Treatment of Older Patients with Mantle-Cell Lymphoma

BACKGROUND: The long-term prognosis for older patients with mantle-cell lymphoma is poor. Chemoimmunotherapy results in low rates of complete remission, and most patients have a relapse. We investigated whether a fludarabine-containing induction regimen improved the complete-remission rate and whether maintenance therapy with rituximab prolonged remission. METHODS: We randomly assigned patients 60 years of age or older with mantle-cell lymphoma, stage II to IV, who were not eligible for high-dose therapy to six cycles of rituximab, fludarabine, and cyclophosphamide (R-FC) every 28 days or to eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days. Patients who had a response underwent a second randomization to maintenance therapy with rituximab or interferon alfa, each given until progression. RESULTS: Of the 560 patients enrolled, 532 were included in the intention-to-treat analysis for response, and 485 in the primary analysis for response. The median age was 70 years. Although complete-remission rates were similar with R-FC and R-CHOP (40% and 34%, respectively; P=0.10), progressive disease was more frequent with R-FC (14%, vs. 5% with R-CHOP). Overall survival was significantly shorter with R-FC than with R-CHOP (4-year survival rate, 47% vs. 62%; P=0.005), and more patients in the R-FC group died during the first remission (10% vs. 4%). Hematologic toxic effects occurred more frequently in the R-FC group than in the R-CHOP group, but the frequency of grade 3 or 4 infections was balanced (17% and 14%, respectively). In 274 of the 316 patients who were randomly assigned to maintenance therapy, rituximab reduced the risk of progression or death by 45% (in remission after 4 years, 58%, vs. 29% with interferon alfa; hazard ratio for progression or death, 0.55; 95% confidence interval, 0.36 to 0.87; P=0.01). Among patients who had a response to R-CHOP, maintenance therapy with rituximab significantly improved overall survival (4-year survival rate, 87%, vs. 63% with interferon alfa; P=0.005). CONCLUSIONS: R-CHOP induction followed by maintenance therapy with rituximab is effective for older patients with mantle-cell lymphom

Development of T3/T cell receptor gene expression in human pre-T neoplasms

Abstract Acquisition of mature T cell function and the T cell antigen receptor repertoire occur in the thymus. In an effort to delineate the cascade of events leading to T cell maturation, we analyzed a series of clonal human precursor T cell neoplasms representing early, middle, and late stages of intrathymic differentiation. Rearrangements of the T cell receptor beta and gamma genes appear concurrently and are preceded by surface expression of the 3A1 (CD7) molecule. Subsequent transcription of the beta gene is coordinated with surface expression of T1 (CD5) and T11 (CD2), transcription of T3 delta mRNA, and the appearance of intracellular T3 (CD3) protein. As late events, T alpha gene transcripts appear and, finally, T3, the multichain complex linked to the T cell receptor, is presented on the cell surface. Findings reported here provide a model of the developmental orchestration of genes encoding antigen recognition in human T cells.</jats:p

Development of T3/T cell receptor gene expression in human pre-T neoplasms

Acquisition of mature T cell function and the T cell antigen receptor repertoire occur in the thymus. In an effort to delineate the cascade of events leading to T cell maturation, we analyzed a series of clonal human precursor T cell neoplasms representing early, middle, and late stages of intrathymic differentiation. Rearrangements of the T cell receptor beta and gamma genes appear concurrently and are preceded by surface expression of the 3A1 (CD7) molecule. Subsequent transcription of the beta gene is coordinated with surface expression of T1 (CD5) and T11 (CD2), transcription of T3 delta mRNA, and the appearance of intracellular T3 (CD3) protein. As late events, T alpha gene transcripts appear and, finally, T3, the multichain complex linked to the T cell receptor, is presented on the cell surface. Findings reported here provide a model of the developmental orchestration of genes encoding antigen recognition in human T cells.</jats:p

Chronic T cell leukemia with unusual cellular characteristics in ataxia telangiectasia

