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Biomedical subjects

M Bendandi

Publications and source records attributed to M Bendandi.

At least 19 recordsLinked to original sources

The results of consolidation with autologous stem-cell transplantation in patients with peripheral T-cell lymphoma (PTCL) in first complete remission: the Spanish Lymphoma and Autologous Transplantation Group experience.

BACKGROUND: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas associated with poor prognosis with standard chemotherapy. Consolidation with autologous stem-cell transplantation (ASCT) may improve survival. We present 74 patients transplanted in first complete response (CR) from the Spanish Lymphoma and Autologous Transplantation Group cooperative group. PATIENTS AND METHODS: Median age was 46 years. Eighty-eight percent presented advanced (III-IV) Ann Arbor stage; 53% had B symptoms; 52% had high lactate dehydrogenase; 65% had two or three risk factors of the adjusted-International Prognostic Index; 58% presented a high Tumor score and in 14% more than two adverse factors of the Prognostic Index for peripheral T-cell lymphoma (PIT) were observed. RESULTS: With a median follow-up of 67 months from diagnosis, the 5-year overall survival (OS) was 68% and progression-free survival (PFS) reached 63%. The multivariate analysis showed that the only factor associated with a shorter OS and PFS was the presence of more than two risk factors from the PIT risk system. CONCLUSIONS: In a retrospective study with a prolonged follow-up, consolidation with ASCT in CR patients who had presented unfavorable prognostic factors at diagnosis substantially increased the OS and PFS when compared with conventional chemotherapy. The PIT risk system identified 14% of patients without benefit from ASCT consolidation. Thus, other innovative therapies are still necessary in certain cases.

Adolescent↗

A single prior course of BCNU-cisplatin chemotherapy has a significant deleterious effect on mobilization kinetics of otherwise untreated patients.

Extensive prior treatment with cytotoxic agents is associated with impaired mobilization of hematopoietic cells. To assess the effect of a single course of standard-dose chemotherapy (CT), we compared the results of filgrastim-induced mobilization among two sequential groups of grade III-IV malignant glioma patients included in a hematopoietic transplantation program. The first group (21 patients) had never been treated with CT until 2 days after surgery, when they received a course of 100 mg/m2 BCNU (i.v.) and 100 mg intracarotid cisplatin for cytoreduction (not for mobilization). At 1 month after this CT, they were mobilized with 12 microg/kg filgrastim. The second group (22 patients) was mobilized with the same dose of filgrastim directly after the surgery, without having ever received any prior CT. The blood level of CD34+ cells was significantly lower in the CT-treated patients, both on the fourth day of filgrastim (15 vs 36 cells x 10(6)/l; P=0.01) and on the fifth (25 vs 58 cells x 10(6)/l; P=0.003), as it was the number of CD34+ cells collected per apheresis (1.3 vs 3.5 x 10(6)/l; P<0.0005). The toxic effect of a single course of BCNU-cisplatin CT led to significant impairment of the filgrastim-induced mobilization response.

Adult↗

Indolent lymphoma: the pathologist's viewpoint.

Indolent lymphomas have recently been the object of numerous studies, which have focused on new aspects relevant both for the better comprehension of their histogenesis and the identification of new therapeutic strategies. As marginal-zone lymphoma (MZL) represents the category of indolent lymphomas that has obtained more benefit from such an approach, the authors focused on the most recent achievements and not yet solved controversies in this area. In spite of their postulated common derivation, the three categories of MZL of the WHO Classification appear dissimilar. In fact, they show significant molecular differences among them as well as a certain heterogeneity within each group. By no means, there is a cogent need of more refined tools to revise these neoplasms and to produce a more rational grouping. The recent identification of the IRTA gene family corresponding to IG-like receptors differentially expressed in B-cells might contribute to their better understanding.

Humans↗

Expression of the c-met proto-oncogene and its ligand, hepatocyte growth factor, in Hodgkin disease.

