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Biomedical subjects

D Neuberg

Publications and source records attributed to D Neuberg.

105 records · Page 6Linked to original sources
PubMed1993

Autologous bone marrow transplantation in poor-prognosis intermediate-grade and high-grade B-cell non-Hodgkin's lymphoma in first remission: a pilot study.

PURPOSE: Using high-dose therapy and autologous bone marrow transplantation (ABMT) to overcome cellular resistance and eradicate minimal disease, we initiated a pilot study during first remission in patients with non-Hodgkin's lymphoma (NHL) to examine whether the long-term disease-free survival (DFS) rate can be improved for patients with poor-prognosis intermediate/high-grade NHL. PATIENTS AND METHODS: Twenty-six patients with advanced-stage diffuse intermediate/high-grade B-cell NHL (including 16 patients with diffuse small cleaved-cell [DSC]) were selected at presentation by histologic and clinical characteristics to have less than a 25% probability of long-term DFS with conventional treatment. After induction chemotherapy, 16 patients were in complete remission (CR) and 10 were in a minimal disease state. Patients were then treated with high-dose cyclophosphamide, total-body irradiation (TBI), and anti-B-cell monoclonal antibody-purged ABMT. RESULTS: Following ABMT, no acute in-hospital treatment deaths occurred, and engraftment of granulocytes and platelets was significantly faster than for patients undergoing ABMT who were in second or subsequent remission. Of 26 patients, 21 remain in CR maintained without continued therapy, three relapsed in sites of prior nodal disease (4.8, 5.4, and 28 months post-ABMT), and two died in remission. The DFS rate is estimated to be 85% at 28 months and thereafter. The median follow-up period for the 21 patients who are alive and disease-free is 32 months. CONCLUSION: This pilot study suggests that consolidation of first remission with ABMT may improve the long-term DFS rate for diffuse intermediate/high-grade NHL patients at high risk for relapse.

Adult↗
PubMed1993

Phase II study of goserelin for patients with postmenopausal metastatic breast cancer.

PURPOSE: To determine the response rate of postmenopausal breast cancer patients to the gonadotropin-releasing hormone (GN-RH) agonist, Zoladex (goserelin; ICI Pharma, Wilmington, DE). PATIENTS AND METHODS: A multi-institutional single-agent trial in postmenopausal patients was conducted. Serum levels of follicle-stimulating hormone (FSH), testosterone, and estradiol were requested before and after Zoladex treatment. RESULTS: For estrogen receptor-positive (ER+) patients, the response rate was 11%, with one complete response (CR) and three partial responses (PRs) among 36 eligible patients. Responses were of short duration. There were no responses among 16 estrogen receptor-negative (ER-) patients. CONCLUSION: GN-RH agonists have activity in ER+ postmenopausal patients, but response rates are not as high as with other available endocrine therapies and the duration of response is short.

Aged↗
PubMed1993

Phase II evaluation of Taxol in advanced head and neck cancer: an Eastern Cooperative Oncology group trial.

The Eastern Cooperative Oncology Group (ECOG) is conducting a phase II trial of Taxol in patients with histologically confirmed, advanced squamous cell carcinoma of the head and neck. Patients entered in the study to date either had recurrent disease or were newly diagnosed with incurable local-regional disease or distant metastases. Prior chemotherapy was limited to induction or adjuvant chemotherapy at least 12 months prior to entry in the study. All patients had an ECOG performance status of 0 or 1 and measurable disease. The treatment schedule was Taxol 250 mg/m2 by 24-hour continuous intravenous infusion followed by r-met Hu granulocyte-colony stimulating factor 5 micrograms/kg/day subcutaneous injection day 3 to 15 or until the absolute neutrophil count was greater than 1500. Cycles were repeated every 3 weeks. As of September 1, 1992, 27 patients were registered in the study. Of these, three patients were determined to be ineligible, and three were too early to evaluate. There were two early deaths, one definitely and one possibly drug related. Two complete and five partial responses have been observed. Twenty-three patients receiving 83 courses were evaluable for toxicity. Myelosuppression was the primary toxicity observed with 17 (74%) patients experiencing grade 3 or 4 leukopenia and with 20 (87%) patients experiencing grade 3 or 4 neutropenia lasting an average of 2 days (range, 1-4). Peripheral neuropathy occurred in nine patients (grade 1, five patients; grade 2, three patients; grade 3, one patient). Other infrequent toxicities were stomatitis, nausea and vomiting, and myalgias. This trial will continue until 30 eligible patients are accrued.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Squamous Cell↗
PubMed1992

