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1.
Long‐term results of high‐dose imatinib in children and adolescents with chronic myeloid leukaemia in chronic phase: the Italian experience
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Fiorina Giona Maria C. Putti Concetta Micalizzi Giuseppe Menna Maria L. Moleti Nicola Santoro Grazia Iaria Saverio Ladogana Roberta Burnelli Caterina Consarino Stefania Varotto Francesca Tucci Chiara Messina Mauro Nanni Daniela Diverio Andrea Biondi Andrea Pession Franco Locatelli Alfonso Piciocchi Enrico Gottardi Giuseppe Saglio Robin Foà 《British journal of haematology》2015,170(3):398-407
Imatinib mesylate (IM) is used for the management of childhood chronic myeloid leukaemia (CML). The most effective dosage of IM and its long‐term efficacy in children are not well defined. The purpose of this multicentre study is to report on the long‐term results of high‐dose IM (340 mg/m2/d) in CML patients in chronic phase (CP‐CML) aged <18 years at diagnosis. A total of 47 CP‐CML patients with a median age at diagnosis of 11 years 9 months were enrolled in nine Italian centres. Complete cytogenetic response was achieved in 91·5% of the evaluable patients at a median time of 6 months. BCR‐ABL1 International Scale ≤ 0·1% (major molecular response; MMR) and ≤0·01% (molecular response; MR) at 12 months were 66·6% and 33%, respectively. During follow‐up, MMR and MR were achieved in 78·6% and 61% of children, respectively. IM was safely discontinued in 3 long‐term treated children with a durable MR. Twelve patients (eight cytogenetic/molecular responders) underwent stem cell transplantation. The progression‐free survival probabilities at 96 months for responding patients who continued IM and for those transplanted were 60% and 50%, respectively. After a median follow‐up of 52 months (range 3–146), all patients are alive . High‐dose IM is a long‐term effective therapy in children and adolescents with CP‐CML. 相似文献
2.
Tim H. Brümmendorf Jorge E. Cortes Hanna J. Khoury Hagop M. Kantarjian Dong‐Wook Kim Philippe Schafhausen Maureen G. Conlan Mark Shapiro Kathleen Turnbull Eric Leip Carlo Gambacorti‐Passerini Jeff H. Lipton 《British journal of haematology》2016,172(1):97-110
The dual SRC/ABL1 tyrosine kinase inhibitor bosutinib is indicated for adults with Ph+ chronic myeloid leukaemia (CML) resistant/intolerant to prior therapy. This analysis of an ongoing phase 1/2 study (NCT00261846) assessed effects of baseline patient characteristics on long‐term efficacy and safety of bosutinib 500 mg/day in adults with imatinib (IM)‐resistant (IM‐R; n = 196)/IM‐intolerant (IM‐I; n = 90) chronic phase (CP) CML. Median treatment duration was 24·8 months (median follow‐up, 43·6 months). Cumulative major cytogenetic response (MCyR) rate [95% confidence interval (CI)], was 59% (53–65%); Kaplan‐Meier (KM) probability of maintaining MCyR at 4 years was 75% (66–81%). Cumulative incidence of on‐treatment progression/death at 4 years was 19% (95% CI, 15–24%); KM 2‐year overall survival was 91% (87–94%). Significant baseline predictors of both MCyR and complete cytogenetic response (newly attained/maintained from baseline) at 3 and 6 months included prior IM cytogenetic response, baseline MCyR, prior interferon therapy and <6 months duration from diagnosis to IM treatment initiation and no interferon treatment before IM. The most common adverse event (AE) was diarrhoea (86%). Baseline bosutinib‐sensitive BCR‐ABL1 mutation was the only significant predictor of grade 3/4 diarrhoea; no significant predictors were identified for liver‐related AEs. Bosutinib demonstrates durable efficacy and manageable toxicity in IM‐R/IM‐I CP‐CML patients. 相似文献
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Dennis D. Kim Honggi Lee Suzanne Kamel‐Reid Jeffrey H. Lipton 《British journal of haematology》2013,160(5):630-639
5.