The receptor for hepatocyte growth factor (HGF) is a transmembrane tyrosine kinase that is encoded by the proto-oncogene c-met. Recently, c-MET was detected in Reed-Sternberg (RS) cells from Epstein-Barr virus-positive (EBV(+)) Hodgkin disease (HD). The c-MET, EBER-1, and LMP-1 expression in 45 lymph node biopsies and 12 bone marrow biopsies obtained from patients with HD was analyzed. In addition, HGF levels in serum samples from 80 healthy individuals and 135 HD patients in different phases of disease. In all 45 lymph node and 12 bone marrow samples examined, RS cells expressed c-MET but not HGF(+). These results were independent of the EBV infection. Interestingly, several HGF(+) dendritic-reticulum cells were found scattered around c-MET(+) RS cells. The mean +/- SEM serum HGF levels in HD patients at diagnosis and at the time of relapse were 1403 +/- 91 (95% confidence interval [CI], 1221-1585) and 1497 +/- 242 pg/mL (95% CI, 977-2017), respectively. HGF values were significantly higher than those of healthy individuals (665 +/- 28 pg/mL; 95% CI, 600-721; and P <.001 for both groups of patients) and of HD patients in remission (616 +/- 49 pg/mL; 95% CI, 517-714; and P <.001 for both groups of patients). A significant correlation was found between serum HGF levels and B symptoms at diagnosis (P =.014). In conclusion, this study indicates that HGF and c-MET constitute an additional signaling pathway between RS cells and the reactive cellular background, thereby affecting adhesion, proliferation, and survival of RS cells. Furthermore, the serum concentration of HGF in HD patients may be a useful tool in monitoring the status of disease.

Adolescent↗

Novel secondary Ig VH gene rearrangement and in-frame Ig heavy chain complementarity-determining region III insertion/deletion variants in de novo follicular lymphoma.

Human germinal center B cell tumors retain the ability of their nontransformed counterparts to somatically hypermutate Ig V genes by nucleotide substitution. Among a survey of 60 primary previously untreated, clonal, follicular lymphomas we have identified a rare V(H) rearrangement variant and two other in-frame nucleotide insertion/deletion variants within complementarity-determining region III of the Ig heavy chain. The neoplastic origin of the V(H) rearrangement variant was directly demonstrated in cells isolated by microdissection from malignant follicles. In all three cases a common clonal origin for the variants was demonstrated by complementarity-determining region III nucleotide sequence homology and shared somatic mutations in germline encoded positions in framework region IV. The monoclonal nature of the tumors was independently confirmed by demonstrating a single t(14;18) translocation breakpoint in the two cases with a detectable translocation. All the variants occurred in functional V(H) rearrangements, which in two cases were directly shown to encode functional Ab molecules. Both recombination-activating genes 1 and 2 were expressed in lymph node tumor cells containing the V(H) rearrangement variant, although recombination-activating gene expression among a panel of lymphomas was not limited to this variant.

Amino Acid Sequence↗

Identification of the B-cell tumor-specific molecular fingerprint using non-radiolabelled PCR consensus primers.

BACKGROUND: The complementarity determining region 3 (CDR3) of the immunoglobulin (Ig) heavy chain variable region (VH) is the most reliable molecular fingerprint for most if not all human B cells. The nucleotide sequence encoding for any B-cell tumor-specific VH CDR3 is currently identified by PCR sequencing based on procedures involving the usage of either radioactive materials, patient/family-specific primers, or bacterial cloning. PATIENTS AND METHODS: In six consecutive patients with follicular lymphoma we assessed the feasibility of a method that allows for identification of the tumor-specific VH CDR3 using consensus primers while avoiding both radioactive materials and bacterial cloning procedures. RESULTS: The tumor-specific VH CDR3 was successfully identified in all six patients in nearly half the time typically required by any other method currently utilized. The feasibility of the proposed method was not significantly affected either by the tumor-specific Ig isotype, or by the tumor infiltration in the original biopsy specimen. In the three patients for whom tumor specimen-derived hybridomas were available, the tumor-specific VH CDR3 was also found in at least 8 of 10 of them. CONCLUSIONS: The proposed method allows the ability to quickly identify the B-cell tumor-specific VH CDR3 using consensus primers while avoiding radioactive materials and bacterial cloning procedures.

Base Sequence↗

Role of anti-idiotype vaccines in the modern treatment of human follicular lymphoma.

Cancer vaccines are currently conceived as therapeutic tools, in contrast to the prophylactic vaccines that have resolved the problem of a number of infectious diseases. Among the former, anti-idiotype vaccines for human follicular lymphoma have begun to produce tangible clinical results. Just 10 years ago it was not even known whether patients could be immunized against their own tumor antigens and now as many as two independent Phase III clinical trials based on this finding are underway. The rapidity of this development encourages the hope that active immunotherapy may soon become decisive in oncology. For the time being, many important results have already been achieved: the evidence of vaccine-induced, tumor-specific humoral/cellular responses and the first documented molecular remissions following vaccination.

