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Biomedical subjects

L J Ettinger

Publications and source records attributed to L J Ettinger.

At least 19 recordsLinked to original sources
PubMed1998

High dose chemotherapy with autologous bone marrow rescue for children with diffuse pontine brain stem tumors. Children's Cancer Group.

PURPOSE: Diffuse pontine tumors are highly lethal, and there are few long-term survivors with the standard treatment of external beam irradiation. We investigated the effectiveness of high-dose thiotepa and etoposide-based chemotherapy regimens with autologous bone marrow rescue (ABMR) in children with pontine tumors. PATIENTS AND METHODS: Sixteen children with diffuse pontine tumors were treated. Ten had resistant or recurrent tumors. All ten had previously received irradiation; five had also received chemotherapy and one, beta-interferon. Three high-dose chemotherapy regimens were employed. Six patients received three days of thiotepa (300 mg/m2/day) and etoposide (250-500 mg/m2/day) (TE); two received three days of carmustine (BCNU) (200 mg/m2/day divided every 12 hours) followed by TE (BTE); and two received three days of carboplatin (500 mg/m2/day) followed by TE (CTE). Six other patients had newly-diagnosed tumors and had not received any prior treatment. They all received the BTE regimen and subsequently were treated with hyperfractionated irradiation (7200-7800 cGy) beginning approximately six weeks post-ABMR. RESULTS: There were two toxic deaths (13%), both in previously treated patients, due to multiorgan system failure and Candida septicemia in one case each. Median survival of the patients with resistant or recurrent disease was 4.7 months (range 0.1-18.7) from time of ABMR. Median survival of the newly-diagnosed patients was 11.4 months (range 7.6-17.1) from the time of ABMR. CONCLUSION: High-dose chemotherapy utilizing these regimens followed by ABMR did not appear to prolong survival compared to conventional therapy in these children with pontine tumors. Alternative strategies need to be developed for this highly lethal disease.

Adolescent↗
PubMed1997

A phase I/IB trial of murine monoclonal anti-GD2 antibody 14.G2a plus interleukin-2 in children with refractory neuroblastoma: a report of the Children's Cancer Group.

BACKGROUND: The murine monoclonal antibody (MoAb) 14.G2a recognizes GD2, a disialoganglioside expressed in tumors of neuroectodermal origin, and facilitates antibody dependent cellular cytotoxicity (ADCC) in vitro. When given in vivo, interleukin-2 (IL-2) can increase ADCC by enhancing the activity and number of circulating lymphocytes. METHODS: Thirty-three pediatric patients with GD2 positive malignancies, ranging in age from 2 to 17 years (median, 9.9 years), received IL-2 and 14.G2a in this Phase I/IB study of the Children's Cancer Group (CCG) and were monitored for toxicities and response to therapy. Seven of these patients also received granulocyte-macrophage-colony stimulating factor. RESULTS: The maximum tolerated dose (MTD) of 14.G2a with IL-2 was 15 mg/m2/day. The most prevalent Grade 3-4 toxicities were generalized pain (n = 14 [42%]) and fever without documented infection (n = 17 [52%]). IL-2 was thought to be the causative agent in most cases of fever. Toxicities attributed to 14.G2a included pain, allergic or anaphylactic reactions, and rash. Human antimouse antibodies were demonstrated in 9 of 21 evaluated patients. One patient with neuroblastoma had a partial response, and one patient with osteosarcoma had a complete response. Immunocytology demonstrated that the number of neuroblastoma cells in bone marrow decreased in three patients. CONCLUSIONS: The murine MoAb 14.G2a was well tolerated at the MTD and appeared to have some antitumor activity. Further development of this approach will involve additional engineered forms of the antibody as well as testing in the adjuvant and minimal residual disease setting.

Adjuvants, Immunologic↗
PubMed1997

A phase II study of carboplatin as a treatment for children with acute leukemia recurring in bone marrow: a report of the Children's Cancer Group.

