Biomedical subjects

A Ferrant

Publications and source records attributed to A Ferrant.

At least 73 records · Page 4Linked to original sources

PubMed1998

Stromal factors support the expansion of the whole hemopoietic spectrum from bone marrow CD34+DR- cells and of some hemopoietic subsets from CD34+ and CD34+DR+ cells.

Ex vivo expanded bone marrow CD34+DR- cells could offer a graft devoid of malignant cells able to promptly reconstitute hemopoiesis after transplant. We investigated the specific expansion requirements of this subpopulation compared to the more mature CD34+ and CD34+DR+ populations. The role of stromal factors was assessed by comparing the expansion obtained when the cells were cultured in (1) long-term bone marrow culture (LTBMC) medium conditioned by an irradiated human BM stroma (CM), (2) medium supplemented with 15% FBS (FBSM) and (3) non-conditioned LTBMC medium (LTM) for 21 days. The effect of the addition of G-CSF (G) and/or of MIP-1alpha (M) to a combination of IL-3, SCF, IL-6 and IL-11 (3, S, 6, 11) was analyzed. Compared to CD34+DR- cells, CD34+ and CD34+DR+ cells gave rise to a similar number of viable cells and to a lower progenitor expansion. The expansion potential of CD34+ and CD34+DR+ cells was equivalent in CM and in FBSM except for both the emergence of CD61 + megakaryocytic cells and LTC-IC maintenance which were improved by culture in CM. In contrast, expansion from CD34+DR- cells was enhanced by CM for all the parameters tested. Compared to FBSM, CM induced a higher level of CFU-GM and BFU-E expansion and allowed the emergence of CD61+ cells. HPP-CFC were maintained or expanded in CM but decreased in FBSM. Compared to input, the number of LTC-IC remaining after 21 days of CD34+DR- expansion culture was strongly decreased in FBSM and variably maintained or expanded in CM. Comparison with LTM indicated that stroma conditioning is responsible for this effect. G-CSF significantly improved CFU-GM and HPP-CFC expansion from CD34+DR- cells without being detrimental to the LTC-IC pool. The growth of CD61+ cells was significantly enhanced by G-CSF in CM. Addition of MIP-1alpha had no significant effect either on progenitor expansion or on LTC-IC, regardless of culture medium. We conclude that factors present in stroma- conditioned medium are necessary to support the expansion of the whole spectrum of hematopoietic cells from CD34+DR- cells and to support the expansion of cell subsets from CD34+ and CD34+DR+.

Antigens, CD↗

PubMed1998

Haemopoietic defect and decreased expansion potential of bone marrow autografts from patients with acute myeloid leukaemia in first remission.

Autologous bone marrow (BM) transplantation for acute myeloid leukaemia (AML) in complete remission (CR) is frequently followed by a slow haemopoietic recovery. We assessed the haemopoietic capacity of purified BM stem cell (CD34+ DR-) and progenitor cell (CD34+ DR+) populations from patients with AML in CR, and compared these data with those of normal BM. The feasibility of ex vivo expansion in stroma-conditioned medium supplemented with cytokines was also investigated. The number of CFU-GM produced by initial patient CD34+ DR- cells was decreased compared to normal, whereas these values were similar to normal for CD34+ DR+ cells. BFU-E, HPP-CFC and LTC-IC were reduced for both patient CD34+ DR- and CD34+ DR+ subpopulations. In contrast to normal, the patient CD34+ DR- fraction was not enriched in LTC-IC. CFU-GM expansion from patient CD34+ DR- cells was poor and decreased after 14 d of culture. No HPP-CFC expansion could be observed for patient cells. LTC-IC were below the level of detection after 14-21 d of expansion culture of CD34+ DR- patient cells, whereas they were variably maintained or expanded for normal cells. After expansion culture, cytogenetic and/or FISH analyses did not reveal the anomalies present at diagnosis, regardless of the cell subpopulation analysed. In conclusion, BM cells of patients with AML in CR show a profound defect at the level of a stem cell enriched population. No meaningful ex vivo expansion could be obtained in culture conditions allowing for a significant expansion from a normal stem cell population.

