Biomedical subjects

Fernando Cabanillas

Publications and source records attributed to Fernando Cabanillas.

46 records · Page 3Linked to original sources

PubMed2002

Quantitative real-time polymerase chain reaction for detection of circulating cells with t(14;18) in volunteer blood donors and patients with follicular lymphoma.

The chromosomal rearrangement t(14;18)(q32;21) involves the major (MBR) or minor (mcr) breakpoint cluster regions and the immunoglobulin heavy chain joining regions (JH) in most follicular lymphomas. As a first step towards determining the clinical significance of circulating cells with t(14;18), we detected and quantitated circulating cells in samples obtained from volunteer blood donors and follicular lymphoma patients. The t(14;18) was co-amplified with beta-actin with real-time quantitative PCR (QRT-PCR) in reactions containing 1 microg of DNA from peripheral blood or bone marrow aspirates. The cell number was quantitated using linear regression and an external standard of serially diluted DNA from cell lines with MBR/JH or mcr/JH rearrangements. At dilutions of 10(5) and 106, sensitivity was 100 and 55% for MBR/JH, and 100 and 10% for mcr/JH rearrangements. Among 102 volunteer blood donors MBR/JH vs. mcr/JH amplicons were detected in 22 vs. 4% with duplicate 1 microg DNA reactions, and in 41 vs. 6% with a total 10 microg DNA analyzed in multiple reactions. Among volunteer blood donors the mean number of circulating cells with MBR/JH vs. mcr/JH rearrangements were 0.8 vs. 0.1/microg DNA, and exceeded the upper normal limit (defined as the mean of all volunteer samples plus two standard deviations) in 3% vs. 2%, respectively. Analysis for MBR/JH rearrangements revealed that follicular lymphoma patients vs. volunteer blood donors were positive in 76% vs. 22% (p = 0.008 by Fisher's exact test); that the mean number of MBR/JH cells per microg of DNA was 91 vs. 0.8 (p = 0.0002 by Mann-Whitney test); and the number of the MBR/JH cells exceeded the upper normal limit in 32% vs. 3% of subjects (p = 0.0001 by Fisher's exact test). Circulating cells with mcr/JH were not detected among any of these 25 lymphoma patients. We conclude that patients with follicular lymphoma are more frequently positive, have higher numbers of circulating cells with t(14;18), which exceed upper normal limit more frequently than in volunteer blood donors.

Blood Cells↗

PubMed2002

Outcomes using doxorubicin-based chemotherapy with or without radiotherapy for early-stage peripheral T-cell lymphomas.

There is little information in the literature on outcomes using doxorubicin-based chemotherapy with or without radiotherapy for early-stage peripheral T-cell lymphomas. The purpose of this study was to analyze The University of Texas M.D. Anderson Cancer Center results in such patients. From 1985 to 1998, 39 patients with Stage I or II World Health Organization classification anaplastic large cell lymphoma (ALCL; n = 20), peripheral T-cell lymphoma, unspecified (PTCLu; n = 11), or nasal-type NK/T-cell lymphoma (NKTCL; n = 8) were treated using doxorubicin-based chemotherapy (median, 6 cycles) with (n = 24) or without (n = 15) radiotherapy (median dose, 40 Gy). Median age was 41 years. Median follow-up of surviving patients was 85 months. Even though patients who presented with bulky disease or who achieved less than a complete response to chemotherapy were the ones typically treated with combined modality therapy rather than chemotherapy alone, there was no significant difference in local control (5-year rates: 60 vs. 70%, p = 0.49), progression-free survival (5-year rates: 65 vs. 60%, p = 0.62), or overall survival (5-year rates: 74 vs. 67%, p = 0.47) between the groups treated with combined modality therapy and chemotherapy alone. Fifteen (38%) patients relapsed. Twelve relapses were limited to the initial site of disease; two involved the initial site and new sites, and one involved only new sites. Based on the significant risk of relapse at the initial site of disease, different approaches, including chemotherapy with concomitant radiotherapy to doses > or = 45 Gy, warrant investigation.

