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Biomedical subjects

J P Fermand

Publications and source records attributed to J P Fermand.

At least 55 records · Page 3Linked to original sources

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↗

Combined chemotherapy-radiotherapy in advanced Hodgkin's disease: results of a prospective clinical trial with 70 stage IIIB-IV patients.

PURPOSE: To evaluate two regimens of chemotherapy followed by high dose total or subtotal nodal irradiation in advanced Stages of Hodgkin's disease. METHODS AND MATERIALS: From October 1980 to September 1985, 70 patients with Hodgkin's disease, with clinical Stages IIIB (35 cases) and IV (35 cases) were treated with combined modality therapy. Patients were randomly assigned to receive four cycles of chemotherapy, mechlorethamine, vincristine, procarbazine and prednisone (MOPP) versus the same regimen alternating with adriamycin, bleomycin, vinblastine and dacarbazine, ABVD-derived regimen, followed by high-dose (40 Gy) total or subtotal nodal irradiation. Because of partial response, 13 patients (18.5%) got additional chemotherapy (1-4 cycles). RESULTS: After chemotherapy, 49 patients (70%) achieved complete remission or good partial response and 15 patients (21.5%) partial response. Five primary failures (7%) and one death (1.5%) occurred. After combined modality therapy, 59 patients (84%) achieved complete remission, one patient partial response (1.5%) and eight patients (11.5%) failed to primary treatment. Two toxic deaths (3%) were observed during initial treatment. There was no significant difference in response rates between MOPP/radiotherapy and MOPP/ABVD/radiotherapy. Nine patients relapsed (15%). A total of 21 patients died, 13 because of Hodgkin's disease and eight from other causes. High dose total or subtotal nodal irradiation following four courses of chemotherapy was feasible, although hematological toxicity grade > or = 2 (World Health Organization) was observed in one-third of the patients, particularly in patients aged over 40. The median duration of follow-up was 75 months. Actuarial survival curves indicate a 8 years disease-free survival and survival of 70% and 65% respectively, without any significant difference between the two regimens. Because of hematological toxicity, the percentage of planned full treatment was lower in MOPP/radiotherapy regimen. CONCLUSION: These results lead to recommend the alternating regimen. Patients restaged as poor responders after initial chemotherapy did not survive for long. More intensive treatment is now proposed for this subgroup of patients.

Adolescent↗

[Benign monoclonal gammopathies].

The finding in serum and/or urine of IgG, IgA or a monoclonal light chain must prompt a systematic search for a myeloma, a solitary plasmocytoma or an immunoglobulins amyloidosis. Clinical and experimental data suggest that some monoclonal immunoglobulins can remain stable after several years of existence, but at the time of diagnosis there is no criterium to assert with certainty that a monoclonal immunoglobulin will or will not be complicated by a malignant proliferation of plasmocytes. Nothing but a prolonged follow-up enables a diagnosis of "benign" monoclonal gammapathy to be made.

Animals↗

Role of granulocyte-macrophage colony-stimulating factor, interleukin-3 and interleukin-5 in the eosinophilia associated with T cell lymphoma.

We studied two patients with a leukaemic T cell lymphoma who presented with a marked increase in blood eosinophilia. To investigate the mechanism of the eosinophilia, supernatants of peripheral blood cells containing more than 80% lymphoma cells were tested by biological assays for the presence of colony stimulating factors (CSF). In one case supernatants stimulated the growth of granulocyte-macrophage (GM), erythroid and eosinophil colonies. These effects were neutralized by anti-GM-CSF antibodies; anti-IL5 antibodies slightly decreased eosinophil colony formation. Supernatants derived from the second patient cells stimulated the same lineages. Neutralizing experiments demonstrated that in addition to GM-CSF it contained interleukin 3 (IL-3) and interleukin 5 (IL-5). In agreement with the biological data, RNA studies using the polymerase chain reaction showed that cells from the first patient expressed GM-CSF transcripts; IL-5 transcripts were also detected in very low amounts. GM-CSF, IL-3 and IL-5 transcripts were detected in cells from the second patient. Thus eosinophilia associated with some T cell lymphoma is likely due to secretion of different combinations of cytokines by malignant cells.

Adult↗

Bullous amyloidosis. Report of 3 cases and review of the literature.

We report 3 cases of bullous immunoglobulinic amyloidosis and review 25 published cases. In 2 of our patients, amyloid deposits were not detected with special staining, but by means of ultrastructural methods. Investigations of the skin lesions permitted the diagnosis of associated plasma cell dyscrasia in 2 patients. Unexplained bullous lesions should be investigated for amyloid deposits and the presence of monoclonal gammopathy by methods including electron microscopy and immunochemical analysis of serum and urine.

Aged↗

Bone densitometry in patients with multiple myeloma.

