Treatment outcome and prognostic factors for relapse after high-dose chemotherapy and peripheral blood stem cell rescue for patients with poor risk high grade non-Hodgkin's lymphoma.
(73/3916)
The aim of the study was to determine treatment outcome and identify a particularly high risk group in a consecutive series of 66 patients with poor prognosis high grade lymphoma (NHL) treated with conventional induction chemotherapy followed by high-dose chemotherapy (HDCT) and peripheral blood stem cells (PBSC) rescue. Fifty-one patients with intermediate grade NHL (Kiel) and two or three adverse prognostic features as defined by the age-adjusted International Prognostic Index (IPI) received induction treatment with 7 weeks of doxorubicin, cyclophosphamide, vincristine, bleomycin, etoposide, prednisolone and methotrexate (VAPEC-B) followed by three cycles of ifosfamide/cytarabine. Fifteen patients with high grade Burkitt's and lymphoblastic NHL received 11 weeks of VAPEC-B followed by three cycles of high-dose methotrexate. HDCT for all 66 patients consisted of busulphan/cyclophosphamide followed by autologous PBSC rescue. Thirty-one patients (47%) received HDCT in first complete remission (CR/CRu) and 34 patients (52%) in first partial remission (PR) after conventional chemotherapy. Following HDCT, 42 patients (64%) were in CR/CRu, 19 patients (29%) in PR and one patient had progressive disease. There were four toxic deaths. After a median follow-up period of 27 months (range 7-73) in 46 surviving patients, the actuarial 3-year estimates of overall survival, event-free survival (EFS) and freedom from progression (FFP) were 67%, 65% and 70%, respectively. In univariate analysis, prognostic factors associated with reduced EFS were mediastinal bulk (P = 0.02), > or = 3 extra-nodal sites (P = 0.02), remission status prior to HDCT (P = 0.05), low albumin (P = 0.08) and raised ESR (P = 0.09). No significant difference was observed between patients with intermediate or high grade NHL or between patients with two or three adverse IPI features. Multivariate analysis identified mediastinal bulk (P = 0.01), > or = 3 extra-nodal sites (P = 0.01) and low albumin (P = 0.03) as joint predictors of poor EFS. Remission status prior to HDCT was not found to be significantly associated with reduced EFS, FFP or survival, suggesting early introduction of HDCT may benefit patients with a PR. Based on these three adverse features, three groups (0, 1 or > or = 2 features) could be identified with differing EFS, survival and freedom from progression (FFP) rates at 3 years; 85%, 63% and 20%, respectively for EFS, 84%, 64% and 25% for survival and 85%, 66% and 33%, respectively for FFP. This prognostic model may identify patients with a particularly poor prognosis despite HDCT, who may benefit from other therapeutic approaches. (+info)
Favorable impact of low-dose fludarabine plus epirubicin and cyclophosphamide regimen (FLEC) as treatment for low-grade non-Hodgkin's lymphomas.
(74/3916)
BACKGROUND AND OBJECTIVE: In recent years, conventional dose of fludarabine (FLU) alone or in combination with other drugs has been reported to be effective in the treatment of low-grade non-Hodgkin's lymphomas (LG-NHL). In particular, FLU and cyclophosphamide (CY) or FLU and mitoxantrone or idarubicin combined regimens have shown considerable therapeutic activity both as first line and salvage therapies, producing overall response rates ranging from 40-50% in previously treated patients and up to 70-90% in untreated ones. However severe neutropenia and infective complications have been reported in a significant number of patients. Based on these premises we evaluated the efficacy and toxicity of a new regimen combining low-doses of FLU with epirubicin (EPI) and CY (FLEC) in a group of advanced treatment-requiring LG-NHL patients. The aim of this study was to evaluate a strategy aimed at lowering therapy-related toxic effects without affecting the reported good response rate. DESIGN AND METHODS: Thirty patients with de novo, relapsed or refractory LG-NHL entered the study. FLEC regimen was as follows: EPI 60 mg/m(2) i.v. on day one, plus FLU 15 mg/m(2)/day i.v. (max 25 mg) and CY 250 mg/m(2)/day i.v. for four days. RESULTS: All 30 patients were evaluable for response, 13 (43%) fulfilled the criteria for CR and 11 (36%) for PR with an overall response rate of 79%. None of the 13 patients who achieved CR had relapsed after a follow-up of 2 to 23 months (median duration 13 months). With regard to age, 13/14 older patients (>/= 70 years) responded to the treatment and 9 of them maintained their response after a median of 13 months (range 2-22); six of the 14 (43%) obtained a CR. Therapy-related toxicity was mild regardless of age, neutropenia (43%) and fever of undetermined origin (26%) being the major side effects. Remarkably, a documented infection was recorded only in 2/30 (6%) patients. INTERPRETATION AND CONCLUSIONS: A low-dose FLU-based FLEC regimen appeared to be effective for advanced treatment-requiring LG-NHL, reproducing a similar overall response rate (79%) reported to have been achieved with other FLU based combination therapies. Toxic side effects were negligible and in particular documented infections were remarkably uncommon even in the group of elderly patients. (+info)
Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy.
