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J P Fermand

Publications and source records attributed to J P Fermand.

At least 37 records · Page 2Linked to original sources
PubMed1998

High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial.

Results to date indicate that high-dose therapy (HDT) with autologous stem cell support improves survival of patients with symptomatic multiple myeloma (MM). We performed a multicenter, sequential, randomized trial designed to assess the optimal timing of HDT and autotransplantation. Among 202 enrolled patients who were up to 56 years old, 185 were randomly assigned to receive HDT and peripheral blood stem cell (PBSC) autotransplantation (early HDT group, n = 91) or a conventional-dose chemotherapy (CCT) regimen (late HDT group, n = 94). In the late HDT group, HDT and transplantation were performed as rescue treament, in case of primary resistance to CCT or at relapse in responders. PBSC were collected before randomization, after mobilization by chemotherapy, and, in the two groups, HDT was preceded by three or four treatments with vincristine, doxorubicin, and methylprednisolone. Data were analyzed on an intent-to-treat basis using a sequential design. Within a median follow-up of 58 months, estimated median overall survival (OS) was 64.6 months in the early HDT group and 64 months in the late group. Survival curves were not different (P = .92, log-rank test). Median event-free survival (EFS) was 39 months in the early HDT group whereas median time between randomization and CCT failure was 13 months in the late group. Average time without symptoms, treatment, and treatment toxicity (TWiSTT) were 27.8 months (95% confidence interval [CI]; range, 23.8 to 31.8) and 22.3 months (range, 16.0 to 28.6) in the two groups, respectively. HDT with PBSC transplantation obtained a median OS exceeding 5 years in young patients with symptomatic MM, whether performed early, as first-line therapy, or late, as rescue treatment. Early HDT may be preferred because it is associated with a shorter period of chemotherapy.

Adult↗
PubMed1998

[Treatment of polycythemia. II.--Comparison of hydroxyurea with pipobroman in 294 patients less than 65 years of age].

AIMS: To compare by a prospective study in low risk polycythemia vera (PV) patients alone two drugs: hydroxyurea and pipobroman. Toxicity, efficiency, and leukemogenic potential were studied. PATIENTS: 294 patients with a documented PV, aged less than 65 years, have been included since 1980 in a prospective study comparing hydroxyurea and pipobroman. Blood cell counts were performed every two months and a clinical evaluation by a specialist was obtained every four or six months. RESULTS: Hematologic toxicity of both drugs was higher than expected, requiring strict surveillance. These drugs were tolerated in some (gastric pain and diarrhea on pipobroman, buccal aphtosis and chronic leg ulcers on hydroxyurea), leading to a change of arm in 10% of the cases. Hydroxyurea did not control the megakaryocitic hyperplasia in 40% of the cases, which probably explains a high rate of progression to myelofibrosis with myeloid metaplasia in this arm. Both drugs were leukemogenic with an actuarial risk of about 15% at the 15th year, not significantly lower than that observed in the 32P treated patients. A significant risk of cutaneous malignancy was observed in the hydroxyurea arm. The mean expectancy of life cannot yet be accurately evaluated, but seems significantly lower than that of the reference population. CONCLUSION: The treatment of PV by hydroxyurea or pipobroman has to account for these results less optimistic than those traditionally well-known to hematologists and internists.

Adult↗
PubMed1997

[Treatment of myeloma: role of intensive treatments].

CURRENT SITUATION: Since the introduction of melphalan, little progress has be obtained in the treatment of multiple myeloma. Complete remission is rarely achieved with classical single-drug or combined chemotherapy protocols: median survival remains low at 2 to 3 years. A NEW APPROACH: High-dose melphalan therapy with hemopoietic stem cell support it a new approach providing promising results. There is a dose effect and 70 to 80% of naive patients, at the cost of severe prolonged aplasia, respond to high-dose melphalan. HEMATOPOIETIC SUPPORT: Allogeneic or autologous bone marrow or blood stem cell grafts are used. Peripheral blood autographs can be used in most patients; contamination with tumoural cells is generally lower. The period of aplasia after chemotherapy and hematopoietic autograft is relatively short. MAIN INDICATIONS: For most authors, high-dose melphalan should be reserved for younger patients with active myeloma: complete remission is achieved in 20 to 30% of cases although relapse still occurs. Other techniques under study (several sequences of high-dose sessions, reduction of graft contamination) should help improve results.

Antineoplastic Agents, Alkylating↗
PubMed1997

[Neuromeningeal sites of multiple myeloma: 3 cases and review of the literature].