PURPOSE, PATIENTS, AND METHODS: We performed dual-energy x-ray absorptiometry in 10 selected patients with aggressive multiple myeloma in whom substantial tumor mass reduction was achieved after high-dose chemoradiotherapy followed by autologous blood stem cell transplantation. RESULTS: In most cases, bone mineral density (BMD) of the spine was initially low (Mean Z score: -2.69, SEM 0.76) and dramatically increased after treatment (mean increase 16.4%; 7.7% with 95% confidence interval 2.2 to 12.2, excluding one patient whose spine BMD increased by 94.8%). In contrast, skeletal roentgenograms, computed tomographic scans, and magnetic resonance imaging did not reveal any significant improvement of patients' bone lesions. CONCLUSIONS: In patients with multiple myeloma, bone densitometry could be a useful way to assess the efficacy of treatment on bone status.

Absorptiometry, Photon↗

Severe hypoxemia-associated intrapulmonary shunt in a patient with chronic liver disease: improvement after medical treatment.

A 20-yr-old woman with chronic liver disease and angioimmunoblastic lymphadenopathy presented with marked hypoxemia caused by intrapulmonary shunt. Her respiratory tract showed her to be free of angioimmunoblastic lymphadenopathy manifestations. After 12 months of treatment with cyclophosphamide and corticosteroid, the immunologic disease disappeared. Unexpectedly, hypoxia-associated intrapulmonary shunt was no longer present either. To the best of our knowledge, this is the first case of dramatic improvement, with medical therapy, of severe hypoxemia related to noncirrhotic liver disease. However, the mechanism by which this treatment caused the regression of intrapulmonary shunt is unknown.

Adult↗

The role of autologous blood stem cells in support of high-dose therapy for multiple myeloma.

During the last few years, high-dose therapy with hemopoietic stem cell support has become a well-admitted therapeutic option for young patients with MM. The role of allogeneic or autologous graft and of blood rather than bone marrow as the source of hemopoietic stem cells must be further investigated. Autologous PBSC transplantation has, however, both practical and theoretic advantages over allogeneic and autologous BMT: (1) It can be applied to most patients, especially if blood stem cells are collected early in the course of therapy. (2) It usually induces relatively rapid hematologic reconstitution. (3) In comparison with autologous BMT, it appears to minimize the hazard of the reinfusion of malignant cells.

Combined Modality Therapy↗

Hodgkin's disease, clinical stages I, II A-B and IIIA. Results of brief chemotherapy followed by irradiation.

From October 1980 to September 1985, 152 patients with Hodgkin's disease (HD) in clinical stages (CS) I, II A-B and IIIA were treated with combined modality therapy (CMT): brief chemotherapy (CT) followed by radiotherapy (RT). CS IA and IIA cases received 3 cycles of MOP, while CS IB, IIB and IIIA cases were randomly assigned to receive MOP or MOP alternating with ABVD (4 cycles). Irradiation was delivered according to the areas initially involved and response to CT. CS I and II subjects in complete remission (CR) received localized fields, whereas CS I, II and IIIA subjects in partial remission (PR) received extended fields, with subtotal nodal RT for CS I and II and CS IIIA without pelvic involvement and total nodal RT for CS I and II below diaphragm and CS IIIA with pelvic involvement. Following CT, CR was 60% (IA-IIA: 71.5%, IB-IIB: 37%, IIIA: 55.5%), PR 35.5% and failure 4.5%. After CT and RT, CR was 98% (IA-IIA: 100%, IB-IIB: 95.5%, IIIA: 94.5%). Responses were similar using MOP and MOP/ABVD regimens. Fifteen patients relapsed (10%) and 15 died, 11 due to HD and 4 due to other causes, while after 7 years overall survival and relapse free survival were respectively 87% and 82% (IA-IIA 90% and 85%, IB-IIB: 80% and 80%, IIIA: 87% and 62%). Results were equivalent irrespective of CT regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The significance of a residual mediastinal mass following treatment for aggressive non-Hodgkin's lymphomas.

The chest radiographs of 252 patients with aggressive non-Hodgkin's lymphoma, prospectively treated according to one of three protocols of combination chemotherapy, were reviewed to determine the incidence and prognostic significance of mediastinal abnormalities following treatment. Residual mediastinal masses were defined as any abnormality, greater than 2 cm in diameter, that had initially responded to chemotherapy and then remained stable in size for at least three months after its maximal response, together with the disappearance of all other clinical and biological signs of active lymphoma. At the end of treatment, 21 (8%) patients had some residual mediastinal abnormality. The predominant histological pattern was the diffuse large cell subtype (p less than 0.001). Disease free survival and overall survival for these patients were similar to those observed among patients in complete remission without a persisting radiological mass after treatment. We conclude that mediastinal residual masses after completion of treatment for aggressive lymphoma are frequent and do not indicate a poorer prognosis. Such patients can be observed clinically without any need for additional chemotherapy or radiotherapy.

Adult↗

[Treatment of myeloma and and expected prognostic progress].

Some progress in the treatment of multiple myeloma (MM) has been recently obtained due to a better knowledge of prognosis factors and of indications of conventional chemotherapies. More over, two new therapeutic approaches appear very promising, including the use of alpha-interferon and the introduction of high dose chemotherapy protocols used alone or in combination with total body irradiation and hematopoietic transplantation. All available therapeutic strategies and their place in the management of patients with MM are successively discussed.