Bosutinib versus imatinib in newly diagnosed chronic‐phase chronic myeloid leukaemia: results from the 24‐month follow‐up of the BELA trial
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Tim H. Brümmendorf Jorge E. Cortes Cármino Antonio de Souza Francois Guilhot Ladan Duvillié Dmitri Pavlov Karïn Gogat Athena M. Countouriotis Carlo Gambacorti‐Passerini 《British journal of haematology》2015,168(1):69-81
Bosutinib is an oral, dual SRC/ABL1 tyrosine kinase inhibitor for resistant/intolerant chronic myeloid leukaemia (CML). We assessed the efficacy and safety of bosutinib 500 mg/d (n = 250) versus imatinib 400 mg/d (n = 252) after >24 months from accrual completion in newly diagnosed chronic phase (CP)‐CML (Bosutinib Efficacy and Safety in Newly Diagnosed CML trial [BELA]). Cumulative complete cytogenetic response (CCyR) rates by 24 months were similar (bosutinib, 79%; imatinib, 80%); cumulative major molecular response (MMR) rates were 59% for bosutinib and 49% for imatinib. Responses were durable; 151/197 vs. 172/204 and 125/153 vs. 117/131 responders remained on treatment and maintained CCyR and MMR, respectively. Since the 12‐month primary analysis, no new accelerated‐/blast‐phase transformations occurred with bosutinib; four occurred with imatinib. Early response (BCR‐ABL1/ABL1 ≤ 10%, 3 months) was associated with better CCyR and MMR rates by 12 and 24 months (both arms). Gastrointestinal events and liver function test elevations were more common, and neutropenia, musculoskeletal events and oedema were less common with bosutinib. Discontinuations due to adverse events were more common with bosutinib versus imatinib (most commonly alanine aminotransferase elevation: 4% vs. <1%); most occurred within the first 12 months. Cardiovascular adverse events were similar in both arms. Bosutinib continues to demonstrate good efficacy and manageable tolerability in newly diagnosed CP‐CML patients. 相似文献
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Analysis of 2013 European LeukaemiaNet (ELN) responses in chronic phase CML across four frontline TKI modalities and impact on clinical outcomes
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Preetesh Jain Hagop Kantarjian Koji Sasaki Elias Jabbour Jyothsna Dasarathula Graciela Nogueras Gonzalez Srdan Verstovsek Gautam Borthakur William Wierda Tapan Kadia Sara Dellasala Sherry Pierce Farhad Ravandi Susan O'Brien Jorge Cortes 《British journal of haematology》2016,173(1):114-126
This study assessed the relevance of 2013 European LeukaemiaNet (ELN) response categories on patients treated with common frontline tyrosine kinase inhibitors (TKI) in chronic myeloid leukaemia in chronic phase (CML‐CP). Four hundred and eighty‐seven patients treated with imatinib (400 mg; IM 400, n = 70; 800 mg; IM800, n = 201), dasatinib (n = 107) or nilotinib (n = 109) were analysed. Intention to treat (ITT) analysis indicated that the proportion of patients falling into optimal, warning and failure ELN categories were 89%, 6%, 6% at 3 months, 78%, 17% and 6% at 6 months, and 75%, 13% and 13% at 12 months, respectively. Rates of optimal response at 3 months were 75% for IM400, 90% for IM800, 89% for dasatinib and 97% for nilotinib; 41%, 80%, 86% and 89% at 6 months; and 47%, 77%, 76% and 87% at 12 months, respectively. Patients achieving optimal response had longer eventfree (EFS), failurefree (FFS), transformationfree (TFS) and overall survival (OS) compared to warning and failure responses at all‐time points. Treatment with imatinib 800, dasatinib or nilotinib predicted for achieving an optimal response. Optimal response predicted for significantly longer EFS, FFS, TFS and OS at 3, 6 and 12 months, irrespective of the TKI modality used. ELN response categories reliably predicted outcomes in CML patients receiving commonly used TKIs. 相似文献
8.