Neurologic manifestations are not unusual in multiple myeloma. Conversely meningeal and cerebral involvement have been very rarely reported. We report here on three patients with multiple myeloma and meningeal or cerebral involvement (two of them with autopsy study): one case of cerebellar involvement associated with secondary plasma cell leukemia and two cases of meningeal involvement. We reviewed the characteristics of 20 cases of meningeal involvement with demonstration of plasma cells at cerebrospinal fluid analysis (18 previously reported cases and our two patients). Meningeal involvement occurs in patients with initially stage III multiple myeloma in 85% of cases and is associated with the occurrence of plasma cell leukemia in 20% of cases. The most frequent neurologic signs are: confusion (60%), altered consciousness (25%), gait disorder (25%), cranial nerve palsy (25%). Meningismus is rarely present. Diagnosis is based on cerebrospinal fluid analysis after lumbar puncture which should be made after cranial magnetic resonance imaging. The diagnosis of intra-cranial haemorrhage and infectious meningitis have to be cautiously ruled out. Despite treatments (systemic and/or intrathecal chemotherapy, radiation therapy), prognosis is very poor: mean time of survival after the occurrence of neurologic signs is about 2 months.

Aged↗
PubMed1996

Hyper-IgM syndrome associated with rheumatoid arthritis: report of RA in a patient with primary impaired CD40 pathway.

We studied a patient who had a typical seronegative rheumatoid arthritis (RA) and an immunodeficiency with hyper-IgM (HIM syndrome). CD40L was normally expressed by activated T cells, but CD40-mediated signal transduction was defective in B cells, preventing heavy chain switching (CD40L+ type of the HIM syndrome). These data suggest that a typical RA can develop in at least some patients with dysfunction of the CD40 pathway, i.e. in the absence of a normal co-operation between T and B cells. Accordingly, the blockade of CD40L-CD40 interactions, which has been proposed as a treatment of RA, might not be adapted to all patients.

Adult↗
PubMed1996

Chest high resolution CT in adults with primary humoral immunodeficiency.

The purpose of this study was to assess the findings on chest high resolution computed tomography (HRCT) in patients with primary humoral immunodeficiency. HRCT was prospectively and consecutively performed in 19 patients with primary humoral immunodeficiency, aged 15-64 years (mean 36), and in 15 healthy subjects. HRCT results were correlated with clinical and biological data. Bronchial lesions were observed in 11 patients (58%), consisting either of bronchial wall thickening in eight or bronchiectasis in eight; both were present in five patients. Lobar and/or segmental collapses were found in seven patients (37%), scars in eight patients (42%), interstitial lesions in six patients (32%), and lobular air-trapping in two patients (11%). Parenchymal collapses were correlated with the annual frequency of infections (p = 0.03) and with the IgA level (p = 0.01). Scars were correlated with the annual frequency of infections (p = 0.04). No correlation was found between bronchial wall thickening or bronchiectasis and the data analysed. In conclusion, HRCT is a useful method to demonstrate lung disease in primary humoral immunodeficiencies, with special emphasis on bronchial changes and interstitial lesions.

Adolescent↗
PubMed1996

Tumoral joint involvement in multiple myeloma and Waldenström's macroglobulinemia--report of 4 cases.

We describe 4 patients, 2 with multiple myeloma and 2 with Waldenström's macroglobulinemia, who developed arthritis due to invasion of articular and periarticular structures by malignant cells. Articular manifestations in lymphoplasmacytic disorders are most often related to metabolic or septic complications, sometimes to immunoglobulin deposits, but can also result from tumoral joint involvement.

Adult↗
PubMed1995

Evolution of bone densitometry in patients with myeloma treated with conventional or intensive therapy.

BACKGROUND: Demineralization is a common hallmark of multiple myeloma (MM) that can be evaluated by dual-energy X-ray absorptiometry (DEXA). The evolution of lumbar and whole body bone density were investigated by DEXA in patients with MM treated by conventional or intensive therapy supported by autologous blood stem cell transplantation. METHODS: Sixty six patients younger than 66 years with MM were randomly assigned to either conventional (30 patients, Group A) or intensive therapy supported by autologous blood stem cell transplantation (36 patients, Group B). For all patients, lumbar bone mineral density (BMD) was measured by DEXA at diagnosis and 13.2 +/- 4.2 months after the initiation of treatment. Whole body examinations were performed in 45 patients; in addition to whole body BMD, independent BMD values were recorded for various skeletal sites. RESULTS: At diagnosis, mean lumbar Z score (lumbar mean BMD value) was low (-1.24 +/- 1.45) without any significant difference between the 2 groups. Under treatment, lumbar BMD increased 0.7% in Group A and 4.6% in Group B (P = 0.02). This difference was mainly related to nonresponders in group A who featured a lumbar BMD change of -3.9%, whereas patients in remission in both groups displayed a 4.1% increase (P < 0.001). There was a correlation between the variation of lumbar BMD and the decrease of the serum or urinary monoclonal component (r = 0.34, P = 0.006). After intensive therapy, increase of lumbar BMD was higher in men than in women (7.2% vs. 1%, P = 0.005) perhaps because of variations in hormonal status in women. Unexpectedly, whole body BMD decreased in responders (-3%) because of a decrease in appendicular BMD outweighing the increase in axial BMD. This suggests a redistribution from cortical to cancellous bone in patients with MM responsive to chemotherapy. CONCLUSION: Bone densitometry is a marker of treatment response that may be particularly useful in nonsecretory and light chain MM. Moreover, it provides new information on bone remodeling in patients treated for MM, which may have therapeutic consequences.

