M Barcos

Barnes Jewish Hospital, San Luis, Missouri, United States

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Publications (46)351.68 Total impact

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    ABSTRACT: An association between the overexpression of proto-oncogene HER-2/neu and resistance to tamoxifen in estrogen receptor (ER)-positive primary and metastatic breast cancer has been suggested. We examine a possible interaction between HER-2/neu or p53 expression and tamoxifen effectiveness in patients with ER-positive, node-positive disease treated with cyclophosphamide, doxorubicin, and fluorouracil in a large adjuvant chemotherapy trial (Cancer and Leukemia Group B [CALGB] 8541). Tamoxifen assignment was not randomized-physician discretion was used for premenopausal and postmenopausal women. Trial protocol then specified assignment to postmenopausal women with ER-positive tumors, although not all took tamoxifen. CALGB 8541 assessed HER-2/neu expression in patients with ER-positive disease by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) and amplification by differential polymerase chain reaction (PCR). IHC assessed expression of p53. Univariate and multivariate proportional hazards models assessed tamoxifen-HER-2/neu status interactions and tamoxifen-p53 status interactions. HER-2/neu status was available for 651 patients with ER-positive disease; 650, 608, and 353 patients were assessed by IHC, PCR, and FISH, respectively. Approximately one half received tamoxifen. Reduction in risk of disease recurrence or death resulting from tamoxifen was approximately 37% (32% with overexpression and 39% with normal expression of HER-2/neu; n = 155 by IHC). The tamoxifen-HER-2/neu status interaction was not significant in multivariate analysis of all three HER-2/neu assessment methods. Tamoxifen-p53 interaction did not significantly predict outcome. Disease-free and overall survival benefit of tamoxifen in patients with ER-positive, node-positive breast cancer does not depend on HER-2/neu or p53 status. Our data suggest that neither HER-2/neu nor p53 expression should be used to determine assignment of tamoxifen.
    Journal of Clinical Oncology 11/2000; 18(20):3471-9. · 18.43 Impact Factor
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    ABSTRACT: Patients with resistant diffuse aggressive non-Hodgkin's lymphoma (DA-NHL) have a poor prognosis. Studies have suggested infusional therapy may be beneficial. This trial used an infusional regimen called I-CHOPE in resistant patients who had previously received only bolus CHOPE or CHOP regimen. Resistance was defined as: a) primary refractory disease, b) progression on therapy, c) partial response, d) complete remission lasting less than one year. Eligibility criteria included a diagnosis of DA-NHL (IWF E-H), no prior irradiation and adequate organ function. Thirty-seven patients were entered and twenty-nine were eligible. Reasons for ineligibility were incorrect histology (5) and other (3). The median age was 57 years (range 29-81) with 21 males. The performance status scores were: 0 (12 patients); 1 (9 patients); 2 (8 patients). Prior therapy consisted of standard CHOP (26 patients), bolus CHOPE (2 patients), high dose CHOP (1 patient). Therapy consisted of a 120 hour continuous intravenous infusion of doxorubicin 10 mg/m2/day, vincristine 0.28 mg/m2/day (maximum 0.4 mg/day), and etoposide 48 mg/m2/day. Cyclophosphamide 750 mg/m2 was given as an i.v. bolus day 6 and prednisone was given at 100 mg/day p.o. on days 1-5. G-CSF was allowed for myelosuppression. The overall response rate was 48% (CR 17%; PR 31%). Freedom from progression was 24% at six months and 8% at one year. Survival was 69% at six months and 40% at one year. In an exploratory analysis a prior CR or PR predicted response to I-CHOPE. Twelve of sixteen patients who had a CR/PR on previous therapy responded while two of thirteen who had no prior response, responded to I-CHOPE (P = 0.003). The toxicity was tolerable with grade 3-4 hematologic toxicity being leucopenia 94% and thrombocytopenia 41%. The grade 3-4 non-hematologic toxicities were infection in 28%, phlebitis in 11%, and stomatitis in 15%. I-CHOPE can induce responses in this group of patients with a poor prognosis, but most were seen in those who had previously had a response to bolus chemotherapy.
