British Journal of Haematology
1365-2141
0007-1048
Anh Quốc
Cơ quản chủ quản: Wiley-Blackwell Publishing Ltd , WILEY
Lĩnh vực:
Hematology
Các bài báo tiêu biểu
Primary analysis of JUMP, a phase 3b, expanded‐access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis, including those with low platelet counts Summary Ruxolitinib is a potent Janus kinase (JAK) 1/JAK2 inhibitor approved for the treatment of myelofibrosis (MF). Ruxolitinib was assessed in JUMP, a large (N = 2233), phase 3b, expanded‐access study in MF in countries without access to ruxolitinib outside a clinical trial, which included patients with low platelet counts (<100 × 109 /l) and patients without splenomegaly – populations that have not been extensively studied. The most common adverse events (AEs) were anaemia and thrombocytopenia, but they rarely led to discontinuation (overall, 5·4%; low‐platelet cohort, 12·3%). As expected, rates of worsening thrombocytopenia were higher in the low‐platelet cohort (all grades, 73·2% vs. 53·5% overall); rates of anaemia were similar (all grades, 52·9% vs. 59·5%). Non‐haematologic AEs, including infections, were mainly grade 1/2. Overall, ruxolitinib led to meaningful reductions in spleen length and symptoms, including in patients with low platelet counts, and symptom improvements in patients without splenomegaly. In this trial, the largest study of ruxolitinib in patients with MF to date, the safety profile was consistent with previous reports, with no new safety concerns identified. This study confirms findings from the COMFORT studies and supports the use of ruxolitinib in patients with platelet counts of 50–100 × 109 /l. (ClinicalTrials.gov identifier NCT01493414).
Tập 189 Số 5 - Trang 888-903 - 2020
The efficacy and safety of continued hydroxycarbamide therapy versus switching to ruxolitinib in patients with polycythaemia vera: a randomized, double‐blind, double‐dummy, symptom study (RELIEF) Summary The randomized, double‐blind, double‐dummy, phase 3b RELIEF trial evaluated polycythaemia vera (PV )‐related symptoms in patients who were well controlled with a stable dose of hydroxycarbamide (also termed hydroxyurea) but reported PV ‐related symptoms. Patients were randomized 1:1 to ruxolitinib 10 mg BID (n = 54) or hydroxycarbamide (prerandomization dose/schedule; n = 56); crossover to ruxolitinib was permitted after Week 16. The primary endpoint, ≥50% improvement from baseline in myeloproliferative neoplasm ‐symptom assessment form total symptom score cytokine symptom cluster (TSS ‐C; sum of tiredness, itching, muscle aches, night sweats, and sweats while awake) at Week 16, was achieved by 43·4% vs. 29·6% of ruxolitinib‐ and hydroxycarbamide‐treated patients, respectively (odds ratio, 1·82; 95% confidence interval, 0·82–4·04; P = 0·139). The primary endpoint was achieved by 34% of a subgroup who maintained their hydroxycarbamide dose from baseline to Weeks 13–16. In a post hoc analysis, the primary endpoint was achieved by more patients with stable screening‐to‐baseline TSS ‐C scores (ratio ≤ 2) receiving ruxolitinib than hydroxycarbamide (47·4% vs. 25·0%; P = 0·0346). Ruxolitinib treatment after unblinding was associated with continued symptom score improvements. Adverse events were primarily grades 1/2 with no unexpected safety signals. Ruxolitinib was associated with a nonsignificant trend towards improved PV ‐related symptoms versus hydroxycarbamide, although an unexpectedly large proportion of patients who maintained their hydroxycarbamide dose reported symptom improvement.