Absorptiometry, Photon↗
PubMed1995

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↗
PubMed1995

Hyperkeratotic spicules and monoclonal gammopathy.

Hyperkeratotic spicules are a rare disorder that has been associated with different types of malignancies. An association with multiple myeloma raises the question of a relation between the monoclonal component and skin manifestations. We describe hyperkeratotic spicules in a 61-year-old man with a monoclonal gammopathy of undetermined significance. Immunofluorescence and immunoelectron microscopic findings demonstrated the deposition of the monoclonal immunoglobulin at the dermoepidermal junction. Our findings support previous reports that the association between hyperkeratotic spicules and monoclonal gammopathy is not fortuitous and may be related to particular properties of the monoclonal immunoglobulin.

Humans↗
PubMed1995

Marrow transplantation for myeloma.

High-dose therapy with hemopoietic stem cell support in multiple myeloma (MM) has been used for 10 years. This approach is currently the most promising form of treatment for this disease. We review here its rationale and the results of clinical trials according to the source of hematopoietic stem cells [allogeneic or autologous, bone marrow or blood]. Finally, we discuss the ongoing uncertainties regarding the utility of this treatment and the future prospects for high-dose therapy in MM.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

[Cost of intensive treatment followed by autograft of circulating stem cells. Application to multiple myeloma].

OBJECTIVES: Legitimate efforts to reduce health care costs, especially of intensive protocols including transplantation for haematological diseases, require realistic economic evaluations. We determined the direct cost of intensive chemotherapy associated with total body irradiation and autologous blood stem cell transplantation in patients with multiple myeloma. METHODS: Ten consecutive patients (7 males, 3 females) with Stage II or II multiple myeloma, who had received no prior treatment and were under the age of 55, were included in the study. Peripheral blood stem cells were collected by successive cytaphereses after a short period of aplasia induced by a CHOP protocol. During this period, the patients were in normal hospital rooms. A VAMP protocol was then administered in three 4-day sessions. Intensive therapy was started 1 month later with CCNU, etoposide, cyclophosphamide and melphalan. Total body irradiation (12 Gy) was performed on days -3, -2, -1. Autologous grafting was done on day 0. The intensive therapy was followed by a period of aplasia and the patients were protected in laminar flow rooms. Regular antibiotic and haematologic protocols were applied. Growth hormone was not given. The patients were seen regularly for follow-up and interferon alpha 2b was prescribed for 5. RESULTS: The mean cost of the two year treatment was 468,392 +/- 167,467 French francs. Personnel accounted for 36% of the total cost, marrow collection 13%, blood products 9.8%, laboratory tests 8.2% and drugs 7.2%. Little data are available in the literature of comparable cost analyses in other French hospitals or in other countries. CONCLUSION: Controlled cost/benefit studies should be conducted to enable a rigorous comparison between different therapeutic strategies.

Adult↗
PubMed1994

Interleukin-6 serum levels in patients with multiple myeloma.

Studying the prognostic value of serum interleukin-6 (IL-6) levels in multiple myeloma, we observed important daily variations in some patients. Therefore a unique serum IL-6 measurement should be interpreted with caution and requires confirmation by multiple determinations performed over a period of several days.

Biological Assay↗
PubMed1994

Myeloma cell contamination of peripheral blood stem cell grafts in patients with multiple myeloma treated by high-dose therapy.

In order to assess the contamination with malignant cells of peripheral blood stem cell (PBSC) transplants used to support high-dose therapy in multiple myeloma (MM), we used the immunoglobulin heavy chain gene radioactive fingerprinting polymerase chain reaction (PCR) method to detect clonal cells in PBSC from 10 patients. The sensitivity of the technique allowed the detection of one clonal cell among 10(4) normal blood mononuclear cells. A clonal band was detected in 4 of 11 leukaphereses samples. The level of contamination was low because a clonal band could never be identified on ethidium bromide-stained agarose gels whose sensitivity is between 1 and 5%. The use of granulocyte-colony stimulatory factor (G-CSF) in combination with chemotherapy in three cases did not seem to increase the contamination of PBSC grafts; in one patient, G-CSF was used during a second course of leukapheresis which was free of detectable clonal cells whereas the first one performed after chemotherapy alone contained clonal cells. Thus, PBSC grafts may rarely be completely devoid of clonal potentially malignant cells but the level of contamination is much lower than in BM grafts. Whether graft contamination is an important adverse prognostic factor for patients with MM undergoing intensive treatment and autografting is still unsettled.

Antineoplastic Agents↗