    Annals of Oncology 10/2000; 11(9):1141-6. DOI:10.1023/A:1008395400069 · 6.58 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate a regimen of sequential chemotherapy and radiotherapy for patients with Hodgkin disease. The Cancer and Leukemia Group B conducted a Phase II study of three cycles of etoposide, vinblastine, and doxorubicin (EVA) chemotherapy followed by subtotal lymph node radiation for patients with localized Hodgkin disease and unfavorable prognostic features. Fifty-nine patients were enrolled in the study. Fifty-three patients met all study eligibility criteria; 48 of them (91%) had mediastinal disease and 29 (55%) had bulky mediastinal disease. A complete response (CR) occurred in 35 of the patients (66%). Of all patients who had CR, 26% had the CR after the chemotherapy and before the radiation, and 74% after the chemotherapy and radiation. Twenty percent of the patients who had CR experienced disease progression; in these patients, the progression was outside the radiotherapy field in the lung and involved widespread disease. EVA offers a nonbleomycin-containing alternative for patients in whom preexisting pulmonary disease may be exacerbated by bleomycin and radiation therapy. EVA, as given in this study (in three cycles), was insufficient chemotherapy for patients who had disease in areas outside the radiation fields (occult disease).
    Cancer 11/1999; 86(8):1590-5. DOI:10.1002/(SICI)1097-0142(19991015)86:83.0.CO;2-4 · 4.90 Impact Factor
  • F Matsuno · Y Haruta · M Kondo · H Tsai · M. and Barcos · B K Seon
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    ABSTRACT: Endoglin (EDG, CD105) is a proliferation-associated antigen on endothelial cells. In this study, two new anti-EDG monoclonal antibodies (mAbs) Y4-2F1 (or termed SN6j) and P3-2G8 (SN6k) were generated and used for treating distinct preformed tumors. These mAbs, both IgG1-kappa antibodies, cross-reacted weakly with mouse endothelial cells but defined epitopes different from the epitope defined by a previously reported anti-EDG mAb K4-2C10 (B. K. Seon et al., Clin. Cancer Res., 3: 1031-1044, 1997). SN6j and SN6k reacted strongly with human endothelial cells and vascular endothelium of malignant human tissues but showed no significant reactivity with tumor cells per se. The deglycosylated ricin A chain (dgRA) conjugates of the two mAbs showed a weak but specific cytotoxic activity against murine endothelial cells in vitro. In the therapeutic studies, severe combined immunodeficient mice were inoculated s.c. with MCF-7 human breast cancer cells and left untreated until palpable tumors of distinct size (4-6 mm in diameter) appeared. Mice with the distinct tumors were treated by i.v. administration of individual anti-EDG conjugates, unconjugated mAbs, or a control conjugate. Long-lasting complete regression of the tumors was induced in the majority of tumor-bearing mice (n = 8 for each conjugate) when 40 microg of the individual conjugates were administered three times via the tail vein. It is remarkable that the tumors remained regressed without further therapy for as long as the mice were followed (i.e., 100 days). Control conjugate did not induce regression of the tumors in any of the treated mice, although weak nonspecific effects were observed in some of the mice (n = 8). The effects of unconjugated mAbs were small with the dose used, i.e., 34 microg three times. The anti-EDG conjugates showed antiangiogenic activity in the dorsal air sac assay in mice. The results suggest good potential of these conjugates for the clinical application.
