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Biomedical subjects

F Cabanillas

Publications and source records attributed to F Cabanillas.

At least 145 records · Page 8Linked to original sources
PubMed1996

Hodgkin's disease variant of Richter's syndrome: experience at a single institution.

Patients developing Hodgkin's disease (HD) after a diagnosis of chronic lymphocytic leukemia (CLL), are frequently included in a series of patients with Richter's syndrome (RS). We sought to determine the natural history of the association of CLL and HD. Over a 21 year period, 1374 patients with CLL have been registered in our computer data base. Seven cases of CLL and HD have been documented and confirmed. The median age of these patients was 71 years (range 44-77) and clinical features included male gender (86%), B symptomatology (86%), rapidly progressive lymphadenopathy (71%), prior CLL therapy (71%), advanced Ann Arbor stage (86%), marrow involvement with HD (43%), and autoimmune hemolytic anemia (29%). HD was documented by excisional lymph node biopsy in six cases and splenectomy in one. Mixed cellularity HD was shown in six and nodular sclerosis in one. Five of the biopsies revealed intervening areas consistent with small lymphocytic lymphoma. The Sternberg-Reed (SR) cells were CD15+ in 6/7 cases, and Ki-1+ in the 6 patients tested. CD45 and CD20 staining of the SR cells was nonreactive. The median time to development of HD was 45 months (range 0 to 96). The overall responses to different chemotherapy regimens was approximately 25% with only one CR. Six patients have died at 3, 9, 10, 13, 15 and 36 months and one patient is alive with progressive disease at 11 months. Our data suggests that CLL patients have a heightened risk for HD, features of advanced HD on presentation, and a poor response rate with short survival.

Adult↗
PubMed1996

Endocrine characterization of primary mediastinal lymphoma.

Because of the characteristic presentation of primary mediastinal large cell lymphoma (PMLCL) in young females its known origin from thymic B-cells, there might be a role in lymphomagenesis for estrogen receptors as well as for known neuroendocrine thymic mediators. A retrospective review of all patients with diffuse large cell lymphoma seen at our institution from January 1985 to January 1994 revealed 75 consecutive cases with a diagnosis of PMLCL. Through retrieval from our pathologic archives and requests to outside pathologists, we recovered and analyzed 17 biopsy specimens for the presence of the following hormone receptors: estrogen, beta endorphin, prolactin, T3, growth hormone, and leutinizing hormone. None of the specimens stained for any of the reagents. The most plausible explanation is that PMLCL tissues are devoid of these hormonal receptors and thus these receptors do not seem to play a role in the pathogenesis of PMLCL.

Biopsy↗
PubMed1996

Mantle cell lymphoma: a lymphoproliferative disorder associated with aberrant function of the cell cycle.

Mantle cell lymphoma is a B cell lymphoproliferative disorder cytogenetically characterized by the t(11;14)(q13;q32) which at molecular level involves the Bcl-1/PRAD-1 gene. Immunophenotypically it is characterized by co-expression of CD5+/CD20+ and CD23- antigens. Histologic patterns are recognized as: diffuse, mantle zone and nodular. Diffuse mantle lymphoma is the most frequent and is associated with a poor prognosis. The rearrangement of the Bcl-1/PRAD-1 increases the synthesis of cyclin D1. Cyclin D1 binds to Cdk4 and forms a complex, then binds to and phosphorylates Rb protein thus triggering cells to progress from G0/G1 to S and thus drives cellular proliferation. The 5-year survival in the MD Anderson series was less than 30% and anthracycline regimens do not appear to have any major impact on the outcomes of cases with nodular or diffuse histopathological patterns. Intensive therapeutic programs and first line autologous or allogeneic bone marrow transplantation remains experimental.

Antineoplastic Agents↗
PubMed1995

Chromosome X numerical abnormalities in patients with non-Hodgkin's lymphoma. A study of 59 patients using fluorescence in situ hybridization.

