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F Cabanillas

Publications and source records attributed to F Cabanillas.

At least 127 records · Page 7Linked to original sources
PubMed1997

Long-range amplification of genomic DNA detects the t(2;5)(p23;q35) in anaplastic large-cell lymphoma, but not in other non-Hodgkin's lymphomas, Hodgkin's disease, or lymphomatoid papulosis.

DESIGN: Determine the frequency of t(2;5)(p23;q35) in anaplastic large-cell lymphoma (ALCL), non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), and lymphomatoid papulosis (LP). PATIENTS AND METHODS: The t(2;5) was detected with a long-range nested polymerase chain reaction (PCR) using 0.5 microgram of DNA (60,000-80,000 cells), 5'-primers from the NPM gene, 3'-primers from the ALK gene, agarose electrophoresis, hybridization, and autoradiography. Patients were evaluable if a 3016 base pair amplicon could be generated from tumor DNA with beta-globin primers. RESULTS: Amplicons were detected by PCR of genomic DNA from three ALCL cell lines and four primary ALCLs known to t(2;5) positive. DNA from t(2;5)-positive cell lines diluted 10(4)-fold or 10(5)-fold generated amplicons in 100% or 20% of reactions, respectively. Archival tumor DNA from 144 patients was amplifiable by beta-globin amplicons in 126 (88%) who are considered evaluable for this study. Twenty-two had ALCL, 69 other NHLs, 30 HD, and five LP. Genomic DNA PCR detected the t(2;5) in 5 of 22 with ALCL (23%, 95% confidence intervals [95% CI] 8%-45%) but not in those with NHLs, HD, or LP. Among ALCLs the t(2;5) was confined to 5 of 20 with nodal presentations (25%, 95% CI 9%-49%), among whom it was seen in 5 of 15 with T-cell or null-cell phenotype (33%, 95% CI 12%-62%), in 4 of 11 with age < 40 years (36%, 95% CI 11%-69%), and in 4 of 9 with nodal presentations, T-cell or null-cell phenotype, and age < 40 years (44%, 95% CI 14%-79%). Amplicon sizes were different between cell lines and patients, reflecting unique genomic DNA breakpoints, as confirmed by DNA sequencing, and served as an internal control against specimen cross-contamination in the laboratory. CONCLUSIONS: Long-range PCR of genomic DNA detects t(2;5) only in ALCL, but not in other NHLs, HD, or LP. Long-range PCR may be useful in establishing diagnosis, determining prognosis, and monitoring minimal residual disease in ALCL.

Adolescent↗
PubMed1997

CD30-ligand and CD40-ligand expression in lymph nodes involved with Hodgkin's disease.

BACKGROUND: Reed-Sternberg cells of Hodgkin's disease express CD30 and CD40 receptors. The ligands for these receptors have been reported to have pleiotropic biologic activities in vitro, including induction of cell death and enhancing cell survival. Co-expression of the ligands for these receptors in lymph nodes involved with Hodgkin's disease is not known. PURPOSE: The purpose of this study was to examine CD30 ligand (L) and CD40L expression in lymph nodes of patients with Hodgkin's disease, and to study CD30L expression on nodal lymphocyte subsets. MATERIALS AND METHODS: CD30L expression on subsets of lymphocytes of five lymph nodes involved with Hodgkin's disease was determined by two-color FACScan. Messenger RNA expression of CD30L and CD40L was determined by the reverse-transcriptase polymerase chain reaction (RT-PCR) method performed on seven specimens involved with Hodgkin's disease (five lymph nodes and two spleens). RESULTS: Four of seven specimens (57%) contained cells that expressed CD30L mRNA and three specimens (43%) contained CD40L-expressing cells. The mean percentage of nodal lymphocytes expressing CD30L surface protein was < or = 20%. CONCLUSION: Hodgkin's disease lymph nodes and spleens frequently lack CD30L- and CD40L-expressing cells, and when CD30L is expressed, it is usually detected on few numbers of lymphocytes. The balance in the level of expression of these ligands in Hodgkin's disease lymph nodes may be related to the disease's clinical behavior.