Adult↗

PubMed2002

Apoptotic rate in peripheral T-cell lymphomas. A study using a tissue microarray with validation on full tissue sections.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas with a wide spectrum of clinicopathologic features, and apoptosis mechanisms may have a role in lymphomagenesis. We assessed apoptotic rate (AR) in 112 PTCLs using a tissue microarray developed in our laboratory and a modified terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. The mean AR was 1.47% +/- 1.38% for the entire group of PTCLs (range, 0.06%-5.15%), and AR varied significantly among different tumor types. In mycosis fungoides, the mean AR was 0.74%; angioimmunoblastic T-cell lymphoma, 1.02%; PTCL, not otherwise specified, 1.38%; cutaneous anaplastic large cell lymphoma (ALCL), 1.41%; anaplastic lymphoma kinase protein (ALK)-negative ALCL, 1.43%; extranodal natural killer/T-cell lymphoma of nasal type, 2.04%; ALK-positive ALCL, 2.95%; and enteropathy-type T-cell lymphoma, 3.06%. Mean AR was higher in PTCL with large cell vs small/medium cell morphologic features (1.66% +/- 1.1% vs 0.99% +/- 1.0%). In a subset of 33 PTCLs, the tissue microarray results comparedfavorably with those obtained in full tissue sections. We conclude that the highest ARs in PTCLs are found in enteropathy-type T-cell lymphoma and ALK-positive ALCL, and that AR can be assessed reliably by using a tissue microarray.

Anaplastic Lymphoma Kinase↗

PubMed2002

Metabolic abnormalities in lymphoma.

Metabolic abnormalities occur relatively frequently in lymphoma patients undergoing chemotherapy. These abnormalities include hyperuricemia, hypercalcemia, hyperphosphatemia, hypocalcemia, hypomagnesemia, hyponatremia, and hyperkalemia. In addition, tumor lysis syndrome can result in several metabolic abnormalities, leading to potential renal failure. If these syndromes are identified promptly, they can be corrected. Guidelines for identifying metabolic abnormalities in lymphoma patients, as well as management suggestions, are presented

Adult↗

PubMed2002

BAX expression in Hodgkin and Reed-Sternberg cells of Hodgkin's disease: correlation with clinical outcome.

PURPOSE: BAX, a proapoptotic member of the BCL-2 family of proteins, has been detected in Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin's disease (HD), but its clinical significance is unknown. Therefore, we correlated BAX expression with presenting features and clinical outcome in untreated patients with HD. DESIGN: Patients with biopsy-proven HD were eligible if they were untreated previously and if pretreatment paraffin-embedded tumor tissue was available. BAX was detected by immunohistochemistry without knowledge of clinical features or outcome. A tumor was considered as positive if any number of HRS cells expressed BAX, but other cutoffs of BAX expression were examined for analysis of clinical outcome. RESULTS: We identified 260 patients with HD. The median age was 31 years, and 55% were male. HRS cells expressed BAX in 181 of 195 (93%) nodular sclerosis, 47 of 48 (98%) mixed cellularity, 1 case of lymphocyte depletion, all 6 unclassified classical HD, and all 10 lymphocyte predominance tumors. Using a cutoff of 50% positive HRS cells for BAX expression, the 5-year failure-free survival (FFS) for patients with high versus low BAX expression was 83 versus 93%, respectively (P = 0.19 by Log-rank) for 116 patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalent regimens; it was 78 versus 79%, respectively, for 79 patients treated with mitoxantrone, vincristine, vinblastine, and prednisone and radiotherapy (P = 0.45 by Log-rank); it was 71 versus 81%, respectively, for 26 patients treated with nitrogen mustard, vincristine, prednisone, and procarbazine (P = 0.6 by Log-rank); and it was 72 versus 82% for 29 patients treated only with radiotherapy (P = 0.57 by Log-rank). The 5-year FFS was not statistically different when we used cutoffs of 20, 30, and 75% for BAX expression. CONCLUSION: BAX is often expressed by HRS cells in HD and does not correlate with FFS.

Adolescent↗

PubMed2002

Quantitative real-time polymerase chain reaction for monitoring minimal residual disease in patients with advanced indolent lymphomas treated with rituximab, fludarabine, mitoxantrone, and dexamethasone.

