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Biomedical subjects

A Ferrant

Publications and source records attributed to A Ferrant.

At least 91 records · Page 5Linked to original sources

Follicular large-cell lymphoma treated with intensive chemotherapy: an analysis of 89 cases included in the LNH87 trial and comparison with the outcome of diffuse large B-cell lymphoma. Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: The aims of this study were as follows: (1) to analyze clinical, histopathologic characteristics, treatment outcome, and prognostic factors of patients with follicular large-cell lymphoma (FLCL); and (2) to compare them with those of patients with diffuse large B-cell lymphoma (DLCL) treated in the same therapeutic trial. PATIENTS AND METHODS: Eighty-nine FLCL patients who were histologically reviewed and who received an intensive chemotherapy regimen according to the LNH 87 protocol were analyzed and compared with 1,096 B-cell DLCL patients included in the same protocol. RESULTS: After intensive induction treatment, 59 patients (67%) achieved a complete remission [CR]. Estimated 5-year survival was 59%, and estimated 5-year freedom from progression (FFP) was 39%. Prognostic factors associated with shorter FFP were age greater than 60 years (P = .02), advanced clinical stage (P = .01), abnormal lactic dehydrogenase (LDH) level (P = .02), abnormal beta-2 microglobulin (P = .02), B symptoms (P = .03), bone marrow involvement (P = .04), and high expression of bcl-2 protein (P = .05). When compared with B-cell DLCL patients, FLCL patients were younger (P = .02), had a better Eastern Cooperative Oncology Group (ECOG) status (P = .05), less bulky mass (P = .04), more advanced clinical stages (P < .001), and more bone marrow involvement (P = .02). No significant difference was observed between FLCL and DLCL patients for response to therapy (67% v 67% of CR), 5-year overall survival (58% v 51%), 5-year disease-free survival (53% v 57%), or FFP survival (39% v 43%). CONCLUSION: FLCL patients have a favorable response rate and survival when treated with intensive chemotherapy. Their outcome is similar to that of B-cell DLCL patients, and a long-term FFP is observed for a substantial number of patients. Some adverse prognostic factors (including those of the International Prognostic Index, bone marrow involvement, and beta-2 microglobulin) have been identified to define a subset of patients who require other therapeutic approach.

Adolescent↗

Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: a retrospective case-matched study from the European Group for Blood and Marrow Transplantation.

A retrospective case-matched analysis was performed comparing 189 myeloma patients treated with allogeneic bone marrow transplantation (allo-BMT) with an equal number of patients who received autologous stem cell transplantation (ASCT). Matching was performed with respect to gender and number of treatment lines before transplantation. The groups were comparable with the exception of median age (43 years for allo-BMT v 49 years for ASCT, P = .0001) and median posttransplant follow-up (46 months for allo-BMT v 30 months for ASCT, P = .0003). The overall survival was significantly better for ASCT than for allo-BMT, with a median survival of 34 months and 18 months, respectively (P = .001). However, this survival advantage was only observed in men, but not in women. The statistically significant survival advantage for ASCT was seen in most subgroups, ie, chemotherapy-responsive patients, patients who had received two or more treatment lines before transplantation, patients in partial remission, patients with an IgG-subtype, patients older than 46 years of age, patients with stage II disease, and patients with a low or high serum-beta-2-microglobulin at diagnosis. The main reason for the poorer survival in allo-BMT patients was higher transplant-related mortality (41% v 13% for ASCT, P = .0001), which was not compensated for by a lower rate of relapse and progression. However, in patients alive at 1 year posttransplant, there was a trend for better long-term survival (P = .09) and significantly better progression-free survival (P = .02) for allo-BMT as compared with ASCT. We conclude that the median survival is superior for ASCT. However, allo-BMT has a lower relapse rate, which results in a similar long-term outcome for both approaches, but a longer follow-up is needed to assess the final outcome.

Acute Disease↗

Analysis of prognostic factors after the first relapse of Hodgkin's disease in 187 patients.