Sonographic scoring index for prenatal detection of chromosomal abnormalities.

Current indications for cytogenetic evaluation leave the majority of Down syndrome fetuses undetected. Using advanced maternal age and low maternal serum alpha-fetoprotein (AFP) levels as criteria, only 40% of fetuses with Down syndrome (trisomy 21) are identified (positive predictive value, 0.4% to 1%). We evaluate the sonographically detectable physical features of second trimester fetuses to determine whether these features are more sensitive and specific than maternal age for detecting fetuses with abnormal karyotypes. From March 1, 1990, to September 1, 1991, more than 5,000 fetuses between 14 and 20 weeks of development were referred for genetic amniocentesis because of advanced maternal age or abnormal AFP levels. Forty-three of these 5,000 fetuses were later found to have autosomal trisomies by karyotype (32 with trisomy 21, nine with trisomy 18, and two with trisomy 13). A sample of 588 consecutive normal fetuses from the total of more than 5,000 amniocenteses performed during this period of time was used as our control group for statistical analysis. The sonographic features of these 588 normal second trimester fetuses and the 43 trisomic fetuses recorded prospectively prior to knowledge of the karyotype were evaluated statistically. The femur and humerus lengths, nuchal fold, renal pelvic dimension, and major structural defects were compared in the normal and trisomic fetuses. On the basis of our results, a weighted sonographic score was developed to optimize the detection of fetuses at risk for aneuploidy. Using our previously published formulas and criteria for a short femur and humerus, 17/32 (53%) fetuses with Down syndrome and 23/588 (3.9%) of the normal fetuses were identified. Twenty two of 32 Down syndrome fetuses (69%) and 2/588 (0.34%) of normals had a nuchal fold > or = 6 mm, and 11 of 32 Down syndrome fetuses and all those with trisomies 18 and 13 had a major anomaly detected sonographically. The following scoring system was developed for the detection of aneuploidy: nuchal fold = 2, major structural defect = 2, and short femur, short humerus, and pyelectasis = 1 each. Selecting fetuses with a score of > or = 2 would identify 26/32 (81%) Down syndrome fetuses, and 9/9 (100%) and 2/2 (100%) fetuses with trisomies 18 and 13 respectively, but only 26/588 (4.4%) of the normal fetuses. Using the sonographic score of 2 results in a positive predictive value for a 1/250 risk group of 6.87% for identifying Down syndrome fetuses and 7.25% for all three trisomies.(ABSTRACT TRUNCATED AT 400 WORDS)

Amniocentesis↗
PubMed1991

Immunologic purging of marrow assessed by PCR before autologous bone marrow transplantation for B-cell lymphoma.