Acute Disease↗

PubMed1998

Prognostic factors for survival and response after high-dose therapy and autologous stem cell transplantation in systemic AL amyloidosis: a report on 21 patients.

We retrospectively investigated the feasibility and the toxicity of autologous stem cell transplantation (ASCT) in 21 cases of systemic amyloidosis (AL). The conditioning regimens consisted of high-dose melphalan (HDM) alone (n = 18) or in combination with 12 Gy total body irradiation (n = 3). Toxic death rate was high: 9/21 patients (43%) died within the first month following ASCT, and 10/12 surviving patients achieved a response. With a median follow-up of 14 months, the OS and the EFS rates at 4 years were 57.1% (+/-10.8) and 29.9% (+/-14.5) respectively for the whole group. The major prognostic factor for both response and survival was the number of clinical manifestations at the time of ASCT, of the following five criteria, i.e. creatinine clearance < 30 ml/min, nephrotic syndrome with urinary protein excretion > 3000 mg/24 h, congestive heart failure, neuropathy, or hepatomegaly associated with alkaline phosphatase level > 200 IU/l. For patients presenting with two or more clinical manifestations the 4-year OS and EFS were both 11.1% compared with 91.7% and 46.3% respectively in patients with fewer than two clinical manifestations at the time of ACST. We conclude that ASCT is feasible in AL in a subset of patients with fewer than two clinical manifestations at the time of ASCT. Given the severe extra-haematological toxicity, ASCT should not be considered in other cases.

Adult↗

PubMed1998

PRAME, a gene encoding an antigen recognized on a human melanoma by cytolytic T cells, is expressed in acute leukaemia cells.

Gene PRAME was found to encode an antigen recognized on a human melanoma cell line by an autologous cytolytic T-lymphocyte clone. This gene is expressed at a high level in a very large fraction of tumours, such as melanomas, non-small-cell lung carcinomas, sarcomas, head and neck tumours and renal carcinomas. It is therefore a candidate for tumour immunotherapy even though some low expression is found in certain normal tissues. We tested by RT-PCR the expression of PRAME on more than 250 bone marrow or blood samples from patients with a haematological malignancy. Approximately 25% of the acute leukaemia samples were positive. Remarkably, all acute myeloblastic leukaemias that carried the chromosomal translocation t(8;21), which fuses the genes AML1 and ETO, expressed PRAME at a high level.

Acute Disease↗

PubMed1998

Stage III multiple myeloma: clinical and prognostic value of spinal bone marrow MR imaging.

PURPOSE: To determine the clinical and prognostic value of spinal bone marrow magnetic resonance (MR) imaging in stage III multiple myeloma. MATERIALS AND METHODS: In 80 patients with untreated, newly diagnosed stage III multiple myeloma, initial MR imaging patterns of spinal bone marrow involvement were correlated with hematologic parameters and response to induction chemotherapy. The influence of these patterns on survival was studied in 57 patients who did not undergo cytotoxic therapy with stem cell transplantation. RESULTS: MR imaging patterns of marrow involvement were normal in 19 (24%) patients, focal in 35 (44%), and diffuse in 26 (32%). Patients with the diffuse pattern had higher marrow plasmacytosis (P < or = .003) and cellularity (P < or = .001), higher serum calcium (P < or = .005) and beta 2-microglobulin (P < or = .008) levels, and lower hemoglobin values (P < or = .001) than did those with the normal or focal patterns. Patients with the normal pattern responded better to therapy (P = .007) and survived longer than patients with an abnormal pattern (P = .026). MR imaging findings and C-reactive protein level were the best independent prognostic indicators of survival. CONCLUSION: MR imaging patterns of spinal bone marrow involvement are correlated with several clinical parameters of disease severity and have prognostic value in stage III multiple myeloma.

Adult↗

PubMed1998

[Therapeutic approach to acute myeloid leukemia].

