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M Divine

Publications and source records attributed to M Divine.

At least 37 records · Page 2Linked to original sources

High-dose therapy and autologous blood stem cell transplantation in multiple myeloma: preliminary results of a randomized trial involving 167 patients.

Since 1986, we have treated young patients with aggressive multiple myeloma (MM) by high-dose chemotherapy (HDC) and total body irradiation (TBI) followed with autologous blood stem cell transplantation (ABSCT). To evaluate this strategy: 1) We conducted a phase II trial that included 63 patients. Within a median follow-up of five years after transplantation, overall survival was 60% and median event-free survival was four years, and 2) In the early 1990s, we initiated a prospective trial where, after collection of chemotherapy-mobilized ABSC, patients under 55 years of age with newly diagnosed MM were randomly assigned either to HDC and TBI supported with ABSCT (high-dose therapy [HDT] arm) or to a conventional vincristine, melphalan, cyclophosphamide and prednisone (VMCP) regimen (VMCP arm). In the latter, HDT with ABSCT was performed as a rescue therapy, in case of primary resistance to VMCP or at relapse in responders. As of June 1994, 167 patients have been enrolled since a median time of 26 months. Fourteen (8%) could not be randomized. Among the randomized patients (n = 153), 30 deaths were observed, 13 in the HDT group and 17 in the VMCP group (p = 0.28, two-sided log rank test). Overall survival rates at two years were estimated at 78% for all 167 patients, at 82% in the HDT group and at 67% in the VMCP group. ABSC, provided they are collected early in the disease course, allow a great majority of myeloma patients to receive HDT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Efficacy of single-agent chemotherapy in low-grade B-cell mucosa-associated lymphoid tissue lymphoma with prominent gastric expression.

PURPOSE: The treatment of low-grade B-cell mucosa-associated lymphoid tissue (MALT) lymphoma with prominent gastric expression is controversial. Total gastrectomy has been proposed, but is associated with significant morbidity. The aim of this monocentric study was to assess the efficacy of continuous oral chemotherapy with a single alkylating agent. PATIENTS AND METHODS: Twenty-four consecutive patients, 13 men and 11 women, were studied. Their mean age was 51 years (range, 22 to 79). Low-grade B-cell MALT lymphoma was diagnosed by histologic and immunohistologic examination of endoscopic biopsies. Seventeen patients had stage I disease and seven stage IV disease, with lung and gastric involvement. Two of these seven patients also had bone marrow involvement. The alkylating agent (cyclophosphamide or chlorambucil) was administered orally and daily for periods of 12 to 24 months. RESULTS: The median follow-up time was 45 months (range, 14 months to 14 years). Complete remission was obtained in 18 patients (75%) after a median treatment duration of 12 months. Five patients relapsed; two of them were successfully re-treated, and one died of MALT lymphoma that had transformed into large-cell lymphoma. Chemotherapy was stopped after 24 months for six patients who only achieved a partial remission; two of them required further treatment for progressive disease (surgery for a small-bowel localization in one case and cyclophosphamide rechallenge in the other). Nine patients had neutropenia that required a reduced chemotherapy dosage. CONCLUSION: In low-grade MALT lymphoma with prominent gastric expression, continuous monochemotherapy may constitute an efficient alternative to gastrectomy, regardless of disease stage.

Administration, Oral↗

Comparison of autologous bone marrow transplantation and peripheral blood stem cell transplantation after first remission induction treatment in multiple myeloma.