BACKGROUND: The use of autologous bone marrow transplantation is increasing in the management of advanced cancers. Many investigators have attempted to "purge" autologous marrow of residual tumor cells because of concern that reinfused tumor cells might contribute to relapse. The efficacy of purging remains unproved. METHODS: We performed clonogenic assays in a tumor cell line in culture to determine the efficiency of immunologic purging. Amplification by the polymerase chain reaction (PCR) was used to detect residual lymphoma cells before and after purging of bone marrow from 114 patients with B-cell non-Hodgkin's lymphoma in whom a translocation (t(14;18] that could be amplified by PCR was detected at the time of their initial evaluation. RESULTS: Immunologic purging in vitro resulted in a 3-to-6-log destruction of cells in the tumor cell line. Residual lymphoma cells were detected by PCR in the bone marrow of all patients before purging. No lymphoma cells could be detected in the marrow of 57 patients after purging. Disease-free survival was increased in these 57 patients as compared with those whose marrow contained detectable residual lymphoma (P less than 0.00001). The ability to purge residual lymphoma cells was not associated with the degree of bone marrow involvement (P = 0.4494) or the previous response to therapy (P = 0.1298). CONCLUSIONS: The inability to purge residual lymphoma cells was the most important prognostic indicator in predicting relapse. These results provide evidence of the clinical usefulness of ex vivo purging of autologous bone marrow in the treatment of patients with lymphoma and suggest that the reinfusion of malignant cells in autologous marrow contributes to relapse

Antibodies, Monoclonal↗
PubMed1991

Autologous bone marrow transplantation in 69 patients with a history of low-grade B-cell non-Hodgkin's lymphoma.

Sixty-nine patients with a history of low-grade B-cell non-Hodgkin's lymphoma (NHL) in sensitive relapse or incomplete first remission underwent high-dose chemoradiotherapy and anti-B-cell monoclonal antibody (MoAb)-treated autologous bone marrow transplantation (ABMT). At ABMT, 51 patients had low-grade histology and 18 patients had a history of low-grade NHL that had undergone histologic transformation to a higher-grade NHL. Before ABMT, only 20 of the 51 low-grade patients and 10 of the 18 patients with transformed histologies were in complete remission. Moreover, at the time of marrow harvest, 24 of the low-grade and eight of the transformed histology patients had histologic evidence of lymphoma cells infiltrating the marrow. Following high-dose therapy, only one acute, in-hospital death was observed. There was no significant difference in the disease-free survival (DFS) between patients with low-grade and patients with transformed histologies. Among patients with low-grade NHL, the patients in complete remission before ABMT experienced significantly longer DFS than those in partial remission (P less than .05). This preliminary study suggests that some patients with relapsed low-grade NHL may experience prolonged DFS following high-dose ablative therapy.

Adult↗
PubMed1991

Hemolytic-uremic syndrome following bone marrow transplantation in adults for hematologic malignancies.

One hundred and sixty eight adult patients with B-cell non-Hodgkin's lymphoma (NHL) and other hematologic malignancies who underwent autologous or allogeneic bone marrow transplantation (BMT) were investigated for the subsequent development of hemolytic-uremic syndrome (HUS). All patients were conditioned with cyclophosphamide and total body irradiation. When examined at 3-month intervals for the first year post-BMT, all patients had uniform measurements of hematocrit (Hct) and serum creatinine. Sixteen patients who initially exhibited Hct and creatinine values that were normal range for the BMT populations developed a sudden decrease in Hct and increase in creatinine between 3 and 11 months post-BMT and fulfilled the clinical and laboratory criteria for HUS. None of these patients had known active cytomegalovirus infection, graft-versus-host disease, or cyclosporine administration. The degree of decrease in Hct and creatinine elevation ranged from solely laboratory abnormalities to a clinically significant syndrome. Twelve of the 16 patients developed acute clinical complications of congestive heart failure, hypertension (HTN), or peripheral edema. Twelve patients required red blood cell support, whereas only four patients required platelet transfusions. Both hemolytic anemia and thrombocytopenia have resolved in virtually all cases. At a mean follow up of 18 months postdiagnosis, creatinine elevations have persisted along with HTN. All patients have survived without life-threatening long-term sequelae. With the increasing use of BMT as a curative modality for patients with hematologic malignancies, it becomes important to prospectively monitor patients for the development of HUS and its potential long-term impact on renal function.

Adult↗
PubMed1991

A pilot study of three sequential chemotherapeutic regimens in metastatic breast cancer.