The treatment of acute myeloid leukemia has evolved considerably over the past decade. While induction therapy appears to have been almost standardized, there continues to be an ongoing debate and controversy regarding the best form of post-remission therapy. Attempts are being made to identify patients at particular risk of relapse to enable appropriate selection of best induction and post-remission therapies. In these respects, cytogenetics are useful. New concepts include the use of growth factors, immunotherapy, MDR modulation and therapies evolving from a better knowledge of the anomalies of the genes that cause leukemia.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Splenic lymphoma presenting as necrotizing glomerulonephritis.

The authors report a case of necrotizing glomerulonephritis, with granular immune deposits, leading to the etiologic diagnosis of splenic non-Hodgkin's Lymphoma (NHL). The serum creatinine, initially markedly elevated, decreased under steroids and chlorambucil. Unfortunately, the patient died from septic complications. The importance of a careful search for a (localized) NHL in case of necrotizing glomerulonephritis with granular immune deposits is emphasized.

Aged↗

PubMed1997

Karyotype in acute myeloblastic leukemia: prognostic significance for bone marrow transplantation in first remission: a European Group for Blood and Marrow Transplantation study. Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT).

The presentation cytogenetic result was correlated with outcome for 999 patients with acute myeloblastic leukemia (AML) having bone marrow transplantation (BMT) in first complete remission (CR1). The karyotype at diagnosis was classified according to the modified Chicago classification. Allogeneic BMT (AlloBMT) was performed in 500 patients and autologous BMT (ABMT) in 499 patients. For both groups, an abnormal chromosome (abn) 5 and/or 7 or a hypodiploid karyotype had a poor outcome, whereas t(15;17), pseudodiploidy, hyperdiploidy and diploidy were associated with a standard prognosis. Abn (16) and t(8;21) were also of standard prognosis for ABMT, but favorable for AlloBMT. When comparing AlloBMT and ABMT in patients with favorable or standard cytogenetics, AlloBMT was of benefit for remission duration and leukemia-free survival (LFS). Patients with an unfavorable karyotype had a similar outcome, regardless of type of BMT. By multivariate analysis, cytogenetics at diagnosis had the strongest prognostic value for relapse, LFS, and survival in AlloBMT. In ABMT, cytogenetics influenced relapse and LFS. We concluded that the karyotype at diagnosis had important prognostic implication in AML grafted in CR1.

Adolescent↗

PubMed1997

Prognosis of patients with advanced Hodgkin's disease: evaluation of four prognostic models using 344 patients included in the Group d'Etudes des Lymphomes de l'Adulte Study.

BACKGROUND: To determine whether a high risk group could be identified within a group of patients with advanced stage Hodgkin's disease (HD), the authors applied several prognostic models to patients treated according to the H89 protocol. METHODS: This study included 344 patients with Stage IIIB-IV HD who were treated with chemotherapy alone (8 cycles) or chemotherapy (6 cycles) plus radiation therapy. Four prognostic models were selected for this study: the numeric prognostic index of the Scotland and Newcastle Lymphoma Group, the Christie Hospital (Manchester)-St. Bartholomew's Hospital (London) model, the Memorial Sloan-Kettering Cancer Center (MSKCC) model, and the criteria used in the European Bone Marrow Transplant (EBMT)/Intergroup Trial. RESULTS: Univariate analysis of H89 protocol patients showed that 5 variables included in the models had prognostic significance: age > 45 years (P = 0.0001), anemia (hemoglobin < 12 g/dL for males and < 10 g/dL for females) (P = 0.0001), number of extranodal sites > or = 2 (P = 0.0013), serum lactic acid dehydrogenase greater than the normal value (P = 0.0018), and lymphocyte count < 0.75 x 10(9) L(-1) (P = 0.0063). All four models divided patients into prognostic subgroups. Significant differences among the subgroups were found by log rank analysis (chi-square test = 11-48; P = 0.01-0.0001). The worst prognostic group defined by the MSKCC model (> or = 3 adverse factors) had an overall survival rate of 59% at 3 years and an estimated 3-year event free survival rate of 43%. CONCLUSIONS: Patients with at least three adverse factors according to the MSKCC model or the EBMT criteria had a higher risk of failure with conventional treatment; however, based on survival rate, no very high risk group could be identified. Nonetheless, these prognostic models may be useful to recognize patients with good prognosis who can be cured with conventional therapy and for whom treatment morbidity and mortality can be minimized.