Camilla Nielsen Henrik S. Birgens Brge G. Nordestgaard Stig E. Bojesen 《British journal of haematology》2013,160(1):70-79
The JAK2 V617F somatic mutation is present in the majority of patients with myeloproliferative cancer (polycythaemia vera, essential thrombocytosis, and primary myelofibrosis). However, the diagnostic value of the JAK2 V617F somatic mutation for myeloproliferative cancer in the general population is unknown. We examined this question in 49 488 individuals from the Copenhagen General Population Study. We also examined the association between JAK2 V617F somatic mutation, rs10974944 germline genotype, haematological phenotype, any cancer, haematological cancer, myeloproliferative cancer, ischaemic heart disease, and venous thromboembolism. The JAK2 V617F somatic mutation was present in 0·1% (n = 68), increasing across rs10974944 germline genotypes (P‐trend = 0·001). JAK2 V617F somatic mutation positives versus negatives had higher erythrocyte (P = 2 × 10−5), thrombocyte (P = 2 × 10−16), and leucocyte (P = 4 × 10−9) counts, and had 2·7‐/2·5‐fold risk of cancer (prevalent/incident), 44‐/28‐fold risk of haematological cancer, 221‐/97‐fold risk of myeloproliferative cancer, 2·2‐/1·2‐fold risk of ischaemic heart disease, and 3·1‐/1·0‐fold risk of venous thromboembolism. By combining conventional haematological parameters with a test for the JAK2 V617F somatic mutation, myelo;?>proliferative cancer could be identified or ruled out with a sensitivity of 47–100% and a specificity of 98–100%. In conclusion, in the general population the JAK2 V617F somatic mutation has a high diagnostic value for myeloproliferative cancer when combined with conventional haematological parameters. 相似文献
9.
Post‐transplantation cyclophosphamide versus conventional graft‐versus‐host disease prophylaxis in mismatched unrelated donor haematopoietic cell transplantation
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Rohtesh S. Mehta Rima M. Saliba Julianne Chen Gabriela Rondon Aimee E. Hammerstrom Amin Alousi Muzaffar Qazilbash Qaiser Bashir Sairah Ahmed Uday Popat Chitra Hosing Issa Khouri Elizabeth J. Shpall Richard E. Champlin Stefan O. Ciurea 《British journal of haematology》2016,173(3):444-455
Post‐transplantation cyclophosphamide (PTCy) is an effective strategy to prevent graft‐versus‐host disease (GVHD) after haploidentical haematopoietic cell transplantation (HCT). We determined the efficacy of PTCy‐based GVHD prophylaxis in human leucocyte antigen (HLA)‐mismatched unrelated donor (MMUD) HCT. We analysed 113 adult patients with high‐risk haematological malignancies who underwent one‐antigen MMUD transplantation between 2009 and 2013. Of these, 41 patients received PTCy, tacrolimus and mycophenolate mofetil (MMF) for GVHD prophylaxis; 72 patients received conventional prophylaxis with anti‐thymocyte globulin, tacrolimus and methotrexate. Graft source was primarily bone marrow (83% PTCy vs. 63% conventional group). Incidence of grade II–IV (37% vs. 36%, P = 0·8) and grade III–IV (17% vs. 12%, P = 0·5) acute GVHD was similar at day 100. However, the incidence of grade II‐IV acute GVHD by day 30 was significantly lower in the PTCy group (0% vs. 15%, P = 0·01). Median time to neutrophil (18 days vs. 12 days, P < 0·001) and platelet (25·5 days vs. 18 days, P = 0·05) engraftment was prolonged in PTCy group. Rates of graft failure, chronic GVHD, 2‐year non‐relapse mortality, relapse, progression‐free survival or overall survival were similar. Our results demonstrate that PTCy, tacrolimus and MMF for GVHD prophylaxis is safe and produced similar results as conventional prophylaxis in patients with one antigen HLA‐MMUD HCT. 相似文献
10.
