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  • 1
    ISSN: 1435-4373
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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.
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  • 2
    ISSN: 1569-8041
    Keywords: liposomal vincristine ; lymphoma ; relapsed
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective:Vincristine is an active agent in lymphomas, but isoften neurotoxic, and the resulting dose reductions have been associated withlower remission and survival rates in Hodgkin's disease. Liposomal vincristine(Onco-TCS) has prolonged half-life, reaches higher concentration in tumors andlymph nodes than in nerves, and administered at full doses appears to be lessneurotoxic, and more active then free vincristine in mice bearing L-1210 andP-388 leukemias. We therefore explored its activity in relapsed non-Hodgkin'slymphomas (NHL) and acute lymphoblastic leukemia (ALL). Patients and methods:Eligible patients had histologically provenrelapse, age ≥16 years, normal renal function, neutrophils〉500/µl, platelets 〉50,000/µl, and no HIV infection, centralnervous system disease, or serious neuropathy. Patients were treated with 2.0mg/m2 of liposomal vincristine i.v. over 60 minutes q 14 days.Responders received up to 12 injections. Results:Of the 51 registered patients, 35 are currently evaluablefor response. Median age was 62 years (range 19–86), and 21 were male.The median number of prior regimens was 3 (range 1–10) and had includedvincristine in all patients, of whom 51% were refractory to their lastregimen. Serum LDH was high in 46%, and β2–microglobulin 〉3.0mg/l in 63% of patients. Of the 155 administered injections, 138(89%) were at the 2.0 mg/m2 level. The median injected dosewas 3.8 mg (range 2.6–4.8 mg), and median number of injections was 4(range 1–12). Responses were seen in 14 of 34 (41%) patients withNHL (95% confidence intervals (95% CI)25%–59%). Response rates were 10% for indolent,71% for transformed, and 47% for aggressive NHL, but the95% confidence intervals overlapped. Median progression-free survivalwas 5.5 months for responders. Grade 3–4 motor or sensory neuropathy wasseen in 11, and caused termination of therapy in five patients. All five hadprior neuropathy, two had previously received paclitaxel, one platinum, andtwo paclitaxel and platinum. Fever was detected in three patients, but therewere no toxic deaths. Conclusions:Liposomal vincristine is active and well toleratedin this heavily pretreated population with relapsed NHL, but can be neurotoxicin a fraction of patients heavily exposed to prior neurotoxic agents. Thesedata, if confirmed, would suggest a potential role for liposomal vincristinein the combination therapy of previously untreated patients with NHL.
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  • 3
    ISSN: 1569-8041
    Keywords: CD30L ; CD40L ; FasL ; Hodgkin's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Reed–Sternberg cells of Hodgkin's disease express CD30and CD40 receptors. The ligands for these receptors have been reported to have pleiotropic biologic activities in vitro, including induction of cell death. 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) andCD40L 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 there verse-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%) containedCD40L-expressing cells. The mean percentage of nodal lymphocytes expressingCD30L surface protein was ≤20%. Conclusion: Hodgkin's disease lymph nodes and spleens frequently lackCD30L- and CD40L-expressing cells, and when CD30L is expressed, it is usually detected on few numbers of lymphocytes. The differences in the level of expression of these ligands in Hodgkin's disease lymph nodes may be related to the disease's clinical behavior.
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  • 4
    ISSN: 1569-8041
    Keywords: aggressive lymphomas ; intermediate grade lymphomas ; CHOP ; ATT ; prognostic factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: CHOP is currently considered the gold standard of treatmentfor intermediate grade lymphomas. We designed a new regimen known as ’ATT‘(alternating triple therapy) which uses three non-cross resistantcombinations in alternating sequence for nine cycles. Materials and methods: This is a phase II clinical trial with comparisonto CHOP/CMED historical controls using prognostic factors. The tumor scoresystem was used to evaluate the results of this trial. Two hundredsixty-eight eligible patients who had one or more of the following adversefeatures: bulky disease, elevated LDH or 〉1 extranodal site wereanalyzed. Outcome measures consist of survival and failure free survival. Results: At a median follow-up of 32 months, there was no statisticallysignificant difference in survival for those with favorable prognosticfactors (tumor score ≤2). However, there was a statistically significantdifference in favor of ATT for those with unfavorable tumor scores. When weexamined the failure-free survival of those with unfavorable tumor scores,we again observed a superiority for the ATT regimen over CHOP/CMED but theopposite was true for those with favorable tumor scores. We also found astatistically significant difference in favor of the ATT regimen whencompared with CHOP/CMED for patients ≤60 years old with a tumor score≥3, while no advantage was found for those 〉60 years. Conclusions: ATT appears more effective but only for patients 〈60 yearsold with unfavorable tumor scores. In those older than 60 years with favorabletumor score, CHOP/CMED appears superior. ATT might be an adequate regimen foryoung patients with poor prognostic features while CHOP/CMED might be a betterchoice for those with good prognosis irrespective of age. For those 〉60years with unfavorable tumor scores neither ATT or CHOP/CMED were adequatetreatment. Because of the phase II nature of this study, these conclusionsshould be considered as hypotheses which require prospective testing.