BACKGROUND: Carboplatin is an analogue of cisplatin with less nonhematologic toxicity and a similar spectrum of antineoplastic activity. Although cisplatin has not been found to be an active agent against leukemia, carboplatin-induced complete remissions have been observed in adults with acute myelogenous leukemia (AML), and antileukemic activity has been observed in a Phase I trial involving children with acute lymphoblastic leukemia (ALL) and AML. Therefore, a pediatric Phase II study was undertaken to determine the degree of activity of carboplatin in childhood ALL and AML. METHODS: Between October 1991 and November 1994, the Children's Cancer Group conducted a Phase II study of carboplatin given by 5-day continuous intravenous infusion to children with acute leukemia recurring in bone marrow. RESULTS: Minimal antileukemic activity was demonstrated in patients with ALL and AML. One of 21 eligible patients with ALL achieved a partial response. Of 23 eligible patients with AML, including 1 patient with chronic myelogenous leukemia in blast crisis, 1 had hypocellular M1 bone marrow with a platelet count of 15,000/mm3, and 2 achieved partial responses. Nonhematologic toxicities, which were infrequent, included mild hepatic and renal dysfunction. CONCLUSIONS: In this pediatric Phase II trial of carboplatin as a treatment for acute leukemia, minimal activity was demonstrated in patients with ALL and AML recurring in bone marrow. Further evaluation of carboplatin as a treatment for childhood leukemia, using the dose schedule of 216 mg/m2/day given by 5-day continuous intravenous infusion, does not appear warranted.

Adolescent↗
PubMed1997

Intravenous anti-D treatment of immune thrombocytopenic purpura: experience in 272 patients.

We report the results of intravenous anti-D (WinRho, WinRho SD) therapy in 261 non-splenectomized patients treated at the New York Hospital-Cornell Medical Center over the period from 1987 to 1994. Children (n = 124) and adult patients (n = 137) with classic immune thrombocytopenic purpura (ITP; n = 156) or human immunodeficiency virus (HIV) related thrombocytopenia (n = 105) and acute (n = 75) or chronic (n = 186) disease at the time of the initial anti-D treatment were studied. In addition, 11 previously splenectomized patients were treated as a separate group. Our objectives were to evaluate the following. (1) Efficacy of anti-D: The response after the initial infusion was analyzed according to clinical parameters, such as patient's age, HIV status, gender, disease duration, pretreatment platelet count, and hemoglobin value, as well as treatment-related factors, including the dose of anti-D, the solvent detergent treatment of the preparation, and the type of administration. (2) Use of anti-D as maintenance therapy: The duration of response after the initial infusion and the results of subsequent treatments were evaluated. (3) Safety/toxicity of anti-D: Postinfusion reactions and hemoglobin decrease after treatment were studied. Anti-D is a safe treatment providing a hemostatic platelet increase in greater than 70% of the Rh+ non-splenectomized patients. The group with the best results is HIV- children, but all patient groups respond and the effect lasts more than 21 days in 50% of the responders. Duration of response is not influenced by HIV status; furthermore, HIV+ patients show no adverse effects on hemoglobin decrease or HIV disease progression. Patients with chronic ITP after splenectomy have minimal or no response to intravenous anti-D.

Adult↗
PubMed1997

Pharmacokinetics of intravenous recombinant human granulocyte colony-stimulating factor (rhG-CSF) in children receiving myelosuppressive cancer chemotherapy: clearance increases in relation to absolute neutrophil count with repeated dosing.