Antibodies, Anti-Idiotypic↗

Primary mediastinal large B-cell lymphoma with sclerosis: a clinical study of 89 patients treated with MACOP-B chemotherapy and radiation therapy.

BACKGROUND AND OBJECTIVES: Primary mediastinal large B-cell lymphoma (PMLBCL) with sclerosis has recently been recognized as a specific clinical and pathologic entity for which the best therapeutic approach seems to be a combination of chemotherapy and radiotherapy. DESIGN AND METHODS: Between 1989 and 1998, 89 previously untreated patients with PMLBCL with sclerosis were treated with a combination of a third-generation chemotherapy regimen (MACOP-B) and mediastinal radiation therapy. The response evaluations were examined after chemotherapy and at the end of radiotherapy. RESULTS: Twenty-three (26%) patients achieved a complete response (CR) and 59 (66%) obtained a partial response (PR) after the MACOP-B regimen. After radiation therapy, 55/59 (93%) of the patients in PR achieved CR. The CR rate at the end of the treatment was 88% (78/89). Only 7 (8%) patients were non-responders. Among the 78 patients who obtained a CR there were 7 (9%) relapses in a median follow-up of 5 months (all relapses occurred within 9 months); the other 71 patients are currently in continuous CR with a median follow-upof 45 months (range, 4-110 months). Projected overall survival was 86% at 9 years; the relapse-free survival curve of the 78 patients who achieved CR was 91% at 9 years. INTERPRETATION AND CONCLUSIONS: In patients with PMLBCL with sclerosis, combined modality treatment using the MACOP-B chemotherapy regimen and radiation therapy induces a good remission rate with the patients having a greater than 90% chance of surviving disease-free at 9 years. Radiotherapy often plays a pivotal role in obtaining CR status.

Adolescent↗

Efficacy of vinorelbine, epirubicin and prednisone combination regimen in pretreated elderly patients with aggressive non-Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES: To assess the efficacy and toxic profile of the NAEPP protocol, a regimen including vinorelbine, epirubicin and prednisone, in a particularly troublesome subset of patients: pretreated elderly patients with aggressive non-Hodgkin's lymphoma (NHL). DESIGN AND METHODS: From November 1998 to January 2000, 20 pretreated patients who had all relapsed after first-line VNCOP-B chemotherapy were enrolled in a phase II trial and treated with the NAEPP regimen: vinorelbine (25 mg/m(2) i.v. on days 1 and 8), epirubicin (40 mg/m(2) i.v. on days 1 and 8), and prednisone (40 mg/m(2) on days 1 and 8) with granulocyte colony-stimulating factor administered at 5 mg/kg/day on days 2-5 and days 9-12. Chemotherapy was repeated every 4 weeks for a total of 6 cycles. RESULTS: Six (30%) patients achieved complete remission (CR) and 7 (35%) had partial responses (PR), giving an overall response rate of 65%. The response rate was not affected either by type of relapse presentation (nodal versus nodal plus extranodal), presence of bulky disease, or time of relapse. No major toxic effects were recorded. INTERPRETATION AND CONCLUSIONS: These preliminary data suggest that the NAEPP regimen is an effective combination with a low toxicity profile in elderly pretreated patients with aggressive NHL. Further trials using NAEPP as a consolidation phase following first-line treatment are needed to establish the advantage in terms of CR rate and relapse-free survival in these patients.

Aged↗

Tumor-specific recognition of human myeloma cells by idiotype-induced CD8(+) T cells.