Chromosome X numerical abnormalities are frequently observed in non-Hodgkin's lymphoma (NHL), with an incidence of 3% to 14% for chromosomal loss and 7% to 33% for chromosomal gain. Because sex chromosome numerical abnormalities are thought to be due to aging, little information is known about their relation to gender, therapy, and prognosis. Therefore, to determine the incidence and clinical relevance of this abnormality in NHL, we studied specimens from 59 NHL patients (31 men and 28 women) by fluorescence in situ hybridization (FISH) using a directly conjugated centromeric probe for chromosome X. The median age for the entire group was 52 years (range, 31-88 years). All specimens were obtained by fine-needle aspiration of diseased lymph nodes. Sex-matched lymphocytes from benign hyperplastic lymph nodes were used as controls. The overall incidence of chromosome X numerical abnormalities was 49.2%. Female patients had a higher overall incidence than males (76% vs. 24%; p < 0.001). The median percentage of cells involved in this abnormality in each specimen was 5.2%. There was no statistically significant difference in the incidence in previously treated than untreated patients (53.1% vs. 44.4%; p < 0.75) and in intermediate-grade NHL than low-grade NHL (61.1% vs. 50%; p < 0.75). There was a trend towards a higher incidence of chromosome X loss in older patients. While the difference in the incidence of chromosome X abnormalities observed between women and men may be due to the difference in the normal copy numbers of this chromosome in each sex group, this abnormality remained higher than any other autosomal chromosome abnormality in NHL previously evaluated by FISH. We conclude that, although FISH detected a high incidence of chromosome X numerical abnormalities and that females had a higher incidence than males, only a small percentage of the cells were involved, suggesting that this abnormality is most likely a secondary genetic defect that is not important in the pathogenesis of NHL.

Adult↗
PubMed1995

Identification of B-cell growth factors (interleukin-14; high molecular weight-B-cell growth factors) in effusion fluids from patients with aggressive B-cell lymphomas.

The molecular basis of neoplastic B-cell growth is complex and poorly understood. Cytokines have been postulated to contribute to neoplastic cell growth, and many in vitro studies have confirmed this prediction, but little is known about the in vivo role of these growth factors. We have examined the production of interleukin-14 (IL-14) (high molecular weight [HMW], B-cell growth factor [BCGF]) by aggressive intermediate (diffuse large cell) lymphomas of the B-cell type non-Hodgkin's lymphoma (NHL-B) in four patients with lymphomatous effusions. In these studies, IL-14 was detected in the effusion fluids by Western blots and IL-14 mRNA was constitutively expressed in the freshly isolated lymphoma cells that also expressed the receptor for IL-14 (IL14R). Lymphoma B cells placed at low serum and cell density proliferated in vitro to either purified IL-14 or IL-14 derived from effusion fluids. Antibodies to IL-14 removed the growth-stimulating cytokine(s) from the effusions. Cell lines developed from these patients produced IL-14 in vitro and antisense oligos to IL-14 blocked their growth in vitro. Thus, autocrine or paracrine production of IL-14 may play a significant role in the rapid proliferation of aggressive NHL-B. Interrupting this pathway could be a useful goal of therapy for patients resistant to conventional chemotherapy.

Aneuploidy↗
PubMed1995

Decreased expression of the deleted in colorectal carcinoma gene in non-Hodgkin's lymphoma.

The putative tumor suppressor gene deleted in colorectal carcinoma (DCC), located on human chromosome band 18q21, is deleted or inactivated in many solid tumors. Its role in the pathogenesis of non-Hodgkin's lymphoma (NHL) has not been studied. Recently, inactivation of this gene was reported in cases of leukemia with monosomy 18. As monosomy 18 is frequently observed in low-grade NHL, we investigated the incidence of altered DCC gene expression in patients with NHL, and correlated it with the number of copies of chromosome 18. Fifteen unselected cases of NHL were studied for evidence of DCC gene expression by reverse transcriptase-polymerase chain reaction. The results were correlated with Southern blot analysis of the DCC gene and with the number of copies of chromosome 18 determined by fluorescent in situ hybridization (FISH). The controls were tissues from normal colon mucosa and normal tonsils. Eight of 15 (53%) NHL cases lacked DCC mRNA, and one expressed substantially less than normal. Southern blot analysis showed normal configuration of the DCC gene in all samples. Two copies of chromosome 18 were found in 9 of 11 samples studied by FISH: one case had a subpopulation of cells with monosomy 18 and one had trisomy 18. All controls expressed DCC. We conclude that DCC gene expression is frequently absent or decreased in NHL and may be involved in the pathogenesis of NHL. Monosomy 18 was not required for DCC inactivation.