Atsushi Manabe Tomohiro Saito Daisuke Hasegawa Keiichi Isoyama Akitoshi Kinoshita Miho Maeda Yuri Okimoto Michiko Kajiwara Takashi Kaneko Kanji Sugita Akira Kikuchi Masahiro Tsuchida Akira Ohara 《British journal of haematology》2014,164(3):376-383
The Tokyo Children's Cancer Study Group conducted a randomized controlled study to evaluate the effect of experimental early intensification using high‐dose cytarabine and L‐asparaginase in paediatric intermediate‐risk (IR) acute lymphoblastic leukaemia (ALL). A total of 310 IR ALL patients were randomized to receive either experimental early intensification (n = 156) or standard early intensification including standard‐dose cytarabine arm (n = 154) after induction therapy. The experimental arm consisted of high‐dose cytarabine and L‐asparaginase, while the standard arm consisted of standard‐dose cytarabine, oral 6‐mercaptopurine and cyclophosphamide. The probabilities of event‐free survival at 8 years in the experimental and standard arms were 72·3 ± 3·7% and 77·5 ± 3·5%, respectively (P = 0·32). The 8‐year overall survival rates for these two arms were 85·0 ± 3·0% and 86·9 ± 2·8%, respectively (P = 0·72). The frequency of infectious events was significantly higher in the experimental arm (66·4%) than in the standard arm (24·6%) (P < 0·001). In conclusion, experimental early intensification including high‐dose cytarabine followed by L‐asparaginase had no advantage over standard early intensification in paediatric IR ALL patients. 相似文献
11.
Victor H. Jimenez‐Zepeda Norman Franke Donna E. Reece Suzanne Trudel Christine Chen Diego H. Delgado Andrew Winter Joseph R. Mikhael Rodger Tiedemann Vishal Kukreti 《British journal of haematology》2014,164(5):722-728
Autologous stem‐cell transplant has been widely used to treat patients with AL amyloidosis. However, transplant‐related mortality rates are high, and a recent randomized trial suggested that non‐transplant regimens produced comparable results with less toxicity. In order to define the role of patient selection in stem cell transplantation, we evaluated 78 consecutive AL amyloidosis patients transplanted at our centre. Transplant‐related mortality occurred in 11·5%. Complete haematological response and organ response were achieved in 56% and 60%. Median overall survival was significantly lower for patients with brain‐type natriuretic peptide (BNP) >300 pg/ml (17·5 months vs. not‐reached) (P = 0·0004), troponin‐I >0·07 ng/ml (13·5 months vs. not‐reached) (P = 0·00001) and those not achieving a complete haematological response (88 months vs. not‐reached) (P = 0·0345); high BNP and troponin‐I were the most important predictive factors in a multivariate analysis. Based on this study, patients with BNP <300 pg/ml and/or normal levels of troponin‐I should be considered transplant candidates. 相似文献
12.
Aurélien Delluc Aurélie Rousseau Mickael Le Galudec Olivier Canceil Barry Woodhams Sylvie Etienne Michel Walter Dominique Mottier Patrick Van Dreden Karine Lacut 《British journal of haematology》2014,164(2):272-279
Past reports have suggested that antiphospholipid (aPL) antibodies may emerge as a response to antipsychotics treatment, as a high prevalence of aPL antibodies in antipsychotics users has been observed. However, no control group of non‐medicated psychiatric patients was included in these reports. In a cross sectional study we determined the prevalence of aPL antibodies in 333 psychiatric inpatients. We compared the proportions of positive aPL antibodytests between users and non‐users of antipsychotics with adjustments for potential confounders. The proportion of antipsychotics users carrying at least one aPL antibody ranged from 10·8% to 27·0% compared with 6·8% to 27·2% in non‐users (P = 0·24, P = 0·24) depending on the method of detection of lupus anticoagulant (LA). The prevalence of LA detected by dilute Russell viper venom time or partial thromboplastin time‐LA was not different between antipsychotics users and non‐users (8·1% vs. 5·4%, P = 0·53 and 18·4% vs. 18·2%, P = 0·22), as well as the prevalence of IgM and IgG anti‐β2‐glycoprotein‐I antibodies, IgM and IgG anti‐cardiolipin antibodies(3·8% vs. 2·0%, P = 0·75, 0·0% vs. 0·0%, P = not applicable, 1·1 vs. 1·4%, P = 0·91, 2·7% vs. 3·4%, P = 0·71). In conclusion, aPL antibodies were frequently found in patients with psychiatric diseases and no significant increase in the prevalence of aPL antibodies was observed in antipsychotics users. 相似文献
13.