CD40 Antigens↗
PubMed1997

Allogeneic transplantation for recurrent or refractory non-Hodgkin's lymphoma with poor prognostic features after conditioning with thiotepa, busulfan, and cyclophosphamide: experience in 44 consecutive patients.

We report the outcomes of 44 consecutive patients with non-Hodgkin's lymphoma (NHL) who participated in prospective studies of allogeneic transplantation after conditioning with thiotepa, busulfan and cyclophosphamide. Within a range of 27-57 years, the median age was 37. Of the 44 patients, 12 (27.2%) had high-grade lymphomas, 27 (61.4%) had intermediate-grade lymphomas, and five (11.3%) had low-grade lymphomas. Twenty-eight (63.6%) patients had chemotherapy refractory disease. Thirty (68.2%) patients had stage IV disease at the time of transplantation, involving the bone marrow in 19 (43.2%). Eight (18.1%) patients had undergone previous transplantation, and 13 (29.5%) patients had received high-dose CVP as induction within 2 months prior to transplantation. Thirty-eight (86.3%) patients had an HLA-identical donor, and 6 (13.6%) had a one-antigen mismatched related donor. Twenty (45.4%) patients received bone marrow and 24 (54.6%) received granulocyte colony-stimulating factor (G-CSF) mobilized stem cells. The graft-versus-host disease (GVHD) prophylaxis contained cyclosporine or tacrolimus in combination with either methylprednisolone in 32 (72.7%) patients or with methotrexate in 12 (27.2%) patients. The actuarial probability of disease-free survival at 2 years is 23% (95% CI 13%-40%). Donor stem cell use was associated with a significantly decreased risk of treatment-related toxicity (p < 0.001), but with an increased risk for GVHD and delayed fungal and viral infections. These infections are linked not only to the use of donor-stem cells, but also to the methylprednisolone in the GVHD prophylaxis regimen. Improvements in the outcome of patients with advanced NHL and undergoing allogeneic transplantation will depend on the development of effective and non-toxic regimens for conditioning, GVHD prophylaxis, and opportunistic infections prophylaxis.

Adult↗
PubMed1997

Retinoid-mediated inhibition of cell growth with stimulation of apoptosis in aggressive B-cell lymphomas.

Retinoids have been shown to modulate cell growth and differentiation in a variety of human tumor cell types, but their effects on B-cell non-Hodgkin's lymphomas (NHL-B) have not been explored. In this study, all-trans retinoic acid (ATRA) in the free form and liposome-encapsulated form (L-ATRA) were used to determine effects on fresh NHL-B patient cells as well as cell lines recently established from both HIV-negative and -positive NHL-B patient biopsies. Both ATRA and L-ATRA were found to inhibit cell proliferation in NHL-B cells. However, L-ATRA was found to be superior to free ATRA in inhibiting cell proliferation of NHL-B cells and resulted in greater than 90% cell growth inhibition in a dose-dependent manner. In addition, L-ATRA also induced high levels of apoptosis in NHL-B cells in vitro. To delineate the apoptotic pathways involved, the expression of the apoptosis suppressor oncogene bcl-2 was evaluated in different NHL-B cells with and without the t(14;18) chromosomal translocation. After L-ATRA exposure, more than a 50% reduction in the expression of bcl-2 protein was observed. bcl-2 message levels were also down-regulated in the L-ATRA-sensitive NHL-B cells. Bax protein levels were analyzed and found to be up-regulated in L-ATRA-sensitive NHL-B cells. Similar results were observed in sensitive AIDS/lymphoma cell lines. Experiments using an RAR-alpha antagonist (RO 41-5253) showed that both the proliferation inhibition and apoptosis induced by L-ATRA could be blocked in NHL-B cells. The findings of the present study indicate that L-ATRA may possess therapeutic potential in blocking cell proliferation, inducing apoptosis, and

Apoptosis↗
PubMed1997

Interferon-inducible protein 10 as a possible factor in the pathogenesis of cutaneous T-cell lymphomas.