Abstract A 27-year-old male patient with ataxia telangiectasia (AT) developed atypical chronic lymphocytic leukemia with increasing bone marrow infiltration in the absence of organomegaly. One-third of the leukemia cells expressed a mature suppressor/cytotoxic T cell phenotype (T3+ T4- T6- T8+ T10-), two-thirds demonstrated additional helper/inducer T cell- associated antigens (T3+ T4+ T6- T8+ T10-), and a small fraction reacted with a natural killer (NK) cell-specific monoclonal antibody (Leu 11+). The proliferative response to stimulation in vitro with lectins and various monoclonal antibodies resembled the proliferation pattern of mature thymocytes: The cells responded to phytohemagglutinin (PHA), concanavalin A (ConA), stimulation of the T3-Ti receptor complex with Sepharose-bound anti-T3, and stimulation of the sheep erythrocyte receptor protein with anti-T11(2) and anti-T11(3) in conjunction with exogenous interleukin-2 (IL 2); they failed, however, to proliferate after stimulation with anti-T11(2) and anti-T11(3) alone. There was no response in the mixed lymphocyte reaction (MLR) and no suppression of the MLR between two healthy donors. Antibody-dependent cell-mediated cytotoxicity and NK activity could not be demonstrated. Cytogenetic analysis revealed complex clonal aberrations, including an interstitial deletion of the long arm of chromosome 14 concerning bands q21–31, loss of chromosome 20, and loss of the Y chromosome. Cytostatic chemotherapy was of little use and caused serious side effects, whereas leukapheresis proved effective in reducing the tumor load. The clinical data and laboratory findings in this case correspond to three previously described patients with AT who developed chronic T cell leukemia. Thus, in adult patients with AT, malignant proliferation of cytogenetically marked and phenotypically heterogeneous mature T cells seems to be a frequent complication.</jats:p

Comparison of Two Different Techniques for Harvesting Peripheral Blood Progenitor Cells (PBPC): Reduced Volume PBPC Collection versus Discontinuous Flow System

&lt;i&gt;Background:&lt;/i&gt; Peripheral blood progenitor cells (PBPC) can be collected by most blood cell separators. The present study was designed to compare two new techniques for PBPC collection. &lt;i&gt;Design:&lt;/i&gt; Prospective, randomized study. &lt;i&gt;Setting:&lt;/i&gt; Haemapheresis Unit and Haematological Division of a University Clinic. &lt;i&gt;Patients:&lt;/i&gt; 20 patients with non-Hodgkin’s lymphoma, Hodgkin’s disease and thyroid cancer. &lt;i&gt;Material and Methods:&lt;/i&gt; 20 patients with malignancies underwent PBPC collection with a ‘reduced-volume’ programme (Fresenius AS 104) and a single-needle technique (Haemone-tics MCS 3p), respectively. PBPC were mobilized by combined chemotherapy and cytokine administration or application of growth factor alone. Blood counts, CD 34 expressing cells and mononuclear cells (MNC) were determined before apheresis and in the PBPC product. Granulocyte macrophage colony-forming units (CFU-GM) were determined in the apheresis product. PBPC were frozen at controlled rates and stored in liquid nitrogen until they were used for autologous transplantation after high-dose chemotherapy. &lt;i&gt;Results:&lt;/i&gt; 32 PBPC collections were carried out with the Fresenius AS 104 and 27 separations with the Haemonetics MCS 3p device. Median product volume was 106 ml using the Fresenius AS 104 apparatus and 156 ml in the case of the Haemonetics MCS 3p machine. The median CD 34-expressing cell count was 1.0×10&lt;sup&gt;6&lt;/sup&gt;/kg body weight for the Fresenius device and 0.6 ×10&lt;sup&gt;6&lt;/sup&gt; for the Haemonetics cell separator. The cell recoveries of the two studied devices were significantly different. Six patients were grafted after high-dose chemotherapy. Five showed signs of haematopoietic recovery after autologous PBPC retrans-fusion. &lt;i&gt;Conclusions:&lt;/i&gt; The study reported here revealed that PBPC could be collected by both techniques. Although the collected amounts of CD34 expressing cells were similar, cell recoveries were significantly higher in the Haemonetics machine. Using the ‘reduced-volume’ procedure no additional centrifugation prior to cryopreservation was necessary to remove the plasma from the apheresis product. Haematopoietic engraftment was achieved after retransfusion of PBCS.</jats:p