    Clinical Cancer Research 03/1999; 5(2):371-82. · 8.19 Impact Factor
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    ABSTRACT: We have previously reported that high expression of the erbB-2 gene (also known as HER-2/neu and ERBB2) in breast cancer is associated with patient response to dose-intensive treatment with cyclophosphamide, doxorubicin (Adriamycin), and 5-flurouracil (CAF) on the basis of short-term follow-up of 397 patients (set A) with axillary lymph node-positive tumors who were enrolled in Cancer and Leukemia Group B (CALGB) protocol 8541. To validate those findings, we conducted immunohistochemical analyses of erbB-2 and p53 protein expression in an additional cohort of 595 patients (set B) from CALGB 8541, as well as a molecular analysis of erbB-2 gene amplification in tumors from all patients (sets A and B). Marker data were compared with clinical, histologic, treatment, and outcome data. Updated analyses of data from set A (median follow-up, 10.4 years) showed an even stronger interaction between erbB-2 expression and CAF dose, by use of either immunohistochemical or molecular data. A similar interaction between erbB-2 expression and CAF dose was observed in all 992 patients, analyzed as a single group. However, for set B alone (median follow-up, 8.2 years), results varied with the method of statistical analysis. By use of a proportional hazards model, the erbB-2 expression-CAF dose interaction was not significant for all patients. However, in the subgroups of patients randomly assigned to the high- or the moderate-dose arms, significance was achieved. When patient data were adjusted for differences by use of a prognostic index (to balance an apparent failure of randomization in the low-dose arm), the erbB-2 expression-CAF dose interaction was significant in all patients from the validation set B as well. An interaction was also observed between p53 immunopositivity and CAF dose. The hypothesis that patients whose breast tumors exhibit high erbB-2 expression benefit from dose-intensive CAF should be further validated before clinical implementation. Interactions between erbB-2 expression, p53 expression, and CAF dose underscore the complexities of predictive markers where multiple interactions may confound the outcome.
    JNCI Journal of the National Cancer Institute 10/1998; 90(18):1346-60. DOI:10.1093/jnci/90.18.1346 · 15.16 Impact Factor
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    ABSTRACT: To evaluate the new anticancer agent, docetaxel, with a novel mechanism of action in patients with non-Hodgkin's lymphoma International Working Formulation (IWF) A through H, to determine the response rate by histologic group and the toxicities of this agent in this population. Sixty-eight patients previously treated for non-Hodgkin's lymphoma with two prior cytotoxic regimens for low-grade and one prior regimen for intermediate-grade lymphoma were entered onto this phase II trial. Central pathologic review was required. Twenty-four IWF A to C and 31 IWF D to H patients with normal hepatic and renal function, performance status (PS) 0 to 2, and adequate hematologic function were eligible. Patients received docetaxel 100 mg/m2 intravenously over 1 hour without corticosteroid premedications every 3 weeks with weekly hematologic monitoring, and tumor assessment every 3 weeks. For grade 3 or 4 hematologic toxicity, the docetaxel dosage was lowered to 75 mg/m2. Patients received a maximum of six cycles of therapy. The major response rate was 13% (95% confidence limits, 3% to 32%) for IWF A to C and 16% (95% confidence limits, 5% to 34%) for IWF D to H; response durations ranged from 1.4 to 20 months. Time to response ranged from 1.3 to 2.8 months. Patients refractory to previous chemotherapy were less apt to respond to docetaxel, but the differences were not statistically different in this small sample size. Twelve percent of IWF A to C and 6% of IWF D to H patients discontinued treatment because of toxicity. The major toxicity was granulocytopenia (grade 3 to 4), which occurred in virtually all patients during the first course of therapy. This study confirms that docetaxel has limited but definite activity in patients with non-Hodgkin's lymphoma and suggests that the previously reported responses with taxanes can not be attributed solely to the use of corticosteroid premedications.
