001) and methotrexate (p=0.051), but not cytarabine (p=0.26) was found among patients receiving anticonvulsants. INTERPRETATION: Long-term anticonvulsant therapy increases the systemic clearance of several antileukaemic agents and is associated with lower efficacy of chemotherapy. Alternatives to enzyme-inducing anticonvulsants should be prescribed for patients receiving chemotherapy for acute lymphoblastic leukaemia.

Anticonvulsants↗

PubMed2000

Hepatitis C infection among survivors of childhood cancer.

Preliminary reports have suggested that survivors of childhood cancer and aplastic anemia who are infected with the hepatitis C virus (HCV) have a low risk for progression to significant liver disease. Among our surviving patients who were transfused between 1961 and March 1992, 77 (6.6% of surviving patients tested thus far) have evidence of HCV infection, whereas 4 surviving patients who were transfused after March 1992 are HCV-infected. One patient chronically infected with HCV died of liver failure, and 2 patients died of hepatocellular carcinoma. To characterize the risk for these and other complications, 65 patients are enrolled in a longitudinal study of HCV infection, of whom 58 (89.2%) had circulating HCV RNA at the time of protocol enrollment, with genotypes 1A and 1B most commonly isolated. Most enrolled patients have few or no symptoms, carry out normal activities, and have normal liver function. To date, 35 patients have undergone liver biopsy for abnormal liver function since the diagnosis of primary malignancy; central pathology review shows 28 (80%) have chronic active hepatitis, 25 (71%) have fibrosis, and 3 (9%) have cirrhosis. These preliminary data suggest that though most survivors of childhood cancer who are infected with HCV are clinically well, some are at risk for clinically significant liver disease. Identification of other HCV-infected patients and prospective monitoring of this cohort are ongoing to determine the risk for, and to identify factors associated with the progression of, liver disease.

Adult↗

PubMed2000

Alternating drug pairs with or without periodic reinduction in children with acute lymphoblastic leukemia in second bone marrow remission: a Pediatric Oncology Group Study.

BACKGROUND: Children with acute lymphoblastic leukemia (ALL) who experience hematologic recurrence while receiving chemotherapy or within 6 months after its cessation have a low cure rate. In this study (Pediatric Oncology Group Protocol 8303) two methods were examined for improving the outcome in these children. METHODS: After remission induction with prednisone, vincristine, daunorubicin, and asparaginase (PVDA) and consolidation chemotherapy with teniposide and cytarabine, patients received weekly continuation chemotherapy with rotating pairs of drugs, comprised of teniposide and cytarabine and vincristine and cyclophosphamide. In addition, they were randomized to receive or not receive repeated reinduction with PVDA. Patients with matched sibling donors were allowed to receive allogeneic bone marrow transplantation (BMT) instead of continued chemotherapy. RESULTS: Of 297 evaluable patients 258 (87%) achieved second complete hematologic remission. However, only 23 of these patients remained continuously free of leukemia > or =7 years after chemotherapy or BMT. Neither PVDA pulses nor BMT appeared to influence outcome at a statistically significant level. CONCLUSIONS: The results of the current study confirm prior reports of the low cure rate of children with ALL who experience hematologic recurrence during initial therapy or shortly after its cessation. New approaches are needed to prevent and retreat hematologic recurrence in pediatric ALL patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Sample size calculation for planning group sequential longitudinal trials.

Procedures are developed in this paper for sample size calculations for planning a group sequential longitudinal trial with various correlation structures, using a test statistic based on generalized estimating equations (Lee, Kim and Tsiatis) and group sequential boundaries based on type I error spending functions (Lan and DeMets).

Adolescent↗

PubMed2000

Long-term results of Total Therapy studies 11, 12 and 13A for childhood acute lymphoblastic leukemia at St Jude Children's Research Hospital.

We present the long-term results of three consecutive clinical trials (Total Therapy studies 11, 12 and 13A) conducted for children with newly diagnosed acute lymphoblastic leukemia (ALL) between 1984 and 1994. In study 11 (1984-1988), the overall event-free survival rates (+/-1 s.e.) were 71.8 +/- 2.4% and 69.3 +/- 2.4%, and the cumulative risks of isolated central nervous system (CNS) relapse 5.6 +/- 1.2% and 5.9 +/- 1.3%, at 5 and 10 years, respectively. In study 12 (1988-1991), event-free survival rates were 67.6 +/- 3.4% and 61.5+/- 9.0%, and isolated CNS relapse rates were 10.4 +/- 2.3% and 10.4 +/- 2.3%, respectively. Early intensive intrathecal therapy in study 13A (1991-1994) has yielded a very low 5-year isolated CNS relapse rate of 1.2 +/- 0.9%, boosting the 5-year event-free survival rate to 76.9 +/- 3.3%. Factors consistently associated with an adverse prognosis included male sex, infant or adolescent age group, leukocyte count >100 x 10(9)/l, nonhyperdiploidy karyotype and poor early response to treatment. Risk classification based on age and leukocyte count had prognostic significance in B-lineage but not T-lineage ALL. Early therapeutic interventions or modifications for patients with specific genetic abnormalities or persistent minimal residual leukemia may further improve long-term results.