(75/3916)
PURPOSE: To determine the safety and efficacy of the combination of the chimeric anti-CD20 antibody, Rituxan (Rituximab, IDEC-C2B8; IDEC Pharmaceuticals Corporation, San Diego, CA), and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. PATIENTS AND METHODS: Forty patients with low-grade or follicular B-cell non-Hodgkin's lymphoma received six infusions of Rituxan (375 mg/m2 per dose) in combination with six doses of CHOP chemotherapy. RESULTS: The overall response rate was 95% (38 of 40 patients). Twenty-two patients experienced a complete response (55%), 16 patients had a partial response (40%), and two patients, who received no treatment, were classified as nonresponders. Medians for duration of response and time to progression had not been reached after a median observation time of 29 + months. Twenty-eight of 38 assessable patients (74%) continued in remission during this median follow-up period. The most frequent adverse events attributable to CHOP were alopecia (38 patients), neutropenia (31 patients), and fever (23 patients). The most frequent events attributed to Rituxan were fever and chills, observed primarily with the first infusion. No quantifiable immune response to the chimeric antibody was detected. In a subset of 18 patients, the bcl-2 [t(14;18)] translocation was positive in eight patients; seven of these patients had complete remissions and converted to polymerase chain reaction (PCR) negativity by completion of therapy. CONCLUSION: This is the first report demonstrating the safety and efficacy of Rituxan anti-CD20 chimeric antibody in combination with standard-dose systemic chemotherapy in the treatment of indolent B-cell lymphoma. The clinical responses suggest an additive therapeutic benefit for the combination with no significant added toxicity. The conversion of bcl-2 from positive to negative by PCR in blood and/or marrow suggests possible clearing of minimal residual disease not previously demonstrated by CHOP chemotherapy alone. (+info)
Pulmonary malignancies in the immunocompromised patient.
(76/3916)
Clinicians should be familiar with immunodeficiency-related malignancies, as their incidence is expected to increase further with the rise in the number and survival of immunocompromised patients. The most common malignancies affecting the lungs in those patients are Kaposi's sarcoma, non-Hodgkin's lymphoma and, to a far less extent, Hodgkin's disease and bronchogenic carcinoma. However, their relative frequency depends on the types of immune deficiency, including those due to congenital disorders, AIDS and drug treatments. This review will summarize epidemiological data on the frequency of immmunodeficiency-related malignancies, recent advances on their pathogenesis and current approaches to their diagnosis and treatment in the various immunosuppressed groups. (+info)
Focal lymphoid aggregates (nodules) in bone marrow biopsies: differentiation between benign hyperplasia and malignant lymphoma--a practical guideline.
(77/3916)
AIMS: To provide practical guidelines for the differentiation between benign and malignant focal lymphoid aggregates (lymphoid nodules) in routinely referred bone marrow trephine biopsies, using a synoptic approach including clinical data and histological workup. METHODS: For easy identification of very small lymphoid infiltrates the chloroacetate esterase stain was applied as a screening procedure. This allowed the identification of 491 formalin fixed, paraffin wax embedded specimens with one or more lymphoid nodules. Examination of lymphoid infiltrates included such variables as histotopography, demarcation, cytology, reticulin fibres, and immunohistochemistry with a set of monoclonal antibodies (CD20, CD45R, CD45R0, CD3, CD43). Evaluation of clinical and morphological data was carried out independently. In case of malignant lymphomas, a correlation with corresponding lymph node findings was made. RESULTS: 352 patients had benign focal lymphoid aggregates usually associated with systemic autoimmune diseases, chronic myeloproliferative disorders, toxic myelopathy, and viral infections. Discrete nodular infiltrates of (small cell) malignant lymphomas (n = 93) simulating benign hyperplasia were found in chronic lymphocytic leukaemia, germinal centre cell lymphomas (CB-CC), and lymphoplasmacytic/cytoid lymphomas (LPI). In addition to immunoreactivity, certain histological variables proved distinctive. These were: (1) histotopography, that is, localisation of the lymphoid aggregates within the bone marrow space; (2) relation to the surrounding tissue: margination or interstitial spillage of lymphoid cells; and (3) increase in reticulin fibres. CONCLUSIONS: A combined diagnostic procedure identifying several distinctive features, in particular histotopography and immunohistochemistry, provides a most promising way of discriminating reactive from neoplastic lymphoid nodules in the bone marrow. (+info)
Cancers in children infected with the human immunodeficiency virus.