The optimal source of stem cells is a controversial issue in the field of autologous stem cell transplantation. A comparison of autologous bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) after first remission induction treatment in multiple myeloma was made by a retrospective analysis of 132 transplants performed in 18 French Centers from 1984 to 1991 (81 autologous BMT, 51 PBSCT). The two groups differed in the median age (PBSCT 49 years; autologous BMT 55 years, P < 0.001), the duration of chemotherapy prior to transplantation, the interval between stem cell collection and transplantation, and in the conditioning regimen (more total body irradiation and higher doses of irradiation in the PBSCT group). The median time to neutrophil recovery was shorter in the PBSCT group (13 days vs. 20 days, P < 0.001), but the median time to platelet recovery did not differ significantly between PBSCT (26 days) and autologous BMT (22 days). There was no significant difference between the two groups regarding overall response rate (PBSCT 84%, autologous BMT 82%) and complete remission rate (PBSCT 37%, autologous BMT 36%). The actuarial relapse-free survival, time to treatment failure and overall survival were not significantly different. A case controlled study comparing 43 autologous BMT and 43 PBSCT matched for age and status at the time of transplantation did not show any advantage of PBSCT over autologous BMT in terms of immediate outcome, relapse-free survival, overall survival and time to treatment failure. Thus, in this retrospective analysis, the only significant benefit for PBSCT was reduced time to neutrophil recovery.

Adult↗

Elevated levels of interleukin-1 beta (IL-1 beta) and IL-6 in serum and increased production of IL-1 beta mRNA in lymph nodes of patients with polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome.

To evaluate a possible implication of cytokines in the pathogenesis of polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome, we studied five consecutive patients with this condition, of which four had sclerotic bone lesions and four had multicentric Castleman's disease. Interleukin-1 beta (IL-1 beta) and IL-6 serum levels were determined in these patients (13 serum samples) and in patients with multiple myeloma (5) and Waldenström's macroglobulinemia (5). In situ hybridization of the relevant mRNAs was performed on lymph node specimens of two patients with POEMS syndrome who had Castleman's disease. Elevated serum levels of IL-1 beta (13/13 samples), and IL-6 (7/13 samples) were found in patients with POEMS syndrome. In the other patients, serum IL-1 beta was undetectable or slightly increased and IL-6 was elevated in a single patient with Waldenström's macroglobulinemia. Abundant IL-1 beta mRNA-producing cells were present in interfollicular spaces in the two tested patients, while IL-6 mRNA-producing cells were rare. We conclude that IL-1 beta and IL-6 serum levels may be chronically elevated in patients with POEMS syndrome, and that lymph node may be one site of IL-1 beta overproduction. These results are in keeping with the hypothesis that cytokines mediate systemic manifestations of POEMS syndrome.

Adult↗

Interleukin-2 treatment in lymphoma: a phase II multicenter study.

A phase II study was undertaken to assess whether continuous infusion of high-dose recombinant interleukin-2 (rIL-2) alone was active against different histologic subtypes of heavily pretreated lymphoma. Sixty one lymphomas were included in the study. rIL-2 (Roussel UCLAF, Romainville, France) was administered by continuous infusion at 20 x 10(6) IU/m2 for three cycles of 5 days, 4 days, and 3 days, during the first week, third week, and fifth week, respectively. Twenty-four low-grade non-Hodgkin's lymphomas (NHL) were resistant to an anthracycline-containing regimen. Twenty-three intermediate and high-grade NHL were refractory to initial treatment or to salvage therapy. Seven Hodgkin's diseases were refractory to at least three regimens or relapsed after autologous bone marrow transplantation. Seven mycosis fungoides were refractory to chemotherapy. In low-grade NHL, one complete response (CR) was observed. In aggressive NHL, there were three CRs and two partial responses (PRs). No response was noted in Hodgkin's disease. One CR and four PRs were observed in mycosis fungoïdes. Complete response durations were 23, 20, 17, 12, and 4 months. Grade 4 toxicity was observed in 29 patients leading to arrest of therapy in 12 patients. The response to rIL-2 therapy in lymphoma differs according to histologic subtypes. Five responses were observed in 23 aggressive lymphomas. Five of seven mycosis fungoïdes responded; these preliminary results warrant testing of a larger number of patients.

Adult↗

Comparison of autografting using mobilized peripheral blood stem cells with and without granulocyte colony-stimulating factor in malignant lymphomas.