Tập 176 Số 1 - Trang 76-85 - 2017
The new ID‐heparin/PF4 antibody test for rapid detection of heparin‐induced antibodies in comparison with functional and antigenic assays Summary. Heparin‐induced thrombocytopenia (HIT) is an immune‐mediated complication of heparin treatment. Several in vitro assays are available to detect the causative HIT antibodies: functional assays, usually requiring freshly prepared platelets and immunological tests based on the enzyme‐linked immunosorbent assay (ELISA) principle. We compared a new, simple and rapid test based on the ID‐microtyping particle agglutination system with 14C‐serotonin release assay, heparin‐induced platelet activation (HIPA) test and two ELISAs. Sera from 100 confirmed HIT patients, 20 serologically negative suspected HIT patients and 20 healthy blood donors were used. The specificity and sensitivity of the new test was similar to the functional assays. Compared with the ELISAs, specificity was better at the cost of reduced sensitivity. As in all other immunological tests, HIT antibodies against less typical antigens, such as interleukin (IL)‐8 or neutrophil‐activating peptide (NAP) 2 could not be detected. Thus, although the ID‐Heparin/PF4 antibody test seems to be a quick, reliable and robust test to determine the presence of HIT antibodies, it should still be combined with a functional assay if possible. Evaluation of the test in a prospective setting as well as interlaboratory variation should be assessed as a next step.
Tập 116 Số 4 - Trang 887-891 - 2002
Pathogenicity of IgA and/or IgM antibodies to heparin–PF4 complexes in patients with heparin‐induced thrombocytopenia Antibodies to heparin–PF4 (H‐PF4) complexes have been tested and isotyped in 38 patients who developed severe heparin‐induced thrombocytopenia (type II HIT). All the patients had a platelet count < 120 × 109 /l or a reduction of >30% of the initial value, occurring at least 5 d after the onset of heparin. Thrombocytopenia, which rapidly reversed following the withdrawal of heparin, was associated with thrombosis in nine patients. Although IgG isotypes were found in most cases (n = 26), the presence of only IgM and/or IgA was observed in 12 patients, including three cases showing a thrombotic complication. Our results indicate that type II HIT may be induced by IgA and/or IgM anti‐H‐PF4 antibodies even in the absence of IgG isotypes. This finding demonstrates that platelet Fc receptors (FcγRII) are not necessarily involved in the pathogenicity of heparin‐dependent antibodies and emphasizes the major role of platelet PF4 receptors. The increased expression of the latter following a slight activation by thrombin, and the subsequent binding of IgM and IgA antibodies to H‐PF4 on the platelet surface, may directly trigger platelet activation, aggregation and thrombosis. Alternatively, thrombocytopenia could be indirectly induced through the mediation of neutrophils, monocytes and lymphocytes which expose receptors for IgA (FcαR) or IgM (FcμR). IgM–platelet complexes may also bind and activate complement, leading to platelet activation or destruction. Moreover, the reactivity of the antibodies with glycosaminoglycans–PF4 complexes present on the endothelial surface could also induce endothelial lesions and promote procoagulant activity and predisposition to thrombosis.
Tập 92 Số 4 - Trang 954-959 - 1996
Immunomodulatory effect of human adipose tissue‐derived adult stem cells: comparison with bone marrow mesenchymal stem cells Summary Like mesenchymal stem cells from bone marrow (BM‐MSCs), adipose tissue‐derived adult stem cells (ADAS cells) can differentiate into several lineages and present therapeutical potential for repairing damaged tissues. The use of allogenic stem cells can enlarge their therapeutical interest, provided that the grafted cells could be tolerated. We investigate here, for the first time, the immunosuppressive properties of ADAS cells compared with the well‐characterized immunosuppressive properties of BM‐MSCs. ADAS cells did not provoke in vitro alloreactivity of incompatible lymphocytes and, moreover, suppressed mixed lymphocyte reaction (MLR) and lymphocyte proliferative response to mitogens. The impairment of inhibition when ADAS cells and BM‐MSCs were separated from lymphocytes by a permeable membrane suggests that cell contact is required for a full inhibitory effect. Hepatocyte growth factor is secreted by both stem cells but, similar to interleukin‐10 and transforming growth factor‐β (TGF‐β ), the levels of which were undetectable in supernatants of MLR inhibited by ADAS cells or BM‐MSCs, it did not seem implicated in the stem cell suppressive effect. These findings support that ADAS cells share immunosuppressive properties with BM‐MSCs. Therefore, ADAS cell‐based reconstructive therapy could employ allogenic cells and because of their immunosuppressive properties, ADAS cells could be an alternative source to BM‐MSCs to treat allogenic conflicts.