BACKGROUND: Patients in the first relapse of Hodgkin's disease comprise a heterogeneous group regarding their primary treatment and their clinical characteristics. Because therapeutic options for these patients vary from radiotherapy to combined modality or high dose therapy, we wanted to identify the prognostic factors that would optimize the treatment choice among the different options available. METHODS: Patients (n = 187) who relapsed for the first time after the end of treatment were included. Characteristics at diagnosis were: male to female ratio: 1.5; Stage III and IV: 59%; B symptoms: 60%; and mediastinal involvement: 76%, bulky in 29%. Chemotherapy (27%) or combined modality (73%) was prescribed. Relapses occurred 3 to 192 months (median: 35 mos) after the end of treatment; for 39% this interval was < 12 months. Characteristics at relapse were: Stage III and IV: 59%; and B symptoms: 46%. At first relapse, treatment was conventional (chemo- and/or radiotherapy) in 44% and intensive (high dose therapy with stem-cell transplantation) in 56%. These regimens led to 85% complete responses; and 15% were refractory. RESULTS: The median follow-up after relapse was 31 months and the median time to second progression was 20 months. The median freedom from second failure (FF2F) was 44 months and the median survival was 72 months. All factors were analyzed for survival and FF2F. Patients given intensive treatment had more adverse prognostic factors at relapse (B symptoms, early relapse, and disseminated relapse). Multivariate analysis identified 2 significant prognostic factors: interval end of treatment-relapse < 12 months (< 10(-4)) and Stage III and IV at relapse (P = 0.0013). For patients with at least one adverse prognostic factor, high dose therapy gave the best survival results. CONCLUSIONS: Using 2 simple prognostic factors, (interval end of treatment-relapse < 12 months and Stage III/IV at relapse), patients in first relapse of Hodgkin's disease can be classified into 3 significant prognostic groups in terms of survival and FF2F.

Adolescent↗

Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients.

BACKGROUND: A randomised trial comparing filgrastim-mobilised peripheral blood progenitor cell (PBPC) transplants with autologous bone marrow transplantation (ABMT) for haematopoietic stem cell support has not been done. We compared the effects of filgrastim-mobilised PBPC or autologous bone marrow reinfused to lymphoma patients after high-dose chemotherapy in a prospective randomised multicentre trial. METHODS: The trial was done at six centres in three European countries. After high-dose chemotherapy (carmustine, etoposide, cytarabine, and melphalan [BEAM protocol]) 58 patients with advanced Hodgkin's disease or high-grade non-Hodgkin lymphoma received either filgrastim-mobilised PBPC (n = 27) or bone marrow (n = 31) for haemopoietic reconstitution. FINDINGS: The median number of days with platelet transfusions after grafting was 6 in the PBPC transplantation group and 10 in the ABMT group (estimate of treatment difference 5 days, 95% CI 3-7 days). Time to platelet recovery above 20 x 10(9)/L was 16 days in the PBPC transplantation group and 23 days in the ABMT group (p = 0.02). Time to neutrophil recovery above 0.5 x 10(9)/L was also reduced in the PBPC transplantation group (11 vs 14 days, p = 0.005). Patients randomised to PBPC transplantation needed fewer red blood cell transfusions (two vs three, p = 0.002) and spent less time in hospital (17 vs 23 days, p = 0.002). Early post-transplant morbidity and mortality as well as overall survival (median follow-up 311 days) were similar in both groups. There was no notable toxicity ascribed to filgrastim administration or the leucapheresis procedures. INTERPRETATION: In patients with lymphoma treated with high-dose chemotherapy, reinfusing filgrastim-mobilised PBPC instead of autologous bone marrow significantly reduced the number of platelet transfusions, the time to platelet and neutrophil recovery, and led to earlier discharge from hospital.

Adult↗

Transient complete remission of acute lymphoblastic leukemia in relapse after allogeneic bone marrow transplantation induced by donor leukocyte transfusions.

We report the case of a young patient with refractory acute lymphoblastic leukemia relapse, after allogeneic bone marrow transplantation, who was treated by donor leukocyte infusions. We observed potent adoptive immunotherapy which produced a cytologic complete remission and total chimeric state. This was of short duration and the patient died of severe graft-versus-host disease. We present a short summary of the literature concerning acute lymphoblastic leukemia and donor leukocyte infusions.

Adolescent↗

Beta-thalassaemia in indigenous Belgian families: identification of a novel mutation.

