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Biomedical subjects

C Gisselbrecht

Publications and source records attributed to C Gisselbrecht.

At least 19 recordsLinked to original sources
PubMed1995

Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma.

BACKGROUND: High-dose chemotherapy followed by autologous bone marrow transplantation is a therapeutic option for patients with chemotherapy-sensitive non-Hodgkin's lymphoma who have relapses. In this report we describe a prospective randomized study of such treatment. METHOD: A total of 215 patients with relapses of non-Hodgkin's lymphoma were treated between July 1987 and June 1994. All patients received two courses of conventional chemotherapy. The 109 patients who had a response to chemotherapy were randomly assigned to receive four courses of chemotherapy plus radiotherapy (54 patients) or radiotherapy plus intensive chemotherapy and autologous bone marrow transplantation (55 patients). RESULTS: The overall rate of response to conventional chemotherapy was 58 percent; among patients with relapses after chemotherapy, the response rate was 64 percent, and among those with relapses during chemotherapy, the response rate was 21 percent. There were three deaths from toxic effects among the patients in the transplantation group, and none among those in the group receiving chemotherapy without transplantation. The two groups did not differ in terms of prognostic factors. The median follow-up time was 63 months. The response rate was 84 percent after bone marrow transplantation and 44 percent after chemotherapy without transplantation. At five years, the rate of event-free survival was 46 percent in the transplantation group and 12 percent in the group receiving chemotherapy without transplantation (P = 0.001), and the rate of overall survival was 53 and 32 percent, respectively (P = 0.038). CONCLUSIONS: As compared with conventional chemotherapy, treatment with high-dose chemotherapy and autologous bone marrow transplantation increases event-free and overall survival in patients with chemotherapy-sensitive non-Hodgkin's lymphoma in relapse.

Adolescent↗
PubMed1995

Intensive therapy with peripheral blood progenitor cell transplantation in 60 patients with poor-prognosis follicular lymphoma.

Intensive therapy, mainly with purged autologous bone marrow transplantation (ABMT), has been proposed in recent years as consolidation treatment in young patients with follicular lymphoma. Reported experience with transplantation of peripheral blood progenitor cells (PBPC) is, so far, limited. The feasibility and the therapeutic efficacy of intensive therapy followed by unpurged autologous PBPC reinfusion were evaluated in 60 patients with poor-prognosis follicular lymphoma. Twelve patients were in first partial remission (PR), 34 were in second partial or complete remission (CR), and 14 were in subsequent progression. At the time of the procedure, 39 patients (65%) had persistent bone marrow involvement, 49 patients (82%) were in PR, and 16 patients had presented with a histologic transformation (HT). PBPC were collected after chemotherapy followed by granulocyte (G) colony-stimulating factor (CSF) or granulocyte-macrophage (GM)-CSF in 50 patients. Conditioning regimens included high-dose chemotherapy alone (14 patients); mainly the BCNU, etoposide, aracytine, melphalan [BEAM] regimen), or cyclophosphamide with or without etoposide plus total body irradiation (46 patients). The median time to reach a neutrophil count greater than 0.5 x 10(9)/L was 13 days. There were five treatment-related deaths, with four being associated with a delayed engraftment and all occurring in patients in third or subsequent progression. At a median follow-up of 21 months, 48 patients were still alive, 18 relapsed, and seven died of lymphomas progression. Estimated 2-year overall survival (OS) and failure-free survival (FFS) rates were 86% and 53%, respectively, without or plateau. Patients treated in PR1 or PR2/CR2 had a significantly longer rate of OS and FFS than those treated in subsequent progression (P = .002 and P = .001, respectively), whereas age, response to salvage treatment, presence or absence of residual bone marrow involvement, or conditioning regimen had no influence on outcome. Patients with HT tended to have a worse FFS rate (P = .04) without an OS difference. Along with an unusual rate of engraftment failure, the poor FFS observed in heavily pretreated patients suggests that intensive therapy should be performed early in the course of the disease. Given the high percentage of patients intensified in PR with residual bone marrow involvement, our results are comparable with those achieved with ABMT published to date. Prospective trials are warranted to compare this strategy with standard therapy in patients with relapsing or PR follicular lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Therapeutic intensification and hematopoietic stem cell autotransplantation in the treatment of solid tumors in adults: principles, realization and application to the treatment of germ cell, trophoblastic, breast, ovarian and small-cell bronchial tumors. 1].