Limited evidence suggests increased efficacy of rhG-CSF by subcutaneous (SQ) compared with intravenous (IV) administration. To examine the possibility that rapid elimination of IV rhG-CSF could substantially shorten the duration of systemic exposure and could explain a difference in pharmacodynamics, we characterized the pharmacokinetic profile of IV rhG-CSF for comparison to that previously reported for SQ administration. Twelve children were randomly assigned to receive 10 or more days of IV rhG-CSF at dosages of 5 or 10 microg/kg a day beginning 24 hr after chemotherapy. Enzyme-linked immunosorbent assay (ELISA) was used to measure rhG-CSF concentrations in timed serum samples on days 1 and 10. Pharmacokinetic parameters were estimated by nonlinear, least squares regression. All serum concentration-time profiles were best described by a two-compartment model of elimination. Mean t1/2beta values ranged from 3.68 +/- 0.86 to 22.4 +/- 12.0 hr. ANC was correlated with log CLT (r = 0.72, P < 0.05), and inversely with log dose-adjusted AUC (r = 0.75, P < 0.05) and log dose-adjusted Cmax (r = -0.65, P < 0.05). Estimated duration of serum rhG-CSF concentrations above 1 ng/ml exceeded 24 hr for all but the 5 microg/kg cohort on day 1. Pharmacokinetic parameters of IV rhG-CSF are similar to those previously reported for SQ administration in children treated with myelosuppressive cancer chemotherapy. Daily IV administration should be a suitable alternative route of administration in this patient population.

Adolescent↗
PubMed1997

Comparison of the cellularity and presence of residual leukemia in bone marrow aspirate and biopsy specimens in pediatric patients with acute lymphoblastic leukemia (ALL) at day 7-14 of chemotherapy.

BACKGROUND: Many pediatric chemotherapy protocols for treatment of ALL require a bone marrow examination at day 7 or day 14 after initiation of therapy. The usefulness of a bone marrow biopsy, in addition to an aspirate, has been a frequently asked question. PROCEDURE: This study addresses the evaluation of bone marrow cellularity and presence of residual leukemia in both aspirate and biopsy specimens in 45 consecutive pediatric patients (ages 1-19 years, 19 females, and 26 males) with ALL 7-14 days after initiation of therapy. DISCUSSION: 20/45 patients showed evidence of residual leukemia by bone marrow biopsy; 16/20 (80%) of these had evidence of residual leukemia in the aspirate specimen. Of the 4 aspirate specimens that did not demonstrate residual leukemia, 2 had <5% blasts and 2 had too few cells in the aspirate for evaluation. Of the 25/45 bone marrow biopsy specimens with no detectable residual leukemia, 14 of the aspirates had <5% blasts, and 11 had too few cells in the aspirate for evaluation. 13/45 (29%) of the aspirates had too few cells for a differential count. The bone marrow cellularity judged from the aspirate specimen was considered to be low (0-1+) in 34/45 patients. Of these 34 patients, the bone marrow biopsy showed hypocellularity (<20% cellularity) in 12/34, moderate cellularity (20-79% cellularity) in 14/34, and hypercellularity (>79% cellularity) in 8/34. CONCLUSIONS: We conclude that both the bone marrow aspirate and biopsy specimens provide important information in evaluating the response to chemotherapy in pediatric patients with ALL at day 7-14 of induction chemotherapy. The aspirate alone may be misleading in terms of cellularity in many patients and may not provide evidence of residual leukemia.

Adolescent↗
PubMed1997

Treatment of nonmetastatic osteosarcoma of the extremity with preoperative and postoperative chemotherapy: a report from the Children's Cancer Group.

PURPOSE: The specific aims of this study were to improve event-free survival (EFS) in patients with newly diagnosed nonmetastatic osteosarcoma of an extremity using the histologic response to neoadjuvant chemotherapy to determine postoperative chemotherapy; to evaluate a uniform histologic grading system that measures tumor response; and to identify patient characteristics that might influence EFS and survival. PATIENTS AND METHODS: Two hundred sixty-eight patients with nonmetastatic osteosarcoma of the extremity were entered between August 1983 and October 1986. Preoperative chemotherapy consisted of four courses of high-dose methotrexate (MTX) and one course of bleomycin, cyclophosphamide, and dactinomycin (BCD). Histologic response to preoperative chemotherapy was determined by morphometric analysis. Good histologic responders (< 5% residual viable tumor) were treated postoperatively with MTX, BCD, and doxorubicin (DOX); poor histologic responders were treated with BCD, DOX, and cisplatin (CDDP). RESULTS: The 8-year EFS and survival rates were 53% and 60%, respectively. Two hundred six patients had their tumors assessed for histologic response: 28% displayed a good histologic response to preoperative chemotherapy. Good histologic responders had an 8-year postoperative EFS rate of 81% and survival rate of 87%; those with a poor histologic response had an 8-year postoperative EFS rate of 46% and survival rate of 52%. A primary tumor site in the proximal humerus or proximal femur and an elevated serum alkaline phosphatase level were associated with an increased risk of an adverse event, whereas the type of surgical procedure was not. CONCLUSION: EFS and survival appear to be directly related to histologic response to neoadjuvant chemotherapy.