Human IFN-gamma-inducible protein 10 (IP-10), a C-X-C chemokine secreted by IFN-gamma-stimulated keratinocytes, is chemotactic for normal CD4-positive lymphocytes and inhibits the proliferation of early subsets of normal and of leukemic hemopoietic progenitors. Cutaneous T-cell lymphoma (CTCL) is an indolent lymphoproliferative disorder of CD4-positive lymphocytes that remain confined to the skin for many years before visceral dissemination. Because IFN-gamma mRNA was detected in the epidermis of CTCL lesions, we decided to investigate the role of IP-10 in the epidermotropism of CTCL by determining its expression in normal skin and in CTCL lesions. Using purified recombinant IP-10 (rIP-10) or a recombinant fusion protein between IP-10 and the straight phi10 protein of phage T7, we generated rabbit antisera that recognized and neutralized rIP-10. Immunoperoxidase staining of normal epidermis demonstrated that IP-10 was expressed by basal keratinocytes but not by the more differentiated cells. In the often hyperplastic epidermis overlying CTCL lesions, IP-10 immunostaining was enhanced compared to normal skin and extended to the suprabasal keratinocytes in 28 of 29 patients for a frequency of 97% and a 95% confidence interval of 82-100%. However, IP-10 was detectable in the dermal or epidermal lymphoid infiltrates in only 3 of 29 patients (10%; 95% confidence interval, 2-29%). Skin clinically free of CTCL demonstrated normal IP-10 immunostaining. In one patient who had matching biopsies performed before and after treatment, IP-10 was overexpressed before treatment but was normally expressed at remission. The in vitro proliferation of primary normal human keratinocytes was inhibited in a dose-dependent manner by rIP-10. These results suggest that IP-10 plays a role in the epidermotropism of CTCL. Additional work is needed to determine whether IP-10 stimulates or inhibits CTCL proliferation. A better understanding of the growth controls operating in CTCL may be useful in the development of curative strategies for this disorder.

Adult↗
PubMed1997

Serial determination of the bcl-2 gene in the bone marrow and peripheral blood after central lymphatic irradiation for stages I-III follicular lymphoma: a preliminary report.

Two-thirds of patients with follicular lymphoma have rearrangement of bcl-2 major breakpoint region (MBR) through t(14;18) (q32;q21). This rearrangement can serve as a sensitive marker for follicular lymphoma cells. This study was undertaken to assess the molecular complete response rate of stages I-III follicular lymphoma to central lymphatic irradiation (CLI) by detection of PCR-amplifiable bcl-2 MBR rearrangement in the bone marrow and peripheral blood before and after CLI. Twenty patients with stages I-III follicular lymphoma were treated with CLI. Twelve of them were part of a prospective randomization trial comparing CLI with multi-agent chemotherapy. Bone marrow and peripheral blood samples were obtained from the patients before the initiation of treatment. By using the PCR technique, the DNA sequences from the bone marrow and peripheral blood samples that flank the bcl-2 MBR involved in t(14;18) (q32;q21) were amplified. In PCR-positive patients, bone marrow and blood samples were followed at regular intervals during and after CLI. The results of the PCR amplification were correlated with clinical findings. All 20 patients achieved clinical complete response after CLI. Median follow-up was 22 months (range, 12-37 months), and no patient has relapsed. Pretreatment PCR results were available in all patients (19 patients for peripheral blood samples and 16 patients for bone marrow samples). Nine of 19 peripheral blood samples and 9 of 16 bone marrow samples were PCR-positive for bcl-2 MBR rearrangement. Eight PCR-positive patients converted to negative (8 of 9 blood samples and 2 of 3 bone marrow samples) 2-20 months from the first day of CLI. Bone marrow and peripheral blood with PCR-amplifiable bcl-2 MBR rearrangement can be converted from positive to negative after chemotherapy in patients with follicular lymphoma. Early results from our study show for the first time that peripheral blood and bone marrow can be converted from positive to negative after CLI. The prognostic significance of the observed conversions requires longer follow-up.

