Relative lymphocytosis-disorder caused by occupational exposure to vinyl chloride monomer.
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Adult↗
Biomedical subjects
B Labar
Publications and source records attributed to B Labar.
Thiorphan stimulates clonal growth of GM-CFU in short-term cultures of bone marrow from a healthy donor and from patients with non-Hodgkin lymphoma.
Thiorphan, a specific inhibitor of membrane neutral endopeptidase (NEP, EC 3.4.24.11) also known as the common acute lymphoblastic leukemia antigen (CALLA, CD10) was added into short-term clonal cultures of the buffy coat concentrates of human bone marrow obtained from a healthy donor (six experiments) and from ten patients with non-Hodgkin lymphoma (NHL) (eight in complete remission, one in partial remission and one in relapse). Thiorphan concentrations ranged from 10(-5) to 10(-13) M. Nanomolar and higher concentrations of the drug mildly stimulated the granulocyte-macrophage colony-forming unit (GM-CFU) counts in the cultures of normal bone marrow, reaching the significance at 10(-7) M. Meaningful alterations of the GM-CFU counts were noted in 31 of 79 thiorphan-treated cultures of NHL bone marrow (39%). In those cultures the stimulatory effects (33%) outnumbered the inhibitory ones (6%). The stimulatory effects occurred mainly in the bone marrow samples of the patients with highly malignant NHL. The observations are compatible with the idea that the membrane endopeptidase (CALLA, CD10) participates in processes controlling the proliferation and differentiation of hematopoetic cells by cleaving the neuropeptides and related hemoregulatory peptides.
Bone Marrow↗
The influence of HLA-matched sibling donor availability on treatment outcome for patients with AML: an analysis of the AML 8A study of the EORTC Leukaemia Cooperative Group and GIMEMA. European Organization for Research and Treatment of Cancer. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto.
To determine whether patients with a HLA-identical sibling donor have a better outcome than patients without a donor, an analysis on the basis of intention-to-treat principles was performed within the framework of the EORTC-GIMEMA randomized phase III AML 8A trial. Patients in complete remission (CR) received one intensive consolidation course. Patients with a histocompatible sibling donor were then allocated allogeneic bone marrow transplantation (alloBMT), the patients without a donor were randomized between autologous BMT (ABMT) and a second intensive consolidation (IC2). 831 patients <46 years old and alive >8 weeks from diagnosis were included. HLA typing was performed in 672 patients. AlloBMT was performed during CR1 in 180 (61%) out of 295 patients with a donor. Another 38 patients were allografted: five in resistant disease, 14 during relapse and 19 in CR2. ABMT was performed in 130 (34%) out of 377 patients without a donor in CR1, in six (2%) patients during relapse and in 38 (10%) patients during CR2. The disease-free survival (DFS) from CR for patients with a donor was significantly longer than for patients without a donor (46% v 33% at 6 years; P=0.01, RR 0.78, 95% confidence interval 0.63-0.96). The overall survival from diagnosis for patients with a donor was longer, but not statistically significant, than for patients without a donor (48% v 40% at 6 years; logrank P=0.24). When patients were stratified according to prognostic risk groups, the same trend in favour of patients with a donor was seen for survival duration and the DFS remained significantly longer for this group of patients.
Adolescent↗
Analysis of clonality in T-lymphoproliferative diseases by multiplex PCR.
Distinction between benign and malignant T-cell lymphoproliferative diseases can be difficult using morphological criteria. Using multiplex polymerase chain reaction system we have tested a series of patients with various lymphoproliferative disorders to detect clonal T-lymphocyte populations. Results show that clonal amplification products were obtained from all 10 patients with T-cell lymphoproliferative disorders while the amplification of DNA samples from B-cell neoplasms and normal individuals revealed polyclonal amplification products. By splitting the multiplex primer mix, the patient specific T-cell receptor gamma rearrangement was determined: five out of ten patients showed the exclusive presence of a single T-cell receptor gamma gene rearrangement. Three patients exhibited two rearranged T-cell receptor gamma genes, while in two patients positive reactions were obtained with three pairs of primers for variable and joining segments. Molecular analysis of rearranged T-cell receptor genes by multiplex polymerase chain reaction represents a useful and rapid tool for confirming diagnosis, to determine the extent of disease and to monitor the response to therapy.
Gene Rearrangement, T-Lymphocyte↗
Relation between urinary cytology abnormalities and cyclosporine A therapy in bone marrow transplant recipients.