Immunoglobulin secreted by myeloma cells contains a unique antigenic determinant (idiotype [Id]) that may serve as a tumor-specific antigen. Although Id-protein-specific T-cell responses have been reported in patients with myeloma, it is not known whether primary myeloma tumor cells can present naturally processed Id peptides on their surface as a target. We immunized 2 healthy human stem-cell donors with Id proteins from their recipients. T cells from the immunized donors released high levels of T-helper 1-type cytokines in response to stimulation with myeloma cells from their recipients. The T-cell-mediated cytokine response to tumor cells was blocked by a major histocompatibility complex (MHC) class I monoclonal antibody, whereas the response to soluble Id protein was dependent on MHC class II. To investigate whether Id-specific CD8(+) T cells can recognize and kill autologous myeloma cells, we generated T cells from peripheral blood mononuclear cells from a third patient with myeloma by means of in vitro stimulation with autologous dendritic cells pulsed with Id protein. Tumor-specific lysis of myeloma cells was demonstrated by the lack of killing of autologous nonmalignant B cells or natural killer-sensitive K562 cells. Lysis of autologous myeloma targets was restricted by MHC class I molecules. These data represent the first report of class I-restricted T-cell recognition of fresh autologous myeloma targets and formally demonstrate that human myeloma cells can serve as targets of an Id-specific T-cell response. (Blood. 2000;96:2828-2833)

Adult↗

Efficacy of fludarabine and mitoxantrone (FN) combination regimen in untreated indolent non-Hodgkin's lymphomas.

PURPOSE: In the last years, fludarabine (FLU) alone or in combination with other drugs has been reported to be effective in the treatment of previously treated low-grade non-Hodgkin's lymphomas (LG-NHL). The aim of this study was to define the therapeutic efficacy and toxicity of a combination of FLU and mitoxantrone (FN regimen) in untreated LG-NHL. PATIENTS AND METHODS: We used a two-drug combination of FLU (25 mg/m2 i.v. on days 1 to 3) and mitoxantrone (10 mg/m2 i.v. on day 1) to treat 27 previously untreated patients with LG-NHL, Chemotherapy was repeated every four weeks for a total of six cycles. Among 27 patients, 17 (63%) were diagnosed with follicular, 6 (22%) with small lymphocytic, and 4 (15%) with immunocytoma subtypes. RESULTS: Of the 27 patients, 18 (67%) achieved complete response (CR) and 6 (22%) partial response, while the remaining 3 (11%) showed no benefit from the treatment. Regarding histology, in the follicular subtype we observed an overall response rate of 94%, with a 76.5% CR rate. The estimated two-year relapse-free survival was 83%, and overall survival was 92%. Hematologic grade 3-4 toxicity was seen in only five (3.3%) patients; no opportunistic infections or deaths were associated with the administration of the FN regimen. CONCLUSIONS: These preliminary data show that the FN regimen is a very active, well-tolerated combination chemotherapy for untreated patients with advanced LG-NHL.

Adult↗

Anti-idiotype vaccines for human follicular lymphoma.

Cancer vaccines are conceived as therapeutic tools, in contrast to the prophylactic vaccines that have resolved the problem of a number of infectious diseases in a highly cost-effective way. Over the last decade, anti-idiotype vaccines for human follicular lymphoma have started to come into their own. Whereas 10 years ago it was not even known whether patients could be immunized against an antigen of their own tumor, a phase III clinical trial based on this finding is now already underway. The rapidity of this development encourages the hope that active immunotherapy may become decisive in oncology sooner than expected. Many important results have already been achieved. These include evidence of vaccine-induced, tumor-specific humoral and cellular responses along with the first documented molecular remissions following vaccination. Crucial questions still awaiting an answer include: do Id vaccines actually cure at least a fraction of FL patients? What is the most effective vaccine formulation? Is it possible to reduce the workload involved in producing an effective Id vaccine?

Animals↗

Gemcitabine treatment in pretreated cutaneous T-cell lymphoma: experience in 44 patients.

PURPOSE: To evaluate the efficacy and toxicity of gemcitabine, a novel pyrimidine antimetabolite with a low-toxicity profile and activity in several solid tumors, in patients with relapsed or refractory cutaneous T-cell lymphomas. PATIENTS AND METHODS: Between May 1997 and February 1999, 44 previously treated patients with mycosis fungoides (MF; n = 30) and peripheral T-cell lymphoma unspecified (PTCLU) with exclusive skin involvement (n = 14) were enrolled onto a two-institution, phase II trial and treated with gemcitabine. This drug was given on days 1, 8, and 15 of a 28-day schedule at a dose of 1,200 mg/m(2) intravenously over 30 minutes for a total of three courses. RESULTS: Of the 44 patients, five (11. 5%) achieved complete responses (CRs), 26 (59%) partial responses (PRs), and the remaining 13 showed no benefit from the treatment. Two of the CRs were histologically confirmed. The CR and PR rates were the same for patients with MF and those with PTCLU, respectively. No difference in terms of overall response rate was observed between relapsed and refractory patients. The median durations of CR and PR were 15 months (range, 6 to 22 months) and 10 months (range, 2 to 15 months), respectively. Treatment was well tolerated; hematologic toxicity was mild, and no nausea/vomiting or organ toxicity was recorded. CONCLUSION: The results of the present phase II study show activity of gemcitabine as a single agent in patients with pretreated cutaneous T-cell lymphoma. Further studies that use gemcitabine alone or in combination with other drugs in earlier stages of the disease are needed.

