Abstract:
BACKGROUND:Prevention of graft-versus-host disease (GvHD) without malignant relapse is the overall goal of allogeneic haemopoietic cell transplantation (HCT). We aimed to evaluate regimens using either maraviroc, bortezomib, or post-transplantation cyclophosphamide for GvHD prophylaxis compared with controls receiving the combination of tacrolimus and methotrexate using a novel composite primary endpoint to identify the most promising intervention to be further tested in a phase 3 trial. METHODS:In this prospective multicentre phase 2 trial, adult patients aged 18-75 years who received reduced-intensity conditioning HCT were randomly assigned (1:1:1) by random block sizes to tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide (cyclophosphamide 50 mg/kg on days 3 and 4, followed by tacrolimus starting on day 5 and mycophenolate mofetil starting on day 5 at 15 mg/kg three times daily not to exceed 1 g from day 5 to day 35); tacrolimus, methotrexate, and bortezomib (bortezomib 1·3 mg/m2 intravenously on days 1, 4, and 7 after HCT); or tacrolimus, methotrexate, and maraviroc (maraviroc 300 mg orally twice daily from day -3 to day 30 after HCT). Methotrexate was administered as a 15 mg/m2 intravenous bolus on day 1 and 10 mg/m2 intravenous bolus on days 3, 6, and 11 after HCT; tacrolimus was given intravenously at a dose of 0·05 mg/kg twice daily (or oral equivalent) starting on day -3 (except the post-transplantation cyclophosphamide, as indicated), with a target level of 5-15 ng/mL. Tacrolimus was continued at least until day 90 and was tapered off by day 180. Each study group was compared separately to a contemporary non-randomised prospective cohort of patients (control group) who fulfilled the same eligibility criteria as the trial, but who were treated with tacrolimus and methotrexate at centres not participating in the trial. The primary endpoint (GvHD-free, relapse-free survival [GRFS]) was defined as the time from HCT to onset of grade 3-4 acute GvHD, chronic GvHD requiring systemic immunosuppression, disease relapse, or death. The study was analysed by modified intention to treat. The study is closed to accrual and this is the planned analysis. This trial is registered with ClinicalTrials.gov, number NCT02208037. FINDINGS:Between Nov 17, 2014, and May 18, 2016, 273 patients from 31 US centres were randomly assigned to the three study arms: 89 to tacrolimus, methotrexate, and bortezomib; 92 to tacrolimus, methotrexate, and maraviroc; 92 to tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide; and six were excluded. Between Aug 1, 2014, and Sept 14, 2016, 224 controls received tacrolimus and methotrexate. Controls were generally well matched except for more frequent comorbidities than the intervention groups and a different distribution of types of conditioning regimens used. Compared with controls, the hazard ratio for GRFS was 0·72 (90% CI 0·54-0·94; p=0·044) for tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide, 0·98 (0·76-1·27; p=0·92) for tacrolimus, methotrexate, and bortezomib, and 1·10 (0·86-1·41; p=0·49) for tacrolimus, methotrexate, and maraviroc. 238 patients experienced grade 3 or 4 toxicities: 12 (13%) had grade 3 and 67 (73%) grade 4 events with tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide; ten (11%) had grade 3 and 68 (76%) had grade 4 events with tacrolimus, methotrexate, and bortezomib; and 18 (20%) had grade 3 and 63 (68%) had grade 4 events with tacrolimus, methotrexate, and maraviroc. The most common toxicities were haematological (77 [84%] for tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide; 73 [82%] for tacrolimus, methotrexate, and bortezomib; and 78 [85%] for tacrolimus, methotrexate, and maraviroc) and cardiac (43 [47%], 44 [49%], and 43 [47%], respectively). INTERPRETATION:Tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide was the most promising intervention, yielding the best GRFS; this regimen is thus being prospectively compared with tacrolimus and methotrexate in a phase 3 randomised trial. FUNDING:US National Health, Lung, and Blood Institute; National Cancer Institute; National Institute of Allergy and Infectious Disease; and Millennium Pharmaceuticals.