The aim of the study was to determine the relationship, if any, between abnormalities in urinary cytology and the administration of cyclosporine A in bone marrow transplant recipients. Specific attention was given to the presence of tubular cells with round inclusions (TCRI). Two bone marrow transplant recipient groups were studied: one with allogeneic bone marrow transplantation (BMT) (20 patients) who were treated with cyclosporine A, and the other with autologous BMT (12 patients) who did not receive cyclosporine A. Urinary cytology showed TCRI in 41.66% of the patients after autologous BMT and in 80% of the patients after allogeneic BMT. In the group of patients treated with allogeneic BMT, the occurrence of TCRI was associated with a high incidence of glycosuria and was followed by an increase in the blood level of cyclosporine A, an increase in the serum creatinine concentration and a decrease in the creatinine clearance. These results demonstrated that TCRI, although related to, were not found to be exclusively specific to the administration of cyclosporine A.
Adult↗
Treatment of chronic myeloid leukemia in relapse after umbilical cord blood transplantation.
Umbilical cord blood (UCB) is increasingly used as a source of hematopoietic progenitor cells for allotransplantation. Donor-derived buffy coat cells are considered optimal treatment for leukemia relapses after transplantation of allogeneic bone marrow. Experience with relapses after UCB transplants are sparse. Here we report a girl who received an UCB transplant for chronic myeloid leukemia, relapsed after three years, failed to respond to donor buffy coat cells, but achieved a complete hematologic, cytogenetic, and molecular remission on interferon-alpha.
Child, Preschool↗
Implication of molecular analysis of HLA-A*02 subtyping for unrelated bone-marrow donor selection.
The HLA-A*02 allele is the most heterogeneous allele at HLA-A locus with 22 different subtypes so far identified. All of these subtype polymorphisms are located in alpha 1 and alpha 2 domains which are responsible for peptide biding and HLA restricted recognition by T-cell receptor. The aim of the present study was to determine the frequency of different HLA-A*02 alleles in 33 healthy unrelated Croatians. HLA-A*02 subtyping has also been retrospectively performed in 2 recipient-unrelated donor pairs and in 4 recipient-HLA phenotypically identical parent pairs. All subjects, previously typed as HLA-A2 by serology were tested using HLA-A*02 ARMS-PCR kit which discriminates 17 different A*02 alleles. Among 17 A*02 alleles we have found 4 different A*02 subtypes in healthy unrelated Croatians. The most frequent A*02 allele was A*0201 (84%). The frequency of the remaining A*02 alleles were as follows: A*0205 (3%), A*0207 (6%) and A*0213 (6%). Among 6 tested bone-marrow transplantation (BMT) pairs, only one has been found to be A*02 subtype incompatible (A*0201/A*0205). Four different A*02 alleles are found in Croatian population with the predominance of A*0201. However these results suggest that A*02 subtyping is also necessary for optimal matching of HLA-A*02 positive donor-recipient pairs in HLA incompatible BMT.
Alleles↗
A randomized phase II study on the effects of 5-Aza-2'-deoxycytidine combined with either amsacrine or idarubicin in patients with relapsed acute leukemia: an EORTC Leukemia Cooperative Group phase II study (06893).
5-Aza-2'-deoxycytidine combined with either amsacrine or idarubicin has been applied in a treatment protocol for patients with a relapse of acute myeloid or lymphocytic leukemia. Sixty-three patients received 5-Aza-2'-deoxycytidine 125 mg/m2 as a 6 h infusion every 12 h for 6 days in combination with either amsacrine 120 mg/m2 as a 1 h infusion on days 6 and 7 (n=30) or idarubicin 12 mg/m2 as a 15 min infusion on days 5, 6 and 7 (n = 33). Twenty-three patients (36.5%) obtained a complete remission (CR); eight of 30 patients treated with amsacrine and 15 of 33 treated with idarubicin. Patients with an interval of more than 1 year between initial diagnosis and start of the protocol achieved CR in 51.4%, compared to 15.4% for patients with an interval of less than 1 year. Patients with normal cytogenetics had a higher CR rate (61%) than those with abnormal cytogenetic findings (15.8%). Digestive tract and hematologic toxicity was prolonged, compared to standard induction schedules. Median disease-free survival was approximately 8 months, with only 20% of patients staying in remission for more than 1 year. 5-Aza-2'-deoxycytidine is a good antileukemic agent with considerable toxicity. Current results merit further investigations in previously untreated leukemia.
