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Biomedical subjects

F Cabanillas

Publications and source records attributed to F Cabanillas.

At least 181 records · Page 10Linked to original sources

Lymphomatous presentation of CD4+/CD8+ HTLV-1-related adult T-cell leukemia/lymphoma in an Iranian woman.

Adult T-cell leukemia/lymphoma (ATLL) remains an uncommon disorder outside well-defined risk groups. We describe the case of an Iranian woman, who presented with isolated meningeal relapse of diffuse large-cell lymphoma. The malignant cells coexpressed CD4 and CD8 and HTLV-1 seropositivity was confirmed. Despite combination chemotherapy disseminated lymphoma developed. Preterminally the characteristic features of ATLL were noted; hypercalcemia, with normal parathyroid hormone-related protein and vitamin D levels, and peripheral blood leukemic involvement.

CD4 Antigens↗

T-cell-rich B-cell lymphoma.

We analyzed 23 cases of T-cell-rich B-cell lymphomas (BCL) to determine if the clinical features are characteristic of a discrete entity. Cases encoded as T-cell-rich BCL in the hematopathology archives of the University of Texas M.D. Anderson Cancer Center between 1988 and 1991 formed the basis of this study. At least 50% of the total population of cells were required to be of T-cell phenotype. Actually, all but one patient had more than 70% T cells in the total population. Sixty-five percent of all cases were referred with other diagnosis such as Hodgkin's mixed cellularity, peripheral T-cell lymphoma (PTCL), or diffuse mixed lymphoma, and had received therapy accordingly. With the exception of splenomegaly, which occurred in 35% of cases, the other clinical characteristics and the response to therapy did not indicate that this entity represents a distinct type of lymphoma. Ann Arbor stage I-II presentations were seen in 10 of 23 (43%) T-cell-rich BCLs. Serum lactate dehydrogenase (LDH) was elevated in eight of 19 patients. Age, sex, and beta 2-microglobulin were not significantly different from classical B-cell large cell lymphoma. The clinical presentation and clinical outcome of T-cell-rich BCL did not differ from that of common B-cell large cell lymphoma, except for the higher proportion of splenomegaly seen in patients with T-cell-rich BCL. The presence of the T-cell-rich infiltrate varied: it frequently was not seen at relapse or at other sites of disease at presentation. It was thus considered an unstable parameter. The major importance of identifying this entity is to distinguish it pathologically from other disorders such as Hodgkin's disease and PTCL, which would be treated in a different manner.

Adult↗

Serum interleukin 6 levels are elevated in lymphoma patients and correlate with survival in advanced Hodgkin's disease and with B symptoms.

Several cytokines including gamma-interferon, tumor necrosis factor alpha, interleukin 1 beta (IL-1 beta), and interleukin 6 (IL-6) are pyrogenic and can inhibit lipogenic processes. Because patients with lymphoma often suffer from fever, weight loss, and night sweats (B symptoms), the etiology of which is unknown, the authors investigated serum levels of these cytokines in normal volunteers and in patients with Hodgkin's and non-Hodgkin's lymphoma. Sixty serum samples from patients with Hodgkin's disease (28 patients) or non-Hodgkin's lymphoma (32 patients), as well as 20 samples from normal volunteers, were collected. The majority of patients had advanced (Stage III or IV) or relapsed disease. The assay for gamma-interferon was a specific and sensitive radioimmunoassay (lower limit of detection = 0.1 unit/ml); the assays for tumor necrosis factor alpha, IL-1 beta, and IL-6 were enzyme-linked immunoassays with lower limits of sensitivity of 10 pg/ml, 20 pg/ml, and 22 pg/ml, respectively. There were no statistically significant differences in gamma-interferon, tumor necrosis factor alpha, or IL-1 beta levels between lymphoma patients and normal subjects. In contrast, 20 of 57 patients (35%) with lymphoma as compared with 0 of 19 normal volunteers (0%) had detectable serum IL-6 levels (P < 0.005, chi 2 test). Interestingly, 17 of 29 lymphoma patients with B symptoms (59%) as opposed to 3 of 28 lymphoma patients without B symptoms (11%) had detectable serum IL-6 levels (P < 0.001, chi 2 test); the median IL-6 level was 28.9 pg/ml (B symptoms present) versus undetectable (no B symptoms) (P < 0.005, Mann-Whitney U test). Analyzing Hodgkin's and non-Hodgkin's lymphoma groups separately revealed similar results. IL-6 levels showed no significant correlation with time from diagnosis, beta 2-microglobulin, or lactate dehydrogenase levels. However, analysis by the method of Kaplan and Meir demonstrated that the median survival of Hodgkin's disease patients with detectable IL-6 levels (> or = 22 pg/ml) was 10 mo, whereas the median survival has not been reached at a median follow-up time of 37.5 mo in those patients with lower values (Wilcoxon P value = 0.0012). There were too few patients in each subset of non-Hodgkin's lymphoma to determine the correlation between IL-6 and survival but, considered as a single group, a statistically significant correlation was not found.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗

Analysis of the expression of the hybrid gene bcl-2/IgH in follicular lymphomas.

To investigate the clinical and biologic significance of the circulating t(14;18)-carrying cells in follicular lymphoma (FL) patients, we analyzed the mbr/JH junction of the hybrid bcl-2/IgH gene simultaneously at the DNA and RNA levels by polymerase chain reaction (PCR) in 37 peripheral blood samples from 37 patients in different remission status: 4 before treatment, 8 during treatment, and 25 in complete remission (CR). Of these 37 patients, 22 were positive either at the DNA or RNA level (8 with active disease and 14 in CR). Among these positive patients, RNA was more often negative for patients in CR (9 of 14 [64%]) than for patients with active disease (2 of 8 [25%]; Fisher's exact test, P = .09). Among the 14 patients in CR with residual disease, 2 of 5 with RNA positivity relapsed, whereas 1 of 9 with RNA negativity and DNA positivity relapsed with a median follow-up after sample collection of 8 months (range, 4 to 18 months). Simultaneous analysis of the bcl-2/IgH gene at the DNA and RNA level showed heterogeneous patterns of PCR positivity in regards to the evaluation of the biologic activity of the t(14;18)-carrying cells. A larger study and long-term follow-up will help in determining whether the expression patterns in turn reflect the functional status of disease activity in FL patients.

Base Sequence↗

Antibody response to a two-dose influenza vaccine regimen in adult lymphoma patients on chemotherapy.

A study was conducted to determine if a two-dose regimen of influenza vaccine would enhance the immunologic response of 41 patients with lymphoma receiving chemotherapy. Hemagglutinin-inhibiting antibody responses to influenza A/H1N1, A/H3N2 and B virus occurred in 32%, 24% and 20% of patients following one dose, and in 49%, 41% and 46% of patients following two doses, respectively. Responses to one or more vaccine components occurred in 42% of patients after one dose and in 71% after two doses. Fifty percent of the patients who did not respond after one dose responded after two doses. A two-dose regimen of influenza immunization may significantly enhance the response rate of cancer patients receiving chemotherapy.

Adult↗

The clinical relevance of t(14;18)/BCL-2 rearrangement and DEL 6q in diffuse large cell lymphoma and immunoblastic lymphoma.

BACKGROUND: t(14;18)/bcl-2 gene rearrangement (R) is claimed to impart a worse rate of complete remission and disease-free survival in diffuse large cell lymphoma (DLCL). DEL 6q has also been associated with poor outcome. DESIGN: Retrospective study of 54 patients with either diffuse large cell or immunoblastic lymphoma who had cytogenetics and/or molecular studies performed. RESULTS: Patient characteristics, complete remission rate, and time to treatment failure (TTF) were similar at three year follow-up for groups with and without t(14;18)/BCL-2R. Survival was worse for the former but the difference was not statistically significant. For DEL 6q, patient characteristics and survival rates were similar at three year follow-up for patients with and without the abnormality. TTF was worse for the former but this was not statistically significant. CONCLUSION: This study, with equal or greater number of patients with t(14;18) than previous reports, fails to show a worse prognosis for patients with the t(14;18) chromosomal abnormality. A definite association will await further accrual of patients and a meaningful multivariate analysis.

Adolescent↗

CHOP-Bleo plus interferon for stage IV low-grade lymphoma.