journal_name
Lancet Haematoljournal_title
The Lancet. Haematologyauthors
Bolaños-Meade J,Reshef R,Fraser R,Fei M,Abhyankar S,Al-Kadhimi Z,Alousi AM,Antin JH,Arai S,Bickett K,Chen YB,Damon LE,Efebera YA,Geller NL,Giralt SA,Hari P,Holtan SG,Horowitz MM,Jacobsohn DA,Jones RJ,Liesveld JL,doi
10.1016/S2352-3026(18)30221-7subject
Has Abstractpub_date
2019-03-01 00:00:00pages
e132-e143issue
3issn
2352-3026pii
S2352-3026(18)30221-7journal_volume
6pub_type
杂志文章,随机对照试验abstract:BACKGROUND:Effective treatment of trauma-induced coagulopathy is important; however, the optimal therapy is still not known. We aimed to compare the efficacy of first-line therapy using fresh frozen plasma (FFP) or coagulation factor concentrates (CFC) for the reversal of trauma-induced coagulopathy, the arising transf...
journal_title:The Lancet. Haematology
pub_type: 杂志文章,随机对照试验
doi:10.1016/S2352-3026(17)30077-7
更新日期:2017-06-01 00:00:00
abstract:BACKGROUND:Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism. METH...
journal_title:The Lancet. Haematology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/S2352-3026(19)30219-4
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Data to inform surveillance and treatment for leukaemia predisposition syndromes are scarce and recommendations are largely based on expert opinion. This study aimed to investigate the clinical features and outcomes of patients with myelodysplastic syndrome or acute myeloid leukaemia and Shwachman-Diamond sy...
journal_title:The Lancet. Haematology
pub_type: 杂志文章,多中心研究
doi:10.1016/S2352-3026(19)30206-6
更新日期:2020-03-01 00:00:00
abstract:BACKGROUND:In patients with pulmonary embolism, right ventricular dysfunction is associated with early mortality. The Hokusai-VTE study used N-terminal pro-brain natriuretic peptide (NT-proBNP) and right to left ventricular diameter ratio on CT as indicators of right ventricular dysfunction and reported that recurrent ...
journal_title:The Lancet. Haematology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/S2352-3026(16)30080-1
更新日期:2016-09-01 00:00:00
abstract:BACKGROUND:Pegylated interferon alfa-2a is an immunomodulatory agent used to treat polycythemia vera. The durability of responses and long-term safety of this drug in patients with polycythaemia vera and essential thrombocythaemia have not been reported. Here, we present long-term efficacy and safety data from a single...
journal_title:The Lancet. Haematology
pub_type: 临床试验,杂志文章
doi:10.1016/S2352-3026(17)30030-3
更新日期:2017-04-01 00:00:00
abstract:BACKGROUND:High-dose melphalan is of little benefit as a regimen for patients with relapsed or refractory myeloma undergoing an autologous stem-cell transplant (ASCT). The poor performance of single-agent melphalan in this setting prompted us to study a new high-dose combination of infused gemcitabine, busulfan, and me...
journal_title:The Lancet. Haematology
pub_type: 杂志文章
doi:10.1016/S2352-3026(17)30080-7
更新日期:2017-06-01 00:00:00
abstract:BACKGROUND:Substantial evidence links exposure to moderate or high doses of ionising radiation, particularly in childhood, with increased risk of leukaemia. The association of leukaemia with exposure to low-dose (<100 mSv) radiation is less certain, although this is the dose range most relevant to the general populatio...
journal_title:The Lancet. Haematology
pub_type: 杂志文章
doi:10.1016/S2352-3026(18)30092-9
更新日期:2018-08-01 00:00:00
abstract::Machine learning is a branch of computer science and statistics that generates predictive or descriptive models by learning from training data rather than by being rigidly programmed. It has attracted substantial attention for its many applications in medicine, both as a catalyst for research and as a means of improvi...
journal_title:The Lancet. Haematology
pub_type: 杂志文章,评审
doi:10.1016/S2352-3026(20)30121-6
更新日期:2020-07-01 00:00:00
abstract:BACKGROUND:Studies in patients with rheumatoid arthritis have shown that the rituximab biosimilar CT-P10 (Celltrion, Incheon, South Korea) has equivalent efficacy and pharmacokinetics to rituximab. In this phase 3 study, we aimed to assess the non-inferior efficacy and pharmacokinetic equivalence of CT-P10 compared wit...
journal_title:The Lancet. Haematology
pub_type: 杂志文章,随机对照试验
doi:10.1016/S2352-3026(17)30120-5
更新日期:2017-08-01 00:00:00
abstract:BACKGROUND:Sintilimab (Innovent Biologics, Suzhou, China), a highly selective, fully humanised, monoclonal antibody, blocks the interaction between PD-1 and its ligands. We aimed to assess the activity and safety profile of sintilimab in Chinese patients with relapsed or refractory classical Hodgkin lymphoma. METHODS:...