Adolescent↗
Salvage treatment for primary resistant acute myelogenous leukemia consisting of intermediate-dose cytosine arabinoside and interspaced continuous infusions of idarubicin: a phase-II study (no. 06901) of the EORTC Leukemia Cooperative Group.
Twenty-one patients with acute myeloid leukemia (AML) who failed to enter complete remission (CR) after first-line standard-dose remission-induction therapy with 7 days of cytarabine and 3 days of daunorubicin were treated with a salvage regimen containing intermediate-dose cytosine arabinoside (Ara-C) 2 x 500 mg/m2/day during 7 days in combination with continuous infusions of idarubicin 12 mg/m2/day on days 1, 3, and 5. Twenty patients were considered primary resistant, and one patient had a partial remission after two remission-induction courses. Overall, 11 patients (52%, 95% confidence interval: 30-74%) entered CR. Three patients died during hypoplasia and seven patients had resistant disease or a partial remission. The remission rate in this study compares favorably with the results obtained in similar patient categories. The toxicity of this salvage regimen was remarkably mild. No extramedullary toxicity was observed except for hepatic dysfunction in seven patients. The median duration of remission was 8.5 months, and ultimately, all complete remitters have relapsed except the patient who died from infectious complications after allogeneic bone marrow transplantation (BMT). This study shows that new intensive chemotherapy regimens may be effective after failure of primary treatment. Salvage regimens containing intermediate/high-dose Ara-C and/or alternative anthracyclines or anthracenes should be induced in the treatment of young patients with de novo AML.
Adolescent↗
2-Chlorodeoxyadenosine treatment in non-Hodgkin's lymphoma and B-cell chronic lymphocytic leukemia resistant to conventional chemotherapy: results of a multicentric experience. International Society for Chemo-Immunotherapy.
Among the purine analogs, 2-chlorodeoxyadenosine (2-CDA) is particularly effective for the treatment of hairy cell leukemia and Waldemstrom's macroglobulinemia. Both efficacy and toxicity of 2-CDA were evaluated in previously treated patients affected with chronic lymphoproliferative disorders such as low-grade non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukemia (CLL). Thirty cases, mainly refractory, 16 affected with CLL, were included from six centers of the International Society for Chemo-Immunotherapy (IGCI). 2-CDA was administered in a 2 h i.v. infusion for 5-7 days at the standard dose of 0.1 mg/kg/day every 4 weeks. The median number of cycles was 3. Of 30 cases, eight (26.7%) achieved a complete remission (CR), nine (30%) a partial remission (PR), and two (6.7%) a minor response, while five cases (16.6%) did not respond, and six (20%) were considered early deaths. The overall response rate (CR + PR) was 56.7%, with a median response duration of 12 months (range 3-28 +) and a better response in CLL patients. Considering that the majority of patients were heavily pretreated, toxicity was acceptable, with 40% of cases not presenting any toxic effect. The main toxicity consisted in infectious complications. Based on the results of the present study, we confirm that 2-CDA is an effective drug in these lymphoproliferative disorders, suggesting its possible use either alone or in combination, also as first-line therapy.
Adult↗
Prognostic factors of patients with acute myeloid leukemia (AML) allografted in first complete remission: an analysis of the EORTC-GIMEMA AML 8A trial. The European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell' Adulto (GIMEMA) Leukemia Cooperative Groups.
The Leukemia Cooperative Groups of the EORTC and the GIMEMA conducted a prospective randomized phase III trial, in order to assess the value of autologous BMT (ABMT) vs a second intensive consolidation course (IC2), following a common intensive consolidation course (IC1) for patients with AML. Patients with an HLA-identical sibling donor were not randomized, but were included in an allogeneic BMT (alloBMT) program. This is an analysis of prognostic factors which influence the outcome of treatment after alloBMT in first complete remission (CR). The study included 730 patients < 46 years of age in CR, 270 having a histocompatible sibling donor. In 169 of these patients alloBMT was performed in first CR. Early remitters (122 patients achieving CR with one course of treatment) had a DFS at 3 years of 67%, significantly longer than that of 44% for late remitters (47 patients achieving CR after more than one course of treatment) (P = 0.006). The relapse risk for early vs late remitters was 16 and 40% at 3 years (P = 0.001) and the treatment-related mortality (TRM) at 2 years was 21 vs 27%. Age appeared to be a prognostic factor for TRM, WBC for DFS, whereas the FAB classification was not of prognostic importance. Patients with poor risk cytogenetic abnormalities showed a trend towards a higher relapse risk. Patients transplanted shortly after achieving CR appeared to have a worse prognosis than those transplanted further into remission. Overall, the number of courses of induction therapy needed to achieve CR was the most important prognostic factor for outcome after allogeneic BMT.