Adult↗
PubMed1995

Serum levels of interleukin-10 in patients with diffuse large cell lymphoma: lack of correlation with prognosis.

Interleukin-10 (IL-10), also known as cytokine synthesis inhibitory factor, has multiple effects on lymphoid development. In addition, it has been previously reported that serum levels of IL-10 correlate with failure-free and overall survival in patients with non-Hodgkin's lymphoma. In this study, we used a sensitive enzyme-linked immunosorbent assay specific for human IL-10 (lower limit of sensitivity, 5 pg/mL) to measure serum levels in 52 newly diagnosed patients with diffuse large cell lymphoma and at least one adverse prognostic feature who were subsequently treated in a uniform way. Lymphoma patients had significantly higher serum levels of IL-10 (median, 7.98 pg/mL; range, < or = 5 to 27,143 pg/mL) than healthy volunteers (N = 50; median, < or = 5 pg/mL; range, < or = 5 to 19.21 pg/mL) (P = .0000012). Individuals with B symptoms had significantly higher serum levels of IL-10 than those without them (P = .03), but there was no correlation between IL-10 levels and any of the other prognostic variables analyzed, including age, lactic dehydrogenase, beta 2-microglobulin levels, performance status, bulky disease, Ann Arbor stage, or International Index score. More importantly, we found no correlation between IL-10 levels and the achievement of complete remission, nor with failure-free survival or overall survival. We conclude that in a uniform population of untreated patients with diffuse large cell lymphoma, serum levels of IL-10 do not appear to have any prognostic value.

Adult↗
PubMed1995

Lymphomatoid papulosis: a T-cell dyscrasia with a propensity to transform into malignant lymphoma.

OBJECTIVE: To describe the diagnostic difficulties, response to therapy, and clinical features of lymphomatoid papulosis and the cumulative frequency of transformation to lymphoma. DESIGN: Case series. SETTING: University hospitals. METHODS: The records of 21 patients with lymphomatoid papulosis who were seen from 1986 to 1993 were retrieved from the archives of two institutions. The entry criteria for the study were lymphomatoid papulosis misdiagnosed at the time of original presentation or lymphomatoid papulosis that later developed into lymphoma. RESULTS: When lymphomatoid papulosis tissues are pathologically examined, they are frequently confused with lymphoma, melanoma, or carcinoma. Eight of the 19 patients whose condition was misdiagnosed as malignant received either chemotherapy or radiotherapy. Although lymphomatoid papulosis responded to cytotoxic chemotherapy, the remissions were transient and promptly recurred after or during treatment. However, all five cases that became malignant responded to chemotherapy and have not recurred. Five of 21 patients (24%) developed lymphoma, but the cumulative risk for transformation after 15 years was 80%. CONCLUSIONS: Lymphomatoid papulosis can only be diagnosed accurately through a careful history in which the characteristic waxing and waning of the skin lesions is identified and through proper communication between clinicians and pathologists. Patients with lymphomatoid papulosis have an increased risk for developing lymphoma that is much higher than the 15% to 20% quoted in the literature. Patients who develop lymphoma respond well to cytotoxic chemotherapy and can be cured with appropriate therapy. Internists and oncologists need to be aware of lymphomatoid papulosis and its characteristic clinical features so that this disorder is accurately diagnosed and so that unnecessary and potentially hazardous treatment is avoided.

Adolescent↗
PubMed1995

Significance of tumor size and radiation dose to local control in stage I-III diffuse large cell lymphoma treated with CHOP-Bleo and radiation.