The aim of this pilot study was to estimate the toxicity and response rate of an alternating chemotherapeutic program in chemotherapy-naive metastatic breast cancer patients. Treatment consisted of regimen A (given days 1-28): cyclophosphamide 100 mg/m2 PO days 1-14, doxorubicin 30 mg/m2 i.v. days 1 and 8, and 5-fluorouracil 500 mg/m2 i.v. days 1 and 8 (CAF regimen); regimen B (given days 29-56): dibromodulcitol 135 mg/m2 p.o. days 30-39, mitoxantrone 9 mg/m2 i.v. day 29, and vincristine 1.2 mg/m2 i.v. (maximum 2.0 mg) day 29 (DMV regimen); and regimen C (given days 57-84): thiotepa 12 mg/m2, doxorubicin 45 mg/m2 and vinblastine 4.5 mg/m2 all i.v. on day 57. There were 27 eligible patients with a median age of 51 years (range 34-78). On 14 episodes the leukocyte count fell to less than 1 X 10(9)/L during the first six cycles of treatment (14% of 99 cycles). There were no treatment-related deaths. Common non-life-threatening toxicities included thrombocytopenia, anemia, vomiting, and alopecia. Despite having no drugs in common, the leukocyte and platelet nadirs after CAF correlated with the nadir counts after DMV (r values of 0.6829 and 0.5892, respectively; p = 0.01). Among the 23 patients with measurable and/or evaluable disease there were five complete responses (22%) and nine partial responses (39%), with a median time to treatment failure of 29 weeks. The overall median survival was 19 months.

Adult↗
PubMed1991

Humeral shortening in second-trimester fetuses with Down syndrome.

Individuals with Down syndrome have abnormally short long bones. Sonography has previously revealed slightly shortened femurs and thickened nuchal folds in affected second-trimester fetuses. Humeral and femoral lengths and nuchal folds were evaluated in 400 normal second-trimester controls and in 24 consecutive Down syndrome fetuses (14-20 weeks) undergoing amniocentesis for advanced maternal age or low maternal serum alpha-fetoprotein (MSAFP). Using the 400 normal control fetuses undergoing amniocentesis, the relationship between humeral length and biparietal diameter (BPD) was: Expected humeral length = -7.9404 + 0.8492 x BPD. A ratio of measured-to-expected humeral length of less than 0.90 identified 12 of 24 fetuses (50%) with Down syndrome and 25 of 400 normals (6.25%). Twelve of the 24 Down syndrome fetuses had a nuchal fold measuring 6 mm or larger. Combining nuchal fold findings with these humeral length criteria identified 18 of 24 affected fetuses (75%) without appreciable change in specificity, yielding a positive predictive value of 4.6% for women with a risk of one in 250 (age 35) of having a Down syndrome fetus. For women with risks of one in 500 and one in 1000 of having an affected fetus based on maternal age, a shortened humerus or thickened nuchal fold yielded positive predictive values of 2.3 and 1.2%, respectively.

Adult↗
PubMed1989

Prevalence and significance of acquired immunodeficiency syndrome-related retinal microvasculopathy.

We performed ophthalmologic examinations on 127 subjects with or at risk for human immunodeficiency virus (HIV) infection over a one-year period to determine the prevalence and significance of retinal cotton-wool spots and hemorrhages (AIDS-related retinal microvasculopathy). Of 26 asymptomatic homosexual men, of whom 13 were HIV seronegative and 13 were HIV seropositive, none manifested this retinopathy. Three of 34 patients (9%) with AIDS-related complex and 29 of 67 patients (43%) with AIDS manifested retinopathy on the initial examination. This difference in the prevalence of retinopathy between groups was statistically significant (P less than .05). Patients with AIDS demonstrated 7.2 times greater odds of manifesting retinopathy than patients with AIDS-related complex (P less than .05). Within the group of patients with AIDS, the T helper (CD4) to suppressor (CD8) cell ratio was significantly associated with retinopathy at the initial ocular examination. The CD4:CD8 ratio of the total group of AIDS and AIDS-related complex patients with retinopathy was significantly lower than that of patients without retinopathy (P less than .05). There was no significant association between retinopathy and any specific past or concurrent opportunistic infection or neoplasm. The presence of retinopathy was not associated with symptoms in any patient. The lesions of AIDS-related retinal microvasculopathy may be an important finding in the evaluation of patients suspected to have HIV-related disease.