The molecular basis of beta-thalassemia was investigated at the DNA level in 28 Belgians from 14 unrelated families. All the patients were heterozygous for beta-thalassaemia. Seven different mutations were identified using a combination of dot-blot hybridization with allele-specific oligonucleotide probes and direct automated fluorescence-based DNA sequencing. Among these mutations, four are commonly found in the Mediterraneans - codon 8 (-AA), IVS-I-1 (G --> A), IVS-I-6 (T --> C) and codon 39 (C --> T)-and two have occasionally been reported-initiation codon (T --> C) and codon 35 (C --> A). The last mutation, a -CC deletion at codons 38/39, appears to be a novel mutation and can routinely be investigated by AvaII restriction on amplified DNA. We report our findings, discuss the diversity of the mutations found in Belgium and show the usefulness of direct DNA sequencing in a population in which the molecular defects of beta-thalassaemia have yet to be characterized and in which screening is hampered by the wide range of potential mutations.

Belgium↗

Dicentric (1;15) in myeloid disorders.

We report three cases of myeloid disorders with a dic(1;15)(p11;p11), resulting in trisomy of the long arm of chromosome 1. A review of the literature showed six cases, reported as t(1;15). We suggest that these cases have the same anomaly and should be reappraised as dic(1;15).

Adult↗

Laparoscopic splenectomy in adults and children: experience with 31 patients.

BACKGROUND: Open surgery is the standard approach for splenectomy in hematologic disorders, but a few cases of successful laparoscopic splenectomy have been reported. METHODS: Thirty-one patients (18 adults, group 1; and 13 children, group 2) underwent laparoscopic splenectomy. Indications for surgery included idiopathic thrombocytopenic purpura (25 patients), congenital spherocytosis (4 patients), and hemolytic anemia (2 patients). In 97% of the patients the diameter of the spleen was less than 15 cm. RESULTS: Laparoscopic splenectomy was successful in 94% of the patients; conversion to open surgery was mainly related to hemorrhage. Accessory spleen was found in 39% in group 1 and 8% in group 2. Two adults received intraoperative autotransfusion. Postoperative morbidity was minimal. The median postoperative stay was 3 days (range, 2 to 12 days) in group 1 and 2 days (range, 2 to 5 days) in group 2. CONCLUSIONS: Laparoscopic splenectomy is safe in both adults and children. Adequate selection of patients (small-size spleen, splenic destruction on preoperative scanning of platelets), appropriate preparation in patients with idiopathic thrombocytopenic purpura (immunoglobulin G), and meticulous surgical technique (with routine opening of the gastrocolic ligament to search for accessory spleen) are key factors in obtaining the same long-term results as with open surgery.

Adolescent↗

Cytogenetic and clinicobiological features of acute leukemia with stem cell phenotype: study of nine cases.

Morphologic, immunologic, cytogenetic, and clinical features were studied in 9 cases of acute undifferentiated leukemia (AUL). These patients were unclassifiable by FAB criteria, they were CD34+ and did not express myeloid- or lymphoid-associated antigens (CD13, CD33, CD14, CD15, CD61, CD19, CD10, CD22, CD7, CD2, CD5, CD3). Clonal abnormalities were seen in 8 of 9 cases. Del(5q) as the sole anomaly was observed in 3 cases; +13 was the primary change in 3 cases, and isolated trisomy 12 was found in 1 patient. A complex karyotype with trisomy 12q, in association with del 17p and trisomy 21q was detected in 1 case. One patient with 5q- relapsed with refractory anemia with excess of blasts; the presence of dysgranulopoiesis and a few blasts with possible monocytoid morphology in the remaining 2 patients point to a "myeloid nature" of these leukemias. Analysis of cytologic features in our 3 patients with +13, in combination with previously reported cases, suggests the occurrence of immature stem cell involvement with limited differentiation potential, possibly more along the myeloid than the lymphoid lineage. The significance of trisomy 12q in this subset of leukemia remains elusive; some clues of minimal differentiation towards the myeloid lineage in our cases are provided by positivity for the CD117 (c-kit) antigen and by relapse with acute myeloid leukemia without maturation (M1) in one patient. We conclude that, with presently available diagnostic techniques, AUL is a rare subset of leukemia, in which cytogenetic changes are confined to a few chromosomes, with prevalent involvement of 5q and of chromosomes 13 and 12. Chromosome findings may be of value in clinical practice, especially in those cases with "myeloid-oriented" karyotype.