Adult↗

PubMed1997

Peripheral blood progenitor cell transplantation as an alternative to autologous marrow transplantation in the treatment of acute myeloid leukemia.

Herein we report on the feasibility of mobilizing peripheral blood progenitor cells (PBPC) in a prospective study of the HOVON-SAKK Groups in 96 cases with newly diagnosed acute myeloid leukemia (AML). Among 96 patients, 76 patients (79%) entered complete remission. Mobilization was undertaken with variable dosages of G-CSF in 63 patients, and 54 patients (87%) were leukapheresed. The comparative yields of pheresis following the G-CSF schedules and hematopoietic recovery data are presented and discussed. PBPC transplantation results in faster hematopoietic regeneration compared to autologous marrow grafting in the prior AML HOVON study.

Acute Disease↗

PubMed1997

Additional myeloablation with 52Fe before bone marrow transplantation.

For many hematological malignancies, high-dose chemoradiotherapy followed by bone marrow transplantation offers the best and sometimes the only chance for cure. However, the main causes of failure of this therapy are relapse and toxicity. In order to selectively deliver higher doses of radiotherapy to the bone marrow and to spare normal organs, we explored 52Fe therapy before a conventional BMT conditioning regimen. Twenty-four patients at high risk for relapse after BMT were included in a phase II study. The median follow-up was 42 months. The median 52Fe dose was 59 mCi. This resulted in a median radiation-absorbed dose (RAD) to the BM of 626 rad. The median RAD to the liver was 338 rad. No untoward effects were noted after the injections of 52Fe. The patients recovered hematopoiesis without toxicity in excess of that expected with conventional conditioning alone. The 3-year DFS probability was 49% (95% CI: 20-78%). Eight patients have relapsed, three of them in extramedullary sites. 52Fe should provide a way to boost the radiation dose to marrow-based diseases before bone marrow transplantation without excessive toxicity.

Adolescent↗

PubMed1997

Allogeneic bone marrow transplantation for AL amyloidosis.

AL amyloidosis is an infiltrative disorder characterized by the extracellular deposition of insoluble fibrillar immunoglobulin light chains whose production results from a plasma cell dyscrasia. Treatment with melphalan has resulted in an improvement in a few patients. Recently, intensive chemotherapy followed by autologous or syngeneic stem cell support has been shown to offer potential benefit. Allogeneic stem cell support after intensive therapy would retain the benefits of autologous transplantation, with the additional advantages of a tumor-free graft and of a possible graft-versus-tumor effect. We report a patient with AL amyloidosis and significant proteinuria. She improved after an allogeneic bone marrow transplantation.

Amyloidosis↗

PubMed1997

Long-term effects of localized spinal radiation therapy on vertebral fractures and focal lesions appearance in patients with multiple myeloma.

The occurrence of new vertebral fractures and focal marrow lesions was determined and compared in irradiated and nonirradiated vertebrae of 12 patients with multiple myeloma (MM), prospectively followed using magnetic resonance imaging (MRI) of the thoraco-lumbar spine after localized spinal radiation therapy. During follow-up (mean 35 months), fractures appeared in 5% of irradiated vertebrae and in 20% of nonirradiated vertebrae: new focal lesions appeared in 4% of irradiated vertebrae and in 27% of nonirradiated vertebrae. This study demonstrates a beneficial long-term effect of localized radiation therapy, consisting of a reduced incidence of vertebral fractures and focal marrow lesions in irradiated vertebrae.

Aged↗

PubMed1997

Nonmyelomatous monoclonal gammopathy: correlation of bone marrow MR images with laboratory findings and spontaneous clinical outcome.