Peripheral blood is becoming widely used as the only source of hematopoietic stem cells to support marrow ablative therapy in advanced lymphoma. We report data from 23 patients with high risk non-Hodgkin's (n = 19) and Hodgkin's lymphoma (n = 4) who underwent high-dose therapy with mobilized peripheral blood stem cell (PBSC) autografting. Peripheral blood progenitors were recruited using cytotoxic chemotherapy followed by administration of recombinant human G-CSF (filgrastim 5 micrograms/kg/day). Myeloablative treatment with autologous PBSC support was administrated to the 23 patients and followed by G-CSF at the same dose after cell reinjection. Hematopoietic reconstitution was compared with a control group of lymphoma patients who received chemotherapy mobilized PBSC transplantation but without G-CSF prior to leukaphereses or after high-dose therapy. The median time to neutrophil recovery > 0.5 x 10(9)/l was significantly shorter in study patients compared with the control patients (10 days and 17 days respectively) (p < 0.05). Self sustaining platelet counts of > 50 x 10(9)/l occurred at a median time of 17 days in both groups. Stable hemopoietic reconstitution was seen with a follow-up of 6 months after PBSC transplantation. In addition, a significant relationship was observed between the number of CFU-GM infused and the time to platelet recovery. We confirm the effectiveness of G-CSF given prior to PBSC harvesting in generating high numbers of progenitor cells. Hematologic recovery following high-dose therapy was improved after PBSC rescue and G-CSF.

Adolescent↗

High-dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma: results of a phase II trial involving 63 patients.

Sixty-three patients with high tumor mass multiple myeloma were treated with high-dose chemotherapy and total body irradiation supported by autologous blood stem cell transplantation. After high-dose therapy, they were monitored for a median of 44 months. Seven patients died early from toxicity. All the other patients, including those whose disease was resistant to previous therapies, showed a tumor mass reduction. At 6 months postengraftment, 40 (71%) of the surviving patients had minimal residual disease and 11 (20%) were in apparent complete remission. During follow-up, 25 out of the 63 (39%) patients relapsed and 16 of these died; 31 (49%) had a sustained remission. The median overall and event-free survival times after transplantation were 59 and 43 months, respectively. The initial serum beta 2-microglobulin value (> or < 2.8 mg/L) and length of previous therapy (> or < 6 courses of chemotherapy) were the only significant prognostic factors. In all surviving patients, blood stem cell autograft provided satisfactory and sustained haematopoietic reconstitution most often within 15 days. High dose chemoradiotherapy followed by autologous blood stem cell transplantation is thus an important therapeutic option for young patients with aggressive multiple myeloma.

Adult↗

Treatment of adult chronic autoimmune thrombocytopenic purpura with repeated high-dose intravenous immunoglobulin.

Intravenous (i.v.) infusions of Ig concentrates are an effective but expensive treatment for patients with autoimmune thrombocytopenic purpura (AITP). The optimal treatment protocol and the long-term results are uncertain, and the precise mechanism by which the platelet count increases is poorly understood. Twenty adult patients with chronic AITP were enrolled in a prospective study to compare the respective efficacy of two high-dose IVIgG induction regimens (1 g v 2 g/kg body weight) and the long-term effect of six 1 g/kg body weight i.v. IgG reinfusions. An initial response was observed in all 18 evaluable patients: the platelet count increased to a mean value of 251 x 10(9)/L (range 72 to 836 x 10(9)/L) and the mean pretreatment platelet count was multiplied by 14.6. No difference in efficiency was observed between the two i.v. IgG dosages. The degree of the platelet count increment correlated in both groups with the increase in the clearance of antibody-coated red blood cells, measured by an isotopic method, but not with the serum IgG elevation. Treatment was considered to have failed in 11 patients, 90 days after the last i.v. IgG reinfusion (D90), because the platelet counts were comparable with pretreatment values. In contrast, a complete response was observed at D90 in five patients (mean platelet count: 184 x 10(9)/L; range: 150 to 250 x 10(9)/L) and a partial response at D90 was obtained in the remaining two patients (platelet counts: 70 and 104 x 10(9)/L). Five of the 7 responders at D90 kept a platelet count above 50 x 10(9)/L during the entire follow-up period (mean 33 months; range: 5 to 66) with no further treatment; unfortunately, no clinical or biologic criteria were found to be predictive of the long-term response. This study shows that an i.v. IgG infusion regimen of 1 g/kg body weight could safely replace the classical 2 g/kg body weight dosage, at least in patients who do not have life-threatening thrombocytopenia. Moreover, repeated i.v. IgG reinfusion could be an alternative for AITP patients in whom splenectomy is contraindicated.