Characteristics and outcomes of patients with multiple myeloma aged 21–40 years versus 41–60 years: a multi‐institutional case‐control study
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Artur Jurczyszyn Hareth Nahi Irit Avivi Alessandro Gozzetti Ruben Niesvizky Sujitha Yadlapati David S. Jayabalan Paweł Robak Tomas Pika Kristian T. Andersen Leo Rasche Krzysztof Mądry Dariusz Woszczyk Małgorzata Raźny Lidia Usnarska‐Zubkiewicz Wanda Knopińska‐Posłuszny Małgorzata Wojciechowska Renata Guzicka‐Kazimierczak Monika Joks Sebastian Grosicki Hanna Ciepłuch Marcin Rymko David H. Vesole Jorge J. Castillo 《British journal of haematology》2016,175(5):884-891
We compared the outcomes of multiple myeloma (MM) patients aged 21–40 and 41–60 years in the novel agent era. This case‐control study included 1089 patients between 2000 and 2015. Cases and controls were matched for sex, International Staging System (ISS) stage and institution. There were 173 patients in the younger group and 916 patients in the older group. Younger patients presented with a higher incidence of lytic lesions (82% vs. 72%; P = 0·04) and high‐risk cytogenetic abnormalities (83% vs. 68%; P = 0·007), but lower rate of elevated lactate dehydrogenase (21% vs. 44%; P < 0·001). Five‐ and 10‐year overall survival (OS) in younger versus older patients was 83% vs. 67% and 56% vs. 39%, respectively (P < 0·001). Similar results were seen when studying the subset of 780 patients who underwent autologous transplantation. Younger patients with ISS stage 1 had a better OS than older patients (P < 0·001). There was no survival difference between younger and older patients with ISS stage 2 or 3. Younger MM patients, aged 21–40 years, treated in the era of novel agents have a better OS than their counterparts aged 41–60 years, but the survival advantage observed in younger patients was lost in more advanced stages of MM. 相似文献
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《British journal of haematology》2017,177(4):567-577
There is limited information regarding the immunological predictors of post‐allogeneic stem cell transplant (alloSCT) outcome in chronic lymphocytic leukaemia (CLL), such as mixed T‐cell chimerism. We analysed 143 consecutive patients with relapsed/refractory CLL, transplanted between 2000 and 2012, to determine the prognostic relevance of mixed chimerism post‐alloSCT and the ability of post‐transplant immunomodulation to treat relapse. Mixed T‐cell chimerism occurred in 50% of patients at 3 months and 43% at 6 months post‐alloSCT; upon 3‐ and 6‐month landmark analysis, this was associated with inferior progression‐free survival (PFS) [Hazard ratio (HR) 1·93, P = 0·003 and HR 2·58, P < 0·001] and survival (HR 1·66, P = 0·05 and HR 2·17, P < 0·001), independent of baseline patient characteristics, and a lower rate of grade II–IV acute graft‐versus‐host disease (GHVD) (16% vs. 52%, P < 0·001). Thirty‐three patients were treated with immunomodulation for relapse post‐alloSCT (immunosuppression withdrawal, n = 6, donor lymphocyte infusion, n = 27); 17 achieved complete response (CR), which predicted superior PFS (53 months vs. 10 months, P < 0·001) and survival (117 months vs. 30 months, P = 0·006). Relapsed patients with mixed chimerism had inferior response to immunomodulation; conversion to full donor chimerism was highly correlated both with CR and with the development of severe acute GVHD, which was fatal in 3/8 patients. Novel therapeutic strategies are required for patients with mixed T‐cell chimerism post‐alloSCT for CLL. 相似文献
15.