PURPOSE: To determine the frequency of abnormal bone marrow magnetic resonance (MR) images in patients with nonmyelomatous monoclonal gammopathy and to compare the outcomes in patients with normal and in those with abnormal MR studies. MATERIALS AND METHODS: In 37 patients with monoclonal gammopathy of undetermined or borderline significance (19 men, 18 women; aged 28-85 years), MR imaging findings of the vertebral, pelvic, and femoral bone marrow were analyzed and correlated with initial laboratory findings and outcome after a follow-up of 15-60 months (median, 31 months) with no treatment. RESULTS: Thirty patients had normal MR studies; none required specific therapy after a median follow-up of 30 months. Seven had either diffuse (n = 4) or focal (n = 3) bone marrow abnormalities. Four required treatment after 15, 20, 50, or 58 months; three did not require treatment after 18, 26, or 40 months. Treatment-free survival curves in patients with normal and in those with abnormal MR studies were statistically significantly different (P = .005). CONCLUSION: Bone marrow abnormalities were detected with MR imaging in seven patients (19%) with monoclonal gammopathy of undetermined or borderline significance. All patients with a normal MR investigation still had not required treatment after a median follow-up of 30 months.

Adult↗

PubMed1997

Vertebral compression fractures in multiple myeloma. Part I. Distribution and appearance at MR imaging.

PURPOSE: To study the appearance and distribution of vertebral compression fractures on magnetic resonance (MR) images in patients with multiple myeloma. MATERIALS AND METHODS: Two hundred twenty-four vertebral compression fractures were studied on 216 sagittal T1-weighted spin-echo and T2*-weighted gradient-echo MR images of the thoracolumbar spine obtained before and during treatment in 37 patients with multiple myeloma. Vertebral compression fractures observed at diagnosis and during follow-up were determined as being benign- or malignant-appearing at MR imaging according to literature criteria, and their distribution along the spine was recorded. RESULTS: One hundred forty-nine (67%) of the 224 vertebral compression fractures appeared benign; 75 (33%) appeared malignant. Of the 37 patients, 14 (38%) had only benign-appearing vertebral compression fractures at diagnosis. One hundred five fractures (87%) were observed between T-6 and L-4, and 112 (50%) occurred between T-11 and L-3. Eight (4%) vertebral compression fractures involved the upper three thoracic vertebrae. CONCLUSION: Most vertebral compression fractures in patients with multiple myeloma appear benign at MR imaging, and their distribution is similar to that observed in osteoporotic fractures. The possibility of multiple myeloma should not be excluded in patients with benign-appearing vertebral compression fractures at MR imaging.

Adult↗

PubMed1997

Vertebral compression fractures in multiple myeloma. Part II. Assessment of fracture risk with MR imaging of spinal bone marrow.

PURPOSE: To determine the utility of bone marrow magnetic resonance (MR) imaging in the assessment of risk of vertebral compression fractures in patients with multiple myeloma. MATERIALS AND METHODS: In 50 patients with stage III multiple myeloma, 280 MR examinations of the thoracolumbar spine obtained at diagnosis and during treatment (mean follow-up, 28 months) were analyzed to determine MR patterns of bone marrow involvement before treatment and the occurrence of vertebral compression fracture at follow-up. Four MR patterns of marrow involvement were determined: A, normal marrow appearance; B, fewer than 10 focal lesions; C, more than 10 focal lesions; and D, diffuse infiltration. Fracture-free survival was compared according to these patterns. RESULTS: During follow-up, 131 vertebral compression fractures appeared in 37 patients. Patients with pattern A (n = 10) or B (n = 16) had significantly longer fracture-free survival before occurrence of the first, second, and third fractures than those with pattern C or D (P < 10(-5)). Relative risks of first, second, and third fracture occurrence for patients with pattern C or D compared with those with pattern A or B were 6.2, 9.1, and 11.0, respectively. CONCLUSION: Determination of MR patterns of spinal bone marrow involvement is a potential relevant factor to predict the risk of vertebral fractures in patients with stage III multiple myeloma.