Autologous bone marrow transplantation for the treatment of solid tumors in adults remains an uncommon therapeutic approach. The feasibility of such high-dose therapies is clearly proved, especially with the advent of hematopoietic growth factors and the rescue by the peripheral stem cells to reduce the duration of the chemotherapy-induced myeloid aplasia. The question is to exactly define the place of high-dose therapy in the land of solid tumors. For the treatment of primary chemoresistant gonadal germ-cell tumors, the possibility to cure the patients and the interest of high-dose therapy with autologous bone marrow transplantation are clearly demonstrated. As consolidation for the treatment of poor prognosis tumors, the place of high-dose therapies remains moot. For the treatment of chemoresistant extragonadal germ-cell tumors, especially for primary mediastinal tumors, the level of resistance to cisplatin-based chemotherapy regimens is generally too high to be overcome by intensive therapies given as single course or as tandem courses. However in association with debulking surgery, this therapeutic approach has to be considered for some patients. In the treatment of poor prognosis breast cancer, high-dose therapy with autologous bone marrow transplantation or with peripheral stem cells support is able to convert some patients with partial response into complete responders. However, the consequences on overall survival and on disease-free survival are not evident. For metastatic breast cancer and for poor-prognosis tumors (inflammatory breast cancer, axillary metastatic nodes > or = 8), the interest of high-dose therapy has to be determined by randomized studies. These studies are ongoing in USA and in Europe. For the treatment of poor-prognosis ovarian cancer, the situation is more difficult to appraise. Once again, randomized studies have to be done to precisely define the place of high-dose therapy. In the land of small-cell lung carcinomas, high-dose therapy is actually forsaken by most of authors, even for limited diseases. The results of previous studies are disappointing. Moreover, occult medullary micrometastases involvement is frequent, once again even in limited diseases. However new therapeutic associations, as the ICE regimen (IFM, Carboplatin, VP-16) delivered as single or tandem therapy, have to be studied, especially as early consolidation therapy for the treatment of limited small-cell lung carcinomas.

Adult↗
PubMed1995

[Treatment of intermediate-grade non-Hodgkin lymphoma in adults].

In the past 20 years increasing incidence 15/100,000 of non Hodgkin's lymphoma (NHL) has been observed. Despite their heterogeneity, intermediate grade NHL are potentially cured with chemotherapy. Advances in our understanding of the biology and in their treatment have been made. Factors, such as age, stage, performance status, and predicting treatment outcome are useful parameters to decide on the intensity of chemotherapy. With conventional treatment, 80% of the patients without adverse prognostic factors can be cured. For patients with at least two adverse factors only 40% are long term survivors. Different dose-escalation chemotherapy regimens have been tested including autologous hematopoietic stem cell transplantation (ASCT). At the present time, no clear improvement has been seen in randomized trial when intensification is made after obtention of complete remission. However, for relapsing patients ASCT can provide 46% disease free survival in patients still sensitive to salvage chemotherapy and ASCT is the therapy of choice under 60 years old. New development of technology with mobilized peripheral stem cell (PBPC) allowed to develop early intensive treatment with acceptable toxicity. Encouraging results have been reported and tested in randomized trial in patients less than 60 years old. Improvement of the treatment of older patients remains problematic considering that chemotherapy can increase hematopoietic and non hematopoietic lethal complications reducing the chance to achieve complete remission.

Adult↗
PubMed1995

High-dose recombinant interleukin-2 in advanced cutaneous T-cell lymphoma.