Haematopoietic cell transplantation with and without sorafenib maintenance for patients with FLT3‐ITD acute myeloid leukaemia in first complete remission
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Andrew M. Brunner Shuli Li Amir T. Fathi Martha Wadleigh Vincent T. Ho Kerry Collier Christine Connolly Karen K. Ballen Corey S. Cutler Bimalangshu R. Dey Areej El‐Jawahri Sarah Nikiforow Steven L. McAfee John Koreth Daniel J. Deangelo Edwin P. Alyea Joseph H. Antin Thomas R. Spitzer Richard M. Stone Robert J. Soiffer Yi‐Bin Chen 《British journal of haematology》2016,175(3):496-504
We performed a retrospective study analysing the effect of sorafenib, an oral fms‐Like Tyrosine Kinase 3 (FLT3)/multikinase inhibitor, as post‐transplant maintenance in adult patients with FLT3‐internal tandem duplication (ITD) acute myeloid leukaemia (AML). We identified consecutive patients with FLT3‐ITD AML diagnosed between 2008 and 2014 who received haematopoietic cell transplantation (HCT) in first complete remission (CR1). Post‐HCT initiation of sorafenib (yes/no) was evaluated as a time‐varying covariate in the overall survival/progression‐free survival (OS/PFS) analysis and we performed a landmark analysis of controls alive without relapse at the median date of sorafenib initiation. We identified 26 sorafenib patients and 55 controls. Median follow‐up was 27·2 months post‐HCT for sorafenib survivors, and 38·4 months for controls (P = 0·021). The median time to initiating sorafenib was 68 days post‐HCT; 43 controls were alive without relapse at this cut‐off. Sorafenib patients had improved 2‐year OS in the d+68 landmark analysis (81% vs. 62%, P = 0·029). Sorafenib was associated with improved 2‐year PFS (82% vs. 53%, P = 0·0081) and lower 2‐year cumulative incidence of relapse (8·2% vs. 37·7%, P = 0·0077). In multivariate analysis, sorafenib significantly improved OS [Hazard ratio (HR) 0·26, P = 0·021] and PFS (HR 0·25, P = 0·016). There was no difference in 2‐year non‐relapse mortality (9·8% vs. 9·3%, P = 0·82) or 1‐year chronic graft‐versus‐host disease (55·5% vs. 37·2%, P = 0·28). These findings suggest potential benefit of post‐HCT sorafenib in FLT3‐ITD AML, and support further evaluation of post‐HCT FLT3 inhibition. 相似文献
16.
High‐dose CD20‐targeted radioimmunotherapy‐based autologous transplantation improves outcomes for persistent mantle cell lymphoma
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Ryan D. Cassaday Philip A. Stevenson Theodore A. Gooley Thomas R. Chauncey John M. Pagel Joseph Rajendran Brian G. Till Mary Philip Johnnie J. Orozco William I. Bensinger Leona A. Holmberg Andrei R. Shustov Damian J. Green Stephen D. Smith Edward N. Libby David G. Maloney Oliver W. Press Ajay K. Gopal 《British journal of haematology》2015,171(5):788-797
Autologous stem cell transplant (ASCT) can improve outcomes for mantle cell lymphoma (MCL) patients, yet relapses are frequent. We hypothesized that high‐dose anti‐CD20 radioimmunotherapy (RIT)‐based conditioning could improve results in this setting. We thus assessed 162 consecutive patients with MCL at our centre undergoing ASCT following high‐dose RIT‐based (n = 61) or standard (n = 101) conditioning. RIT patients were less likely to be in first remission (48% vs. 72%; P = 0·002), be in complete remission (CR) (26% vs. 61%; P < 0·001) and have chemosensitive disease (84% vs. 96%; P = 0·006). RIT‐based conditioning was associated with a reduced risk of treatment failure [hazard ratio (HR) 0·40; P = 0·001] and mortality (HR 0·49; P = 0·01) after adjusting for these imbalances. This difference increased as disease status worsened (from CR to partial remission to stable/progressive disease), with respective HRs of 1·14, 0·53 and 0·04 for mortality, and 0·66, 0·36 and 0·14 for treatment failure. RIT‐based conditioning appears to improve outcome following ASCT for MCL patients unable to achieve CR after controlling for imbalances in important risk factors. These data support the further study of RIT and radiation‐based strategies in a risk‐adapted approach to ASCT for persistent MCL. 相似文献
17.