    Journal of Clinical Oncology 11/1997; 15(10):3275-9. · 18.43 Impact Factor
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    B K Seon · F Matsuno · Y Haruta · M. and Kondo · M Barcos
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    ABSTRACT: In the present study, we developed an antitumor immunoconjugate that appears to be promising as a novel curative antitumor agent against a variety of human solid tumors. We generated a new antihuman endoglin (EDG) monoclonal antibody (mAb) K4-2C10 (or termed SN6f) that cross-reacts with mouse endothelial cells. Such cross-reactive anti-EDG mAbs have not been reported previously. This mAb was used to target tumor-associated vasculature in SCID mice inoculated with human tumors. No anti-EDG mAb or its immunoconjugates have previously been successfully used for targeting vasculature in vivo. In this study, MCF-7 human breast cancer cells were inoculated s.c. into SCID mice. K4-2C10 did not react with the MCF-7 cells but showed a weak reactivity with mouse endothelial cells. The mAb reacted with the proliferating endothelial cells more strongly than with the quiescent endothelial cells. The mAb exhibited much stronger reactivity (>10-fold) with human endothelial cells than with mouse endothelial cells and reacted strongly with vascular endothelium of tumor-associated blood vessels in a variety of human malignant tissues. Conjugates of K4-2C10 with ricin A chain (RA) and deglycosylated ricin A chain (dgRA) showed a weak but specific cytotoxic activity against murine endothelial cells in vitro; the 50% inhibitory dose of the RA and dgRA conjugates was 54 nm and 29 nm, respectively. Remarkable antitumor efficacy was observed when a small amount (a total of 60 microgram corresponding to 24% of the LD50 dose) of the dgRA conjugate was administered i.v. into SCID mice that had been inoculated s.c. with MCF-7. Unconjugated mAb K4-2C10 was not significantly effective in the inhibition of the tumor growth. The immunotoxin (IT) completely inhibited growth of the tumor in all of the treated mice (n = 8). Furthermore, similar antitumor efficacy was observed when the IT was administered i.v. into the tumor-inoculated SCID mice that had been pretreated with unconjugated K4-2C10 to block the potentially available weak binding sites of normal tissues. The strong therapeutic effects of the IT were reproduced in another set of therapeutic experiments. No significant side effects were observed in the mice. The differences in the tumor growth between the control group and the IT-treated groups were statistically significant. The IT showed antiangiogenic activity in the dorsal air sac method. The results indicate that K4-2C10 IT effectively treated the tumor-bearing mice by selectively inhibiting the tumor-associated blood vessels and by disrupting tumor-associated angiogenesis. The strong antitumor efficacy of the K4-2C10 IT is remarkable in view of the fact that K4-2C10 and its IT showed only a weak reactivity with mouse endothelial cells, and a relatively small amount of the IT was administered i.v. to treat s.c. tumors. We anticipate that the K4-2C10 IT will show much stronger antitumor efficacy and antiangiogenic activity in patients with solid tumors and other angiogenesis-associated diseases. The present results demonstrate for the first time that an anti-EDG mAb or its immunoconjugate can effectively target tumor-associated vasculature in vivo.
    Clinical Cancer Research 08/1997; 3(7):1031-44. · 8.19 Impact Factor
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    ABSTRACT: To evaluate the activity and toxicity of combined etoposide, vinblastine, and doxorubicin (EVA) in advanced Hodgkin's disease (HD) in relapse from or refractory to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). Eligible patients were more than 15 years of age and had received only one prior course of MOPP and were in relapse with measurable disease. The EVA regimen (etoposide 100 mg/m2 intravenously [IV] on days 1, 2, and 3; vinblastine 6 mg/m2 IV on day 1; and doxorubicin 50 mg/m2 IV on day 1) was administered every 28 days for a minimum of four and a maximum of six cycles. Patients were restaged at 3 and 6 months. Forty-five eligible patients were treated, with an overall response rate of 73%. There were 40% complete responses (CRs) and 33% partial responses (PRs). The median follow-up time in 42 months. The median time to treatment failure (TTF) is 10 months, with 31% continuing progression-free. Eighteen patients achieved a second CR, with only seven recurrences in that group. Failure-free survival and overall survival were significantly better in patients whose first MOPP-induced remission was longer than 12 months and who were free of B symptoms at relapse. Toxicity was primarily myelosuppression, which resulted in two toxic deaths. Pulmonary toxicity was not observed. EVA is an effective second-line regimen for the treatment of HD in relapse following MOPP chemotherapy.