Antineoplastic Combined Chemotherapy Protocols↗

Surgical restaging of advanced Hodgkin's disease after first line chemotherapy.

47 patients with stages IIIB and IV Hodgkin's disease underwent laparotomy with splenectomy as restaging procedure after first-line chemotherapy (CT) which included 4 cycles of CT ABV/IMEP/PCAV/ABV. After surgical restaging (SR), all patients were scheduled to receive 2 additional cycles IMEP/PCAV followed by TNI 20 Gy and patients with residual clinical abnormality or positive restaging surgery received a 20 Gy boost to these areas. 11 patients (23.4%) were found to have active disease in the spleen (10 patients) and/or the lymph nodes (3 patients) after SR. In the spleen, foci of active disease had a size in millimeters and confirm the limits of clinical restaging. According to the response to CT, 5 of the 35 patients (14%) clinically restaged as good responders had active disease; 6 of the 12 patients (50%) clinically restaged as poor responders had active disease. SR is of interest in selected patients with slowly responding disease to determine the indication of an extended field RT for responding patients and salvage therapy for patients resistant to CT.

Adult↗

High dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma.

We report the results of peripheral blood stem cell (PBSC) collection performed after priming with a semi-intensive CHOP regimen in 70 patients with aggressive multiple myeloma (MM). Forty-one of the 44 previously untreated patients compared to 17 of the 26 patients with a refractory disease yielded stem cells enough for autotransplantation. Phenotypic and genotypic studies of collected mononuclear cells, even performed after depletion of monocytes and/or of T lymphocytes, did not reveal contamination by tumor plasma cells or clonal B cell precursors in any studied case. Forty-eight of the 58 patients with successful PBSC collection have been presently treated by high dose therapy followed by autologous blood stem cell transplantation (ABSCT). Among the 43 patients who received a regimen including total body irradiation, four died within six months after the autograft. All remainders responded and most often achieved an impressive tumor mass reduction. Ten relapsed and four died from disease progression. Nine to 70 months (median: 35 months) after blood stem cell collection, 29 patients are either in apparent complete remission or with a state of stable residual disease, most often minimal. Blood stem cell autograft was successful in all evaluable patients and the kinetic of hematologic recovery was roughly related to the amount of reinfused CFU-GM (2.1 to 50 x 10(4)/kg). Median delays for granulocytes greater than 500/mm3 and platelets greater than 25,000/mm3 were 15 days and 20 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Phenotype and immunoglobulin gene configuration of blood B cells from patients with multiple myeloma.

We have studied the phenotype and the immunoglobulin gene configuration of blood B cells from 15 patients with stage III multiple myeloma (MM) at diagnosis. Highly purified B cells (greater than 90% CD20 positive cells) were obtained after L-leucine methyl ester monocyte depletion and elimination of T cells by rosetting. The percentage of B cells with surface immunoglobulin (sIg) featuring the same light and heavy chain isotype as the serum monoclonal immunoglobulin was very low, except in one patient, in whom 25-30% of B cells displayed surface and cytoplasmic immunoglobulin (cIg) sharing idiotypic determinants with the serum monoclonal IgG kappa. In all cases but one the percentage of circulating plasma cells accounted for less than 2% of the enriched B cell preparations. In one patient purified B cell population contained 30% of plasma cells and the immunoglobulin gene study revealed a rearranged JH hybridizing fragment identical in bone marrow and blood B cell DNA samples. In the other 14 cases no rearranged fragment was detected although we used a technique allowing the detection of at least 2% clonal cells. The absence of clonal cells in the patient whose B cells contained a high percentage of cells featuring surface IgG molecules was confirmed on purified sIgG-positive cells. In addition CD20-positive cells from this patient did not contain gamma mRNA. Therefore the IgG molecules were clearly extrinsic. Although the existence of clonal B lymphocytes or of myeloma idiotype related B cells cannot be ruled out, they escape detection by sensitive genetic studies of immunoglobulin genes.

B-Lymphocytes↗

Detection of Epstein-Barr virus in epidermal skin lesions of an immunocompromised patient.

Using in-situ hybridizaiton, we showed the presence of the Epstein-Barr (EB) virus genome in epidermal cells from a patient with chronic lymphocytic leukemia and unusual cutaneous lesions characterized clinically by a maculopapular eruption and histologically by epidermal cell degeneration and lymphoid cell infiltration. Such histologic changes are similar to those seen in graft-versus-host disease. The EB virus genome was mainly detected in the basal, germinative cells of the abnormal epithelium. Specimens of our patient's healthy skin were negative. The presence of EB virus DNA in skin lesions was confirmed by polymerase chain reaction adapted for analysis of paraffin-embedded tissue. These findings indicate that EB virus can infect the human epidermis and that the viral infection may produce a distinctive cutaneous disease.

Aged↗