Acute Disease↗

Splenic irradiation before bone marrow transplantation for chronic myeloid leukaemia. Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)

A total of 229 patients with chronic myeloid leukaemia (CML) in chronic phase were randomized between 1986 and 1990 to receive or not receive additional splenic irradiation as part of their conditioning prior to bone marrow transplantation (BMT). Both groups, 115 patients with and 114 patients without splenic irradiation, were very similar regarding distribution of age, sex, donor/recipient sex combination, conditioning, graft-versus-host disease (GvHD) prevention method and blood counts at diagnosis or prior to transplant. 135 patients (59%) are alive as of October 1995 with a minimum follow-up of 5 years. 52 patients have relapsed (23%), 26 patients in the irradiated, 26 patients in the non-irradiated group (n.s.) with a relapse incidence at 6 years of 28%. The main risk factor for relapse was T-cell depletion as the method for GvHD prevention, and an elevated basophil count in the peripheral blood prior to transplant. Relapse incidence between patients with or without splenic irradiation was no different in patients at high risk for relapse, e.g. patients transplanted with T-cell-depleted marrows (P = n.s.) and in patients with low risk for relapse, e.g. patients transplanted with non-T-cell-depleted transplants and basophil counts < 3% prior to transplant (P = n.s.). However, relapse incidence differed significantly in patients with non-T-cell-depleted transplants and high basophil counts (> 3% basophils in peripheral blood). In this patient group, relapse incidence was 11% at 6 years with splenic irradiation but 32% in the non-irradiated group (P = 0.05). Transplant-related mortality was similar whether patients received splenic irradiation or not. This study suggests an advantage in splenic irradiation prior to transplantation for CML in this subgroup of patients and illustrates the need for tailored therapy.

Adolescent↗

Deletions of the long arm of chromosome 7 in myeloid disorders: loss of band 7q32 implies worst prognosis.

Clinical and cytogenetic data were analysed in 54 patients with acute non-lymphocytic leukaemias (ANLL) or MDS (myelodysplastic syndromes) and deletion of the long arm of chromosome 7 (7q-), in order to determine if there is a commonly deleted region in 7q and to establish possible correlations between karyotypic features, such as karyotype pattern, karyotype complexity, associated anomalies, and/or the type of deleted segments, and outcome of patients with these disorders. The median follow-up of our patients was 4 months (range 1-89), as was the median survival. In 30% of the cases there was a history of preceding MDS or previous chemotherapy. Clinical and cytogenetic remission was obtained in 7/36 patients treated with chemotherapy (CT). At the time of 7q- detection, three patients previously treated with CT for ANLL were in clinical remission. 5q- was the most recurrent associated abnormality. Complex karyotypes were observed in 68% of the cases. In univariate analysis, statistical differences in survival were observed according to diagnosis (therapy-related and secondary diseases had a worse prognosis than primary disorders), the chromosomal segments deleted (the loss of band 7q32 was of poor prognostic value), the karyotype complexity (patients with single anomalies did better than patients with complex anomalies) and the response to therapy (patients who achieved complete remission had a better survival probability). In multivariate analysis, the loss of band 7q32 was found to be significantly related to very poor prognosis. This finding suggests that band 7q32 may contain critical genes that should be explored at the molecular level.

Adolescent↗

Primary mediastinal large B-cell lymphoma. A clinicopathologic study of 141 cases compared with 916 nonmediastinal large B-cell lymphomas, a GELA ("Groupe d'Etude des Lymphomes de l'Adulte") study.