PURPOSE: The purpose of this study was to evaluate the possible effect of adjunctive involved field (IF) radiotherapy on long-term local control for patients with Ann Arbor Stage I-III diffuse large cell lymphoma (DLCL) who achieved a complete remission on a combined modality program which included cyclophosphamide, doxorubicin, vincristine, prednisone, and Bleomycin (CHOP-Bleo). METHODS AND MATERIALS: One hundred and ninety patients with Ann Arbor Stage I-III DLCL were treated with CHOP-Bleo and radiotherapy. Analyses were undertaken to determine (a) response to treatment according to stage, extent of maximum local disease, and irradiation dose either < 40 Gy or > or = 40 Gy and (b) relapse patterns. RESULTS: A complete remission (CR) was achieved in 162 patients. Among patients who achieved a CR, local control was better for those who received tumor doses of > or = 40 Gy (97%) than for those who received < 40 Gy (83%) (p = 0.002.) Among those with extensive local disease, the corresponding control rates were 88% and 71%, respectively. A study of distant relapse patterns following a CR showed that the first relapse usually involved an extranodal site. CONCLUSION: Radiotherapy was an effective adjunctive treatment to CHOP-Bleo for patients with stage I-III DLCL who achieved a CR. Patterns of relapse suggested that total nodal irradiation (TNI) possibly could have benefited a small subset of patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Primary lymphoma of the prostate: good outcome with doxorubicin-based combination chemotherapy.

Primary lymphoma of the prostate was diagnosed in 3 patients corresponding to 0.1% of those with previously untreated lymphoma and 0.09% of those with previously untreated prostatic malignancy presenting to our cancer center between January 1, 1980 and December 31, 1993. All 3 patients had prostatism at presentation that caused renal failure in 2. After treatment with doxorubicin-based combination chemotherapy appropriate for the stage and the specific histological subtype, all 3 patients achieved a complete remission and remained free of disease after a minimum followup of 3 years. Our results suggest that primary prostatic lymphoma is not necessarily associated with a poor outcome. Review of the literature suggests that the poor prognosis reported for prostatic lymphoma might be explained by treatment that was acceptable at the time but would be considered suboptimal by current criteria. We recommend thorough staging in all patients with prostatic lymphoma and treatment with a doxorubicin-based regimen according to disease stage and histological classification.

Adolescent↗
PubMed1995

Cyclosporin plus doxorubicin, vincristine and etoposide in the treatment of refractory non-Hodgkin's lymphoma: a phase II study.

In an attempt to circumvent clinical multidrug resistance, we conducted a Phase II trial of cyclosporin plus combination chemotherapy in patients with relapsed or refractory non-Hodgkin's lymphoma. Thirteen patients, all of whom had been previously treated with a doxorubicin-containing regimen, received doxorubicin 50 mg/m2 intravenous continuous infusion (IVCI) over 96 h (days 1-4), vincristine 2 mg i.v. (day 1), and etoposide 75 mg/m2 i.v. daily for 4 days (days 1-4). Four days prior to chemotherapy, patients received a loading dose of cyclosporin (0.88 mg/kg i.v. over 2 h), followed by a maintenance dose (1.8 mg/kg per day IVCI for 9 days). Cyclosporin dose escalation was permitted, conventionally defined therapeutic levels of cyclosporin were achieved; this drug was well tolerated at these doses. The study was closed due to a poor response rate; only one patient achieved a complete remission of 33 weeks' duration. Grade 3 and 4 toxicities included gastrointestinal haemorrhage (one patient), sensory neuropathy (two patients), stomatitis (two patients), and transaminase elevation (one patient). Asymptomatic grade 1-2 toxicities (elevated creatinine and transaminase levels) occurred in 33% of patients. There were no treatment associated deaths. Prolonged neutropenia and thrombocytopenia were the primary haematological toxicities. Although the addition of cyclosporin at this dose and schedule did not improve response rates in this patient group, future trials using higher doses of cyclosporin with combination chemotherapy may warrant further investigation.

Adult↗
PubMed1995

Serum interleukin-6 levels correlate with prognosis in diffuse large-cell lymphoma.