Adolescent↗
Allogeneic bone marrow transplantation for acute leukaemia--IGCI experience. International Group for Chemo-Immunotherapy.
From October 1984 to December 1994, 142 patients from six IGCI-BMT centers (78 acute myelogenous leukemia and 64 acute lymphoblastic leukemia) received allogeneic bone marrow from their HLA-identical sibling. The probability of LFS at 60 months is 41% for AML patients and 39% for ALL patients. A better LFS was documented in patients allografted in first CR compared to the patients treated in advanced stage of the disease. The overall relapse rate is 27% for AML patients and 45% for ALL patients. The relapse rate is higher for patients allografted in advanced stage of the disease (47 vs 26% at 60 months for AML and 55 vs 38% at 60 months for ALL). The incidence of moderate to severe acute GVHD is between 45-50% for both AML and ALL patients. Chronic GVHD was documented in 30% of AML patients and 38% of ALL patients. Transplant-related mortality for both AML and ALL is about 25%. Relapse and GVHD with or without infection are the main causes of death. These results confirmed that allogeneic BMT is very effective therapy for patients with acute leukemia, especially for patients transplanted in first CR.
Adolescent↗
Anxiety as a possible predictor of acute GVHD.
In order to determine the influence of anxiety on the development of BMT complications and survival, we analysed data on 35 consecutive patients undergoing BMT in our Centre between June 1992 and December 1994. All patients received bone marrow from HLA-identical MLC non-responsive siblings. For GVHD prophylaxis, all patients received cyclosporin (CsA) and short methotrexate (MTX). The diagnosis and severity of acute GVHD were defined according to the Seattle Transplant Team criteria. The patients were tested with the Spielberger STAI test as a measure of anxiety as a state (STAI-S) and as a trait (STAI-T). The STAI-S/1 and STAI-T/1 were performed during the first week of isolation (day -5 to day -3 prior BMT) and STAI-S/2 and STAI-T/2 at the end of the discharge from laminar air flow units (day +35 to day +40 post-transplant). During isolation all patients had daily psychiatric support. Out of 35 patients, 31 (89%) fulfilled the STAI-S and STAI-T during the first week and at discharge from laminar air flow isolation. The level of anxiety at the beginning of isolation as measured by STAI-S/1 and STAI-T/1 tests had been significantly higher in patients who subsequently developed acute grade II-IV GVHD as compared to patients with GVHD grade 0-I (P < 0.001), irrespective of age, sex or stage of the disease prior to BMT. In those patients who died, the STAI-S/1, STAI-T/1 and STAI-T/2 tests had been almost identical to those of surviving patients, while STAI-S/2 had been significantly higher (P = 0.034). These data clearly indicate an association between the level of anxiety and the risk for BMT complications, but this should be confirmed in further controlled clinical trials.
Adolescent↗
Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups.
BACKGROUND: Allogeneic or autologous bone marrow transplantation and intensive consolidation chemotherapy are used to treat acute myelogenous leukemia in a first complete remission. METHODS: After induction treatment with daunorubicin and cytarabine, patients who had a complete remission received a first course of intensive consolidation chemotherapy, combining intermediate-dose cytarabine and amsacrine. Patients with an HLA-identical sibling were assigned to undergo allogeneic bone marrow transplantation; the others were randomly assigned to undergo autologous bone marrow transplantation (with unpurged bone marrow) or a second course of intensive chemotherapy, combining high-dose cytarabine and daunorubicin. Comparisons were made on the basis of the intention to treat. RESULTS: A total of 623 patients had a complete remission; 168 were assigned to undergo allogeneic bone marrow transplantation, and 254 were randomly assigned to one of the other two groups. Of these patients, 343 completed the treatment assignment: 144 in the allogeneic-transplantation group, 95 in the autologous-transplantation group, and 104 in the intensive-chemotherapy group. The relapse rate was highest in the intensive-chemotherapy group and lowest in the allogeneic-transplantation group, whereas the mortality rate was highest after allogeneic transplantation and lowest after intensive chemotherapy. The projected rate of disease-free survival at four years was 55 percent for allogeneic transplantation, 48 percent for autologous transplantation, and 30 percent for intensive chemotherapy. However, the overall survival after complete remission was similar in the three groups, since more patients who relapsed after a second course of intensive chemotherapy had a response to subsequent autologous bone marrow transplantation. Other differences were also observed, especially with regard to hematopoietic recovery (it occurred later after autologous transplantation) and the duration of hospitalization (it was longer with bone marrow transplantation). CONCLUSIONS: Autologous as well as allogeneic bone marrow transplantation results in better disease-free survival than intensive consolidation chemotherapy with high-dose cytarabine and daunorubicin. Transplantation soon after a relapse or during a second complete remission might also be appropriate.
