National Cancer Institute®
Last Modified: January 1, 2002
UI - 10944137
AU - Haioun C; Lepage E; Gisselbrecht C; Salles G; Coiffier B; Brice P; Bosly
TI - A; Morel P; Nouvel C; Tilly H; Lederlin P; Sebban C; Briere J; Gaulard P; Reyes F Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: final analysis of the prospective LNH87-2 protocol--a groupe d'Etude des lymphomes de l'Adulte study.
SO - J Clin Oncol 2000 Aug;18(16):3025-30
AD - Hopital Henri Mondor, Assistance Publique-Hopitaux de Paris (AP-HP), Creteil, France. firstname.lastname@example.org
PURPOSE: To present the final analysis, with a median follow-up of 8 years, of the LNH87-2 randomized study, which compares consolidative sequential chemotherapy (ifosfamide plus etoposide, asparaginase, and cytarabine) with high-dose therapy (HDT) using cyclophosphamide, carmustine, and etoposide (CBV regimen) followed by stem-cell transplantation in patients with aggressive non-Hodgkin's lymphoma in first complete remission after induction, focusing on high/intermediate- and high-risk patients identified by the age-adjusted international prognostic index. PATIENTS AND METHODS: Among the 916 eligible patients, 451 presented with two (n = 318) or three (n = 133) risk factors. After reaching complete remission to induction therapy, 236 of these higher risk patients were assessable for the consolidation phase, with 125 patients in the HDT arm and 111 in the sequential chemotherapy arm. RESULTS: Among these 451 higher risk patients, 277 (61%) achieved complete remission after induction treatment. In the population of 236 randomized patients, HDT was superior to sequential chemotherapy, with 8-year disease-free survival rates of 55% (95% confidence interval [CI], 46% to 64%) and 39% (95% CI, 30% to 48%), respectively (P =.02; relative risk, 1.56). The 8-year survival rate was significantly superior in the HDT arm (64%; 95% CI, 55% to 73%) compared with the sequential chemotherapy arm (49%; 95% CI, 39% to 59%) (P =.04; relative risk, 1.51). CONCLUSION: On the basis of the final analysis of this prospectively treated series of patients, retrospectively analyzed on the basis of the International Prognostic Index, we hypothesize that HDT benefits patients at higher risk who achieve complete remission after induction treatment.
UI - 11148572
AU - Vaccher E; Spina M; di Gennaro G; Talamini R; Nasti G; Schioppa O;
TI - Vultaggio G; Tirelli U Concomitant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy plus highly active antiretroviral therapy in patients with human immunodeficiency virus-related, non-Hodgkin lymphoma.
SO - Cancer 2001 Jan 1;91(1):155-63
AD - Division of Medical Oncology A, National Cancer Institute, Aviano, Italy.
BACKGROUND: The feasibility and efficacy of concomitant chemotherapy and highly active antiretroviral therapy (HAART) is still unknown in patients with human immunodeficiency virus (HIV)-related malignancies. To evaluate the impact of chemotherapy plus HAART on the clinical course of patients with HIV-related, systemic, non-Hodgkin lymphoma (HIV-NHL), the authors compared retrospectively a group of 24 patients with HIV-NHL who were treated with the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy regimen plus HAART with a group of 80 patients who were treated with CHOP chemotherapy or a CHOP-like regimen (i.e., cyclophosphamide, doxorubicin, teniposide, and prednisone with vincristine plus bleomycin) without receiving antiretroviral therapy. METHODS: All patients were enrolled in two sequential trials performed Antiretroviral regimens consisted of two reverse transcriptase inhibitors and one protease inhibitor. RESULTS: The two treatment groups were well matched with regard to patient demographics, NHL characteristics, HIV status, and treatment, i.e., the number of cycles and chemotherapy dose. The response rates were similar between the two groups. Severe anemia (Grade 3-4 according to the World Health Organization criteria) was significantly greater in the patients who received CHOP-HAART compared with the patients who received CHOP alone (33% vs. 7%, respectively; P = 0.001). Leukopenia was similar between the two groups, but colony stimulating factor support was significantly greater in the CHOP-HAART group than in the control group (92% vs. 66%, respectively; P = 0.03). Seventeen percent of CHOP-HAART patients developed severe autonomic neurotoxicity, whereas none of the CHOP patients developed neurotoxicity (P = 0.002). At similar median follow-up, opportunistic infection (OI) rates and mortality were significantly lower in the CHOP-HAART patients than in the CHOP patients (18% vs. 52%, respectively; P = 0.05; and 38% vs. 85%, respectively; P = 0.001). The median survival for CHOP-HAART patients was not reached, whereas the medial survival of CHOP patients was 7 months (P = 0.03). CONCLUSIONS: The combination of CHOP plus HAART is feasible and may reduce the morbidity from OIs in HIV-NHL patients. However, careful attention must be directed to cross toxicity and possible pharmacokinetic interactions between antiretroviral and antineoplastic drugs. The impact of the combined chemotherapy plus HAART treatment on patient survival needs urgently to be evaluated in prospective studies. Copyright 2001 American Cancer Society.