Central Nervous System Neoplasms↗

PubMed2000

Testing secondary hypotheses following sequential clinical trials.

Sequential monitoring in a clinical trial poses difficulty in hypotheses testing on secondary endpoints after the trial is terminated. The conventional likelihood-based testing procedure that ignores the sequential monitoring inflates Type I error and undermines power. In this article, we show that the power of the conventional testing procedure can be substantially improved while the Type I error is controlled. The method is illustrated with a real clinical trial.

Biometry↗

PubMed2000

Low-stage medulloblastoma: final analysis of trial comparing standard-dose with reduced-dose neuraxis irradiation.

PURPOSE: To evaluate prospectively the effects on survival, relapse-free survival, and patterns of relapse of reduced-dose (23.4 Gy in 13 fractions) compared with standard-dose (36 Gy in 20 fractions) neuraxis irradiation in patients 3 to 21 years of age with low-stage medulloblastoma, minimal postoperative residual disease, and no evidence of neuraxis disease. PATIENTS AND METHODS: The Pediatric Oncology Group and Children's Cancer Group randomized 126 patients to the study. All patients received posterior fossa irradiation to a total dose of 54 Gy in addition to the neuraxis treatment. Patients were staged postoperatively with contrast-enhanced cranial computed tomography, myelography, and CSF cytology. Of the registered patients, 38 were ineligible. RESULTS: The planned interim analysis that resulted in closure of the protocol showed that patients randomized to the reduced neuraxis treatment had increased frequency of relapse. In the final analysis, eligible patients receiving standard-dose neuraxis irradiation had 67% event-free survival (EFS) at 5 years (SE = 7.4%), whereas eligible patients receiving reduced-dose neuraxis irradiation had 52% event-free survival at 5 years (SE = 7.7%) (P =.080). At 8 years, the respective EFS proportions were also 67% (SE = 8.8%) and 52% (SE = 11%) (P =.141). These data confirm the original one-sided conclusions but suggest that differences are less marked with time. CONCLUSION: Reduced-dose neuraxis irradiation (23.4 Gy) is associated with increased risk of early relapse, early isolated neuraxis relapse, and lower 5-year EFS and overall survival than standard irradiation (36 Gy). The 5-year EFS for patients receiving standard-dose irradiation is suboptimal, and improved techniques and/or therapies are needed to improve ultimate outcome. Chemotherapy may contribute to this improvement.

Adolescent↗

PubMed1999

High incidence of secondary brain tumours after radiotherapy and antimetabolites.

BACKGROUND: Brain tumours rarely occur in survivors of childhood acute lymphoblastic leukaemia after cranial radiotherapy. An unusually high frequency of brain tumours seen among children enrolled in one of our leukaemia treatment protocols, Total Therapy Study XII, prompted us to identify the potential causes of this complication. METHODS: We assessed clinical, biological, and pharmacokinetic features in all 52 children who received prophylactic cranial radiotherapy. We compared the cumulative incidence of brain tumours between subgroups, and with that of 421 children who received radiotherapy in previous studies. FINDINGS: The incidence of brain tumours among irradiated children (six of 52, 12.8% [SE 5.0]) was high compared with patients in the same study who did not receive radiotherapy (none of 101; p=0.0008) and with other protocols that included cranial radiotherapy (p<0.0001). Of the six children, four had erythrocyte concentrations of thioguanine nucleotide metabolites higher than the 70th percentile for the entire cohort, and three had a genetic defect in thiopurine catabolism. The 8-year cumulative incidence of brain tumour among children with defective versus wild-type thiopurine methyltransferase phenotype was 42.9% (SE 20.6) versus 8.3% (4.7; p=0.0077). This protocol differed from previous protocols, in that more intensive systemic antimetabolite therapy was given before and during radiotherapy. INTERPRETATION: These data support the elimination of prophylactic radiotherapy for acute lymphoblastic leukaemia except in patients at high risk of central-nervous-system relapse. Underlying genetic characteristics and treatment variables may be associated with an increased risk of radiation-associated brain tumours.

Adolescent↗

PubMed1999

Prognostic importance of 6-mercaptopurine dose intensity in acute lymphoblastic leukemia.