Adolescent↗
PubMed1996

Successful treatment of a primary cardiac leiomyosarcoma with ifosfamide and etoposide.

PURPOSE: Primary cardiac leiomyosarcoma is a rare malignant tumor in childhood. Patients with unresectable or partially resected cardiac leiomyosarcoma typically have a poor prognosis. The role of chemotherapy in the treatment of these patients has not been well defined. PATIENT AND METHODS: A 6-week-old infant with an incompletely resected cardiac leiomyosarcoma was treated postoperatively with ifosfamide and etoposide. RESULTS: The patient is disease-free and without apparent late effects 5 years following the completion of therapy. CONCLUSION: The combination of ifosfamide and etoposide warrants further evaluation in patients with leiomyosarcoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

An open-label, multicenter study of polyethylene glycol-L-asparaginase for the treatment of acute lymphoblastic leukemia.

BACKGROUND: L-asparaginase has been a mainstay of therapy along with vincristine and prednisone in the treatment of acute lymphoblastic leukemia (ALL) in children for almost 30 years. Because L-asparaginase is a foreign protein, the potential exists for severe, dose-limiting hypersensitivity reactions. To reduce this toxicity, L-asparaginase has been linked with polyethylene glycol (PEG). METHODS: Patients with ALL in relapse were entered in a Phase II, open-label clinical trial (ASP-201A) to evaluate the toxicity and efficacy of PEG-L-asparaginase. PEG-L-asparaginase has demonstrated potential low immunogenicity and a prolonged plasma half-life relative to native enzyme. PEG-L-asparaginase (2000 IU/m2 every 2 weeks) was used as single-agent induction therapy during an initial 14-day investigational window. Thereafter, the regimen consisted of PEG-L-asparaginase, vincristine, and prednisone. Patients also were allowed to receive doxorubicin and intrathecal chemotherapy beginning on day 14. All patients had been treated previously with one or more courses of native L-asparaginase; one of these patients was hypersensitive to L-asparaginase at enrollment. RESULTS: During the 14-day investigational window with PEG-L-asparaginase monotherapy, 22% of patients examined achieved a complete or partial remission. By completion of the 35-day induction period, 78% (or 14 of 18) of evaluated patients achieved complete or partial remission. Anaphylaxis did not occur during treatment. Mild urticaria and mild local allergic reactions occurred in five patients but did not cause discontinuation of treatment. The incidence of hyperglycemia and pancreatitis was less than expected from historic data published for previous studies with native L-asparaginase. CONCLUSIONS: As administered in this study, PEG-L-asparaginase can be given safely with a spectrum of toxicity similar to that of native L-asparaginase. Single-agent activity was documented in patients with ALL in bone marrow relapse.

Adolescent↗
PubMed1994

A phase II study of carboplatin in children with recurrent or progressive solid tumors. A report from the Childrens Cancer Group.