Adult↗
PubMed1996

Amplification of genomic DNA demonstrates the presence of the t(2;5) (p23;q35) in anaplastic large cell lymphoma, but not in other non-Hodgkin's lymphomas, Hodgkin's disease, or lymphomatoid papulosis.

Anaplastic large cell lymphoma (ALCL) is a distinct clinicopathologic variant of intermediate grade non-Hodgkin's lymphomas (NHL) composed of large pleomorphic cells that usually express the CD30 antigen and interleukin (IL)-2 receptors, and is characterized by frequent cutaneous and extranodal involvement. With variable frequency ALCL bear the t(2;5)(p23;q35) chromosomal translocation that fuses the nucleophosmin (NPM) gene on chromosome 5q35 to a novel protein kinase gene, Anaplastic Lymphoma Kinase (ALK), on chromosome 2p23. We determined the frequency of this translocation with a novel DNA polymerase chain reaction (PCR) technique using 0.5 microgram of genomic DNA, 5'-primers derived from the NPM gene and 3'-primers derived from the ALK gene and hybridization with internal probes. The presence of amplifiable DNA in the samples was tested with the inclusion in the PCR reaction of oligonucleotide primers designed to amplify a 3016-bp fragment from the beta-globin locus. NMP-ALK fusion amplicons were detected using DNA isolated either from all three ALCL cell lines tested, or from all four primary ALCL tumors known to contain the t(2;5)(p23;q35) translocation. Nested amplicons were detected by hybridization in 100% of specimens diluted 10(4)-fold and in 20% of those diluted 10(5)-fold. We subsequently examined archival genomic DNA from 20 patients with ALCL, 39 with diffuse large cell, 2 with mantle cell, 20 with peripheral T cell, 13 with low-grade NHL, 31 with Hodgkin's disease (HD), and 6 with lymphomatoid papulosis. Fusion of the NPM and ALK genes was detected in three of 18 patients with ALCL who had amplifiable DNA (17%, 95% confidence intervals 4% to 41%), but not in any patients with other NHL, HD, or lymphomatoid papulosis. The amplicon sizes were different in all cell lines and patients reflecting unique genomic DNA breakpoints. We conclude that with genomic DNA-PCR the rearrangement of the NPM and ALK loci is restricted to patients with ALCL. Further studies are needed to determine the prognostic significance of the NPM-ALK rearrangement, to determine whether its detection can aid in the differential diagnosis between ALCL. Hodgkin's disease, and lymphomatoid papulosis, and to establish the usefulness of the genomic DNA PCR in the monitoring of minimal residual disease in those patients whose tumors bear the t(2;5).

Adolescent↗
PubMed1996

Alterations in tretinoin pharmacokinetics following administration of liposomal all-trans retinoic acid.