    Journal of Clinical Oncology 09/1995; 13(8):2005-11. · 18.43 Impact Factor
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    ABSTRACT: The follicular non-Hodgkin's lymphomas (NHL) have been among those tumors demonstrated to show frequent responses to alpha interferon in phase I and II clinical trials. In addition, there are data suggesting that alpha interferon demonstrates synergistic antitumor activity with alkylating agents in animal models for a number of tumors. Based on these data, Cancer and Leukemia Group B (CALGB) undertook a phase II pilot study of the combination of interferon rIFN alpha 2b (2 x 10(6) IU/m2 s.c. tiw) and cyclophosphamide (100 mg/m2 per day orally) with the ultimate purpose of examining this combination as long-term therapy of follicular lymphoma in comparison to oral cyclophosphamide alone. One hundred five advanced stage III or IV eligible patients with pathologically diagnosed International Working Formulation B or C histology were entered on CALGB 8553 to determine toxicity and response rates to the combination. Both previously chemotherapy-treated patients (32) and patients without prior chemotherapy (73) were entered on study. For patients without prior chemotherapy the overall response rate to the combination regimen was 86% with 58% of chemotherapy-treated patients achieving complete response. Chemotherapy-treated patients had a total response rate of 62% with only 25% complete responders. Complete responses in patients without prior chemotherapy were positively correlated with absence of B symptoms, and good performance status and negatively correlated with the histological subtype of follicular mixed small-cleaved and large cell histology (IWF C); only performance status was significantly correlated with response in patients who had previously had chemotherapy. Survival at 5 years is estimated to be 63% for those without chemotherapy and 39% for those previously treated with chemotherapy patients. The maximum toxicities experienced during therapy with the combination regimen of cyclophosphamide and interferon alpha were primarily related to myelosuppression. Sixty-seven percent of patients without prior chemotherapy and 65% of patients receiving prior chemotherapy experienced severe leukopenia while severe thrombocytopenia and anemia occurred in 6-31% of these patients. Non-myelosuppressive toxicities were less frequently seen. These response rates are similar to those achieved in a previous CALGB trial with oral cyclophosphamide as a single agent, although severe myelotoxicity was increased to approximately 60% of patients from less than 10% with the single-agent therapy. The combination of alpha interferon and cyclophosphamide administered in this fashion is safe when peripheral counts are carefully monitored. Randomized studies of this regimen in comparison to oral cyclophosphamide are currently in progress.
    Medical and Pediatric Oncology 02/1994; 22(4):228-35.
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    ABSTRACT: In an attempt to improve the efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy for intermediate-grade and high-grade non-Hodgkin's lymphomas, a phase II evaluation of a regimen consisting of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), methotrexate, Oncovin (vincristine; Eli Lilly Co, Indianapolis, IN), prednisone, leucovorin, cytarabine (ara-c), cyclophosphamide, and etoposide (AMOPLACE) was conducted. This regimen includes three additional agents not found in CHOP, uses weekly doses of alternating myelosuppressive and nonmyelosuppressive drugs, and incorporates most single agents active against diffuse lymphomas. Ninety-one previously untreated patients were enrolled and 60 patients were confirmed eligible after central pathology review. Fifty-eight percent of patients had diffuse large-cell lymphoma (DLCL), 83% had stage III or IV disease, and 45% had B symptoms. Patients were treated with six to eight cycles of AMOPLACE and analyzed for response and survival. With a median follow-up of 48 months, complete responses (CRs) were seen in 68% of all patients with failure-free survival (FFS) and overall survival (OS) estimates at 4 years of 45% and 54%. In the DLCL subset, the CR rate was 69% and FFS and OS estimates at 4 years were 49% and 60%, respectively. The major toxicity was myelosuppression, with 73% of patients having WBC nadirs less than 1,000/microL; two treatment-related deaths occurred. We conclude that AMOPLACE is associated with CR and OS rates comparable with those of other third-generation regimens.
    Journal of Clinical Oncology 03/1993; 11(2):248-54. · 18.43 Impact Factor
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    ABSTRACT: Presence of megakaryocytic cells in patients with myeloid disorders were investigated by staining plastic embedded biopsy sections with an anti-Factor VIII antibody (AFA). Two hundred and fifty cases were studied, 207 of whom had acute myeloid leukemia (AML) while 43 had myelodysplastic syndromes (MDS). Abnormal clusters of AFA positive cells indicating multilineage disease were identified in 17% with primary AML (30/175), 38% with secondary AML (12/32) and 42% cases of MDS (18/43). Biological characteristics of these 60 AFA positive cases were investigated. No unique differences in cell cycle characteristics following bromodeoxyuridine (BrdU) were identified. We confirm several recent reports that the incidence of multilineage involvement in AML is substantial.