UI - 11148559
AU - Hsu C; Chen CL; Chen LT; Liu HT; Chen YC; Jan CM; Liu CS; Cheng AL
TI - Comparison of MALT and non-MALT primary large cell lymphoma of the stomach: does histologic evidence of MALT affect chemotherapy response?
SO - Cancer 2001 Jan 1;91(1):49-56
AD - Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
BACKGROUND: Although the clinicopathologic features of low grade gastric MALToma (lymphoma of mucosa-associated lymphoid tissue) recently have been well delineated, the significance of identifying histologic evidence of MALT origin in a primary high grade gastric lymphoma is less clear. The authors sought to address this issue and, in particular, to clarify if MALT and non-MALT primary large cell gastric lymphoma might have a different response to systemic chemotherapy. METHODS: The authors reviewed the pathologic specimens of all patients who had a diagnosis of primary large cell lymphoma of the stomach and who had been treated primarily by systemic chemotherapy in our institutions January 1, 1988-December 31, 1998. The patients were divided into two groups by experienced hematopathologists, based on the presence or absence of histologic features suggestive of MALToma, including typical lymphoepithelial lesions and infiltration of characteristic centrocyte-like cells. Disease staging was done according to the AJCC/UICC system with Musshoff modification. The median number of gastric biopsies for each patient was 7 (range, 1-21). RESULTS: Seventeen patients with and 26 patients without histologic evidence of MALToma were identified. Clinical features were similar between the two groups except that a greater proportion of patients without evidence of MALToma had elevated levels of serum lactate dehydrogenase (50% vs. 12%, P = 0.01). The median duration of follow-up for the 43 patients was 46.5 months (range, 17-124 mos). All patients received standard systemic chemotherapy including anthracyclines or anthracenedione. The response rate was 88.2% for patients with evidence of MALToma and 57.7% for those without (P = 0.03). The 5-year overall survival rate was 80.5% for patients with evidence of MALToma and 48.9% for those without (P = 0.02). Multivariate analysis indicated that response to chemotherapy, disease stage (Stage I and II-1 vs. Stage II-2, III, and IV), and the presence of MALToma features were independent prognostic factors for overall survival. CONCLUSION: The results of this relatively small study series suggested that the presence of histologic features of MALToma in patients with primary large cell gastric lymphoma might have been associated with a better response to systemic chemotherapy and a better prognosis. Further studies to consolidate this conclusion are necessary. Copyright 2001 American Cancer Society.
UI - 11251023
AU - Kennedy RD; Cuthbert RG; Kettle PJ; Morris TC
TI - Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: concerns about omissions in the data presented.
SO - J Clin Oncol 2001 Mar 15;19(6):1884
UI - 11401189
AU - Smith AL; Haider K; Schachtner JM; Mathur S; Vanorden R; Gentile TC
TI - Fatal hemolysis after high-dose etoposide: is benzyl alcohol to blame?
SO - Pharmacotherapy 2001 Jun;21(6):764-6
AD - Department of Pharmacy, State University of New York, Syracuse, USA.
A 53-year-old African-American man with relapsed non-Hodgkin's lymphoma developed seizures and respiratory arrest 2 hours after an infusion of high-dose etoposide in preparation for an autologous bone marrow transplant. Laboratory tests revealed both rapid hemolysis and severe metabolic acidosis. The patient died the following day. Based on toxicities observed, we suspect that our patient possessed an ethnic polymorphism of the enzyme alcohol dehydrogenase. Further research is required to determine the relationship between the benzyl alcohol metabolic rate and toxicity and genetic polymorphisms of alcohol dehydrogenase in African-Americans.