We administered liposome-encapsulated all-trans retinoic acid (L-ATRA) to 48 patients with refractory hematologic malignancies using an every-other-day schedule for 28 days and doses of 15 to 175 mg/m2. In 19 patients, pharmacology studies were conducted after the first (day 1) and seventh (day 15) doses. In contrast to the decline in tretinoin concentration seen within 3 to 4 days of administration of daily oral ATRA, there were no differences between the area under the curve (AUC) of tretinoin concentration versus time on day 1 and day 15 (P = .98, Wilcoxon signed-rank test). Peak day 1 concentrations after 15 mg/m2 were higher than those reported after 45 mg/m2 oral ATRA. Six patients with relapsed acute promyelocytic leukemia (APL) were treated. Three, each in first relapse and at least year from the last exposure to oral ATRA, achieved a complete response (CR). Disease recurred in two (one at 3 months despite maintenance L-ATRA and similarity in tretinoin AUC on days 1 and 85, and the other at 5 months, 2 months after discontinuation of L-ATRA) and the third was transplanted 1 month into CR. The three nonresponders were in at least a second relapse and failed to respond to oral ATRA before or immediately after receiving L-ATRA. Severe toxicity developed in three of eight patients treated at 175 mg/m2 (joint pains in two, skin in one). The maximum tolerated dose (MTD) was determined to be 140 mg/m2, at which dose grade 2 toxicity (primarily headache and skin) occurred in eight of eight patients, but grade 3 to 4 toxicity in none. Compared with oral ATRA, L-ATRA apparently results in greater exposure to tretinoin and for a longer time.

Drug Carriers↗
PubMed1996

A pilot study of high-dose interleukin-3 treatment of relapsed follicular small cleaved-cell lymphoma: hematologic, immunologic, and clinical results.

The growth stimulatory effects of interleukin-3 (IL-3) on normal hematopoietic progenitor cells are well established, and clinical trials using IL-3 after bone marrow transplantation for various malignancies including lymphomas are frequently conducted. Although the IL-3 receptor is expressed on the surfaces of follicular small cleaved-cell lymphoma (FSCCL) cells, the in vivo effects of IL-3 on FSCCL have not been studied previously. Because our preclinical data suggested that IL-3 may have dose-dependent inhibitory effects on FSCCL cells in vitro, we treated eight FSCCL patients with high-dose IL-3 in an outpatient setting. Each patient received 1 mg/m2 of IL-3 subcutaneously daily for 14 days followed by 7 days without IL-3. After three courses (9 weeks), the patients were evaluated for clinical responses. One patient had a minor response, and four had no responses. Three patients who had progressive disease before IL-3 treatment continued to have progressive disease. In two patients with bone marrow involvement with lymphoma, IL-3 had no effect on FSCCL cells. One patient with peripheral blood involvement with FSCCL cells that expressed IL-3 receptors had temporary growth arrest of the circulating malignant cells. IL-3 significantly increased the absolute neutrophil count in seven patients (87%) but had little effect on the number of normal circulating B cells. There was an increase in the number of circulating natural killer cells and CD8+ cells in four patients. Treatment was very well tolerated; no life-threatening toxicities were observed. The most common toxicities were injected conjunctivae (100%), fever (100%), fatigue (87%), and skin rash (75%). Most of the side effects subsided with the continued use of IL-3. These preliminary results suggest that high-dose IL-3 does not stimulate the growth of FSCCL cells in vivo and, in some instances, may cause growth inhibition.

Aged↗
PubMed1996

CD30 ligand is expressed on resting normal and malignant human B lymphocytes.

CD30, a member of the tumour necrosis receptor superfamily, is physiologically expressed on a subpopulation of T helper cells in normal individuals but is also expressed on several malignant and virally transformed cells. Its ligand (CD30L) is a pleiotropic cellular transmembrane protein that can induce cell death in several CD30+ cell lines. CD30L expression has been reported on activated human peripheral blood T lymphocytes and macrophages but not on B cells. Here we show that the CD30L is expressed on resting normal and on malignant B cells in addition to both CD4+ and CD8+ subsets of activated T cells, making it the second tumour necrosis family member, in addition to the CD27 ligand, that can be expressed on both T and B cells. These findings raise the possibility that the CD30L has a role in B-cell/T-cell communication and that B and T cells are likely to be involved in the growth regulation of CD30+ tumours.

B-Lymphocytes↗
PubMed1996

Preliminary experience with paclitaxel for the treatment of relapsed and refractory Hodgkin's disease.