journal_title:The Lancet. Haematology
pub_type: 杂志文章,多中心研究
doi:10.1016/S2352-3026(18)30192-3
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:High-dose methotrexate-based chemotherapy is standard for primary CNS lymphoma, but most patients relapse. High-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) is supposed to overcome the blood-brain barrier and eliminate residual disease in the CNS. We aimed to investigate the safety ...
journal_title:The Lancet. Haematology
pub_type: 杂志文章,多中心研究
doi:10.1016/S2352-3026(16)30050-3
更新日期:2016-08-01 00:00:00
abstract:BACKGROUND:Venous thromboembolism is a common complication of cancer, but the risk of developing venous thromboembolism varies greatly among individuals and depends on numerous factors, including type of cancer. We aimed to develop and externally validate a clinical prediction model for cancer-associated venous thrombo...
journal_title:The Lancet. Haematology
pub_type: 杂志文章,多中心研究
doi:10.1016/S2352-3026(18)30063-2
更新日期:2018-07-01 00:00:00
abstract:BACKGROUND:Hodgkin's lymphoma is one of the most common lymphoid neoplasms in young adults, but the low abundance of neoplastic Hodgkin/Reed-Sternberg cells in the tumour hampers the elucidation of its pathogenesis, biology, and diversity. After an incidental observation that genomic aberrations known to occur in Hodgk...
journal_title:The Lancet. Haematology
pub_type: 杂志文章
doi:10.1016/S2352-3026(14)00039-8
更新日期:2015-02-01 00:00:00
abstract:BACKGROUND:The ability of the pulmonary embolism rule-out criteria (PERC) to exclude pulmonary embolism without further testing remains debated outside the USA, especially in the population with suspected pulmonary embolism who have a high prevalence of the condition. Our main objective was to prospectively assess the ...
journal_title:The Lancet. Haematology
pub_type: 杂志文章,多中心研究
doi:10.1016/S2352-3026(17)30210-7
更新日期:2017-12-01 00:00:00
abstract:BACKGROUND:The introduction of donors other than HLA-matched siblings has been a pivotal change in stem cell transplantation. We aimed to assess the evolution of outcomes within donor groups over time and explore whether donor-recipient HLA disparity might be advantageous in patients with aggressive disease. METHODS:I...
journal_title:The Lancet. Haematology
pub_type: 杂志文章
doi:10.1016/S2352-3026(19)30158-9
更新日期:2019-11-01 00:00:00
abstract:BACKGROUND:Fit patients with mantle cell lymphoma aged 18-65 years are usually given cytarabine and rituximab-based induction regimens followed by autologous haematopoetic stem-cell transplantation (HSCT). We investigated whether post-autologous HSCT maintenance with lenalidomide improves progression-free survival in t...
journal_title:The Lancet. Haematology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/S2352-3026(20)30358-6
更新日期:2021-01-01 00:00:00
abstract:BACKGROUND:Intravenous rituximab is the standard of care in B-cell non-Hodgkin lymphoma, and is administered over 1·5-6 h. A subcutaneous formulation could reduce patients' treatment burden and improve resource utilisation in health care. We aimed to show the pharmacokinetic non-inferiority of subcutaneous rituximab to...
journal_title:The Lancet. Haematology
pub_type: 杂志文章,随机对照试验
doi:10.1016/S2352-3026(17)30078-9
更新日期:2017-06-01 00:00:00
abstract:BACKGROUND:The optimum preparative regimen for unrelated donor marrow transplantation in patients with severe aplastic anaemia remains to be established. We investigated whether the combination of fludarabine, anti-thymocyte globulin, and total body irradiation (TBI) would enable reduction of the cyclophosphamide dose ...
journal_title:The Lancet. Haematology
pub_type: 杂志文章
doi:10.1016/S2352-3026(15)00147-7
更新日期:2015-09-01 00:00:00
abstract:BACKGROUND:Multiple myeloma is one of the most common haematological malignancies in the USA and is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). We aimed to assess the association between metformin use and progression of MGUS to multiple myeloma. METHODS:We did a retrospective co...
journal_title:The Lancet. Haematology
pub_type: 杂志文章
doi:10.1016/S2352-3026(14)00037-4
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Although cytomegalovirus viral load is commonly used to guide pre-emptive therapy in the post-transplantation setting, few data are available correlating viraemia with clinical endpoints. We therefore investigated the association between cytomegalovirus viral load and mortality in the first year after haemop...
journal_title:The Lancet. Haematology
pub_type: 杂志文章
doi:10.1016/S2352-3026(15)00289-6
更新日期:2016-03-01 00:00:00
abstract::Evaluation of tolerability is increasingly relevant for patients with haematological malignancies treated with chronically administered therapies. Adverse events from these agents might affect the ability of patients to tolerate treatment over time. Conventional toxicity tables that include the incidence of high-grade...