    Leukemia Research 02/1991; 15(1):51-7. · 2.69 Impact Factor
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    ABSTRACT: Survival data from eight Cancer and Leukemia Group B (CALGB) protocols were examined for patients with lung cancer (N = 961), multiple myeloma (N = 577), gastric cancer (N = 231), pancreatic cancer (N = 174), breast cancer (N = 87), and Hodgkin's disease (N = 58). After accounting for differences in survival rate attributable to type of cancer, initial performance status, age, and 14 other protocol-specific prognostic indicators, the additional predictive value of socioeconomic status (SES) was evaluated. Race (white v non-white) was not a significant predictor of survival time, but income and education were. People with lower annual incomes (below $5,000 per year in the years 1977 to 1981) and those with lower educational level (grade school only) showed survival times significantly shorter than those with higher income or education, respectively. These survival differences were associated with, but could not be fully explained by, severity of disease at initial presentation. SES continued to exert a small but significant impact on cancer survival, even after controlling for all known prognostic variables. Economically and educationally disadvantaged cancer patients may require treatment programs that include education about treatment and compliance, even after an initial diagnosis is made and treatment is initiated. Because SES is related to survival independent of all known prognostic variables, it should be included in the data bases of clinical trial groups to provide a more accurate test of the effectiveness of new therapies.
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    ABSTRACT: Cell cycle characteristics including labeling indices (LI), duration of S-phase (Ts), and total cell cycle time (Tc) were determined in 54 standard-risk, newly diagnosed patients with acute myeloid leukemia following an infusion of bromodeoxyuridine. Remission induction therapy consisting of cytosine arabinoside and daunomycin was then administered to all patients, followed by three courses of consolidation to those who achieved complete remissions (CR). Older patients appeared to have more rapidly cycling cells (P = .003). No unique cell cycle characteristics were identified for patients who achieved remission versus those who had resistant disease. However, the pretherapy cell cycle characteristics were a strong prognosticator for remission duration. CR patients were divided into those whose leukemic cell Tc were above median (A) and below median (B). Among 14 B patients, median duration of response was 211 days, and all relapsed by day 600. Among 18 A patients, the median has not as yet been reached, with nine patients in continuous complete remission (log rank P = .007, Wilcoxon P = .04). We conclude that cell cycle characteristics of leukemic cells play a role in determining remission duration, perhaps because the leukemic cells of the former patients regrow slowly between courses of chemotherapy.
    Blood 01/1991; 76(11):2191-7. · 10.43 Impact Factor
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    ABSTRACT: Between February 1972 and February 1989, splenectomies were performed in 30 patients with chronic lymphocytic leukemia (CLL) and three with prolymphocytic leukemia (PLL) at our institution. Indications for splenectomy included anemia and/or thrombocytopenia (hypersplenism) in 31 patients and symptomatic splenomegaly in two patients. Median time from the diagnosis of CLL to splenectomy was 25 months. Twenty (87%) of the 23 patients splenectomized for thrombocytopenia with or without anemia had platelet increments of greater than or equal to 50 x 10(9)/liter. Hemoglobin increments of greater than or equal to 3 gm/dl were noted in 12 (71%) of 17 patients splenectomized for anemia with or without thrombocytopenia. The median duration of platelet response was 18 months for 19 evaluable patients, and the median duration of hemoglobin response was 62 months for 10 evaluable patients. Median survival time from splenectomy was 36 months. Median survival from diagnosis was 103 months for 10 patients with stage III or IV disease at diagnosis and 79 months for 10 patients with stage II. A prospective study of the effect of splenectomy in a larger number of patients with advanced CLL should be considered.
    Leukemia 12/1990; 4(11):758-60. · 9.38 Impact Factor
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    M Chatterjee · M Barcos · T Han · X L Liu · Z Bernstein · K A Foon
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    ABSTRACT: Antiidiotype (Id) antibodies identify unique determinants within the surface immunoglobulin (Ig) that are present on B-cell tumors. Anti-Ids have been used for diagnosis and therapy of B-cell lymphoma and leukemia. A panel of 29 anti-Id monoclonal antibodies (MoAbs) that recognize shared idiotypes (SIds) on B-cell lymphomas was tested for reactivity with both B-cell leukemias and lymphomas. Ten of 40 (25%) cases of chronic lymphocytic leukemia (CLL) reacted with at least one of the 29 anti-SId MoAbs. Three cases reacted with more than one anti-SId MoAb, but there was no repetitive pattern of a single anti-SId MoAb reacting with a large proportion of CLL cases. In contrast, for B-cell lymphoma, in which 11 of 31 (36%) cases reacted, one anti-SId (B4-1) reacted with five of the positive cases; all were diffuse histology. Restricted anti-SId reactivity may lead to important insights into the etiology of certain B-cell lymphomas. In addition, these anti-SIds may obviate the need to develop "tailor-made" antibodies for individual patients.