Subjects with chronic lymphocytic leukaemia‐like B‐cell clones with stereotyped B‐cell receptors frequently show MDS‐associated phenotypes on myeloid cells
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Ignacio Criado Anton W. Langerak Sergio Matarraz Antonio López Ana Balanzategui Marcos González Wendy G. Nieto Emília Cortesão Artur Paiva Alberto Orfao 《British journal of haematology》2015,168(2):258-267
An increasing body of evidence suggests the potential occurrence of antigen encounter by the cell of origin in chronic lymphocytic leukaemia (CLL) and CLL‐like monoclonal B‐cell lymphocytosis (MBL). However, the scenario in which this event might occur remains unknown. In order to gain insight into this scenario we investigated the molecular, cytogenetic and haematological features of 223 CLL‐like (n = 84) and CLL (n = 139) clones with stereotyped (n = 32) versus non‐stereotyped (n = 191) immunoglobulin heavy chain variable region (IGHV) amino acid sequences. Overall, stereotyped CLL‐like MBL and CLL clones showed a unique IGHV profile, associated with higher IGHV1 and lower IGHV3 gene family usage (P = 0·03), longer IGHV complementary determining region 3 (HCDR3) sequences (P = 0·007) and unmutated IGHV (P < 0·001) versus non‐stereotyped clones. Whilst the overall size of the stereotyped B‐cell clones in peripheral blood did not appear to be associated with the CLL‐related cytogenetic profile of B‐cells (P > 0·05), it did show a significant association with the presence of myelodysplastic syndrome (MDS)‐associated immunophenotypes on peripheral blood neutrophils and/or monocytes (P = 0·01). Altogether our results point to the potential involvement of different selection forces in the expansion of stereotyped vs. non‐stereotyped CLL and CLL‐like MBL clones, the former being potentially favoured by an underlying altered haematopoiesis. 相似文献
18.
Dragana Milojkovic Nicholas C. P. Cross Sahra Ali Jenny Byrne Gavin Campbell Fiona L. Dignan Mark Drummond Brian Huntly Scott Marshall Mary Frances McMullin Pratap Neelakantan Manoj Raghavan Muttuswamy Sivakumaran Jane Tighe Farooq Wandroo Fenella Willis Fiona Glen Louise Fildes Sarah J. Collington Jacqueline Ryan Richard E. Clark Adam J. Mead 《British journal of haematology》2021,192(1):62-74
Management of chronic myeloid leukaemia (CML) has recently undergone dramatic changes, prompting the European LeukemiaNet (ELN) to issue recommendations in 2013; however, it remains unclear whether real‐world CML management is consistent with these goals. We report results of UK TARGET CML, a retrospective observational study of 257 patients with chronic‐phase CML who had been prescribed a first‐line TKI between 2013 and 2017, most of whom received first‐line imatinib (n = 203). Although 44% of patients required ≥1 change of TKI, these real‐world data revealed that molecular assessments were frequently missed, 23% of patients with ELN‐defined treatment failure did not switch TKI, and kinase domain mutation analysis was performed in only 49% of patients who switched TKI for resistance. Major molecular response (MMR; BCR‐ABL1IS ≤0·1%) and deep molecular response (DMR; BCR‐ABL1IS ≤0·01%) were observed in 50% and 29%, respectively, of patients treated with first‐line imatinib, and 63% and 54%, respectively, receiving a second‐generation TKI first line. MMR and DMR were also observed in 77% and 44% of evaluable patients with ≥13 months follow‐up, receiving a second‐generation TKI second line. We found little evidence that cardiovascular risk factors were considered during TKI management. These findings highlight key areas for improvement in providing optimal care to patients with CML. 相似文献
19.
