PubMed Health⌕ Search

Biomedical subjects

C Fruchart

Publications and source records attributed to C Fruchart.

12 recordsLinked to original sources

Hypodiploidy is a major prognostic factor in multiple myeloma.

Conventional karyotypes performed before any treatment in 208 patients with multiple myeloma were reviewed by the Groupe Français de Cytogénétique Hématologique. A total of 138 patients displayed complex chromosomal abnormalities (CCAs). According to the chromosome number pattern, a first group of 75 patients had a hyperdiploid karyotype. A second group of 63 patients referred to as the hypodiploid group had either pseudodiploid, hypodiploid, or near-tetraploid karyotypes. Of 159 treated patients available for survival analysis, 116 had an abnormal karyotype. The comparison of overall survival (OS) between hyperdiploid and hypodiploid patients showed a highly significant difference (median OS 33.8 vs 12.6 months, respectively, P <.001). The presence of 14q32 rearrangements (36 of 116 patients) worsened the prognosis (median OS 17.6 vs 29.9 months, P <.02). The presence of chromosome 13q abnormalities (13qA, 63 patients) did not modify OS in CCA patients (median OS 20.6 vs 27.8 months, P <.59). However, taking into account the whole series including normal karyotypes, 13qA (63 of 159 patients) had a significant impact on OS (median 20.6 vs 37.1 months, P <.04). In the same way, the presence of a hypodiploid karyotype (52 of 159 patients) had a strong prognostic value (OS 12.8 vs 44.5 months, P <.000 01). A multivariate analysis including stage, beta2-microglobulin, bone marrow plasmocytosis, treatment type, 13qA, and hyperdiploidy and hypodiploidy showed that a hypodiploid karyotype was the first independent factor for OS (P <.001), followed by treatment approach. These results confirm that the chromosome number pattern of malignant plasma cells is a very powerful prognostic factor in newly diagnosed multiple myeloma patients.

Adult↗

[Intramedullary spinal cord metastasis and leptomeningeal involvement in Hodgkin's disease. Case report and review of the literature].

INTRODUCTION: Central nervous system, especially spinal cord involvement, is unusual in Hodgkin's disease. We report the case of a patient with refractory Hodgkin's disease who presented with intramedullary involvement. EXEGESIS: A 36-year-old woman presented with weakness of the right lower extremity and sphincter dysfunction 13 years after initial diagnosis of Hodgkin's disease. Magnetic resonance imaging showed intraspinal tumor with contrast enhancement extending from C7 to D1. Cerebrospinal fluid examination revealed the presence of Reed-Sternberg cells. Specific intramedullary spinal cord metastasis and leptomeningeal involvement were confirmed. Despite intrathecal chemotherapy the neurologic deficit progressed to paraplegia and the patient died 2 months later. CONCLUSION: Intramedullary spinal cord metastases rarely occur in the course of Hodgkin's disease. Except for the initial presentation, their prognosis is poor despite early diagnosis with magnetic resonance imaging. Other causes such as epidural cord compression, paraneoplasic myelopathy, granulomatous angiitis and radiation myelopathy are still delated.

Adult↗

Early intensive therapy with autologous stem cell transplantation in advanced Hodgkin's disease: retrospective analysis of 158 cases from the French registry.