6-Mercaptopurine (6MP) and methotrexate are the backbone of continuation therapy for childhood acute lymphoblastic leukemia (ALL). In studies of oral 6MP and methotrexate, indices of chronic systemic exposure to active metabolites of these agents, namely, red blood cell (RBC) concentrations of methotrexate polyglutamates (MTXPGs) and thioguanine nucleotides (TGNs) have positively correlated with event-free survival (EFS). Our objective was to evaluate whether MTXPGs, TGNs, and the dose intensity of administered methotrexate and 6MP were prognostic in the setting of a treatment protocol in which all treatment was coordinated through a single center, and the weekly doses of methotrexate were given parenterally. On protocol Total XII, 182 children achieved remission and received weekly methotrexate 40 mg/m2 parenterally and daily oral 6MP, interrupted every 6 weeks during the first year by pulse chemotherapy. A total of 709 TGN, 418 MTX-PG, and 267 thiopurine methyltransferase (TPMT) measurements, along with complete dose intensity information (dose received divided by protocol dose per week) for 19,046 weeks of 6MP and methotrexate, were analyzed. In univariate analyses, only higher dose intensity of 6MP and of weekly methotrexate were significant predictors of overall EFS (P =.006 and. 039, respectively). The occurrence of neutropenia was associated with worse outcome (P =.040). In a multivariate analysis, only higher dose intensity of 6MP (P =.020) was a significant predictor of EFS, with lower TPMT activity (P =.096) tending to associate with better outcome. 6MP dose intensity was also associated (P =.007) with EFS among patients with homozygous wild-type TPMT phenotype. Lower 6MP dose intensity was primarily due to missed weeks of therapy and not to reductions in daily dose. We conclude that increased dose-intensity of oral 6MP is an important determinant of EFS in ALL, particularly among those children with a homozygous wild-type TPMT phenotype. However, increasing intensity of therapy such that neutropenia precludes chemotherapy administration may be counterproductive.

Administration, Oral↗

PubMed1999

Regimen-related toxicity of myeloablative chemotherapy with BCNU, thiotepa, and etoposide followed by autologous stem cell rescue for children with newly diagnosed glioblastoma multiforme: report from the Children's Cancer Group.

BACKGROUND: The survival of children with glioblastoma multiforme (GBM) remains poor. In an effort to improve the cure rate of children with this disease, high-dose chemotherapy followed by autologous stem cell rescue (ASCR) has been evaluated. We report the regimen-related toxicity (RRT) and survival seen in 11 children with newly diagnosed GBM treated with high-dose chemotherapy on a Children's Cancer Group study (CCG-9922). PROCEDURES: This phase II pilot study, intended to treat 30 patients, accrued 11 patients from July, 1993, to April, 1995. The pre-ASCR preparative regimen included BCNU 100 mg/m2 every 12 hr for a total of six doses on days -8, -7, -6; thiotepa 300 mg/m2/day on days -5, -4, -3; and etoposide 250 mg/m2/day on days -5, -4, -3. All patients received delayed radiotherapy at a dose of 5,400 cGy to the primary site commencing on approximately day +42 after ASCR. RESULTS: Five patients (45%) developed significant, nonfatal (grade III or IV) pulmonary and/or neurological toxicities. Three patients developed signs and/or symptoms of idiopathic interstitial pneumonitis. Eight patients (73%) have died, two (18%) of toxicity, and six (55%) of disease progression. Three patients (27%) achieved and remain in complete radiographic remission 2.9, 3.9, and 5.1 years from ASCR. One of these three, developed a lymphoblastic non-Hodgkins lymphoma (NHL) 3. 5 years post-ASCR. The survival rates for these 11 children at 1 year and 2 years are 73% +/- 13% and 46% +/- 14%, respectively. The progression-free survival rates at 1 year and at 2 years are 64% +/- 14% and 46% +/- 14%, respectively. CONCLUSIONS: We conclude that high-dose chemotherapeutic regimens followed by ASCR is a feasible treatment of childhood GBM. The BCNU-based preparative regimen utilized in this study was associated with prohibitive pulmonary toxicity.

Adolescent↗

PubMed1999

Chemotherapy for high-grade gliomas of childhood.

Astrocytomas are the most common group of childhood brain tumors. Approximately 20% of these lesions are histologically malignant tumors that often prove fatal within 2 years of diagnosis, despite the use of surgery and conventional radiotherapy. During the last 15 years, considerable attention has been focused on evaluating the potential role of chemotherapy as a means of improving survival. Although several agents have been observed to have modest therapeutic activity against these tumors, the optimal strategies for improving disease control have yet to be defined. This article will review the results that have been achieved in previous studies using a variety of single and multi-agent chemotherapeutic regimens, and also the rationale for ongoing trials of the major cooperative groups, and will discuss the challenges that are inherent in designing and interpreting therapeutic studies for these tumors. Ways in which currently available approaches may be incorporated into future therapeutic strategies will also be discussed and a brief review of the extensive array of promising new treatment approaches will be presented.

Antineoplastic Agents↗