BACKGROUND AND DESIGN: Treatment of cutaneous T-cell lymphoma is still a difficult challenge, once the usual therapies (topical chemotherapy, phototherapy, radiation therapy, and chemotherapy) have proved to be unsuccessful. New therapies, mostly immunotherapies, are currently under investigation. The use of recombinant interleukin-2 has already been evaluated in hematopoietic malignancies. We decided to treat patients with advanced cutaneous T-cell lymphoma relapsing or progressing in spite of the usual treatments with high-dose recombinant interleukin-2. Seven patients (three with mycosis fungoides, three with Sézary syndrome, and one with nonepidermotropic large-cell cutaneous lymphoma) were included in this open study. They were scheduled to receive recombinant interleukin-2 at a dose of 20 x 10(6) IU/m2 per day, administered by continuous infusion during three fortnightly induction cycles and five monthly consolidation cycles. RESULTS: Three complete responses (two responses to mycosis fungoides; one response to large-cell lymphoma) and two partial responses were obtained. The clinical response appeared after the first cycle of treatment in the good responders. The complete responses are still ongoing 33, 28, and 6 months after completion of recombinant interleukin-2 therapy and without any further treatment. Sequential immunophenotypic studies showed an increase of the CD1+ cells in the dermal infiltrates. No significant modification of natural killer or cytotoxic T cells could be seen. CONCLUSIONS: Despite our low number of cases, our results clearly show that some advanced cutaneous T-cell lymphomas can benefit from high-dose recombinant interleukin-2 therapy. Further studies are necessary to determine the exact place of recombinant interleukin-2 in the therapeutic arsenal of cutaneous T-cell lymphoma.

Adult↗
PubMed1994

[Influence of the granulocyte growth factor on the cost of bone marrow autografts in oncologic hematology].

OBJECTIVE: It is now possible to achieve prolonged remission of malignant lymphoma and certain cancers with high-dose chemotherapy followed by autograft with haematopoietic stem cells. We tested such a protocol, evaluating haematologic recovery, in order to determine the total cost of hospitalization. METHODS: Sixteen patients were included in the study, 7 had severe or relapsing lymphoma, 7 had breast cancer or cancer of the ovary and 2 had cancer of the testicule. Mean age was 34 years, 14 patients reached complete remission and relapse occurred in 2. Ten patients were given granulocyte growth factor and 6 were given a placebo. RESULTS: The duration of aplasia (number of days with a white cell count below 1 x 10(9)1) ranged from 10 to 32 days. In patients treated with granulocyte growth factor, it was shorter (16 vs 22 days) as was hospitalization time (27 vs 33 days). The cost of the autograft ranged from 100,000 FF to 250,000 FF and the average cost for the 16 patients was 149,500 FF including: 83,600 FF (56.4%) for hospitalization itself, 33,200 FF (22%) for drugs, mostly antibiotics, and 19,000 FF (13%) for laboratory examinations and 14,000 FF (9%) for blood transfusions. Total cost was lower in patients given granulocyte growth factor, 142,000 FF vs 166,000 FF for those given placebo. CONCLUSION: In order to shorten the duration of the aplasia period, haematopoietic growth factors are widely used in autograft protocols. Our findings give an evaluation of the cost in 16 patients and show that cost decreases in patients given granulocyte growth factor. This reduction is cost is related to a lower hospitalization cost and not a reduction in the number of drugs and transfusions required.

Adult↗
PubMed1994

Administration of an anti-interleukin-6 monoclonal antibody to patients with acquired immunodeficiency syndrome and lymphoma: effect on lymphoma growth and on B clinical symptoms.