Fludarabine and rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA) are active against indolent lymphomas. We have previously shown the safety and efficacy of the combination of FND (fludarabine/mitoxantrone/dexamethasone) in relapsed and subsequently untreated patients with stage IV indolent lymphomas. Currently, we treat patients with stage IV indolent lymphomas who are previously untreated, younger than 60 years, human immunodeficiency virus-negative, and have adequate organ and marrow function with FND and random assignment to concurrent or delayed administration of rituximab. We have developed a quantitative real-time polymerase chain reaction assay for t(14;18). With 1 microg of DNA, this assay detects 0.6 copies in 55% of reactions, as expected for the Poisson distribution. When 1microg of DNA was analyzed in duplicate, cells with the t(14;18) were detected in peripheral blood of 22% of 152 volunteer blood donors. Quantitation showed that numbers of t(14;18) cells were higher than the statistical upper normal limit (mean of all volunteer values plus standard deviations) in 2% of volunteer blood donors. By contrast, 36% of blood or marrow specimens from follicular lymphoma patients were positive, and the number of cells with t(14;18) was higher than the normal upper limit in 26%. The presence of cells with t(14;18) and their numbers are prospectively quantitated in blood and marrow of patients treated with FND plus rituximab to determine their clinical significance both at presentation and during therapy.

Actins↗

PubMed2000

Managing Indolent Lymphomas in Relapse: Working Our Way Through a Plethora of Options.

The front-line management of stage IV indolent non-Hodgkin's lymphoma has ranged from the watch-and-wait approach to intensive experimental regimens such as high-dose chemotherapy and bone marrow transplant. With this broad spectrum of regimens to choose from the decision has become a challenging exercise for both patients and oncologists. With the recent introduction of new agents such as rituximab, fludarabine, and combinations based on these, the management of relapsed cases can be similarly confusing. More aggressive approaches such as high-dose chemotherapy with autologous bone marrow transplant and more recently allogeneic bone marrow transplant have also been used. Recently the technique of "mini-allo transplants" has been introduced. It utilizes a less myelosuppressive conditioning chemotherapy regimen based on fludarabine which is immunosuppressive enough to allow engraftment of the donor marrow. Since it is less myelotoxic it is better tolerated, and this has allowed us to significantly extend the age cut-off for allogeneic transplants. All these advances provide us with a more extensive armamentarium, but at the same time they confront physicians with new challenges in choosing from a large and continuously growing therapeutic menu. In this review of the alternative therapies a panel of three expert hemato-oncologists each discuss their approach to the management of a 49-year-old patient with a relapsed indolent follicular lymphoma. Dr. Horning discusses the traditional alternatives available for this patient such as standard chemotherapy combinations or the watch-and-wait approach in Section I. In Section II, Dr. Kaminski reviews the different therapeutic monoclonal antibody options such as rituximab, Bexxar (Iodine-labeled anti-CD20) and Ytrium-labeled anti-CD20 antibody. Allogeneic transplants are increasingly more popular for the treatment of indolent lymphomas because they can provide an immune-mediated graft-versus-lymphoma effect. In Section III, Dr. Richard Champlin reviews various transplant options including autologous, allogeneic and mini-allogeneic transplants.

Journal Article↗

PubMedDate not supplied

Radiotherapy alone for lymphocyte-predominant Hodgkin's disease.