PURPOSE: To determine the activity of paclitaxel (Taxol; Bristol-Myers Squibb Co., Princeton, NJ) in patients with relapsed and primary treatment-refractory Hodgkin's disease. PATIENTS AND METHODS: Fifteen patients with relapsed (n = 8) or primary treatment-refractory (n = 7) Hodgkin's disease were treated at two cancer centers. Patients received paclitaxel 200 mg/m2 intravenously over three hours every three weeks. All patients also received premedication with dexamethasone, cimetidine, and diphenhydramine. The median age was 33 years (range 19 to 69 years), and the median number of prior treatment regimens was three. Seven patients had previously received treatment with autologous bone marrow transplantation. RESULTS: Fourteen patients were evaluable for response after receiving one to six courses (median, two courses) of paclitaxel. Two patients (14%) had partial remissions; both of them had relapsed after achieving a complete remission with high-dose therapy and autologous bone marrow transplantation. One of these patients was given involved field radiation to consolidate the partial remission and remains free of disease two years after paclitaxel therapy. Three patients had stable disease, and nine had progressive disease. Therapy was well tolerated, with a toxicity profile similar to that previously reported for paclitaxel in patients with non-Hodgkin's lymphoma. CONCLUSION: Paclitaxel, at this dose and schedule, has modest activity in this group of heavily pretreated patients. Studying its activity in patients with more favorable disease characteristics is warranted.

Adult↗
PubMed1996

High rate of prolonged remissions following combined modality therapy for patients with localized low-grade lymphoma.

PURPOSE: Involved field (IF) radiation can cure as many as 40% to 50% of patients with stage I-II low-grade lymphoma. We sought to improve these results by prospectively evaluating the combination of IF radiation and chemotherapy consisting of 10 courses of cyclophosphamide, vincristine, prednisone, and bleomycin, with doxorubicin added in a risk-adapted manner (COP/CHOP-Bleo). PATIENTS AND METHODS: From 1984 until December 1992, 91 patients, median age 56 years (range 28 to 77 years), with clinical stage I-II low-grade lymphoma were treated. No patients were excluded on the basis of age or organ function. RESULTS: A complete response was attained in 99% of evaluable patients. Treatment-related toxicity was mild, and no deaths occurred during therapy. With a median follow-up of 60 months, there have been only 16 relapses. The actuarial freedom from relapse rate at five years is 82% (95% confidence interval 71% to 89%) and at 10 years is 73%. At five years the overall survival rate is 90% (95% confidence interval 81% to 95%) and at ten years it is 82%. Of the clinical features examined, only older age (> 56 years; p = 0.07) was associated with shorter survival. No features examined were predictive of disease relapse. CONCLUSION: The combination of IF radiation and risk-adapted COP/CHOP-Bleo chemotherapy is well-tolerated, produces a very high rate of complete remission, and with a median follow-up of five years, has produced lower rates of relapse and better overall survival than has been reported for IF radiation alone in patients with clinically-staged I-II low-grade lymphoma.

Adult↗
PubMed1996

T-cell-rich B large-cell lymphoma simulating lymphocyte-rich Hodgkin's disease.

Immunophenotypic analysis of 50 cases fulfilling the histologic criteria for mixed cellularity Hodgkin's disease disclosed nine cases with a B-cell, non-Hodgkin's phenotype (CD20+, CD15-, CD30-, EMA-). The cases were characterized by a diffuse small lymphocytic milieu, interspersed atypical large cells including classic Reed-Sternberg cells, and infrequent plasma cells, eosinophils, and L&H cells. The male:female ratio was 7:2 (aged 22-65 years, median 39 years). Three patients were Ann Arbor stage II, two stage III, and four stage IV. The patients presented with generalized lymphadenopathy (four), mesenteric lymph node involvement (two), splenomegaly (four), and bone marrow involvement (three). Four patients were treated with standard Hodgkin's disease protocols. Two attained a complete response and two a partial response; all relapsed and died. Four of five patients treated for large-cell lymphoma achieved a complete response and are currently alive without evidence of disease. The one patient with an initial partial response relapsed and died. We conclude that immunophenotypic analysis is essential in cases of histologic mixed cellularity Hodgkin's disease, especially in those with lymphocyte-rich morphology. Cases with a B-cell phenotype should be diagnosed and treated as T-cell-rich B large-cell lymphoma.