Increased interleukin-6 (IL-6) production and expression by malignant cells of the IL-6 receptor has been evidenced in a subgroup of non-Hodgkin's lymphomas, suggesting that this cytokine plays a role in lymphoma growth and in B clinical symptoms. In this study, the effect of the administration of an anti-IL-6 monoclonal antibody (MoAb) was analyzed in 11 patients seropositive for human immunodeficiency virus-1 and suffering from an immunoblastic or a polymorphic large-cell lymphoma. The antibody (BE-8, 10 to 40 mg/day) was administered for 21 days. Neutralization of in vivo IL-6 effect was assessed by monitoring C-reactive protein levels in the serum. In 5 patients, the lymphoma progressed during treatment. Among them were the 2 patients in whom endogenous IL-6 effect was not neutralized. Five patients experienced a stabilization, and 1 a partial remission. This effect on lymphoma growth lasted for 8 to 28 weeks. The anti-IL-6 MoAb had a clear effect on lymphoma-associated fever and cachexia. The mean body weight increase was 1.4 +/- 0.5 kg between day 1 and day 21, and reached 12 kg in 120 days in 1 patient who received three courses of treatment. Side effects were a consistent but moderate thrombocytopenia, and an occasional and moderate decrease of neutrophil counts. Immunization against the MoAb was observed in only 2 patients. These results indicate that in some cases of lymphomas growth of malignant cells may be partially IL-6-dependent and that neutralizing endogenous effect of IL-6 completely abrogates B clinical symptoms.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Placebo-controlled phase III trial of lenograstim in bone-marrow transplantation.

Haemopoietic growth factors are accepted as accelerating haemopoietic recovery after bone-marrow grafting, yet no large randomised trials have been published that convincingly show benefit. Lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) was given to 315 patients after bone-marrow transplantation in a prospective randomised placebo-controlled multicentre trial. 1 day after bone-marrow infusion, 163 patients received lenograstim 5 micrograms/kg per day by 30-min infusion, and 152 patients received placebo daily for 28 days or until neutrophil recovery. 137 patients had lymphoma, 35 myeloma, 85 acute lymphoblastic leukaemia, and 58 a solid tumour. Patients were stratified by age and by type of bone-marrow transplantation (BMT). Neutrophil recovery to above 10(9)/L for 3 consecutive days was seen earlier in lenograstim-treated patients (16 vs 27 days, p < 0.001). Time to neutrophil recovery above 0.5 x 10(9)/L was reduced (14 vs 20 days, p < 0.001). The difference was significant both in autograft (20 vs 14 days, p < 0.001) and allograft (20 vs 14 days, p < 0.01) patients, in children (20 vs 13 days, p < 0.001), and adults. Lenograstim-treated patients had fewer days of infection, and of antibiotic administration, and also spent less time in hospital. However, clinical and microbiological sepsis was similar in both groups. There was no significant toxicity ascribed to lenograstim. Survival was the same at days 100 and 365. In patients undergoing autologous or allogeneic BMT for neoplastic disease, lenograstim significantly reduced duration of neutropenia and led to earlier hospital discharge.

Adjuvants, Immunologic↗
PubMed1994

Endobronchial presentation of Hodgkin's disease: a report of nine cases and review of the literature.

Although mediastinal involvement by Hodgkin's disease is frequent, the initial presentation of the lymphoma by an endobronchial lesion is rare. Therefore, the question of whether patients with Hodgkin's disease should undergo fibreoptic bronchoscopy as a staging procedure remains unresolved. In a series of 469 patients with newly diagnosed Hodgkin's disease during a 10 year period, we reviewed the clinical features of nine patients who presented with an endobronchial tumour. They were compared to 34 previously published cases. The major presenting symptoms were cough, wheezing and haemoptysis. Bulky mediastinum was seen in six cases. The three other patients presented respiratory symptoms evocative of endoluminal invasion. All but one of the patients received combined modality therapy, as currently accepted for patients with poor prognostic factors. The overall actuarial survival was 74% after 4 yrs of follow-up. A selective subgroup of patients with stage I-II supradiaphragmatic and endobronchial Hodgkin's disease may, thus, present without poor prognostic factors (but generally with respiratory symptoms), and might be undertreated if this localization is not recognized. We propose that these patients should undergo fibreoptic bronchoscopy.