PURPOSE: The purpose of the study was to analyze the results with radiotherapy alone in a select group of asymptomatic adults with nonbulky, early-stage lymphocyte-predominant Hodgkin's disease. PATIENTS AND METHODS: Between 1963 and 1995, 36 patients with nonbulky stage IA (N = 27) or IIA (N = 9) supradiaphragmatic (N = 27) or subdiaphragmatic (N = 9) lymphocyte-predominant Hodgkin's disease were treated with radiotherapy alone. Eleven of the patients underwent laparotomy. Limited-field radiotherapy involving only one side of the diaphragm and extended-field radiotherapy encompassing both sides of the diaphragm were used in 28 and 8 cases, respectively. Median dose to involved areas was 40.0 Gy given daily in 20 2.0-Gy fractions. Salvage treatmentconsisted of MOPP (mechlorethamine, vincristine, prednisone, procarbazine), CVPP/ABDIC (cyclophosphamide, vinblastine, procarbazine and prednisone/doxorubicin, bleomycin, dacarbazine, lomustine, and prednisone), or ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy and/or involved-field radiotherapy. RESULTS: Median follow-up was 8.8 years (range, 3.0-34.4 years). None of the 15 patients with supradiaphragmatic disease who received limited-field radiotherapy to regions that did not include the mediastinal or hilar nodes subsequently experienced relapse there. Only one of 20 patients who received supradiaphragmatic limited-field radiotherapy alone experienced relapse in the paraaortic nodes or spleen. The 5-year relapse-free and overall survival rates for the 20 patients with stage IA lymphocyte-predominant Hodgkin's disease treated with involved-field or regional radiotherapy were 95% and 100%, respectively. There were no cases of severe or life-threatening cardiac toxicity. No solid tumors have been observed in-field in patients treated with limited-field radiotherapy, even though they have been followed up longer than those treated with extended-field radiotherapy (median follow-up, 11.6 vs 5.5 years); two solid tumors have developed in-field in patients who received extended-field radiotherapy. DISCUSSION: Involved-field or regional radiotherapy alone may be adequate in stage IA lymphocyte-predominant Hodgkin's disease patients. Longer follow-up will help to more clearly define the risks of cardiac toxicity and solid tumors that result from involved-field or regional radiotherapy, which appear to be low based on follow-up to date.

Adolescent↗

PubMedDate not supplied

Importance of esophagogastroduodenoscopy in the evaluation of non-gastrointestinal mucosa-associated lymphoid tissue lymphoma.

PURPOSE: Mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal low-grade B-cell lymphoma that most commonly presents in the gastrointestinal (GI) tract. However, it can present in non-GI primary sites. This study was conducted to determine the incidence of gastric involvement in non-GI presentation of MALT lymphoma. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 36 consecutive patients who presented with non-GI MALT lymphoma and had EGD as a part of the initial staging work-up between 1992 and 2001. RESULTS: The median age was 62 years (range, 27-82); 27 were female patients. The frequency of the primary site was; salivary gland/parotid gland (N = 14), ocular adnexa (N = 7), lung (N = 3), oral cavity (N = 3), skin (N = 3), thyroid (N = 2), nasopharynx (N = 2), larynx (N = 1), breast (N = 1). Twelve patients were found to have gastric involvement; 2 additional patients progressed in the stomach 5 and 6 months later, respectively. DISCUSSION: Routine evaluation of the stomach should be a part of the initial staging work-up of non-GI MALT lymphoma.

Adult↗

PubMedDate not supplied

Molecular response of follicular lymphoma to cyclophosphamide, doxorubicin, vincristine, prednisone C(H)OP or COP-based therapy as measured by polymerase chain reaction evidence of translocation (14;18)(q32;q21).

PURPOSE: Existing data suggest that conventional C(H)OP (cyclophosphamide, doxorubicin, vincristine, prednisone) regimen may not be intensive enough to achieve molecular response, as measured by polymerase chain reaction (PCR) evidence of translocation (14;18)(q32:q21) for follicular lymphoma. This study was undertaken to study the molecular response rate of follicular lymphoma to C(H)OP-based therapy and to analyze prognostic factors for molecular response. PATIENTS AND METHODS: Twenty patients with pretreatment PCR evidence of t(14;18)(q32; q21) and at least one posttreatment PCR analysis after the initiation of the treatment with C(H)OP with or without radiation therapy constituted the basis for this analysis. The random effects logistic model was used to analyze the data. The following factors were investigated for their relationship to molecular response: gender, age, beta2-microglobulin, use of radiation therapy, Ann Arbor stage, and international Prognostic Index for malignant lymphoma. RESULTS: Median follow-up was 56 months (range, 23-153 months). A total of 135 PCR results were available, 33 from bone marrow and 102 from peripheral blood. Overall, there was a clear and steady decreasing trend toward loss of PCR positivity with increasing time aftertreatment. By univariate analysis, stage > or = 3, stage = 4, International Prognostic Index > or = 2, and no radiation therapy were adverse factors for molecular response. On multivariate analysis, Ann Arbor stage IV and no radiation therapy were independent risk factors for PCR positivity, both for the peripheral blood data analyzed alone and for all data combined. DISCUSSION: It is possible to achieve molecular response with C(H)OP with or without radiation therapy in patients with follicular lymphoma. Response rate depends on the Ann Arbor stage and radiation therapy.

Adult↗