PURPOSE: Interleukin-6 (IL-6) is a potent immunomodulatory cytokine that may have pathogenetic and prognostic significance in a number of disorders. The objective of this study was to examine the correlation between serum IL-6 levels and phenotypic characteristics, as well as outcome of patients with diffuse large-cell lymphoma (DLCL). PATIENTS AND METHODS: Using an enzyme-linked immunosorbent assay (ELISA; lower limit of sensitivity, 0.35 pg/mL), we measured IL-6 levels in frozen sera from 33 healthy controls and 58 untreated patients with DLCL who were enrolled onto a single combination chemotherapy protocol. Serum IL-6 levels were correlated with clinical and laboratory features at diagnosis and with failure-free and overall survival. RESULTS: Serum IL-6 levels in the lymphoma patients (median, 4.37 pg/mL; range, < 0.35 to 110 pg/mL) were significantly higher than in the control group (median, < 0.35 pg/mL; range, < 0.35 to 1.87 pg/mL) (P < .0001). Serum IL-6 levels were higher in patients with B symptoms (P = .012), an elevated beta 2-microglobulin level (> or = 3.0 mg/L) (P = .017), and a poor performance status (P = .02). Direct linear correlations with the erythrocyte sedimentation rate (ESR), platelet count, and total WBC count, and an inverse linear correlation with the serum albumin level, were observed (all P < .02). Patients with elevated serum IL-6 levels had inferior failure-free (P = .042) and overall survival (P = .05) compared with those with normal serum IL-6 levels. CONCLUSION: In patients with DLCL, elevated serum levels of IL-6 at diagnosis are frequent, strongly associated with many adverse disease features, and predictive of a poor failure-free and overall survival.

Adult↗
PubMed1995

Testicular lymphoma: late relapses and poor outcome despite doxorubicin-based therapy.

PURPOSE: To determine the significance of the International Prognostic Index (IPI) score in adults with testicular lymphoma treated with doxorubicin-based regimens. PATIENTS AND METHODS: Untreated adults with testicular lymphoma who presented between 1969 and 1993 were studied. Those with Ann Arbor stages III and IV were included if they had a testicular mass at presentation. RESULTS: We identified 22 patients, 21 with intermediate-grade and one with high-grade lymphoma. All 10 patients with an IPI score < or = 1 had Ann Arbor stage I disease, whereas the 12 with an IPI score more than 1 had Ann Arbor stage II to IV disease. Complete remission (CR) was achieved in 73% of patients. At 153 months, 22% of all complete responders and 40% and 0% of those with IPI scores < or = 1 and more than 1, respectively, remained in CR (P = .01). With a median follow-up time of 113 months for survivors, the failure-free survival (FFS) rate at 153 months was 16% for all patients or 32% and 0% for those with IPI scores < or = 1 and more than 1, respectively (P = .02). The CNS or contralateral testis were involved in all patients who failed to respond to primary therapy and in 50% of those who relapsed from CR. CONCLUSION: The prognosis of patients with testicular lymphoma appears poor despite doxorubicin-based chemotherapy. On the basis of failures in the CNS and contralateral testis, we recommend prophylactic intrathecal chemotherapy and scrotal radiotherapy for all patients. Those with an IPI score < or = 1 can be treated with conventional doxorubicin-based regimens, but those with an IPI score more than 1 should be considered for investigational systemic therapy.

Adult↗
PubMed1995

16-year experience at M. D. Anderson Cancer Center with primary Ki-1 (CD30) antigen expression and anaplastic morphology in adult patients with diffuse large cell lymphoma.

One hundred and seven adult cases of untreated diffuse large cell lymphoma (DLCL) were retrospectively analyzed for primary CD30 antigen expression, anaplastic morphology, and long-term prognosis. Tissue samples from 36 patients stained strongly for CD30, and of these, 22 showed anaplastic morphology. Patients with CD30-positive DLCL presented more frequently with skin involvement, constitutional symptoms, more advanced Ann Arbor stage disease, and at a younger age when compared to patients with CD30-negative DLCL. Both groups had a similar complete response rate (78%). Patients with CD30-positive DLCL had a favorable survival rate when compared to patients with CD30-negative DLCL, although the difference was not statistically significant (73% vs. 55%, p = 0.28). Among the CD30-positive DLCL patients, those with anaplastic morphology presented more frequently with extranodal disease and T-cell phenotype when compared to patients with non-anaplastic morphology, but both groups had similar rates of complete response and long-term survival. All 107 patients were treated initially with a doxorubicin-containing chemotherapy regimen. These findings suggest a favorable outlook for adult patients with DLCL that has primary CD30 antigen expression regardless of the presence or absence of anaplastic morphology. Which support our previous observations.

Follow-Up Studies↗