UI - 11432625
AU - Borchmann P; Schnell R; Knippertz R; Staak JO; Camboni GM; Bernareggi A;
TI - Hubel K; Staib P; Schulz A; Diehl V; Engert A Phase I study of BBR 2778, a new aza-anthracenedione, in advanced or refractory non-Hodgkin's lymphoma.
SO - Ann Oncol 2001 May;12(5):661-7
AD - Klinik I fur Innere Medizin der Universitat Koln, Germany.
BACKGROUND: BBR 2778 is a novel aza-anthracenedione showing no cardiotoxicity and superior activity compared to doxorubicin and mitoxantrone in animal models. Objectives of this phase I study included the determination of the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), clinical pharmacokinetics (PK), and antitumor activity. Patients with relapsed or refractory, advanced non-Hodgkin's lymphoma were included. PATIENTS AND METHODS: Patients were treated with a q1w x 3 schedule on the basis of a modified Fibonacci dose escalation method. Seven groups with a total of twenty-six patients were treated at dosages of 5, 10, 16.5, 25, 34, 56 or 84 mg/m2/w, respectively. RESULTS: DLT was observed on the seventh dose level with neutropenia WHO grade 4 in three of six patients. Pharmacokinetic analysis showed a large volume of distribution (13.5-17.5 l/kg), a high plasma clearance (0.65-1.74 l/h/kg) and a long elimination half-life (14.7-31.9 h). Tumor response included three complete remissions and two partial remissions. CONCLUSIONS: Neutropenia is the DLT of the new aza-anthracenedione BBR 2778. The recommend dose is 84 mg/m2 in a q1w x 3 schedule. PK data are consistent with a linear kinetic of BBR 2778 comparable to mitoxantrone. This new drug shows promising activity in intensively pretreated patients with relapsed or refractory NHL. Based on this results, phase II studies with this new compound are underway.
UI - 11418315
AU - Wiseman GA; White CA; Sparks RB; Erwin WD; Podoloff DA; Lamonica D;
TI - Bartlett NL; Parker JA; Dunn WL; Spies SM; Belanger R; Witzig TE; Leigh BR Biodistribution and dosimetry results from a phase III prospectively randomized controlled trial of Zevalin radioimmunotherapy for low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma.
SO - Crit Rev Oncol Hematol 2001 Jul-Aug;39(1-2):181-94
AD - Mayo Clinic and Foundation, Division of Nuclear Medicine, Charlton Building 1-223, 200 First Street S.W., Rochester, MN 55905, USA. email@example.com
Radiation dosimetry studies were performed in patients with non-Hodgkin's lymphoma (NHL) treated with 90Y Zevalin (90yttrium ibritumomab tiuxetan, IDEC-Y2B8) on a Phase III open-label prospectively randomized multicenter trial. The trial was designed to evaluate the efficacy and safety of 90Y Zevalin radioimmunotherapy compared to rituximab (Rituxan, MabThera) immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed NHL. An important secondary objective was to determine if radiation dosimetry prior to 90Y Zevalin administration is required for safe treatment in this patient population. METHODS: Patients randomized into the Zevalin arm were given a tracer dose of 5 mCi (185 MBq) (111)In Zevalin (111indium ibritumomab tiuxetan) on Day 0, evaluated with dosimetry, and then administered a therapeutic dose of 0.4 mCi/kg (15 MBq/kg) 90Y Zevalin on Day 7. Both Zevalin doses were preceded by an infusion of 250 mg/m(2) rituximab to clear peripheral B-cells and improve Zevalin biodistribution. Following administration of (111)In Zevalin, serial anterior and posterior whole-body scans were acquired and blood samples were obtained. Residence times for 90Y were estimated for major organs, and the MIRDOSE3 computer software program was used to calculate organ-specific and total body radiation absorbed dose. Patients randomized into the rituximab arm received a standard course of rituximab immunotherapy (375 mg/m(2) weekly x 4). RESULTS: In a prospectively defined 90 patient interim analysis, the overall response rate was 80% for Zevalin vs. 44% for rituximab. For all patients with Zevalin dosimetry data (N=72), radiation absorbed doses were estimated to be below the protocol-defined upper limits of 300 cGy to red marrow and 2000 cGy to normal organs. The median estimated radiation absorbed doses were 71 cGy to red marrow (range: 18-221 cGy), 216 cGy to lungs (94-457 cGy), 532 cGy to liver (range: 234-1856 cGy), 848 cGy to spleen (range: 76-1902 cGy), 15 cGy to kidneys (0.27-76 cGy) and 1484 cGy to tumor (range: 61-24274 cGy). Toxicity was primarily hematologic, transient, and reversible. The severity of hematologic nadir did not correlate with estimates of effective half-life (half-life) or residence time of 90Y in blood, or radiation absorbed dose to the red marrow or total body. CONCLUSION: 90Y Zevalin administered to NHL patients at non-myeloablative maximum tolerated doses delivers acceptable radiation absorbed doses to uninvolved organs. Lack of correlation between dosimetric or pharmacokinetic parameters and the severity of hematologic nadir suggest that hematologic toxicity is more dependent on bone marrow reserve in this heavily pre-treated population. Based on these findings, it is safe to administer 90Y Zevalin in this defined patient population without pre-treatment (111)In-based radiation dosimetry.