Adult↗
PubMed1996

Cyclosporin A does not reverse clinical resistance to paclitaxel in patients with relapsed non-Hodgkin's lymphoma.

PURPOSE: Cyclosporin A has been shown to reverse paclitaxel resistance in vitro by inhibiting P-gp function. Therefore, we determined whether addition of cyclosporine to paclitaxel reversed clinical paclitaxel resistance in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patients with relapsed NHL were eligible if they had no intervening treatment after failure to respond to paclitaxel (200 mg/m2 over 3 hours), and if they had adequate marrow, renal, and hepatic function, no serious cardiac disease, no CNS involvement, and no antibodies to human immunodeficiency virus-1. A cyclosporin A bolus dose (5 mg/kg over 3 hours) was followed by intravenous infusion (15 mg/kg) over 24 hours. Six hours after the beginning of cyclosporin A, the immediately preceding paclitaxel dose was administered over 3 hours. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine. Response was assessed after two cycles, and those patients who achieved at least a partial response received a maximum of six courses. RESULTS: All 26 patients entered were assessable for toxicity and 25 were assessable for response. One patient whose disease had progressed during paclitaxel treatment had a partial remission after the addition of cyclosporin A (response rate, 4%; 95% confidence interval, 1% to 20%). Disease progressed in 17 patients (71%) and did not respond in seven (25%). Serum cyclosporin A A levels measured at the time of initiation of paclitaxel infusion were greater than 2,000 ng/mL during 81% of cycles. Treatment toxicity included peripheral neuropathy in 57%, myalgia or arthralgia in 30%, neutropenia in 53%, neutropenic fever in 8%, and thrombocytopenia in 42% of patients. One patient with preexisting asthma had an acute bronchospasm during the first cycle and was removed from the study. There were no renal or hepatic toxicity and no infectious or hemorrhagic deaths. CONCLUSION: Cyclosporin A administered on this schedule did not reverse established clinical resistance to paclitaxel, which suggests that P-gp-mediated drug efflux is unlikely to be the only cause of paclitaxel resistance in this patient population.

Adult↗
PubMed1996

No effect of 96-hour paclitaxel infusion in patients with relapsed non-Hodgkin's lymphoma refractory to a 3-hour infusion schedule.

PURPOSE: Preclinical data suggest that the efficacy of paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) is schedule-dependent. Schedule dependency is currently under investigation in ongoing randomized trials. PATIENTS AND METHODS: Twelve patients with relapsed non-Hodgkin's lymphoma (NHL) refractory to a 3-hour infusion of 200 mg/m2 Taxol were crossed over to receive a 96-hour infusion of 140 mg/m2 Taxol every 3 weeks in an outpatient setting. Premedication with corticosteroids and antihistamines was not used. Patients who did not achieve at least a partial remission (PR) after two courses or whose disease progressed after one course were removed from the study. RESULTS: All 12 patients were assessable for response. Eleven patients received at least two courses and one patient received one course of 96-hour Taxol infusion. None of the 12 patients crossed over to receive 96-hour Taxol infusion achieved a PR or complete response (CR). Eight patients (67%) developed progressive lymphoma, three (25%) had stable disease, and only one (8%) had a minor response. No major hypersensitivity reactions or life-threatening toxicities were observed. CONCLUSION: Ninety-six-hour Taxol infusion does not produce significant responses in patients with NHL refractory to 3-hour Taxol infusion. Until the results of an ongoing multicenter trial comparing a 3- with a 96-hour infusion are published, the use of 96-hour Taxol infusion in NHL patients should be restricted to investigational programs. Because 48- to 72-hour infusions can produce higher plasma concentrations of Taxol than a 96-hour infusion, these schedules should be investigated to determine if they can induce better clinical responses.