Adult↗

PubMed1997

Early chronic lymphocytic leukemia: prognostic value of quantitative bone marrow MR imaging findings and correlation with hematologic variables.

PURPOSE: To determine the frequency of abnormal findings from quantitative bone marrow magnetic resonance (MR) imaging in patients with early-stage chronic lymphocytic leukemia, to correlate these findings with clinical parameters, and to compare spontaneous outcome in patients with normal or abnormal MR imaging findings. MATERIALS AND METHODS: In 21 patients with Binet stage A (Rai stage 0-I) disease, bulk T1 values of the vertebral bone marrow were determined and correlated with initial clinical, laboratory, histopathologic, and cytogenetic findings and with treatment-free survival. RESULTS: Bulk T1 values were normal (< 600 msec) in 14 patients and prolonged in seven. Patients with increased T1 had significantly higher blood (P = .017) and bone marrow (P = .015) lymphocytosis. None of the 14 patients with normal T1 values required specific therapy after a median follow-up of 13 months. Of the seven patients with abnormal T1 values, five required treatment after progression to Binet stage B or C disease at a median of 10 months. CONCLUSION: In patients with abnormal quantitative MR imaging findings, treatment-free survival appears to be significantly shorter (P < .001) than in patients with normal MR imaging findings.

Adult↗

PubMed1997

Economic analysis of a randomized clinical trial to compare filgrastim-mobilized peripheral-blood progenitor-cell transplantation and autologous bone marrow transplantation in patients with Hodgkin's and non-Hodgkin's lymphoma.

PURPOSE: High-dose chemotherapy (HDC) with peripheral-blood progenitor cell (PBPC) and autologous bone marrow (ABM) transplant (T) has documented survival benefits for relapsed Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). Treatment costs associated with HDC and its supportive care have restricted its use both on and off clinical trial. In a prospective randomized clinical trial, filgrastim-mobilized PBPCT resulted in faster recovery of bone marrow function, with less hospitalization and supportive care than ABMT. This study was undertaken to analyze the costs of the two strategies using prospectively collected data from a randomized clinical trial that compared filgrastim-mobilized PBPCT versus ABMT. PATIENTS AND METHODS: Clinical results and resource utilization from a randomized clinical trial that compared filgrastim-mobilized PBPCT versus ABMT following carmustine, etoposide, cytarabine, and melphalan (BEAM) HDC for HD and NHL are presented. The trial was performed in six centers in Germany, the United Kingdom, and Belgium. Resource utilization data were used to project costs and Massay Cancer Center (MCC) in the United States incurred the cost of treating the cohort. Costs were projected to the United States, because the economic implications to United States centers are significant, costs of care vary markedly among countries but resource utilization on this trial did not, and a randomized trial is unlikely to be performed in the United States. RESULTS: Fifty-eight patients with relapsed HD or NHL underwent HDC with BEAM. The PBPCT and ABMT groups had similar short-term survival after BEAM. PBPCT patients had a shorter hospitalization (median, 17 v 23 days; P = .002), neutrophil recovery (11 v 14 days; P = .005), platelet recovery to > or = 20 x 10(9)/L (16 v 23 days; P = .02), and days of platelet transfusions (6 v 10; P < .001). Estimated costs were $8,531 for ABM harvest and $5,760 for PBPC collection, including filgrastim mobilization. The total estimated average cost was $59,314 for each ABMT patient versus $45,792 for each PBPCT patient. Cost savings of $13,521 (23%) were due to shorter hospitalizations with less supportive care. CONCLUSION: PBPCT is as safe and more effective than ABMT for HD and NHL in the short term. PBPCT represents a significant cost savings due to lower autograft collection costs, shorter hospital stays, and less supportive care. The savings exceed the costs for filgrastim mobilization and PBPC collection. Actual savings will vary depending on local practice patterns, charges, and costs.

Adolescent↗