BACKGROUND: Carboplatin is an analogue of cisplatin with less nonhematologic toxicity than the parent compound. It has been demonstrated previously to have activity against a spectrum of pediatric brain tumors. This Phase II study was undertaken to assess the activity of carboplatin in children with various solid tumors. METHODS: Between October 1985 and March 1988, the Childrens Cancer Group entered 117 patients with drug-resistant, recurrent lymphomas and solid tumors, excluding primary central nervous system tumors, into a Phase II trial of carboplatin given intravenously at a dosage of 560 mg/m2 over 1 hour every 4 weeks. RESULTS: A complete response was seen in 1 of 15 evaluable patients with Ewing's sarcoma. Partial responses were seen in 2 of 17 evaluable patients with neuroblastoma, 1 of 16 with soft tissue sarcoma, 2 of 5 with Wilms' tumor, and 1 with an endodermal sinus tumor of the testis. Objective responses were not seen in patients with malignant lymphoma, osteosarcoma, or hepatoma. Four of 7 patients who responded to carboplatin had previously received cisplatin. Sixty-two percent of patients had a platelet count nadir of less than 50,000/mm3, and 41% had an absolute neutrophil count nadir of less than 1,000/mm3. Ototoxicity, nephrotoxicity, hypomagnesemia, hypertransaminasemia, and nausea and vomiting each were seen in fewer than 10% of patients. CONCLUSIONS: Carboplatin has some activity against Wilms' tumor, Ewing's sarcoma, neuroblastoma, soft tissue sarcoma, and endodermal sinus tumor of the testis. Activity was not demonstrated against osteosarcoma, malignant lymphoma, hepatoma, and miscellaneous other tumors. Myelosuppression was seen commonly, and nonhematologic toxicity was infrequent.

Adolescent↗
PubMed1994

Human immunodeficiency virus infection presenting as pancytopenia in an infant.

CASE REPORT: A 14-month-old infant presented with pancytopenia and Mycobacterium avium intracellularae (MAI) as the initial manifestation of acquired immunodeficiency syndrome (AIDS). CONCLUSION: Human immunodeficiency virus (HIV-1) infections should be considered in the differential diagnosis of infants and children with cytopenias.

AIDS-Related Opportunistic Infections↗
PubMed1993

A phase I study of carboplatin in children with acute leukemia in bone marrow relapse. A report from the Childrens Cancer Group.

BACKGROUND: Carboplatin is an analogue of cisplatin with less nonhematologic toxicity and a similar spectrum of antineoplastic activity as the parent compound. Although cisplatin has not been found to be an active agent in leukemia, carboplatin induced complete remissions in adults with acute myelogenous leukemia (AML). Therefore, a pediatric Phase I study in acute leukemia was performed. METHODS: Between January 1988 and April 1990, the Childrens Cancer Group performed a Phase I study of carboplatin administered by a 5-day continuous intravenous infusion to children with acute leukemia in bone marrow relapse. RESULTS: Mild to moderate glomerular and tubular nephrotoxicity was seen in most patients treated at the initial dose level of 336 mg/m2/day. Therefore, patients at the second dose level were treated at 270 mg/m2/day. At this level, one patient died of acute hepatic necrosis and hepatic encephalopathy, and a second patient had presumed hemorrhagic cystitis develop. The third dose level tested, 216 mg/m2/day, was not associated with unacceptable toxic effects and was considered the maximum tolerated dose (dose-limiting toxicity was not observed). Within the confines of this Phase I study, antileukemic activity was shown in patients with acute lymphoblastic leukemia (ALL) and AML. CONCLUSIONS: In this pediatric Phase I trial of carboplatin in acute leukemia, glomerular and tubular nephrotoxicity was considered dose-limiting. In addition, hepatotoxicity and hemorrhagic cystitis were observed. Antileukemic activity was shown in patients with ALL and AML. The recommended Phase II dose is 216 mg/m2/day by 5-day continuous intravenous infusion.

Adolescent↗
PubMed1993

Significance of increased proportion of CD10-positive cells in nonmalignant bone marrows of children.

An immunophenotypic pattern characterized by increased proportions of CD10, CD19, and HLA-DR+ cells is observed in the bone marrow of some children with nonmalignant hematologic diagnoses. The purpose of this study was to ascertain the clinical and pathologic significance of this immunophenotype. The morphologic and immunophenotypic results of bone marrow specimens from 23 children with nonmalignant hematologic conditions are presented. In 11 children, an increased percentage of immature B-cell precursors was observed, suggesting the presence of B-lineage malignancy. None of the children have developed malignant lymphoproliferative disease in as long as 4 years of follow-up, despite the demonstration of a clonal lymphocyte proliferation in one patient. Although the biologic significance of the bone marrow immunophenotype is not yet understood, it is important to recognize that this lymphocyte pattern occurs commonly in children with nonmalignant hematologic conditions, and may reflect an increase in normally occurring lymphoid precursor cells.