UI - 11418316
AU - Goldenberg DM
TI - The role of radiolabeled antibodies in the treatment of non-Hodgkin's lymphoma: the coming of age of radioimmunotherapy.
SO - Crit Rev Oncol Hematol 2001 Jul-Aug;39(1-2):195-201
AD - Garden State Cancer Center, Center for Molecular Medicine and Immunology, 520 Belleville Avenue, Belleville, NJ 07109, USA. firstname.lastname@example.org
This review summarizes the current clinical status of radioimmunotherapy (RAIT) in the treatment of patients with non-Hodgkin's lymphoma (NHL), as a prototype of the advances of RAIT in the management of cancer. Four radiolabeled antibody products are progressing towards commercialization for the RAIT of NHL: 131I-tositumomab (Bexxar), 90Y-ibritumomab tiuxetan, 90Y-epratuzumab (hLL2), and 131I-Lym-1. All except epratuzumab are murine monoclonal antibodies (Mabs) labeled with an isotope, except that ibritumomab (Zevalin) adds chimeric rituximab to the product, whereas epratuzumab is solely a humanized Mab. Bexxar and Zevalin target CD20, epratuzumab binds to CD22, and Lym-1 reacts with HLA-DR. Clinical studies have shown that all four antibody products can be safe and efficacious. Bexxar has been shown to induce responses that are relatively better than the prior chemotherapy, and has also been shown to be effective in combination with chemotherapy as a frontline therapy of low-grade and transformed NHL. However, since it is a fully murine Mab, it did show a approximately 60% HAMA rate in untreated patients. Zevalin has been found to be more effective than rituximab, its naked chimeric Mab counterpart, as well as in chemotherapy-relapsed low-grade NHL patients. Both radiolabeled epratuzumab and Lym-1 have shown efficacy in patients who have failed chemotherapy, either with low-grade or aggressive forms of NHL. It appears that Bexxar and Zevalin will be the first two radiolabeled antibodies that may be available for widespread use in the U.S., and will mark the final introduction of RAIT as an approved cancer treatment modality. Future studies will help define the role of these RAIT products in the management of NHL, especially as part of a multimodal therapy of this disease.
UI - 11467381
AU - Kawamura T; Koga S; Okamoto M; Kanno T; Iwamura H
TI - Results of combined-modality therapy for primary and secondary malignant lymphoma of the central nervous system (CNS).
SO - Radiat Med 2001 May-Jun;19(3):145-9
AD - Department of Radiology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
PURPOSE: We consider that whatever the vital prognosis of secondary CNS lymphoma (SCNSL), its local control is as serious as that of primary CNS lymphoma (PCNSL). In this study, both the treatment outcomes and local control of patients with SCNSL and PCNSL were compared, with the aim of improving the treatment of SCNSL. MATERIALS AND METHODS: This study included 11 patients with PCNSL and 14 with SCNSL treated from January and received systemic chemotherapy. All SCNSL patients received systemic chemotherapy, and eight also received intrathecal anticancer drug infusion. Nine PCNSL patients and 11 SCNSL patients underwent whole-brain radiation therapy with 4-MV photons. Among the SCNSL patients, three patients underwent localized-brain irradiation and two patients also received whole-spine irradiation. RESULTS: Five-year survival rates were 34% for PCNSL and 33% for SCNSL. In SCNSL, survival times after CNS involvement were very short, irrespective of treatment. One-year local control rates after CNS irradiation were 38% for PCNSL and 14% for SCNSL. Recurrence was mainly found in the cranial region, in seven of 11 PCNSL patients and 10 of 14 SCNSL patients. CONCLUSIONS: Patients with SCNSL had a poor prognosis, and local control in them was more problematic than in patients with PCNSL. It is necessary to develop new combined modality therapy for patients with SCNSL,including the participation of a radiation oncologist, before the disease becomes progressive.