journal_title:The Lancet. Haematology
pub_type: 杂志文章,随机对照试验
doi:10.1016/S2352-3026(20)30067-3
更新日期:2020-06-01 00:00:00
abstract:BACKGROUND:The INO-VATE study demonstrated efficacy and safety of inotuzumab ozogamicin versus standard care in adults with relapsed or refractory B-cell acute lymphoblastic leukaemia. Here, we report the frequency of, and potential risk factors for, hepatotoxicity in patients in this trial and after treatment and subs...
journal_title:The Lancet. Haematology
pub_type: 杂志文章,随机对照试验
doi:10.1016/S2352-3026(17)30103-5
更新日期:2017-08-01 00:00:00
abstract:BACKGROUND:Among the syndromes characterised by thrombotic microangiopathy, thrombotic thrombocytopenic purpura is distinguished by a severe deficiency in the ADAMTS13 enzyme. Patients with this disorder need urgent treatment with plasma exchange. Because ADAMTS13 activity testing typically requires prolonged turnaroun...
journal_title:The Lancet. Haematology
pub_type: 杂志文章
doi:10.1016/S2352-3026(17)30026-1
更新日期:2017-04-01 00:00:00
abstract:BACKGROUND:Anaemia and iron deficiency are common after post-bariatric abdominoplasty, which can involve removal of large areas of skin with associated blood loss. Because the oral absorbability of iron is reduced after bariatric surgery (through reduced intake, reduction of gastric acid secretion for conjugation of ir...
journal_title:The Lancet. Haematology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/S2352-3026(18)30071-1
更新日期:2018-07-01 00:00:00
abstract:BACKGROUND:In patients with chronic lymphocytic leukaemia, achievement of a complete response with minimal residual disease of less than 0·01% (ie, <1 chronic lymphocytic leukaemia cell per 10 000 leukocytes) in bone marrow has been associated with improved progression-free survival. We aimed to explore the activity of...
journal_title:The Lancet. Haematology
pub_type: 杂志文章,多中心研究
doi:10.1016/S2352-3026(19)30113-9
更新日期:2019-09-01 00:00:00
abstract:BACKGROUND:Mechanisms of red blood cell delivery and their contribution to the incidence of venous thromboembolism are not well understood in the clinical setting. We assessed whether red blood cell transfusion through peripherally inserted central catheters (PICCs) affects the risk of venous thromboembolism compared w...
journal_title:The Lancet. Haematology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/S2352-3026(16)30132-6
更新日期:2016-12-01 00:00:00
abstract:BACKGROUND:Gilbert's syndrome is a common inherited disorder of bilirubin metabolism, characterised by mild, unconjugated hyperbilirubinaemia. However, the effect of Gilbert's syndrome on the disposition of some drugs can lead to unexpected toxicity. We tested the hypothesis that patients undergoing myeloablative condi...
journal_title:The Lancet. Haematology
pub_type: 杂志文章
doi:10.1016/S2352-3026(16)30149-1
更新日期:2016-11-01 00:00:00
abstract:BACKGROUND:Leukoencephalopathy is observed in some children undergoing chemotherapy for acute lymphoblastic leukaemia, although its effects on long-term outcomes is unknown. This study examines the associations between acute leukoencephalopathy and neurobehavioural, neurocognitive, and brain white matter imaging outcom...
journal_title:The Lancet. Haematology
pub_type: 杂志文章
doi:10.1016/S2352-3026(16)30110-7
更新日期:2016-10-01 00:00:00
abstract:BACKGROUND:Deep vein thrombosis (DVT) and pulmonary embolism are collectively known as venous thromboembolism (VTE), which is a common vascular disease and a major cause of morbidity and mortality worldwide. We compare effectiveness and safety of rivaroxaban versus warfarin in a prospective cohort of routine care patie...
journal_title:The Lancet. Haematology
pub_type: 杂志文章
doi:10.1016/S2352-3026(17)30054-6
更新日期:2017-05-01 00:00:00
abstract:BACKGROUND:Panobinostat (a pan histone deacetylase inhibitor) is approved in combination with bortezomib and dexamethasone for patients with relapsed multiple myeloma who have received two or more previous lines of therapy. We aimed to improve the safety of this combination and investigate efficacy by incorporating low...
journal_title:The Lancet. Haematology
pub_type: 杂志文章,多中心研究
doi:10.1016/S2352-3026(16)30165-X
更新日期:2016-12-01 00:00:00