BACKGROUND: Alpha interferon (IFN) is an effective single agent for patients with low-grade lymphoma, but until 1982 had not been integrated with standard chemotherapy for these patients. Since relapse from complete remission (CR) is the rule for patients with advanced stage low-grade lymphoma, a maintenance IFN schedule was explored for patients in CR. PATIENTS AND METHODS: From 1982-1987, 127 patients with stage IV low-grade lymphoma were treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo) for 9-18 mo. (median 13 mo.), followed by interferon alfa-n-1 (Wellferon) maintenance therapy for 24 mo. for CRs. RESULTS: The overall response rate for the entire treatment program was 73% CR and 23% partial remission. The median follow up was 59 months. At 5 years, survival was 74%, failure-free survival (FFS) 47%, and FFS of CRs 60%. Compared to a group of 96 patients with similar pretreatment clinical features treated with CHOP-Bleo from 1972-1982, this represents a significant improvement for both overall FFS (p = 0.01) and FFS of CRs (P < 0.01). Toxicity from the IFN maintenance was generally acceptable, but even at the modest dose employed in this trial (3 x 10(6) U/m2 three times weekly), dose modification was required in more than 30% of patients, usually because of fatigue. CONCLUSIONS: The integration of IFN and conventional chemotherapy is feasible and effective. Maintenance IFN prolongs remission duration for patients with stage IV low-grade lymphoma.

Adult↗

Richter's syndrome: a report on 39 patients.

PURPOSE: The incidence, clinical features, laboratory findings, and treatment results of 39 patients with Richter's syndrome (RS) are reported. PATIENTS AND METHODS: Thirty-nine of 1,374 patients with chronic lymphocytic leukemia (CLL) developed RS. RESULTS: Features associated with RS included systemic symptoms (59%), progressive lymphadenopathy (64%), extranodal involvement (41%), elevation of lactate dehydrogenase (LDH; 82%), and a monoclonal gammopathy (44%). Analysis of the CLL karyotype showed no specific chromosomal abnormality that conferred increased risk; however, multiple abnormalities were common. Patients at all Rai stages and in complete response (CR) were at risk, including three CR patients with no residual disease at the level of detection by dual-parameter flow cytometry or restriction analysis for immunoglobulin (Ig) gene rearrangements. The incidence was not higher in patients who had received prior fludarabine or chlorodeoxyadenosine. The median survival duration was only 5 months, despite multiagent therapy. Patients who responded had prolonged survival durations (P < .001). Three of eight patients who survived more than 1 year had a de novo presentation of both CLL and large-cell lymphoma (LCL). Comparison of surface light-chain analysis from both low- and high-grade components demonstrated isotypic light-chain expression in 12 of 15 patients. Ig heavy- and light-chain gene rearrangement analysis showed identical rearrangement patterns in five of five patients. CONCLUSION: The clinical, laboratory, and survival characteristics of our RS patients were similar to those reported in earlier studies. Ig gene rearrangement and light-chain isotype analysis support a common origin for CLL and LCL. Despite progress in the treatment of CLL, the development of LCL remains a serious complication and continued surveillance in all CLL patients is warranted.

Antineoplastic Combined Chemotherapy Protocols↗

Prognostic role of serum beta 2-microglobulin in Hodgkin's disease.

PURPOSE: To evaluate the role of serum beta 2-microglobulin (beta 2M) in the prognosis of patients with Hodgkin's disease. PATIENTS AND METHODS: One hundred sixty previously untreated patients with Hodgkin's disease had serum beta 2M levels determined before initiation of treatment. Serum beta 2M was tested for its correlation with known prognostic factors for patients with Hodgkin's disease. These variables, including beta 2M, were correlated with complete remission (CR) rate and time to treatment failure (TTF). Univariate and multivariate analyses were performed. RESULTS: Serum beta 2M levels greater than 2.5 mg/L were found in 29% of patients. Such elevation was more common in patients with more advanced-stage disease. Elevated serum beta 2M was an independent and powerful factor in the prediction of lower response rate and shorter TTF. Its impact appeared to be more significant in patients with advanced disease. CONCLUSION: Serum beta 2M appears to correlate with tumor stage in patients with Hodgkin's disease and elevated serum levels of this polypeptide predict a less favorable prognosis.

Female↗

Cisplatin-CBV with autologous bone marrow transplantation for relapsed Hodgkin's disease.