This retrospective study was undertaken to evaluate cure rates, toxicity and late effects of early intensive therapy followed by autologous stem cell transplantation (ASCT) in patients with advanced Hodgkin's disease (HD). One hundred and fifty-eight cases of ASCT registered in the French database (SFGM) were retrospectively analyzed. Disease status at the time of ASCT was first partial response (PR) in 85, first complete remission (CR1) in 45 or primary refractory in 28 cases. The median time interval between diagnosis and ASCT was 7 months (range 4-13). At the time of analysis in December 1995, 121/158 patients (76.6%) were alive, including 111 (70.2%) in continuous CR with a median follow-up for surviving patients of 46 months (range 8-123). Peri-ASCT toxic death rate was 3%, and the actuarial risk of new malignancies was 4.9% at 5 years. The cumulative probability of 5-year overall survival (OS) was 75.2% for the entire group of patients, 80.6% for the chemosensitive ones, and 33.9% for the primary refractory (chemosensitive vs refractory, P < 0.0001). The cumulative probability of 5-year event-free survival (EFS) was 66.1% for the entire group of patients, 73.7% for the chemosensitive ones, and 26.1% for the primary refractory (chemosensitive vs refractory, P < 0.0001). The only significant prognostic factor for both OS and EFS was disease status at the time of ASCT. Early ASCT in advanced HD is feasible, with a low risk of toxicity and without a higher rate of late effects compared with conventional treatment. Results achieved in chemosensitive patients at the time of transplantation lay the basis of future prospective randomized trials comparing ACST as front-line treatment to conventional treatment in high-risk cases.

Adolescent↗

Chromosomal analysis in multiple myeloma: cytogenetic evidence of two different diseases.

We report the cytogenetic results obtained in 81 multiple myeloma (MM) patients with abnormal karyotypes. Most karyotypes were complex with numerical and structural abnormalities but the analysis of chromosomal abnormalities allowed identification of two cytogenetic patterns depending on the chromosome number: a first hyperdiploid pattern (54%) with recurrent trisomies 3, 5, 7, 9, 11, 15 and 19 and a second pattern (46%) showing either pseudodiploid, hypodiploid or near-tetraploid karyotypes. Structural abnormalities were present in all but five hyperdiploid karyotypes, and frequently involved lymphoid breakpoints: immunoglobulin gene regions (36 cases) or chromosome 11q13 region (21 cases). Numerous other structural aberrations were detected; the most frequent involved chromosome 1 and chromosome 13. Structural abnormalities were significantly more frequent in the second hypodiploid group. When analyzing the results obtained in the 60 patients studied at the time of diagnosis, a prognostic correlation was found between the cytogenetic pattern and overall survival: hyperdiploid patients had a longer survival than patients belonging to the pseudo/hypo/near-tetraploid group (median survival 36.8 vs 18.2 months, P < 0.04). These results suggest that MM could correspond to two closely related diseases.

Adult↗

Lactobacillus species as emerging pathogens in neutropenic patients.

The intensive use of broad-spectrum antibiotics in the context of prolonged and severe neutropenia has contributed to the emergence of unusual pathogens. Four new cases of severe Lactobacillus infections-three of septicemia and one of pneumonia-are reported. They occurred in patients with acute leukemia who had chemotherapy-induced neutropenia. All patients were treated in the same intensive care unit and received the same antimicrobial prophylaxis which included a total bowel decontamination containing vancomycin. The four patients were treated with a combination of intravenous ceftazidime and vancomycin prior to the development of Lactobacillus infection. Improvement in the condition of all patients was obtained with a treatment including penicillin and concurrent recovery of granulopoiesis.

Adult↗

Peripheral blood stem cell transplantation for relapsed or refractory aggressive lymphoma in patients over 60 years of age.

Intensive chemotherapy with autologous bone marrow transplantation is now considered the treatment of choice for young patients with sensitive relapse of non-Hodgkin's lymphoma (NHL) but results of this procedure in older patients remain unknown. We evaluated the feasibility of two cycles of salvage therapy followed by an autologous peripheral blood stem cell (PBSC) transplantation in 13 patients aged more than 60 years (median age: 62; range 61-72) suffering from relapsed (n = 10) or refractory (n = 3) aggressive NHL. All patients had previously received first-line treatment containing doxorubicin. An association of ifosfamide, VP16, cytosine-arabinoside with or without high-dose methotrexate was used as salvage and priming therapy prior to collection of PBSC. All patients received G-CSF following salvage therapy. PBSC collection could be performed in 10 patients and yielded a median number of CFU-GM: 98.4 x 10(4)/kg (range 68-369). Nine patients underwent a transplantation using BEAM conditioning regimen. The median time to granulocyte and platelet recovery was 13 days (range respectively: 9-25 and 9-16). One patient died from sepsis after transplantation. The main adverse experience occurring after transplantation was a prolonged decline of performance status. Seven patients achieved a complete remission and one failed to respond. Three patients are still alive in CR. We conclude that PBSC collection was possible in selected patients over 60 years of age with refractory or relapsed aggressive NHL and myeloablative therapy could be used with tolerable toxicity. Hematologic recovery and organ toxicity appears to be similar to those observed in younger patients. Deterioration of performance status after transplantation is the most important factor that could limit this procedure. Further investigations are necessary to determine which patients will be able to benefit by this procedure in terms of survival and quality of life.