Among non-Hodgkin's lymphomas, primary mediastinal large B-cell lymphoma (PMLCL) has been considered a separate entity that has specific clinical and histological aspects and a poor prognosis. In this study, we reexamined the clinicopathologic features and the response to current treatment of 141 PMLCL and compare them with 916 nonmediastinal large B-cell lymphomas (NMLCL) recorded in the same period and treated with similar combined chemotherapy. The clinical features of PMLCL at diagnosis were largely homogeneous and distinct from NMLCL, with a predilection for young women (59% with a mean age of 37 years versus 42% with a mean age of 54 years), bulky tumor (77% versus 7%, p < 10(4)), high serum lactic dehydrogenase (LDH) level 76% versus 51%, p < 10(4)), and frequent intrathoracic extension to adjacent organs such as pleura, pericardium, and lung. By contrast, extrathoracic or hematologic dissemination was uncommon (2% of bone marrow involvement versus 17%). All patients had diffuse large B-cell nonimmunoblastic, nonanaplastic lymphomas. Histological analysis of the 141 PMLCL evaluated two common patterns: the presence of large cells with clear cytoplasm (found in 38% of cases) and the presence of fibrosis (marked in 25% of cases). The presence of clear cells or intense fibrosis did not constitute prognostic indicators. Immunologic and molecular analysis assessed the profile of bcl-2 expression and the presence of Epstein-Barr virus (EBV) in PMLCL: 30% expressed a high level of bcl-2 protein; EBER RNAs were detected by in situ hybridization in only two of the 41 cases tested. Monotypic light chain restriction could be demonstrated in seven of the 41 PMLCL tested on fixed-section. Treated with polychemotherapy regimens without radiotherapy, 79% of PMLCL patients achieved a complete remission compared with 68% in the NMLCL patient group (p = 0.01). Overall, 3-year survival rates were estimated at 66 and 61%, respectively (p = 0.05), and disease-free survival rates were not significantly different (61 versus 64%). Stratified analysis on the International Prognostic Index (based on age, tumor stage, serum LDH level, and performance status) showed no difference in the overall and disease-free survivals between the two lymphoma groups. In conclusion, PMLCL can be combined with other diffuse large B-cell lymphomas on morphologic grounds; it is not associated with EBV. It responds favorably to treatment and should be managed like other high-grade lymphomas of equivalent histology. However, the uncommon clinical presentation makes it a distinct entity.

Adolescent↗

Infectious complications after 2-chlorodeoxyadenosine therapy.

Infection is a common adverse event after therapy with nucleoside analogs, including 2-chlorodeoxyadenosine (CdA). However, the incidence of CdA-related infections has been poorly documented. In this study we compare, in the same patient population, the incidence of infectious episodes during the 6-month period before CdA to their incidence during the 6 months after initiating therapy. Ninety-five patients with hematological malignancies were studied. The incidence of infectious episodes almost doubled after CdA (0.87 vs. 0.47 during the pre-CdA period). The following factors were associated with an increased risk of infection after therapy: a history of previous chemotherapy, infection during the pre-CdA period and a diagnosis of chronic lymphocytic leukemia or of non-Hodgkin's lymphoma. Age, neutrophil and lymphocyte count at onset of CdA and time interval between diagnosis and therapy with CdA did not correlate with the infectious risk. The pattern of infections was modified after therapy with an increase of herpes virus infections ( 1 vs. 8 episodes, p=0.04) and of fever of unknown origin (6 vs. 17 episodes, p=0.03). In conclusion, a population at high risk for developing infectious complications after CdA therapy can be identified. Specific measures aimed at reducing the incidence of infectious events should concentrate on this population.

Adult↗

Stage I multiple myeloma: value of MR imaging of the bone marrow in the determination of prognosis.

PURPOSE: To determine the prognostic value of bone marrow findings at magnetic resonance (MR) imaging in patients with stage I multiple myeloma. MATERIALS AND METHODS: In 24 patients with stage I multiple myeloma, findings from MR imaging of the vertebral, pelvic, and femoral bone marrow were analyzed and correlated to spontaneous outcome. Progressive multiple myeloma was observed in 12 patients and stable stage I multiple myeloma was observed in 12 after a follow-up period of 4-67 months (median, 27 months). RESULTS: In 17 patients, MR imaging findings were normal, and in seven patients, bone marrow abnormalities were depicted on MR images. Of the 12 patients with progressive multiple myeloma, six had bone marrow abnormalities that were depicted at MR imaging. In the group of patients with progressive multiple myeloma, the six patients with abnormal MR imaging findings showed earlier disease progression (median, 10 months) than the six patients in whom MR imaging findings were normal (median, 32 months) (P < .0001). Multivariate analysis of clinical and MR imaging findings showed that MR imaging (P = .006) were two independent factors in the prediction of disease progression. CONCLUSION: MR imaging of the bone marrow in patients with stage I multiple myeloma is an independent factor in the prediction of disease progression.