Tập 129 Số 1 - Trang 118-129 - 2005
Characterization of the blast cell population in two neonates with Down's syndrome and transient myeloproliferative disorder Summary The phenotype and in vitro growth properties of blood and marrow blast cells detected in two neonates with Down's syndrome and a transient leukaemic picture are presented. In both patients, blast cells at diagnosis were heterogeneous and expressed predominantly megakaryocyte and erythroid markers identified by membrane fluorescence using monoclonal antibodies or ultrastructural detection of platelet peroxidase and ferritin. An additional trisomy involving chromosome 22 was detected in blast cells from one patient. Blood and marrow cells colony‐assays performed at diagnosis revealed precursors with an abnormal differentiation capacity similar to those found in acute myelogenous leukaemia colony assays. However, an unusual feature was the persistence of high numbers of precursor cells (namely erythroid) following a normal differentiation pathway. Phenotypically and cytogenetically abnormal cells spontaneously disappeared by week 4‐6, but overt relapse occurred in one patient 20 months later. These results bring strong arguments in favour of the neoplastic nature of the transient leukaemic picture observed in some neonates with Down's syndrome. Furthermore, we suggest that this disorder can be individualized as a separate entity with specific phenotypic and biological properties.
Tập 66 Số 1 - Trang 69-76 - 1987
Impact of imatinib therapy on the use of allogeneic haematopoietic progenitor cell transplantation for the treatment of chronic myeloid leukaemia Summary The discovery and approval of imatinib drastically changed the therapeutic algorithm for chronic myeloid leukaemia (CML). Imatinib is now considered the therapy of choice for patients with newly diagnosed CML, including those previously considered candidates for allogeneic haematopoietic cell transplantation (HCT). We compared numbers and types of allogeneic HCTs performed for CML in North America before and after the introduction of imatinib, and publication of the International Randomized Trial of Interferon and STI571 (IRIS) using transplants reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). The number of HCTs for CML registered with the CIBMTR in 1998 was 617; 62% were performed in first chronic phase (CP1). Only 1% of patients had received imatinib prior to transplantation. In 2003, the number of HCTs reported was 223; 44% were performed in CP1 and 77% of patients received imatinib prior to transplantation. The introduction of imatinib therapy has had a profound impact on the use of allogeneic transplantation for CML, with a marked decrease in the number of transplants for CML and an accompanying decrease in the proportion done in CP1. Most patients now receive a trial of imatinib before proceeding to HCT.
Tập 137 Số 5 - Trang 461-467 - 2007
Chimaeric anti‐CD20 monoclonal antibody (rituximab) in post‐transplant B‐lymphoproliferative disorder following stem cell transplantation in children Post‐transplant lymphoproliferative disorder (PTLD) after haemopoietic stem cell transplantation is a serious complication that occurs in 8–22% of patients with high‐risk factors. We retrospectively investigated tolerance and efficacy of humanized anti‐CD20 monoclonal antibody (rituximab) as first‐line treatment in 12 children with B‐cell PTLD. At diagnosis, eight patients had tumoral involvement. The other four patients had fever, associated with raised Epstein–Barr virus (EBV) viral load and monoclonal gammopathy. Rituximab was given at the dose of 375 mg/m2 once a week by intravenous infusion (1–9 infusions). Only 1/48 infusions was associated with a grade 2 clinical adverse event. Eight out of 12 (66%) patients responded to the treatment and were in complete remission. All patients without tumoral involvement responded to the treatment. A rapid decrease in fever within 1 week was observed in all responders. Non‐responders did not show any clinical response during the first week. Tumoral involvement and immunodepression seemed to be more marked in non‐responders. Rituximab was an effective and well‐tolerated treatment of B‐cell PTLD. Early treatment before tumoral involvement seemed to be the most effective approach. Lack of rapid response should lead to intensification of PTLD treatment. Pre‐emptive treatment should be considered and evaluated in further longitudinal multicentre studies.
Tập 115 Số 1 - Trang 112-118 - 2001