UI - 11488114
AU - Alcaide Matas F; Garcia Munoz-Najar A; Menchen Trujillo BJ; Campano Cruz
TI - I; Fernandez Monge C; Sanchez-Bustos Cobaleda F; Quadros Borrajo M; Garrote Nieto E; Sierra Garcia A [Conservatively treated primary lymphoma of the rectum]
SO - Rev Esp Enferm Dig 2001 May;93(5):335-6
UI - 11497233
AU - Sarris AH; Romaguera J; Hagemeister FB; Rodriguez MA; McLaughlin P; Pro
TI - B; Younes A; Mesina O; Cabanillas F; Medeiros LJ; Samuels B Irinotecan in relapsed or refractory non-Hodgkin's lymphoma.
SO - Oncology (Huntingt) 2001 Jul;15(7 Suppl 8):53-6
AD - Department of Lymphoma and Myeloma, The University of Texas, M. D. Anderson Cancer Center, Houston 77030, USA. email@example.com
Irinotecan (CPT-11, Camptosar) is a topoisomerase I inhibitor with a broad spectrum of antitumor clinical activity. Various schedules and doses have been studied, and major complications were delayed diarrhea and myelosuppression. We explored the activity of irinotecan in patients with relapsed or refractory non-Hodgkin's lymphoma, using a 3-week schedule of administration. Eligible patients had histologically proven relapse, had received no more than two previous regimens, were > or = 15 years and < or = 75 years old, had normal renal function, neutrophil count > 1,500/microL, platelet count > 100,000/microL, and no human immunodeficiency virus infection or central nervous system involvement. Patients were treated with irinotecan 300 mg/m2 i.v. every 21 days with intensive loperamide management of diarrhea. Responders received up to six treatment cycles. Of 25 patients registered so far, 22 are evaluable for response. The median age was 67 years (range: 25 to 74 years) and 11 were male. The median number of previous regimens was 2 (range: 1 to 4 regimens), and 16 patients had disease that was refractory to their last regimen. Serum lactate dehydrogenase level was high in 75%, and beta2-microglobulin was > 3.0 mg/L in 26% of patients. Responses were seen in 8 of 22 (36%) patients with non-Hodgkin's lymphoma. Response rates were 40% for indolent, 0% for mantle cell, 45% for relapsed aggressive, and 33% for refractory aggressive lymphomas. Grade 3/4 toxicities included myelosuppression, neutropenic fever, and delayed diarrhea. Irinotecan appears active and relatively well tolerated in patients with relapsed aggressive non-Hodgkin's lymphoma. Accrual to this study is continuing for better determination of the response rate in all histologic subtypes of non-Hodgkin's lymphoma.
UI - 11508931
AU - Solal-Celigny P
TI - Rituximab as first-line monotherapy in low-grade follicular lymphoma with a low tumor burden.
SO - Anticancer Drugs 2001 Jun;12 Suppl 2():S11-4
AD - Centre Jean Bernard, Le Mans, France. firstname.lastname@example.org
Patients with follicular lymphoma and a low tumor burden have a median overall survival of more than 10 years. Toxic conventional chemotherapy regimens are inappropriate in these patients, as they do not improve overall survival and the patients do not require palliation of symptoms. However, as most of these patients will ultimately die of their lymphoma, new therapies, with curative intent, are required. Rituximab is a human-mouse chimeric monoclonal antibody that has shown efficacy in patients with non-Hodgkin's lymphoma (NHL). The benign tolerability profile of rituximab makes it a suitable candidate for first-line treatment of follicular NHL patients with a low tumor burden. In a trial of 49 patients, 73% achieved a clinical response (26% complete response) with rituximab treatment. Molecular studies showed that 57% of patients achieved molecular remission (clearance of the bcl-2 molecular translocation from the blood, evaluated by polymerase chain reaction), 62% of these remaining bcl-2- for at least 1 year. There was a good correlation between molecular and clinical responses, with patients failing to achieve a molecular response at higher risk of disease progression. Rituximab monotherapy is therefore an effective and well-tolerated treatment for patients with low-grade lymphoma and a low tumor burden.