Adult↗
PubMed1994

Comparison of autologous bone marrow transplantation with sequential chemotherapy for intermediate-grade and high-grade non-Hodgkin's lymphoma in first complete remission: a study of 464 patients. Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: Intensive chemotherapy followed by autotransplantation has given promising results in partially responding or sensitive relapsed patients with aggressive non-Hodgkin's lymphoma. In 1987, we designed a randomized study to evaluate the potential benefit of a high-dose regimen containing cyclophosphamide, carmustine, and etoposide (CBV) followed by autotransplantation over a consolidative sequential chemotherapy (ifosfamide, etoposide, asparaginase, and cytarabine) in patients in first complete remission with intermediate- and high-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients were younger than 55 years and had at least one adverse prognostic factor. Induction treatment was that of the LNH84 protocol with an open randomization on the anthracycline. Patients in complete remission were further randomly assigned to receive either consolidation procedure. RESULTS: After induction treatment, 464 patients were assessable for the consolidation phase. With a median follow-up duration of 28 months, the 3-year disease-free survival rate was 52% (95% confidence interval, 45% to 59%) in the sequential chemotherapy arm and 59% (95% confidence interval, 52% to 66%) in the autologous transplant arm (P = .46, relative risk = 0.90). The 3-year survival rate did not differ between sequential chemotherapy and autotransplantation, at 71% (95% confidence interval, 64% to 78%) and 69% (95% confidence interval, 62% to 76%), respectively (P = .60, relative risk = 1.11). CONCLUSION: For such a subset of patients, consolidation with the CBV regimen followed by autologous bone marrow transplantation is not superior to sequential chemotherapy.

Adolescent↗
PubMed1994

Chemotherapy dose intensity facilitated by use of lenograstim--implications for quality of life and survival.

Increasingly more aggressive chemotherapeutic regimens are being used in pursuit of better tumour response and patient survival. Studies in advanced breast cancer, small cell lung cancer (SCLC), urothelial cancer and sarcoma indicate that recombinant human granulocyte colony stimulating factor (rHuG-CSF) (lenograstim) facilitates modest dose intensification (20-30%), but at high intensity doses, chemotherapy-related toxicity remains a problem. Survival outcome in SCLC patients is still uncertain although in one randomised trial lenograstim facilitated a 20% increase in chemotherapy dosage which resulted in a 25% increase in complete remissions. In studies of breast cancer, an initially improved response rate was not maintained. However, increased dose intensity of chemotherapeutic agents in aggressive lymphoma was possible using lenograstim. Studies to date with haematopoietic growth factors have not been designed to specifically address the issue of survival and/or quality of life, although they have inferred that this is possible through dose intensification. The use of haematopoietic growth factors will allow the design of such studies, but a modest chemotherapy dose increase may be insufficient to improve survival. The future for dose intensification in cancer therapy may lie in the use of lenograstim-primed peripheral blood progenitor cells (PBPC) transplants to enhance haematopoietic recovery after high-dose sequential or myeloablative chemotherapy.

Adjuvants, Immunologic↗
PubMed1994

Pregnancy after autologous bone marrow transplantation for malignant lymphomas.

In the present paper, we report two cases of normal pregnancy after high dose chemotherapy and autologous stem cell transplantation (ASCT) in two of the 72 women belonging to a group of 188 patients transplanted in our unit for advanced malignant lymphoma. These pregnancies occurred 19 and 33 months after high dose therapy in two women aged 27 and 28, neither of whom had received previous total body irradiation or pelvic radiotherapy. There are several reasons for the relatively low frequency of pregnancies after ASCT. In particular, the median age of the patients is 35 years, most of these women are transplanted in relapse and have received previous pretreatment with alkylating agents and the disease free survival rate does not exceed 40%. The preservation of long term fertility should be taken into account when deciding therapeutic options for young women with curable disease.

Adolescent↗