Bone Marrow↗

Sequential quantitative MR analysis of bone marrow: differences during treatment of lymphoid versus myeloid leukemia.

PURPOSE: To assess the use of bulk T1 measurements with magnetic resonance (MR) imaging for monitoring treatment response in leukemic patients, with separate analysis of patients with acute lymphoid (ALL) and those with acute myeloid leukemia (AML). MATERIALS AND METHODS: Bulk T1 values were determined repeatedly during the first 4 weeks of treatment in 16 patients with ALL (age range, 16-72 years) and the first 6 weeks of treatment in 51 patients with AML (age range, 17-75 years). Bulk T1 values were compared in all patients with AML or ALL and in those who did or did not respond to treatment. RESULTS: MR imaging of lumbar bone marrow demonstrated statistically significant differences in initial bulk T1 values and in changes in bulk T1 values during treatment between patients with ALL and those with AML. Changes in bulk T1 after the 2nd week of treatment were statistically significantly different between patients with and those without a response who had ALL but not in those with AML. CONCLUSION: Sequential quantitative MR imaging during treatment appears valuable for prediction of response in patients with ALL but not in those with AML. Further investigations are needed to determine what influence MR imaging can have on patient care, but patients with ALL should be analyzed separately from those with AML.

Acute Disease↗

Limited activity of mini-dose interferon alpha-2a in the treatment of myelodysplastic syndrome.

Impairment in marrow function often characterizes the evolution of myelodysplastic syndrome. As a differentiating agent, interferon alpha 2a (INF alpha) has been shown to be active in the correction of cytopenias related to myelodysplastic syndromes (MDS). We report the clinical course of 9 patients with MDS treated with low-dose subcutaneous INF alpha (1 x 10(6), 3 times per week). A significant effect on anemia was only demonstrated in one patient (11%). In the other, eight, therapy was totally ineffective and four of them could not receive the complete treatment due to worsening cytopenias or leukemic transformation. In conclusion, in our study, INF alpha had only limited activity in the treatment of myelodysplastic syndrome.

Drug Evaluation↗

Indium-111-pentetreotide uptake in endocrine tumors and lymphoma.

UNLABELLED: The biodistribution of 111In-pentetreotide was assessed in patients with gastroenteropancreatic (GEP) neuroendocrine tumors or lymphoma and in control patients and analyzed as a function of scanning time, presence or absence of tumor uptake, tumor type and previous octreotide treatment. METHODS: Patients underwent imaging 4 and 24 hr after injection of approximately 200 MBq 111In-pentetreotide. The frequency of organ visualization was assessed on planar views. Total organ and tumor uptake (% injected dose [ID]) was determined using the geometric mean method and regional tissue uptake (% ID/100 ml) by semiquantitative SPECT. RESULTS: Liver, spleen, kidneys and urinary bladder were visualized in all patients. Thyroid, bowel and pituitary were more often visualized at 24 hr than at 4 hr. Activity in the gallbladder, breast, ureters and ascites was only occasionally observed. Total liver, spleen and thyroid uptake was stable over time, whereas kidney activity decreased slightly. At 24 hr, regional uptake was threefold lower in the liver than in the spleen or kidneys and was similar in the three groups. In patients with long-term octreotide therapy, a positive correlation was found between the duration of octreotide therapy and liver or spleen uptake. Total and regional tumor uptake showed high intraindividual and interindividual variations. Total tumor activity was stable over 24 hr in patients with GEP and decreased in those with lymphoma. The mean regional tumor uptake was 10-fold lower in patients with lymphoma than in those with GEP. Cold octreotide injected 24 hr after tracer administration did not result in any displacement of organ and tumor activity. CONCLUSION: Organ uptake seems not to be influenced by the presence of 111In-pentetreotide-positive lesions or by tumor type. Tumor uptake is highly variable among patients and clearly lower in patients with lymphoma than in those with GEP. The widespread of uptake values in tumors indicates that radiotherapy using radiolabeled somatostatin analogs may not be applicable to all patients with 111In-pentetreotide-positive tumors.

Antineoplastic Agents, Hormonal↗