(78/3916)
The AIDS epidemic continues unabated in Africa, Asia, and South America, and since patients survive longer, the number of chronically immunocompromised individuals is increasing in Europe and the United States. The number of children with HIV infection who will ultimately develop a malignancy is not known. Currently, tumors represent about 2% of the AIDS-defining events in children in the United States, but the incidence might be different in developing countries. The most common tumors in HIV-infected children are non-Hodgkin's lymphoma, smooth muscle tumors (leiomyosarcomas), and Kaposi's sarcoma (only in Africa). This article provides an overview of epidemiology and clinical and pathological presentations, as well as preliminary data regarding treatment options in children with HIV-associated malignancies. (+info)
Heteroduplex analysis of VDJ amplified segments from rearranged IgH genes for clonality assessments in B-cell non-Hodgkin's lymphoma. A comparison between different strategies.
(79/3916)
BACKGROUND AND OBJECTIVE: The main difficulty of PCR-based clonality studies for B-cell lymphoproliferative disorders (B-LPD) is discrimination between monoclonal and polyclonal PCR products, especially when there is a high background of polyclonal B cells in the tumor sample. Actually, PCR-based methods for clonality assessment require additional analysis of the PCR products in order to discern between monoclonal and polyclonal samples. Heteroduplex analysis represents an attractive approach since it is easy to perform and avoids the use of radioactive substrates or expensive equipment. DESIGN AND METHODS: We studied the sensitivity and specificity of heteroduplex PCR analysis for monoclonal detection in samples from 90 B-cell non Hodgkin's lymphoma (B-NHL) patients and in 28 individuals without neoplastic B-cell disorders (negative controls). Furthermore, in 42 B-NHL and in the same 28 negative controls, we compared heteroduplex analysis vs the classical PCR technique. We also compared ethidium bromide (EtBr) vs. silver nitrate (AgNO(3)) staining as well as agarose vs. polyacrylamide gel electrophoresis (PAGE). RESULTS: Using two pair consensus primers sited at VH (FR3 and FR2) and at JH, 91% of B-NHL samples displayed monoclonal products after heteroduplex PCR analysis using PAGE and AgNO(3) staining. Moreover, no polyclonal sample showed a monoclonal PCR product. By contrast, false positive results were obtained when using agarose (5/28) and PAGE without heteroduplex analysis: 2/28 and 8/28 with EtBr and AgNO(3) staining, respectively. In addition, false negative results only appeared with EtBr staining: 13/42 in agarose, 4/42 in PAGE without heteroduplex analysis and 7/42 in PAGE after heteroduplex analysis. INTERPRETATION AND CONCLUSIONS: We conclude that AgNO(3) stained PAGE after heteroduplex analysis is the most suitable strategy for detecting monoclonal rearrangements in B-NHL samples because it does not produce false-positive results and the risk of false-negative results is very low. (+info)
Interleukin-6 regulation of matrix metalloproteinase (MMP-2 and MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) expression in malignant non-Hodgkin's lymphomas.
(80/3916)
We showed previously that human malignant non-Hodgkin's lymphomas (NHL) degrade extracellular matrix (ECM) components through the action of metalloproteinases and that elevated expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) correlated with a poor clinical outcome in patients with NHL. In the present study we sought to investigate whether there is any correlation between the expression of gelatinases (MMP-2 and MMP-9), TIMP-1, and the expression of cytokines and growth factors such as interleukin-1beta (IL-1beta), IL-6, IL-10, tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGFbeta), and basic fibroblast growth factor (bFGF) in human NHL. In lymphoma tissues obtained from 32 patients, elevated expression of IL-6 correlated significantly with elevated messenger RNA (mRNA) levels of MMP-9, MMP-2, and TIMP-1. Moreover, in human lymphoid cell lines of B- and T-cell origin (Raji, Jurkat, and NC-37), IL-6 stimulated production of MMP-9 and MMP-2 but not TIMP-1. In the Matrigel invasion assay IL-6 significantly upregulated transmigration of Raji and Jurkat cells, which in turn was inhibited by recombinant human TIMP-1 and anti-MMP-9 and MMP-2 antibodies. We postulate that IL-6 may play a role in the clinical aggressiveness of human NHL by stimulating MMP production. (+info)