Adult↗

Nasal T-cell lymphoma: a clinicopathologic entity associated with peculiar phenotype and with Epstein-Barr virus.

Recent evidence has shown that most nasal lymphomas (NL) are associated with a T-cell phenotype and are thus called nasal T-cell lymphomas (NTCL), but little information is available about the T-cell receptor (TCR) expression. The presence of Epstein-Barr virus (EBV) genome has been recently reported in NTCL in Oriental populations in which NL and EBV-associated tumors are more common and in occasional Occidental cases. This prompted us to investigate lymphoma biopsies from 7 non-Oriental patients with NTCL for the expression of natural killer (NK) and T-cell antigens, including TCR proteins, for the presence of EBV-encoded latent membrane protein (LMP) using immunohistochemistry and for the presence of EBV DNA and Epstein-Barr early region (EBER) RNA using in situ hybridization (ISH). Six cases displayed a CD3-, TCR alpha beta-, TCR gamma delta-, CD2+, CD7+, CD5-, CD4-, CD8-, CD56+ phenotype, suggesting that these tumors may be peripheral T-cell lymphomas (PTCL) with extensive loss of T-cell antigens and expression of the NK-cell (CD56) antigen or, alternatively, NK-cell neoplasias. The remaining case was a gamma delta PTCL, as shown by the CD3+, TCR gamma delta+ phenotype and the biallelic gamma and delta TCR gene rearrangements. Using ISH, EBER RNA transcripts were detected in tumor cells in all cases and EBV DNA was shown in the 6 tested cases. In all cases, tumor cells expressed LMP. These findings support the concept that NTCL constitute a distinct group of lymphomas that, in addition to their peculiar clinical features, exhibit an unusual TCR "silent" CD56+ or TCR gamma delta+ phenotype and harbor the EBV. In view of the LMP transforming potential, these data suggest that EBV may play a role in the pathogenesis of NTCL.

Adolescent↗

Detection of multiple myeloma involving the spine: efficacy of fat-suppression and contrast-enhanced MR imaging.

OBJECTIVE: To determine the efficacy of fat-suppressed sequences and contrast-enhanced MR imaging for the detection of focal spinal lesions caused by multiple myeloma, we obtained MR images in 32 patients with newly diagnosed myeloma who had back pain. SUBJECTS AND METHODS: All patients had biopsy-proved myeloma and had MR imaging at the painful level of the spine. Spin-echo T1-weighted, T2-weighted, and short TI inversion-recovery (STIR) images; dynamic ultrafast low-angle shot (turbo-FLASH) images after IV injection of a bolus of paramagnetic contrast material; and contrast-enhanced T1-weighted images were obtained. We qualitatively compared the signal intensities and contrast enhancement of focal lesions with those of the surrounding vertebral bodies. RESULTS: Multiple lesions were detected in all but two of the 32 patients. On T2-weighted and STIR images, all lesions had homogeneously high signal intensity. On T1-weighted images, the lesions were visible as hypointense areas compared with surrounding bone in all except four patients, in whom the lesions were isointense or hyperintense. All tumor nodules enhanced on turbo-FLASH images obtained in the arterial phase. No additional lesions were seen on STIR or contrast-enhanced images. MR findings resulted in a change in the staging of the disease in one patient and led to prompt treatment in five patients with epidural involvement. CONCLUSION: MR imaging appears to be helpful in detecting spinal involvement in patients with multiple myeloma. The diagnosis of spinal lesions is best achieved by using either fat-suppressed or T2-weighted images. Although myeloma lesions enhanced in all patients, contrast material appears to be of no value for the detection of additional lesions.

Contrast Media↗

MR appearance of multiple myeloma of the spine before and after treatment.