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  • 5
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 6
    ISSN: 1569-8041
    Keywords: anaplastic large-cell lymphoma ; genomic DNA PCR ; t(2;5)(p23;q35)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 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 nested polymerase chain reaction (PCR) using 0.5 µg of DNA (60000–80000 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 β-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 104-fold or105-fold generated amplicons in 100% or 20% of reactions, respectively. Archival tumor DNA from 144 patients was amplifiable by β-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 who 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: PCR of genomic DNA detects t(2;5) only in ALCL, but not in other NHLs, HD, or LP, and may be useful in establishing diagnosis, determining prognosis, and monitoring minimal residual disease in ALCL.
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  • 7
    ISSN: 1569-8041
    Keywords: anaplastic large-cell lymphoma ; genomic DNA PCR ; t(2;5)(p23;q35)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Design: Determine the frequency of t(2;5)(p23;q35) in anaplasticlarge-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 nested polymerasechain reaction (PCR) using 0.5 µg of DNA (60000–80000 cells),5′-primers from the NPM gene, 3′-primers from the ALK gene,agarose electrophoresis, hybridization, and autoradiography. Patients wereevaluable if a 3016 base pair amplicon could be generated from tumor DNAwith β-globin primers. Results: Amplicons were detected by PCR of genomic DNA from three ALCLcell lines and four primary ALCLs known to t(2;5) positive. DNA fromt(2;5)-positive cell lines diluted 104-fold or105-fold generated amplicons in 100% or 20% ofreactions, respectively. Archival tumor DNA from 144 patients wasamplifiable by β-globin amplicons in 126 (88%) who are consideredevaluable for this study. Twenty-two had ALCL, 69 other NHLs, 30 HD, andfive 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. AmongALCLs the t(2;5) was confined to 5 of 20 with nodal presentations(25%, 95% CI 9%–49%), among who it wasseen 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 withnodal presentations, T-cell or null-cell phenotype, and age 〈40 years(44%, 95% CI 14%–79%). Amplicon sizes weredifferent between cell lines and patients, reflecting unique genomic DNAbreakpoints, as confirmed by DNA sequencing, and served as an internalcontrol against specimen cross-contamination in the laboratory. Conclusions: PCR of genomic DNA detects t(2;5) only in ALCL, but notin other NHLs, HD, or LP, and may be useful in establishing diagnosis,determining prognosis, and monitoring minimal residual disease in ALCL.
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  • 8
    ISSN: 1569-8041
    Keywords: CD30L ; CD40L ; FasL ; Hodgkin's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Reed–Sternberg cells of Hodgkin's disease express CD30and CD40 receptors. The ligands for these receptors have been reported tohave pleiotropic biologic activities in vitro, including induction of celldeath. Expression of the ligands for these receptors in lymph nodes involvedwith Hodgkin's disease is not known. Purpose: The purpose of this study was to examine CD30 ligand (L) andCD40L expression in lymph nodes of patients with Hodgkin's disease, and tostudy CD30L expression on nodal lymphocyte subsets. Materials and methods: CD30L expression on subsets of lymphocytes of fivelymph nodes involved with Hodgkin's disease was determined by two-colorFACScan. Messenger RNA expression of CD30L and CD40L was determined by thereverse-transcriptase polymerase chain reaction (RT-PCR) method performed onseven specimens involved with Hodgkin's disease (five lymph nodes and twospleens). Results: Four of seven specimens (57%) contained cells thatexpressed CD30L mRNA and three specimens (43%) containedCD40L-expressing cells. The mean percentage of nodal lymphocytes expressingCD30L surface protein was ≤20%. Conclusion: Hodgkin's disease lymph nodes and spleens frequently lackCD30L- and CD40L-expressing cells, and when CD30L is expressed, it is usuallydetected on few numbers of lymphocytes. The differences in the level ofexpression of these ligands in Hodgkin's disease lymph nodes may be relatedto the disease's clinical behavior.
