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 melphalan. METHODS:We did a phase 2 trial at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). We enrolled patients with primary refractory or relapsed myeloma who had received treatment with bortezomib, an immunomodulatory drug, or both, or who were receiving a salvage ASCT. Gemcitabine was infused at 1875 mg/m2 for 3 h for 2 days, followed by busulfan (target area under the curve 4000 μmol/L per min per day for 4 days) and melphalan (60 mg/m2 per day for 2 days). The primary endpoint of this trial was to establish the proportion of patients with measurable disease at ASCT receiving gemcitabine, busulfan, and melphalan who achieved stringent complete remission in accordance with the International Myeloma Working Group criteria. We then retrospectively compared the patients in this study with all other concurrent patients at the MD Anderson Cancer Center who were eligible for this trial but declined to participate or had no financial coverage for ASCT in a clinical trial and instead received melphalan at 200 mg/m2 intravenously over 30 min on 1 day, followed by ASCT (control group). To compare survival outcomes, we used a statistical algorithm to select a subset of patients from this control cohort who were matched in a 1-2:1 ratio with the patients in the gemcitabine, busulfan, and melphalan group by sex, age, disease status, refractory to both proteasome inhibitors and immunomodulatory imide drugs, time from diagnosis to ASCT, and cytogenetic risk. All analyses were per protocol. This is the final analysis of the clinical trial, which is registered at ClinicalTrials.gov, number NCT01237951. FINDINGS:Between Nov 30, 2010, and Dec 11, 2013, we enrolled 74 patients into the gemcitabine, busulfan, and melphalan trial. In these patients, median age was 58 years (IQR 51-62), median number of previous lines of therapy was two (2-5), 38 patients had high-risk cytogenetics, 17 were unresponsive to all previous treatments, and 32 were receiving a salvage ASCT. We identified 184 patients for the concurrent control cohort. The study patients and the concurrent controls received similar post-ASCT maintenance. Among patients with measurable disease at ASCT, 16 of 65 patients (24·6%, 95% CI 14·2-35·0) in the gemcitabine, busulfan, and melphalan group had stringent complete remission compared with 22 of 174 patients (12·6%, 10·1-15·1) in the concurrent control group (p=0·040). Median follow-up time was 36 months (IQR 30-46) in the patients receiving gemcitabine, busulfan, and melphalan and 34 months (25-53) in the matched control subset (n=111). With respect to the secondary survival endpoints, the gemcitabine, busulfan, and melphalan cohort had significantly longer median progression-free survival than the matched control cohort (15·1 months [95% CI 8·7-22·1] vs 9·3 months [8·0-10·7]) with a significantly reduced risk of progression or death (HR 0·55, 95% CI 0·38-0·81, log-rank p=0·030), as well as significantly longer median overall survival (37·5 months [26-not reached] vs 23·0 months [16·6-30·5]) and a lower risk of death (HR 0·60, 0·34-0·84, log-rank p=0·0092). For only the patients treated with gemcitabine, busulfan, and melphalan, grade 3 or worse adverse events included grade 3 mucositis (12 patients), grade 3 dermatitis (five patients), grade 3 aminotransferase elevation (seven patients), grade 3 diarrhoea (two patients), and three treatment-related deaths. One death was cardiac sudden death and two were due to sepsis. INTERPRETATION:Gemcitabine, busulfan, and melphalan is a comparatively safe and active regimen for ASCT in patients with refractory or relapsed myeloma. Better outcomes were achieved in patients who received this regimen than in a concurrent matched cohort receiving melphalan, although this will need to be confirmed in a prospective, randomised trial. FUNDING:Otsuka Pharmaceutical Development & Commercialization and US National Cancer Institute.
journal_name
Lancet Haematoljournal_title
The Lancet. Haematologyauthors
Nieto Y,Valdez BC,Pingali SR,Bassett R,Delgado R,Nguyen J,Shah N,Popat U,Jones RB,Andersson BS,Gulbis A,Ahmed S,Bashir Q,Parmar S,Patel K,Myers A,Rondon G,Orlowski RZ,Champlin R,Qazilbash Mdoi
10.1016/S2352-3026(17)30080-7subject
Has Abstractpub_date
2017-06-01 00:00:00pages
e283-e292issue
6issn
2352-3026pii
S2352-3026(17)30080-7journal_volume
4pub_type
杂志文章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: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: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: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:BACKGROUND:Ponatinib has shown efficacy in patients with refractory chronic myeloid leukaemia (CML) and in those with CML with a Thr315Ile mutation. We aimed to investigate the activity and safety of ponatinib as first-line treatment for patients with chronic-phase CML. METHODS:We did a single-arm, phase 2 trial at MD...
journal_title:The Lancet. Haematology
pub_type: 杂志文章
doi:10.1016/S2352-3026(15)00127-1
更新日期:2015-09-01 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: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: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: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::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: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: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:Bortezomib with lenalidomide and dexamethasone (VRd) is a standard regimen for the front-line treatment of multiple myeloma. Panobinostat is approved in combination with bortezomib and dexamethasone in patients with myeloma who 'have been given at least two previous regimens including bortezomib and an immun...
journal_title:The Lancet. Haematology
pub_type: 杂志文章
doi:10.1016/S2352-3026(18)30174-1
更新日期:2018-12-01 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: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: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: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: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: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: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: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: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: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: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: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::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: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: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: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
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