UI - 11508932
AU - Czuczman MS
TI - Combination chemotherapy and rituximab.
SO - Anticancer Drugs 2001 Jun;12 Suppl 2():S15-9
AD - Roswell Park Cancer Institute, Buffalo, NY 14263, USA. email@example.com
Rituximab is a human-mouse chimeric monoclonal antibody that has demonstrated efficacy against non-Hodgkin's lymphoma (NHL). There is a powerful rationale for combining rituximab treatment with chemotherapeutic agents that have also shown efficacy in NHL, since the mechanisms of action are distinct and there is also evidence that rituximab may sensitize chemoresistant tumor cells to the actions of cytotoxic drugs. A study of rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) chemoimmunotherapy has been carried out in 40 patients with low-grade NHL. In the 35 patients who completed the study, the overall response rate was 100%, with 63% achieving a complete response. Median time to progression has not yet been reached at 47.2+ months. Molecular analysis (polymerase chain reaction) showed that CHOP plus rituximab (unlike CHOP alone) could completely clear blood and bone marrow of cells containing the bcl-2 gene translocation, a molecular marker of NHL cells. Rituximab can therefore add to the efficacy of CHOP without significantly increasing toxicity. A further study is underway to determine whether similar efficacy with less overall toxicity can be achieved using rituximab in combination with fludarabine.
UI - 11508933
AU - Schmitz N
TI - Rituximab in autologous stem cell transplantation for follicular lymphoma.
SO - Anticancer Drugs 2001 Jun;12 Suppl 2():S21-4
AD - Second Department of Internal Medicine, Christian-Albrechts-University, Kiel, Germany. firstname.lastname@example.org
Contamination of stem cell harvests with residual tumor cells is a significant problem hampering the success of autologous peripheral blood stem cell transplantation in non-Hodgkin's lymphoma (NHL). Techniques have therefore been introduced to attempt to remove these cells, either in vivo, prior to harvesting, or ex vivo, before reinfusion into the patient. Rituximab is a human-mouse chimeric anti-CD20 monoclonal antibody that has been administered to patients prior to stem cell harvesting, to purge the blood of residual malignant cells. Clinical studies have shown that rituximab is safe to use during stem cell mobilization since administration did not adversely affect the yield of CD34+ stem cells or the functional capability of these progenitors. Rituximab was also effective in purging stem cell harvests of malignant cells. Translocation of the bcl-2 gene was found in a significantly smaller proportion of stem cell harvests from patients who had received a purging infusion of rituximab than controls. Rituximab may also be useful as salvage therapy following post-transplant relapse or as maintenance therapy for patients in remission. Prospective randomized trials will ultimately define the role of rituximab in the autologous transplantation setting.
UI - 11508934
AU - Linch D
TI - Current treatment of follicular and low-grade non-Hodgkin's lymphoma.
SO - Anticancer Drugs 2001 Jun;12 Suppl 2():S5-9
AD - Department of Haematology, Royal Free and University College Medical School, London, UK. email@example.com
Patients with low-grade non-Hodgkin's lymphoma (NHL) have a median survival of 4-8 years from diagnosis and a cause-specific survival of about 10 years. Radiotherapy can be curative in a small proportion of patients with very localized disease, but the majority of patients have advanced disease at diagnosis and it is not clear that any current therapy is curative in this situation. While in many instances patients with high-grade NHL are cured by chemotherapy, those with low-grade NHL, despite impressive response rates, almost invariably relapse. A 'watch-and-wait' strategy can therefore delay the onset of chemotherapy by 2-3 years, without affecting survival. Results with autologous stem cell transplantation have been similarly disappointing to date. Rituximab is a human-mouse chimeric monoclonal antibody that represents a novel approach to treatment of low-grade NHL, targeting malignant cells without the side effects associated with chemotherapy. A pivotal study has demonstrated a response rate of 56% in relapsed or refractory low-grade NHL. The relatively benign side-effect profile means rituximab can be used early in the disease process, and in combination with chemotherapeutic regimens and autologous transplantation. Ongoing and future studies will define the optimal role of rituximab in treatment of low-grade NHL.
UI - 11512599
AU - Dowling AJ; Prince HM; Wirth A; Wolf M; Januszewicz EH; Juneja S;
TI - Seymour JF; Gates P; Smith JG High-dose therapy and autologous transplantation for lymphoma: The Peter MacCallum Cancer Institute experience.