Adolescent↗
An autopsy study of systemic fungal infections in patients with hematologic malignancies.
The aim of this study was to determine the incidence of fungal infections detected on autopsy in a group of 40 patients with hematologic malignancies treated with intensive chemotherapy or bone marrow transplantation, and to evaluate the risk factors for fungal infections. A control group included 38 patients with nonhematologic diseases and without granulocytopenia but with at least one of the known risk factors for fungal infections. Standard histopathological and microbiological methods were used. A higher incidence of invasive fungal infections was found in patients with hematologic malignancies as compared to the control group (p < 0.01). The predominant causes of fungal infections were Candida albicans and Aspergillus spp. The incidence of fungal infections caused by Aspergillus was higher (p < 0.05) in patients with hematologic malignancies than in the control group. The independent risk factors for fungal infections were fungal colonization, number of antibiotics and duration of antibiotic therapy, duration of fever and skin rash. A higher proportion of fungal infections was diagnosed on autopsy than during the patients' life (p < 0.01).
Adolescent↗
Autologous bone marrow transplantation for haematological malignancies--experiences of the centre of Zagreb.
From April 1988 to May 1993, 71 patients (32 acute myelogenous leukaemia [AML], 24 acute lymphoblastic leukaemia [ALL], 7 Hodgkin's disease [HD], 5 non-Hodgkin lymphoma [NHL], 2 neuroblastoma, 1 chronic myelogenous leukaemia [CML]) were treated with myeloablative therapy followed by reinfusion of cryopreserved autologous bone marrow (ABMT). The majority of patients with acute leukaemia were in first complete remission (CR), while 11 AML patients and 9 ALL patients were in advanced stage of the disease (> I CR or relapse). The BM was reinfused without purging. The conditioning regimen for all ALL and proportion of AML patients consisted of cyclophosphamide (CY) 120 mg/kg and fractionated total body irradiation (TB) in a total dose of 12 Gy. 18 AML patients received busulfan 16 mg/kg instead of TBI. Leukaemia-free survival (LFS) for first CR AML patients was 48% at 43 months with the median follow-up of 17 months. Probability of relapse was 44%. LFS for advanced AML was only 9% and the probability of relapse 89%. LFS for first CR ALL patients was 72% at 53 months with the median follow-up of 15 months, while probability of relapse was only 23%. For advanced ALL, LFS was 32% at 33 months and probability of relapse 64%. Probability of toxic death for first CR patients was 11%. We found a predictive value of viability testing and in vitro CFU-GM assay for haematologic recovery after ABMT. We conclude that ABMT with cryopreserved BM is a relatively safe method for consolidation therapy of AL. The results of treatment are encouraging.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
High incidence of conservative RAS mutations in acute myeloid leukemia.
RAS mutations are found in about 25% of acute myeloid leukemia (AML) cases. The importance of these changes is unknown. If RAS mutations confer growth advantage to leukemia subclones in which they emerge, substantially more nonconservative than conservative mutations should be found. The incidence of conservative mutations was not reported previously. We sequenced N-RAS and K-RAS codons 12 and 13 and N-RAS codon 61 in 20 subjects with newly diagnosed AML. Four nonconservative N-RAS mutations and 4 conservative K-RAS mutations were found. There were no differences between subjects with AML and nonconservative RAS mutations and those with conservative or without RAS mutations. Additional studies are needed to examine the incidence of conservative RAS mutations in subjects with AML.
Acute Disease↗
EORTC-GIMEMA AML8 protocol. A phase III study on autologous bone-marrow transplantation in acute myelogenous leukemia (AML).
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Bone Marrow Transplantation↗