Antigens, CD↗
PubMed1990

Carboplatin in childhood brain tumors. A Children's Cancer Study Group Phase II trial.

Between October 1985 and March 1988, Children's Cancer Study Group institutions entered 95 patients with recurrent brain tumors into a Phase II trial of carboplatin 560 mg/m2 every 4 weeks. Complete or partial responses were observed for one of 19 evaluable children with brainstem glioma, two of 14 with ependymoma, six of 19 with medulloblastoma or central nervous system primitive neuroectodermal tumor (PNET), and none of 15 with high-grade astrocytoma. Of 33 children with medulloblastoma, ependymoma, or central nervous system PNET, five of 12 with no prior cisplatin exposure had responses, and two of 21 with prior cisplatin exposure had responses (P = 0.03). Thirty-four percent of patients had absolute neutrophil count nadirs less than 500/microliters, and 37% had platelet count nadirs less than 25,000/microliters. Sixteen percent had moderate to severe otoxicity, 10% had nausea and vomiting, and none had nephrotoxicity.

Adolescent↗
PubMed1990

Pharmacology of fludarabine phosphate after a phase I/II trial by a loading bolus and continuous infusion in pediatric patients.

Fludarabine phosphate is a nucleotide analogue of adenine arabinoside with antitumor activity in murine and human lymphoid malignancies; it has occasional, unpredictable neurotoxicity after high dose bolus injections in adults. To avoid this toxicity, we studied a loading dose plus 5-day continuous infusion in 47 evaluable pediatric patients. Dose limiting myelosuppression was seen in children with solid tumors after a loading dose of 8 mg/m2 followed by 23.5 mg/m2/day for 5 days. In children with leukemia, no dose limiting toxicity was seen at dose level 6, consisting of a loading dose of 10 mg/m2 and an infusion of 30.5 mg/m2/day for 5 days. One complete and 3 partial remissions were seen in 26 evaluable children with acute lymphoblastic leukemia. 9-beta-D-arabinofuranosyl-2-fluoroadenine plasma concentrations and the area under the moment curve increased linearly with dose. The terminal half-life was similar, while the total body clearance was shorter than that reported for adults receiving bolus or continuous doses. Lymphoblasts isolated from 2 patients during fludarabine phosphate (9-beta-D-arabinofuranosyl-2-fluoroadenine) treatment increased their ability to convert 1-beta-D-arabinofuranosylcytosine to 1-beta-D-arabinofuranosylcytosine 5'-triphosphate by more than 10-fold. The antileukemic activity of 9-beta-D-arabinofuranosyl-2-fluoroadenine 5'-phosphate and its ability to alter the metabolism of 1-beta-D-arabinofuranosylcytosine indicate that timed combinations of these 2 agents should be tested.

Antimetabolites, Antineoplastic↗
PubMed1990

A phase II study of diaziquone in children with recurrent or progressive primary brain tumors: a report from the Childrens Cancer Study Group.

Seventy-five children with recurrent, progressive or metastatic primary brain tumors were treated with aziridinylbenzoquinone (AZQ; Diaziquone) at 9 mg/m2/day by 30-minute intravenous infusion for five days every three weeks. Sixty-six patients were evaluable for response by imaging studies. There were five partial responses and one complete response for a combined response rate of 9%. A complete response lasting for 35+ months occurred in one of twelve patients with metastatic or locally recurrent ependymoma. Objective responses were also seen in patients with primitive neuroectodermal tumors (PNET) (1/8), low-grade glioma (1/6), and primary central nervous system lymphoma (1/1). Stable disease of greater than six months duration was seen in patients with ependymoma, PNET and medulloblastoma. Profound and prolonged myelo-suppression was the significant toxicity observed. As administered in this study, AZQ has marginal activity and severe toxicity.

Adolescent↗