SO - Intern Med J 2001 Jul;31(5):279-89
AD - Department of Medical Oncology, St Vincent's Hospital, Melbourne, Victoria, Australia.
BACKGROUND: High-dose therapy (HDT) with autologous bone marrow or blood cell transplantation for the treatment of lymphoma commenced at Peter MacCallum Cancer Institute in 1986. AIM: To examine the patient characteristics and outcomes of patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) treated with HDT and autologous transplantation at our Institute in the first 10 years of the service (1986-95). METHODS: A retrospective analysis was performed examining patient characteristics, prior chemotherapy regimens, pretransplant disease status, HDT regimen, source of stem cells, time for haematopoietic recovery, complications of transplantation, response rates, overall survival (OS) and progression-free survival (PFS). RESULTS: Sixty-seven patients with NHL were treated with an estimated 5-year OS rate of 44% (95% confidence interval (CI) 32-56%) and PFS rate of 34% (95% CI 21-44%). Factors independently predictive of an unfavourable PFS on multivariate analyses were presence of constitutional symptoms at transplant (P < 0.002) and chemotherapy-resistant disease at transplant (P = 0.02). Twenty-three patients with HD were treated with a 5-year predicted OS rate of 74% (95% CI 56-92%) and PFS rate of 57% (95% CI 36-77%). There was no difference in PFS for HD patients who relapsed either within 12 months of completion of front-line therapy or after this time (P= 0.5). The transplant-related mortality for the entire cohort was 17%, with a progressive decrease over time. CONCLUSION: HDT with autologous transplantation achieves durable PFS and OS in patients with lymphoma. Improved patient selection, therapy modifications according to prognostic factors and ongoing improvements in supportive care should improve outcomes further.
UI - 11544694
AU - Laine K; Valavaara R; Rouru J
TI - [Drug interaction behind the toxicity of chemotherapy]
SO - Duodecim 1998;114(11):1128-30
AD - TYKS:n kliinisen farmakologian yksikko 20520 Turku. firstname.lastname@example.org
UI - 11527816
AU - Perez CL; Rudoy S
TI - Anti-CD20 monoclonal antibody treatment of human herpesvirus 8-associated, body cavity-based lymphoma with an unusual phenotype in a human immunodeficiency virus-negative patient.
SO - Clin Diagn Lab Immunol 2001 Sep;8(5):993-6
AD - Departamento Virologia, Instituto Nacional de Enfermedades Infecciosas-ANLIS Dr. Carlos G. Malbran, Av. Velez Sasrsfield 563 (1281), Buenos Aires, Argentina. Cperez@anlis.gov.ar
Human herpesvirus 8 (HHV-8), or Kaposi's sarcoma-associated herpesvirus, is a gammaherpesvirus first detected in Kaposi's sarcoma tumor cells and subsequently in primary effusion lymphoma (PEL) tumor cells and peripheral blood mononuclear cells from PEL patients. PEL has been recognized as an individual nosologic entity based on its distinctive features and consistent association with HHV-8 infection. PEL is an unusual form of body cavity-based B-cell lymphoma (BCBL). It occurs predominantly in human immunodeficiency virus (HIV)-positive patients but occasionally also in elderly HIV-negative patients. We describe a case of PEL, with ascites, bilateral pleural effusions, and a small axillary lymphadenopathy, in a 72-year-old HIV-negative man. PCR performed on a lymph node specimen and in liquid effusion was positive for HHV-8 and negative for Epstein-Barr virus. The immunophenotype of the neoplastic cells was B CD19+ CD20+ CD22+ with coexpression of CD10 and CD23 and with clonal kappa light chain rearrangement. The patient was treated with Rituximab, a chimeric (human-mouse) anti-CD20 monoclonal antibody. Thirteen months later, the patient continued in clinical remission. This is the first report of an HHV-8-associated BCBL in an HIV-negative patient in Argentina.
UI - 11564066
AU - Di Gaetano N; Xiao Y; Erba E; Bassan R; Rambaldi A; Golay J; Introna M
TI - Synergism between fludarabine and rituximab revealed in a follicular lymphoma cell line resistant to the cytotoxic activity of either drug alone.
SO - Br J Haematol 2001 Sep;114(4):800-9
AD - Laboratory of Molecular Immunohaematology and Department of Oncology, Istituto Ricerche Farmacologiche Mario Negri, via Eritrea 62, 20157 Milan, Italy.