Adult↗
PubMed1996

Fludarabine, mitoxantrone, and dexamethasone: an effective new regimen for indolent lymphoma.

PURPOSE: Although most patients with indolent lymphomas respond to initial therapy, virtually all experience relapse. Secondary therapy is often beneficial, but responses are rarely, if ever, durable. We conducted this phase II trail to evaluate the therapeutic efficacy and toxicity of fludarabine, mitoxantrone, and dexamethasone (FND) in patients with relapsed indolent lymphoma. PATIENTS AND METHODS: Fifty-one patients with recurrent or refractory indolent lymphoma were treated with a regimen of fludarabine 25 mg/m2/d intravenously (IV) on days 1 to 3, mitoxantrone 10 mg/m2 IV on day 1, and dexamethasone 20 mg/d IV or orally on days 1 to 5. Treatment was repeated at 4-week intervals for a maximum of eight courses. Late in the course of this trial, trimethoprim-sulfamethoxazole (TMP-SMX) was incorporated for Pneumocystis carinii (PCP) prophylaxis. RESULTS: Responses were complete (CR) in 24 patients (47%) and partial (PR) in 24 (47%). The median failure-free survival time was 21 months for CR patients and 9 months for PR patients. Notable activity of FND was seen even in the elderly, in those with high serum lactate dehydrogenase (LDH) or beta2-microglobulin levels, and in those with multiple prior treatment regimens. The predominant toxic effects were myelosuppression and infections; other toxic effects were modest. Infections occurred in 12% of courses. Almost half of the infections were proven or suspected opportunistic infections, including six cases of dermatomal herpes zoster and two cases of proven PCP pneumonia. CONCLUSION: The FND combination is highly active in patients with recurrent or relapsed indolent lymphoma and results in a high percentage of CRs. Because of the risk of opportunistic infections, we currently recommend prophylaxis with TMP-SMX and advise deletion of corticosteroids for patients who develop opportunistic infections.

Aged↗
PubMed1996

Interferon-inducible protein-10 and the pathogenesis of cutaneous T-cell lymphomas.

Human interferon-g inducible protein-10 (IP-10), a small basic protein secreted by interferon (INF)-g stimulated keratinocytes, is chemotactic for normal CD4-positive lymphocytes and inhibits early normal and leukemic hemopoietic progenitor proliferation. Cutaneous T-cell lymphoma (CTCL) is an indolent CD4-positive lymphoma characterized by multiple skin relapses before visceral dissemination. We investigated the role of IP-10 in the biology of CTCL by using immunocytochemistry to define IP-10 expression in normal and CTCL skin biopsies. Using purified recombinant (r) IP-10, we generated a rabbit antiserum that recognized and neutralized rIP-10 but did not cross-react with any keratinocyte proteins or any other chemokine. Immunoperoxidase staining of normal epidermis demonstrated that IP-10 was expressed by basal but not by differentiated keratinocytes. The epidermis overlying CTCL lesions was often hyperplastic, IP-10 immunostaining was enhanced compared to normal skin, and extended to the suprabasal keratinocytes in 25 of 26 patients for a frequency of 96%; and 95% confidence interval (CI) of 80% to 100%. However, IP-10 was detectable in the dermal or epidermal lymphoid infiltrates in only three of these 26 patients (12%; 95% Cl, 2% to 39%). Skin clinically free of CTCL demonstrated normal IP-10 immunostaining. In one patient who had matching biopsies performed before and after treatment, IP-10 was initially overexpressed before treatment but was normally expressed when he achieved remission. These results suggest that IP-10 may play a role in the epidermotropism of CTCL. More work is required to determine whether IP-10 stimulates or inhibits CTCL proliferation. A better understanding of the growth controls operating in CTCL may be used to develop curative therapies for this disorder.

Adult↗