Aged↗

Ifosfamide, etoposide, cytarabine, and methotrexate as salvage chemotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma.

BACKGROUND: Patients with relapsed or resistant non-Hodgkin's lymphoma (NHL) have a poor prognosis and are rarely cured with usual salvage chemotherapy. Intensive treatment with the support of peripheral blood stem cells (PBSC) may be an effective therapy for these patients. We used a combination of ifosfamide, etoposide, cytarabine, and methotrexate (IVAM) with the intention both to reduce tumor burden and collect PBSC prior to transplantation. METHODS: Thirty-one patients (17 with relapsed NHL and 14 with refractory NHL) were treated with 2 courses of chemotherapy: IVAM regimen (ifosfamide, 1500 mg/m2 daily for 5 days plus mesna; etoposide, 150 mg/m2 daily for 3 days; cytarabine, 100 mg/m2 daily for 3 days; and methotrexate, 3 g/m2 on Day 5, with leucovorin rescue). Twenty-three patients had an intermediate grade and 8 patients had a high grade lymphoma. RESULTS: After IVAM therapy, 19 patients (61%) achieved complete response, 8 patients (26%) achieved partial response and 4 patients (13%) failed to respond. The major toxicity of IVAM was myelosuppression, but there were no toxic deaths. PBSC harvest could be performed in 29 patients (94%) with a median granulocyte-macrophage colony-forming unit count of 55 x 10(4)/kg (range, 2-391 x 10(4)/kg). Three patients could not undergo transplantation because of disease progression. One patient received a syngeneic transplant, 25 patients received PBSC transplantation, and 2 patients received a bone marrow transplant. In an intent-to-treat analysis, the overall survival rate at 4 years was 37% for the whole group (95% confidence interval: 22-55). CONCLUSIONS: We conclude that IVAM is an effective salvage chemotherapy for refractory or relapsed NHL and permits PBSC collection in most of these patients.

Adult↗

Correlation between CD34 expression and chromosomal abnormalities but not clinical outcome in acute myeloid leukemia.

The hemopoietic stem cell marker CD34 has been reported to be a useful predictor of treatment outcome in acute myeloid leukemia (AML). Previous data suggested that CD34 expression may be associated with other poor prognosis factors in AML such as undifferentiated leukemia, secondary AML (SAML), and clonal abnormalities involving chromosome 5 and 7. In order to analyze the correlations between the clinicopathologic features, cytogenetic and CD34 expression in AML, we retrospectively investigated 99 patients with newly diagnosed AML: 85 with de novo disease and 14 with secondary AML (SAML). Eighty-six patients who received the same induction chemotherapy were available for clinical outcome. Defining a case as positive when > or = 20% of bone marrow cells collected at diagnosis expressed the CD34 antigen, forty-five patients were included in the CD34 positive group. Ninety patients had adequate cytogenetic analysis. Thirty-two patients (72%) with CD34 positive AML exhibited an abnormal karyotype whereas 15 patients (28%) with CD34 negative AML had abnormal metaphases (P < 0.01). Monosomy 7/7q- or monosomy 5/5q- occurred in 10 patients and 8 of them expressed the CD34 antigen (P < 0.05). All patients with t(8;21) which is considered as a favorable factor in AML had levels of CD34 >/= 20% (P < 0.05). We did not find any association between CD34 expression and attainment of complete remission, overall survival, or disease-free survival. In conclusion, the variations of CD34 expression in AML are correlated with cytogenetic abnormalities associated both with poor and favorable outcome. The evaluation of the correlations between CD34 antigen and clinical outcome in AML should take into account the results of pretreatment karyotype.