OBJECTIVE: The aim of this study was to describe the changes in the MR appearance of painful lesions of the spine before and after treatment in 18 patients with multiple myeloma and to correlate these changes with the clinical response to treatment. SUBJECTS AND METHODS: Eighteen patients with multiple myeloma and tumor nodules in the spine had MR imaging of the same site in the spine before and after treatment. Unenhanced T1- and T2-weighted spin-echo images, dynamic ultrafast low-angle shot (turbo-FLASH) images before and after IV bolus injection of paramagnetic contrast material, and contrast-enhanced T1-weighted spin-echo images were obtained. Characteristic signal and contrast enhancement before and after treatment were compared and were correlated with clinical data and the results of immunochemical and pathologic tests. RESULTS: Changes in signal intensity and enhancement of the lesions occurred after treatment in 14 of 18 patients. The characteristics of the lesions after treatment had three patterns: (1) rim enhancement or no enhancement of the lesions, (2) early enhancing lesions associated with other nonenhancing lesions or lesions with rim enhancement, and (3) no change from the enhancement pattern seen before treatment. In 13 of 18 patients, these patterns correlated well with the response to treatment. A discrepancy was observed in five patients. CONCLUSION: The MR appearance of spinal myeloma is different before and after treatment. MR images, particularly contrast-enhanced images, may be helpful in monitoring the response to treatment of focal bone lesions of myeloma.

Combined Modality Therapy↗

Hematologic, serologic values, histopathologic and fecal evaluations of bison from Yellowstone Park.

Hematologic and blood chemistry parameters were measured in 149 free-ranging American bison (Bison bison) from Yellowstone National Park, Wyoming (USA). Additionally, histopathologic evaluations of lung, liver, spleen, kidney, and mesenteric and bronchial lymph nodes were made from ten animals. Forty-five fecal samples were screened for the presence of helminth ova. Leukopenia and markedly low blood urea nitrogen concentrations were the most notable differences observed from other bison populations. All tissues examined were essentially normal; there was evidence of moderate intestinal parasite burdens.

Animals↗

[Role of x-ray computed tomography in the follow-up of the course of Hodgkin's disease].

Fourteen files of patients having had Hodgkin's disease have been analyzed retrospectively to assess the justification of systematic surveillance after complete remission has been achieved. The data of successive CT exams, compared with the findings of clinical and biological studies performed on the same dates, confirm the primordial role of imaging, since computed tomography was predictive for 7 of 18 events (14 relapses and 4 second progressions). The occurrence of subphrenic recurrence in 3 cases for which the initial site was mediastinal leads to discussing the merits of a yearly thoraco-abdomino-pelvic examination during the two years following complete remission.

Adult↗

[Corneal crystalline deposits in benign monoclonal gammopathies. Apropos of 3 cases].

Unusual corneal crystalline opacities at the level of Bowman's membrane and superficial stroma were observed in 3 patients with benign monoclonal gammopathy. Corneal immunohistochemical examination showed that the deposits consisted of immunoglobulin crystals identical to the paraprotein found in the serum (with the same light chain: Kappa in 2 cases and Lambda in the third case). The factors and mechanisms governing intracorneal immunoglobulin deposition in the cornea are discussed.

Adult↗

Clinical and biological analysis of peripheral T-cell lymphomas: a single institution study.