    Blood 12/1990; 76(9):1825-9. · 10.43 Impact Factor
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    ABSTRACT: A phase II trial of alpha 2b-interferon in patients with relapsed or refractory Hodgkin's disease was conducted by the Cancer and Leukemia Group B. Nineteen patients were eligible for study. These patients had received at least two (median of four) previous chemotherapeutic programs and 79% had received prior radiation therapy. Three patients had undergone intensive chemotherapy and autologous bone marrow transplantation. The treatment regimen consisted of interferon-alpha 2b 10 X 10(6) IU/m2 subcutaneously three times per week. Only limited antineoplastic activity was seen in this heavily pretreated group of patients. There was one partial response and four patients had reduction in measurable disease not meeting the criteria for partial response. The drug was well tolerated. Toxicity was predominantly myelosuppression. Thrombocytopenia was particularly severe in patients with bone marrow involvement. The observed antineoplastic activity, albeit limited, in this heavily pretreated group of patients suggests a potential role for this agent in combination regimens in patients with earlier disease.
    Journal of biological response modifiers 03/1990; 9(1):1-4.
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    ABSTRACT: . Patients with acute myeloid leukaemia who fail to show substantial bone marrow cytoreduction by day 6 of induction therapy enter complete remission (CR) less frequently than patients with good bone marrow leukaemic cytoreduction. The objective of the current study was to determine whether an increase in the intensity of therapy on days 8, 9 and 10 (‘augmentation’ of remission induction therapy) for patients with poor bone marrow cytoreduction detected in the day 6 bone marrow could improve the complete remission rate without increasing the number of toxic deaths. Patients from six centres were entered and treated with standard dose ara-C for 7 or 10 d and an anthracycline for the first 3 d. Patients aged less than 60 years and with > 30% bone marrow biopsy cellularity or > 10% abnormal cells on the aspirate obtained 6 d after the start of therapy were augmented with cytosine arabinoside 3 g/m2 every 12 h on days 8, 9 and 10. Therapy was augmented in 116 of the 252 patients <60 years. There was a highly statistically significant difference between augmented and nonaugmented patients (P<0.001) for the per cent biopsy cellularity and per cent abnormal cells in the day 6 marrow. The CR rate for augmented patients was 69% and for nonaugmented patients 60% suggesting that augmentation therapy abrogated the prognostic significance of more extensive residual leukaemia in the day 6 bone marrow. The results suggest that augmentation of remission induction for patients with poor bone marrow cytoreduction detected 6 d after initiation of therapy, may salvage patients who are destined to fail remission induction because of resistant disease without producing excessive toxicity.
    British Journal of Haematology 04/1989; 71(4). DOI:10.1111/j.1365-2141.1989.tb06308.x · 4.96 Impact Factor
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    M Laughlin · A Islam · M Barcos · P Meade · H Ozer · M Gavigan · E Henderson · T Han
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    ABSTRACT: Iliac crest trephine biopsy specimens from 16 patients treated with recombinant alpha 2-interferon (alpha-IFN) for hairy cell leukemia (HCL) were examined for reticulin and collagen content. These data were compared with the hairy cell index (HCl), the proportion of hairy cells to the overall cellularity of the bone marrow. Specimens were studied immediately before alpha-IFN therapy, at 6-month intervals during, and in six patients 6 months after cessation of therapy. All patients presented with increased bone marrow fibrosis ranging from focally increased reticulin to a diffuse increase in both reticulin and collagen content. This fibrosis was observed to decrease during alpha-IFN therapy inasmuch as the hairy cell population was diminished in the bone marrow in 13 patients. Regression analysis of HCl v bone marrow fibrosis showed a positive correlation (r = .73, P less than .02). Six patients demonstrated a reduction in bone marrow reticulin and collagen to normal levels during alpha-IFN therapy. Two of six patients demonstrated increased bone marrow fibrosis and HCl 6 months after cessation of alpha-IFN therapy. Three of 16 patients exhibited no decrease in bone marrow reticulin content during therapy despite a decreased bone marrow hairy cell population.