AIDS-Related Complex↗
PubMedDate not supplied

An allelic variant at the ATM locus is implicated in breast cancer susceptibility.

We have tested a simple procedure, disease association by locus stratification, for identifying breast cancer patients with pathogenetic allelic variants at several candidate loci. The strategy was based on the assumption of epistatic interactions of the candidates. We analyzed 66 independent cases from sib pairs affected with breast cancer that had previously been collected during an investigation of pathogenetic-allele-sharing at the HRAS1 mini-satellite locus. An exon 24 polymorphism of ATM, substituting arginine for proline was associated with breast cancer in these cases with an overall odds ratio of 4.5 (95% confidence interval, 1.2-20.5, nominal p = 0.02, 2-tail Fisher exact test). In the presence of a rare HRAS1 allele, the odds ratio increased to 6.9 (95% CI, 1.2-38.3, p = 0.03). Thus, our procedure identified at least one allelic variant of ATM associated with breast cancer, and indicated that the ATM locus may interact with HRAS1.

Adult↗
PubMedDate not supplied

Prognostic implications of c-Ki-ras2 mutations in patients with advanced colorectal cancer treated with 5-fluorouracil and interferon: a study of the eastern cooperative oncology group (EST 2292)

PURPOSE: Mutations in c-Ki-ras2 (ras) occur in about 40% of patients with colorectal cancers and occur early in the pathogenesis of this disease. To evaluate the prognostic value of mutations in ras, the Eastern Cooperative Oncology Group (ECOG) conducted a retrospective study (EST 2292) to determine the frequency of mutations in patients with advanced colorectal cancer, and to determine whether ras mutations were associated with altered response to therapy and survival. PATIENTS AND METHODS: Patients were enrolled from four studies: P-Z289, an ECOG phase II trial of 5-fluorouracil (5-FU) and interferon (IFN) in patients with advanced colorectal cancer; P-Z991, an ECOG phase I trial of 5-FU and IFN in patients with advanced malignancies; and two trials from the Albert Einstein College of Medicine in patients with advanced colorectal cancer treated with 5-FU and either IFN-alpha or IFN-beta. All patients had advanced colorectal carcinoma and had sufficient histologic material available for analysis for the presence and type of ras, using polymerase chain reaction and dot-blot analysis with sets of probes sufficient to detect all the common mutations of ras at codons 12, 13, and 61. RESULTS: Seventy-two patients were enrolled in this trial. Mutations in ras were detected in 25 (35%), including 17 (23%) in codon 12, four (6%) in codon 13, and four (6%) in codon 61. There was no correlation between the presence of a ras mutation and age, sex, Dukes' stage, histology, or tumor markers. Thirty-one of 72 patients (43%) responded to therapy with 5-FU and IFN, and 10 of 31 responders (32%) and 15 of 41 nonresponders (37%) had mutations in ras. There was no difference in response rates or overall survival between the groups with and without ras mutations. CONCLUSIONS: It is unlikely that ras mutations will have significant prognostic value for either response to therapy or survival in patients with colorectal carcinomas treated with 5-FU and IFN.

Adult↗
PubMedDate not supplied

Incongruence between nurses' and parents' perceptions of nurses' caring behaviors in a neonatal intensive care unit.