Peripheral T-cell lymphoma (PTCL) accounts for 15-20% of non-Hodgkin's lymphoma in the Western World. Clinical, histopathologic, phenotypic and genotypic data were received from 33 cases of PTCL referred to our institution. The median age order was 50 years, 78% were males, and 18% had a history of a preceding disorder of the lymphoid system. 60% had stage 4 at diagnosis and B symptoms were also present in 60%. The most frequent sites of extranodal involvement were bone marrow (54%), liver (45%) and skin (33%). Twenty-eight of 33 cases were histologically classified according to the Working Formulation (most in the diffuse mixed and large-cell subgroups) and the Kiel updated system. Phenotypic and genotypic studies of malignant cells showed a considerable heterogeneity with respect to the expression of either T-cell receptor (TCR) alpha beta and gamma delta and pan-T differentiation molecules. Of the studied cases 63% expressed TCR-alpha beta. All five patients with PTCL of the TCR-gamma delta subtype had a peculiar extra-nodal presentation. The vast majority of cases expressed an abnormal T-cell phenotype with respect to the expression of pan-T antigens, including the lack of expression of the TCR-associated CD3 molecule in 2 cases. Rearrangements of the TCR beta and/or delta-chain genes showed clonality in 21 of the 23 studied cases. Twenty-five patients were treated with a multiagent chemotherapy regimen with curative intent and the remainder received a less intensive palliative regimen. Only 9 patients achieved CR (8 of whom had received an anthracycline-containing regimen) and the 4-year survival rate was 25%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Bone marrow histologic and immunohistochemical findings in peripheral. T-cell lymphoma: A study of 38 cases.

The histologic and immunohistochemical findings in bone marrow (BM) biopsies from 38 patients with peripheral T-cell lymphoma (PTCL) are reported. Routine light microscopy showed that BM involvement was unequivocal in 12 cases and questionable in 14 cases. There was no histologic evidence of lymphoma in the remaining 12 cases. Immunohistochemistry performed on BM frozen sections demonstrated the T-cell origin of the infiltrating lymphoid cells in 24 of the 26 patients with unequivocal or questionable involvement. The malignant nature of these cells was suggested by demonstration of an aberrant T-cell phenotype identical to that observed in the other sites of involvement. In addition, in four of the 12 cases with apparently normal BM at routine light microscopy, immunohistochemistry revealed a minimal but phenotypically abnormal T-cell population, suggesting mild infiltration by lymphoma. These combined histologic and immunohistochemical data documented a high incidence (73%) of BM involvement by PTCL. In addition, a very peculiar sinusal pattern of BM involvement was found in five patients who presented an unusual type of hepatosplenic T-cell lymphoma expressing the gamma delta T-cell receptor. The present study demonstrates the high incidence of BM involvement by PTCL and emphasizes the value of frozen section immunohistochemistry to establish this diagnosis, especially when routine light microscopy findings are questionable.

Adolescent↗

Recombinative events of the T cell antigen receptor delta gene in peripheral T cell lymphomas.

Recombinative events of the T cell antigen receptor (TCR) delta-chain gene were studied in 37 cases of peripheral T cell lymphoma (PTCL) and related to their clinical presentation and the expression of the alpha beta or gamma delta heterodimers as determined by immunostaining of frozen tissue samples. There were 22 cases of alpha beta, 5 cases of gamma delta, and 10 cases of silent TCR expressing neither the alpha beta nor gamma delta TCR. 5 different probes were used to examine the delta locus. The 22 cases of alpha beta PTCL displayed biallelic and monoallelic deletions; a monoallelic V delta 1 J delta 1 rearrangement was observed in 1 case and a monoallelic germ line configuration in 7 cases. The 5 cases of gamma delta PTCL displayed biallelic rearrangements: the productive rearrangements could be ascribed to V delta 1J delta 1 joining in 3 cases and VJ delta 1 joining in 2 cases according to the combined pattern of DNA hybridization with the appropriate probes and of cell reactivity with the TCR delta-1, delta TCS-1, and anti-V delta 2 monoclonal antibodies. In the VJ delta 1 joining, the rearranged V segments were located between V delta 1 and V delta 2. Interestingly, in the third group of 10 cases of silent PTCL, 5 cases were found to have a TCR gene configuration identical to that in the TCR alpha beta PTCL, as demonstrated by biallelic delta gene deletion. These 5 cases were CD3 positive. The 5 remaining cases showed a monoallelic delta gene rearrangement with a monoallelic germ line configuration in 4 and a monoallelic deletion in 1. Four of these cases were CD3 negative, which was consistent with an immature genotype the TCR commitent of which could not be ascertained. Finally, TCR gamma delta PTCL consisted of a distinct clinical morphological and molecular entity whereas TCR alpha beta and silent PTCL had a similar presentation.

Alleles↗