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  • 9
    ISSN: 1569-8041
    Keywords: allogeneic transplantation for mantle-cell lymphoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The presence of a graft-versus-tumor effect has been well established for various hematological malignancies but not for mantle-cell lymphoma (MCL). We report preliminary results suggestive of a graft-versus-lymphoma effect in such patients post allogeneic hematopoietic transplantation. Patients and methods: Sixteen patients with the diffuse type of MCL received allogeneic transplantation. Three had blastic features. Fifteen had an HLA-identical and one, a one HLA antigen mismatched sibling donor. Fifteen had stage IV disease. Eleven patients were previously treated, including one who failed prior autologous transplantation. Five patients were newly diagnosed and received transplantation after cytoreduction with three to eight courses of HYPER-CVAD (fractionated cyclophosphamide, doxorubicin, vincristine, dexamethasone) alternating with high-dose methotrexate and cytarabine. Results: Eleven patients received high-dose cyclophosphamide 120 mg/kg and total body irradiation (TBI) (12 Gy given in four daily fractions). Three patients were not eligible for TBI and received the BEAM regimen. Twelve (85.7%) achieved complete and two (14.3%) partial response. Two additional patients received a nonablative preparative regimen consisting of cisplatin, cytarabine and fludarabine. One failed to engraft and later relapsed. The other patient had progressive disease one month post transplant but later achieved complete remission now durable for 14+ months after developing graft-versus-host disease (GVHD). Residual lymphoma was assessed in seven patients by polymerase chain reaction assay (PCR) forbcl-1 or immunoglobulin gene rearrangement. All had detectable disease at the time of transplant. When tested within four months post transplant, four of these patients attained molecular remission. One of the three molecular non-responders converted to a negative PCR status seven months later and one fluctuates between positive and negative PCR fourteen months post transplant. Overall survival (OS) and failure-from-progression (FFP) at three years were both 55% (95% confidence interval (95% CI): 28%–83%). For patients with chemosensitive disease, FFP and OS at one year were both 90% (95% CI: 71%–100%) compared with 44% (95% CI: 1%–88%) (P = 0.04) for those who were refractory to conventional chemotherapy at the time of transplantation. There were six deaths. These were related to GVHD (three cases), infection (one case), multiorgan failure (one case), and graft failure (one case). Conclusions: This report demonstrates the potential efficacy of allogeneic hematopoietic transplantation for MCL and provides the first evidence suggestive of graft-versus-malignancy in MCL. Data supportive of this concept include 1) achievement of remission concomitant with GVHD, 2) the conversion from a positive PCR status early after transplant to negative PCR status over time and 3) that the only relapse was in a patient who failed to engraft.
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  • 10
    ISSN: 1569-8041
    Keywords: failure-free survival ; IL-10 ; Hodgkin's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Interleukin-10 (IL-10) is a pleiotropic cytokine that protects B- or T-lymphocytes and hemopoietic progenitors from apoptosis induced by doxorubicin, glucocorticoids, or deprivation of growth factors. IL-10 is also immunosupressive, and tumor cells secreting IL-10 can grow in syngeneic or allogeneic hosts, and can inhibit the generation of tumor-specific cytotoxic T cells. Hodgkin-Reed–Sternberg cells are derived from follicular center B cells and they may be latently infected by EBV. When this occurs they often express IL-10. Based on these considerations we investigated the relationship between pretreatment serum IL-10 levels and failure-free survival (FFS) in Hodgkin's disease (HD). Patients and methods: Untreated patients, older than 16 years, with biopsy-proven HD, were included if treated with ABVD or equivalent regimens, and if pretreatment serum was available. IL-10 levels were determined with a capture enzyme-linked immunoassay specific for cellular IL-10. Results: Among healthy adult volunteers serum IL-10 levels ranged from 4.8–9.8 pg/ml (mean 7.1, standard deviation 1.5 pg/ml). Therefore levels ≥10 pg/ml were considered elevated. We identified 101 patients with available serum. Their median age was 32 years, and 60% had B-symptoms. Ann Arbor stage was I in 4, II in 21, III in 35, and IV in 41 patients. Histology was nodular sclerosis in 74, mixed cellularity in 12, lymphocyte predominance in six, lymphocyte depletion in one, and unclassified in eight patients. Pretreatment serum IL-10 levels were elevated in 51 patients, and were higher in those with serum albumin 〈3.5 g/dl, B symptoms, serum β2-microglobulin ≥2.5 mg/l, anemia, and AAS III or IV. After a median follow-up of 32 months for survivors, 20 patients have progressed, and the three-year FFS of those with high vs. normal serum IL-10 was 60% ± 9 vs. 91 ± 9% (50% vs. 50% of the population; P = 0.004 by log-rank). Among patients with Ann Arbor stage III or IV the three-year FFS for those with high vs. normal serum IL-10 (58 vs. 42% of the population) was 57 ± 9% vs. 92 ± 6% (P = 0.008 by log-rank). Multivariate analysis using Cox's proportional hazards model confirmed that IL-10 was an independent variable associated with inferior FFS in this population. Conclusions: Elevation of serum IL-10 levels is frequent and is associated with inferior FFS in adults with ABVD-treated HD. This observation should be verified in other patient populations. In addition, the source and the role of IL-10 in the biology of HD should be further investigated.
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