Acute Disease↗

Durable remission of a relapsing primary central nervous system lymphoma after autologous bone marrow transplantation.

A 30-year-old patient with a relapsing primary central nervous system lymphoma (PCNSL), was successfully treated with salvage chemotherapy and high-dose therapy including drugs that cross the blood-brain barrier followed by ABMT. Cerebrospinal irradiation was administered after hematological recovery. Six years after transplantation the patient is alive without evidence of recurrent disease with a good neuropsychological status. This result could justify further studies of aggressive management of PCNSL in relapse.

Adult↗

LAZ3 rearrangements in non-Hodgkin's lymphoma: correlation with histology, immunophenotype, karyotype, and clinical outcome in 217 patients.

We have recently shown that an evolutionary conserved gene LAZ3, encoding a zinc finger protein, is disrupted and overexpressed in some B-cell lymphomas (mainly with a large cell component) that show chromosomal rearrangements involving 3q27. Because the breakpoints involved in these rearrangements are focused in a narrow major translocation cluster (MTC) on chromosome 3, we used genomic probes from this region to study the molecular rearrangements of LAZ3 in a large series of patients (217) with non-Hodgkin's lymphoma (NHL). Southern blot analysis showed LAZ3 rearrangement in 43 patients (19.8%). Rearrangement was found in 11 of the 84 patients (13%) with follicular lymphoma but was most frequent in aggressive lymphoma (diffuse mixed, diffuse large cell, and large cell immunoblastic subtypes), in which 31 of the 114 patients (27%) were affected. The highest proportion of LAZ3 alteration was observed in B-cell aggressive lymphoma (26 of 71 cases, 37%). Eleven of the 32 patients with 3q27 chromosomal abnormality had no LAZ3 rearrangement, suggesting the possibility of LAZ3 involvement outside the MTC. On the other hand, 18 of the 39 patients with LAZ3 rearrangement and available cytogenetic results did not have visible chromosomal break at 3q27, suggesting that almost a half of the rearrangements are not detectable by cytogenetic methods. No statistical association could be found between LAZ3 status and initial features of the disease or clinical outcome in either follicular or aggressive lymphomas. We conclude that LAZ3 alteration is a relatively frequent event in B-cell lymphoma, especially in those of aggressive histology. It could be used as a genomic marker of the disease, and further studies are needed to clarify clinical implications of these alterations.

Blotting, Southern↗

Residual disease in B-cell chronic lymphocytic leukemia patients and prognostic value.

Twenty-two B-cell chronic lymphocytic leukemia (CLL) patients were investigated to evaluate residual disease in clinico-hematological remission. Residual disease was determined by monotypy of surface light-chain expression and by dual-color staining with CD5 and CD19 markers. Samples were analyzed on flow cytometer. Total CD19+ cells above 25%, the CD5+CD19+/total CD19+ cells ratio above 0.25, clonal excess above 0.4 were considered positive for residual disease. According to these immunological criteria, only four cases achieved phenotypic remission. Our data confirm that dual marker analysis is more sensitive than clonal excess and may predict an early relapse. Ig gene rearrangements were studied by Southern blot analysis using IGHJ and IGKC probes in fifteen cases. All 12 cases that retained a detectable rearrangement displayed a phenotypic residual disease. Conversely, in two cases, DNA analysis failed to detect the residual disease characterized by flow cytometry. In conclusion, this study suggests that in B-CLL, dual marker analysis is sensitive in predicting an early relapse in sequential evaluations of residual disease, whereas rearranged bands are undetectable when the proportion of malignant cells is low.

Adult↗