We have shown previously that the anti-CD20 chimaeric monoclonal antibody rituximab exerts its effects on neoplastic B-lymphoma cell lines in part via complement-dependent cytotoxicity. In addition, membrane expression levels of complement inhibitory proteins CD55 and CD59 play a role in determining susceptibility to lysis. We have identified one t(14;18)-positive human B-cell non Hodgkin's lymphoma cell line (Karpas 422) that is resistant to rituximab and complement and used it for subsequent studies on the possible interaction between this novel therapeutic agent and established antineoplastic drugs. We have exposed Karpas to several chemotherapeutic agents (doxorubicin, idarubicin, cisplatin, taxol) for different time periods and subsequently exposed the cells to rituximab and human complement. The combination of these drugs with rituximab induced an additive cytotoxic effect. In contrast, exposure to fludarabine (1 microg/ml for 48-72 h) showed a synergistic effect, with cell lysis increasing from 10% to 20% using fludarabine or rituximab and complement alone to about 70% with both cytotoxic agents. Analysis of the mechanism for this synergistic effect showed that fludarabine downmodulates the membrane expression of CD55 (from 96% to 55% positive cells) without significantly altering CD20 levels. Northern analysis demonstrated that fludarabine induced a general downmodulation of steady state mRNA levels with no change in transcription rate detected in run-off assays. The study of the effect of fludarabine and rituximab in six freshly isolated B-cell chronic lymphocytic leukaemia (B-CLL) samples showed that, in most cases, fludarabine has an additive cytotoxic activity with rituximab and complement. This report gives a rational support for clinical studies with combinations of drugs, including monoclonal antibodies and fludarabine.
UI - 11583015
AU - Ribeiro JM; Lucas M; Palhano MJ; Victorino RM
TI - Remission of a high-grade gastric mucosa associated lymphoid tissue (MALT) lymphoma following Helicobacter pylori eradication and highly active antiretroviral therapy in a patient with AIDS.
SO - Am J Med 2001 Sep;111(4):328-9
UI - 11593318
AU - Gutierrez-Delgado F; Maloney DG; Press OW; Golden J; Holmberg LA;
TI - Maziarz RT; Hooper H; Buckner CD; Appelbaum FR; Bensinger WI Autologous stem cell transplantation for non-Hodgkin's lymphoma: comparison of radiation-based and chemotherapy-only preparative regimens.
SO - Bone Marrow Transplant 2001 Sep;28(5):455-61
AD - The Fred Hutchinson Cancer Research Center, 1100 Fairview Av North D5-390, Seattle, WA 98109, USA.
The aim of this study was to compare toxicity and efficacy of total body irradiation (TBI), cyclophosphamide (CY) and etoposide (E) (TBI/CY/E) vs busulfan, melphalan and thiotepa (Bu/Mel/T) in patients receiving autologous stem cell infusion (ASCI) for malignant lymphoma (NHL). with TBI/CY/E (n = 221) or Bu/Mel/T (n = 130) followed by ASCI. Patients in first, or second remission, first responding or untreated relapse were defined as having less advanced disease before transplantation. The median follow-up was 5 years (range 1-9) and 3.5 years (1-6) for patients receiving TBI/CY/E and Bu/Mel/T, respectively. The cumulative probabilities of survival, event-free survival (EFS) and relapse at 5 years were 44%, 32%, 49% following TBI/CY/E and 42%, 34% and 42% following Bu/Mel/T. The probability of EFS at 5 years for patients who had prior dose-limiting radiation (n = 59) was 32% after Bu/Mel/T therapy. Transplant-related mortality was 16% for TBI/CY/E and 21% for Bu/Mel/T. In univariate and multivariate analyses, more advanced disease status was associated with poor outcome (TBI/CY/E: RR 0.70, CI 0.50 to 0.97 P = 0.04; Bu/Mel/T: RR 0.61, CI 0.39 to 0.97 P = 0.03). No significant differences in toxicities and outcomes were observed between these two regimens despite the inclusion of patients who had received dose-limiting irradiation in the Bu/Mel/T regimen.
UI - 11584710
AU - Spath-Schwalbe E
TI - [Treatment of malignant non-Hodgkin's lymphomas in elderly patients]
SO - Z Gerontol Geriatr 2001 Aug;34(4):263-8
AD - Krankenhaus Spandau 2, Abteilung fur Innere Medizin Neue Bergstrasse 6