Adult↗

Randomized trial of fludarabine versus fludarabine and idarubicin as frontline treatment in patients with indolent or mantle-cell lymphoma.

PURPOSE: A first comparative trial of fludarabine (FLU) alone versus FLU plus idarubicin (FLU-ID) for indolent or mantle-cell lymphomas. PATIENTS AND METHODS: From September 1995 to July 1998, 199 patients aged 25 to 65 years (median, 54 years) with newly diagnosed stages II to IV indolent or mantle-cell lymphomas (standard risk according to the International Prognostic Index) were enrolled onto a multicenter, 1:1 randomized study. Of the 199 patients who were able to be assessed, 101 were assigned to the FLU group (six monthly cycles of FLU 25 mg/m(2)/d on days 1 through 5) and 98 to the FLU-ID group (six monthly cycles of FLU 25 mg/m(2)/d on days 1 through 3 and idarubicin 12 mg/m(2) on day 1). RESULTS: In the FLU group, complete response (CR) and partial response rates were 47% and 37%, respectively, whereas in the FLU-ID group, they were 39% and 42%, respectively. In-depth analysis of the CR rate with respect to histologic type showed that FLU seemed to be superior to FLU-ID in treating follicular lymphomas (60% v 40%, respectively), whereas FLU-ID seemed to be more effective than FLU in treating nonfollicular lymphomas (small lymphocytic, 43% v 29%, respectively; immunocytoma, 38% v 23%, respectively; P = not significant), excluding the mantle-cell subset (in which there was no difference between the two groups). No striking differences were observed between the two protocols in terms of overall response or toxicity, which was generally mild. However, with a median follow-up of 19 months, only 29 patients (62%) who received FLU alone have maintained their initial CR, compared with 32 (84%) of those who received FLU-ID therapy (P =.021). CONCLUSION: Although the FLU-ID regimen may not significantly improve the induction of CR in most indolent-lymphoma patients, our preliminary data do suggest that, with respect to FLU alone, it may be capable of conferring a longer-lasting CR and that it might be superior in terms of CR rate in small lymphocytic and immunocytoma subtypes.

Adult↗

Efficacy of the VBM regimen in the treatment of elderly patients with Hodgkin's disease.

BACKGROUND AND OBJECTIVES: No specific chemotherapy regimens have yet been recommended for elderly Hodgkin's disease (HD) patients. We investigated the therapeutic efficacy and toxicity of the three-drug-combination VBM (vinblastine, bleomycin, and methotrexate) regimen in a group of 19 elderly HD patients. DESIGN AND METHODS: Vinblastine (6 mg/m(2) i.v.), bleomycin (10 mg/m(2) i.v.) and methotrexate (25 mg/m(2) i.v.) were administered on days 1 and 8. Chemotherapy was repeated every 28 days for a total of 6 cycles. Local radiotherapy was given only to patients who presented bulky disease at the time of diagnosis. Of the 19 patients, 13 patients had stage II, 2 stage III, and 4 stage IV disease; the median age was 68 years (range 60 to 75). RESULTS: Of the 19 patients, 15 (79%) achieved complete response (CR) and 3 (16%) partial response, while the remaining patient showed no benefit from the treatment. With a median follow-up of 48 months, the estimated 5-year relapse-free survival was 79%, and overall survival was 64%. Hematologic grade 3-4 toxicity was seen in only 1 (5%) patient; no severe non-hematologic side effects or deaths were associated with the administration of the VBM regimen. INTERPRETATION AND CONCLUSIONS: These preliminary data indicate that the VBM regimen provides a safe and effective therapeutic option for elderly patients with untreated HD.

Age Factors↗