    Blood 10/1988; 72(3):936-9. · 10.43 Impact Factor
  • M Barcos · W Lane · G A Gomez · T Han · A Freeman · H Preisler · E Henderson
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    ABSTRACT: Autopsy data on 1,206 children and adult patients with acute myelocytic leukemia (AML) (585), chronic granulocytic leukemia (CGL) (204), acute lymphocytic leukemia (ALL) (308), and chronic lymphocytic leukemia (CLL) (109) obtained from 1958 to 1982 were reviewed. This analysis has shown that, whereas the proportion of patients with residual AML at any anatomic site decreased significantly and uniformly over the entire study period, significant corresponding decreases in patients with CGL and ALL occurred only since 1976 and 1978, respectively. No significant corresponding decreases were noted in patients with CLL at any time. Significant decreases were also noted over time in the rates of extramedullary site involvement by AML, CGL, and ALL. Whereas the lymphoreticular organs, kidneys, adrenals, and pituitary were most often involved at autopsy by CLL, the testes, leptomeninges, dura mater, uterus, large bowel, and pancreas were most often involved by ALL. In general, patients with AML and CGL showed the lowest relative rates of involvement of the various organs by leukemia during the 24-year period. Whereas patients with AML and ALL showed significant decreases in the rates of involvement of nearly all anatomic sites during the most recent study periods, those with CGL and CLL showed corresponding decreases in only a few organ sites. The lower rates of organ involvement in patients with AML and ALL attest to the more aggressive eradication of leukemic cells by therapeutic regimens in these diseases over time. In particular, the significant decrease in the rate of meningeal involvement by ALL during the most recent period is probably attributable to central nervous system prophylaxis.
    Cancer 09/1987; 60(4):827-37. · 4.90 Impact Factor
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    ABSTRACT: Increased mitotic activity is associated with significantly shorter patient survival in some of the subtypes of diffuse non-Hodgkin's lymphomas. This study on 105 cases of follicular lymphoma was undertaken to determine the clinical significance of mitotic activity in follicular lymphomas. For each case, two pathologists independently counted mitotic figures in 20 random high-power fields. The difference of the average mitotic counts over 20 high-power fields for the two pathologists showed a Gaussian distribution with a median difference of -0.26 counts per high-power field and a standard error of 0.10 per cent. In 94 cases (91 per cent), the difference was less than two mitotic counts per high-power field, indicating good interobserver agreement. There was a statistically significant difference in mitotic counts between subtypes of follicular lymphoma as well as a gradient among subtypes, with the lowest mitotic activity in the poorly differentiated lymphocytic subtype and highest in the undifferentiated subtype. A multivariate statistical analysis of clinical and pathologic variables showed that mitotic figures were not of prognostic significance.
    Human Pathlogy 06/1987; 18(5):502-5. DOI:10.1016/S0046-8177(87)80035-7 · 2.81 Impact Factor

Publication Stats

1k Citations
351.68 Total Impact Points

Institutions

  • 1999
    • Barnes Jewish Hospital
      San Luis, Missouri, United States
  • 1980–1997
    • Roswell Park Cancer Institute
      • • Department of Pathology
      • • Department of Medicine
      • • Department of Medical Oncology
      Buffalo, New York, United States
  • 1994
    • University of North Carolina at Chapel Hill
      • Department of Medicine
      Chapel Hill, NC, United States
  • 1993
    • University of California, San Diego
      San Diego, California, United States
  • 1991
    • University of Cincinnati
      • Division of Hematology Oncology
      Cincinnati, Ohio, United States
  • 1990
    • University of Massachusetts Medical School
      • Division of Rheumatology
      Worcester, MA, United States