The primary purpose of this study was to test an instrument designed to assess nurses' caring behaviors in a neonatal intensive care unit, the setting for the study. The convenience sample (n = 88) was 42 nurses who worked in a neonatal intensive care unit and 46 parents whose infants were hospitalized there. The Wilcoxon two-sample rank-sum test was used to test the difference in ranking of the 15 items (nurses' caring behaviors) between the nurses and parents. There was agreement on the most caring behavior, "The nurses understood my need to touch my baby and encouraged me to do so" and the least caring behavior, "The nurses did not know the sex of my child." However, a significant difference was found between the nurses and parents on 4 of the 15 behaviors. The findings serve to sensitize the clinicians to their caring behaviors by heightening their awareness of how caring behaviors are perceived by parents.

Adult↗
PubMedDate not supplied

Clinical trial of weekly intensive therapy with 5-fluorouracil on two different schedules combined with interferon alpha-2a and filgrastim in patients with advanced solid tumors: Eastern Cooperative Oncology Group Study P-Z991.

PURPOSE: The hematopoietic growth factor filgrastim has been shown to reduce both chemotherapy-induced myelosuppression and mucosal toxicities. The aim of this study was to conduct four separate pilot trials to determine the maximum-tolerated doses at which interferon alpha (IFN alpha) followed by 5-fluorouracil (5-FU) could be administered in combination with filgrastim support. PATIENTS AND METHODS: Patients were required to have a histologically documented solid tumor with either measurable or evaluable lesions. All patients were fully ambulatory; had adequate bone marrow, renal, and hepatic function; had recovered from surgery; and gave informed consent. Trials were conducted sequentially. In parts A and B, patients received 5-FU as a continuous intravenous infusion daily for 5 days, followed by weekly bolus therapy at the same dose. In parts C and D, patients received 5-FU as a weekly high-dose, 24-hour infusion. Interferon was administered immediately before the 5-FU three times a week. Filgrastim was administered at 5 micrograms/kg subcutaneously either four (parts A, B) or five (parts C, D) times a week. In part A, the starting doses were as follows: 5-FU, 750 mg/m2, and IFN alpha, 3 MU subcutaneously, and the IFN alpha was escalated between patient cohorts to a maximum of 9 MU. Part B used the dose of IFN alpha established from part A, and the 5-FU was escalated to the maximum-tolerated dose between patient cohorts. In part C, the starting dose of IFN alpha was 3 MU subcutaneously, and that of 5-FU, 2.6 g/m2, and the dose of IFN alpha was escalated to a maximum of 9 MU. In part D, the dose of IFN alpha was determined from part C, and the dose of 5-FU was escalated. The maximum tolerated dose was the highest dose at which three of three or five of six patients were able to tolerate therapy. RESULTS: There were 71 patients entered into the four parts of this trial. In part A (12 patients), the dose of IFN alpha, was escalated to 9 MU subcutaneously three times a week with only one patient experiencing dose-limiting toxicity. In part B (13 patients), the dose of 5-FU could not be escalated beyond 750 mg/m2 because of sepsis (one patient) and gastrointestinal hemorrhage (one patient). The predominant toxicities were diarrhea (46%), vomiting (23%), and mucositis (31%). In part C (24 patients), two patients experienced dose-limiting toxicities (staphylococcal sepsis [one patient] and neuropsychiatric [one patient]). The dose of IFN alpha was escalated to 9 MU. In part D (21 patients), the dose of 5-FU was escalated to 3.4 g/m2 administered weekly. No patients at this dose level experienced serious toxicities. At the next highest dose level, 3.6 g/m2, one patient each experienced gastrointestinal hemorrhage and diarrhea. There were no additive constitutional symptoms resulting from the combination of IFN alpha and filgrastim. In parts C and D, filgrastim could be administered 6 hours after the end of the 5-FU infusion without excessive myelosuppression. CONCLUSIONS: The addition of filgrastim allowed escalation of the dose of 5-FU on the weekly, high-dose schedule, but not on the weekly bolus schedule. IFN alpha and filgrastim can be administered without additive toxicities. Filgrastim can be safely administered < 24 hours after completion of the weekly, high dose 5-FU infusion.

Adult↗