The use of high-dose cyclophosphamide, carmustine, and etoposide (CBV) with autologous bone marrow transplantation (ABMT) results in long-term disease-free survival of about 30% in patients with relapsed Hodgkin's disease. Laboratory and clinical data show that cisplatin is synergistic with etoposide and carmustine, with non-overlapping extramedullary toxicity. Twenty-one patients with relapsed Hodgkin's disease that had progressed after both MOPP-like and ABVD-like regimens were treated with CBV plus cisplatin (90 mg/m2) and ABMT. The CR rate was 55%; the three-year disease-free and overall survival were 29% and 38% respectively; these results are comparable to prior experience with CBV. Performance status was strongly correlated with achievement of CR, survival, and time to treatment failure. Nephrotoxicity was seen in 3 patients, and ototoxicity in 1 patient. Although cisplatin could be added to CBV with minimal additional toxicity, the results obtained in this small patient population were not better than those of the earlier regimen. A larger trial in patients not previously exposed to cisplatin may better define the role of its addition to CBV.

Adolescent↗

Human B cell lymphomas: in vitro and in vivo studies on growth factors and cell growth.

The B cell non-Hodgkin's lymphomas (NHL-B) are a common, but heterogeneous group of human lymphoid neoplasms, consisting of monoclonal populations of neoplastic B lymphocytes demonstrating non-random chromosomal abnormalities, often associated with proto-oncogene translocations. Clinically and pathologically, these lymphomas are classified as low, intermediate, or high grade, according to the clinical aggressiveness of the NHL-B subtype. The clinical behavior can also be correlated with biological function regarding proliferative capabilities of the tumor cells. Our studies have shown that the low grade B cell lymphomas have low constitutive proliferative capacity in vitro and do not respond to cytokine growth factors (CGF), while the high grade NHL-B respond to the B cell growth factor (BCGF) family of CGFs. The high grade NHL-B also secrete BCGFs both in vitro and in vivo, as autocrine growth factors that may provide a target for new therapeutic approaches to therapy.

Animals↗

New initiatives with fludarabine monophosphate in hematologic malignancies.

Fludarabine monophosphate (fludarabine) was initially discovered to have significant activity in indolent lymphoma and chronic lymphocytic leukemia (CLL). The major clinical experience with fludarabine is in previously treated patients with CLL. In such patients the complete and partial response rate (CR + PR) is over 50%. These results were obtained with 5-day schedules of fludarabine 25 to 30 mg/m2/d. Subsequent schedules have explored once-a-week fludarabine and a 3-day schedule every 4 weeks. These strategies, in particular the once-a-week schedule, have obtained inferior results. The addition of prednisone has not been associated with an improvement in response rate or survival. The application of fludarabine to previously untreated patients demonstrated a CR + PR rate of 75% to 80%. The addition of prednisone did not improve the response rate or survival in this group of patients. A significant concern in patients with CLL treated with fludarabine is a decrease in the CD4 and CD8 counts. Despite median posttreatment counts of approximately 200 CD4 lymphocytes/microL, the incidence of infections in patients in remission off therapy is low. Major clinical activity has been demonstrated with fludarabine in Waldenstrom's macroglobulinemia, in which more than one third of refractory patients achieve a CR or PR. Responding patients with anemia or thrombocytopenia have a marked improvement in blood counts. The duration of response has been long (> 30 months) in most responders. The early activity of fludarabine as a single agent in phase I/II studies in indolent lymphoma subsequently has been confirmed by a number of investigators. Fifty percent to 60% of patients with follicular lymphomas respond to fludarabine as a single agent. A number of these responses are complete despite the patients having received extensive prior treatment. A number of combination programs are being developed in CLL and indolent lymphoma. The combination of fludarabine with doxorubicin and prednisone has been developed and is being studied in phase I/II clinical trials. In addition, combinations of fludarabine and cytarabine with or without cisplatin based on elegant preclinical pharmacokinetic rationales have been applied to CLL with impressive cytoreductive activity but significant myelosuppression. A new combination of fludarabine, mitoxantrone, and dexamethasone has been developed for use in lymphoma. Phase I studies demonstrated a high response rate, especially in follicular lymphomas, with a number of patients achieving complete remission. Subsequent phase II studies demonstrate a response rate of 89% in patients with indolent lymphoma.(ABSTRACT TRUNCATED AT 400 WORDS)

Antimetabolites, Antineoplastic↗