Peripheral blood late mixed chimerism in leucocyte subpopulations following allogeneic stem cell transplantation for childhood malignancies: does it matter?
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Herbert Pichler Gerhard Fritsch Margit König Helga Daxberger Evgenia Glogova Ulrike Pötschger Sabine Breuer Anita Lawitschka Ece D. Güclü Susanne Karlhuber Wolfgang Holter Oskar A. Haas Thomas Lion Susanne Matthes‐Martin 《British journal of haematology》2016,173(6):905-917
The impact of persistent mixed chimerism (MC) after haematopoietic stem cell transplantation (HSCT) remains unclarified. We investigated the incidence of MC in peripheral blood beyond day +50 after HSCT and its impact on rejection, chronic graft‐versus‐host disease (c‐GvHD) and relapse in 161 children receiving allogeneic HSCT for haematological malignancies. The 1‐year incidence of late MC was 26%. Spontaneous conversion to complete donor chimerism (CC) occurred in 43% of patients as compared to 62% after donor lymphocyte infusions. No graft rejection occurred. The 1‐year incidence of c‐GvHD was 20 ± 7% for MC, and 18 ± 4% for CC patients (P = 0·734). The 3‐year cumulative incidence of relapse (CIR) according to chimerism status at days +50 and +100 was 22 ± 4% for CC patients vs. 22 ± 8% for MC patients (day +50; P = 0·935) and 21 ± 4% vs. 20 ± 7% (day +100; P = 0·907). Three‐year CIRs in patients with persistent MC and patients with CC/limited MC were comparable (8 ± 7% vs. 19 ± 4%; P = 0·960). HSCT for acute leukaemia or myelodysplastic syndrome as secondary malignancies (hazard ratio (HR) 4·7; P = 0·008), for AML (HR 3·0; P = 0·02) and from mismatched donors (HR 3·1; P = 0·03) were independent factors associated with relapse. Our data suggest that late MC neither protects from c‐GvHD nor does it reliably predict impending disease relapse. 相似文献
20.
Single versus tandem high‐dose melphalan followed by autologous blood stem cell transplantation in multiple myeloma: long‐term results from the phase III GMMG‐HD2 trial
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Elias K. Mai Axel Benner Uta Bertsch Peter Brossart Annette Hänel Volker Kunzmann Ralph Naumann Kai Neben Gerlinde Egerer Anthony D. Ho Jens Hillengass Marc S. Raab Andreas Neubauer Astrid Peyn Yon‐Dschun Ko Norma Peter Christof Scheid Hartmut Goldschmidt 《British journal of haematology》2016,173(5):731-741
The prospective, randomized phase III trial GMMG‐HD2 aimed at demonstrating non‐inferiority of single (Arm A) versus tandem (Arm B) high‐dose melphalan followed by autologous transplantation (HDM/ASCT) with regard to 2‐year event‐free survival (EFS) in newly‐diagnosed multiple myeloma (MM) and included 358 evaluable patients [Intention‐to‐treat population, (ITT), single/tandem HDM/ASCT: n = 177/181]. After a median follow‐up of more than 11 years, non‐inferiority of single versus tandem HDM/ASCT was demonstrated using the planned non‐inferiority threshold of 15% of the 2‐year EFS rate. Neither EFS (P = 0·53) nor overall survival (OS) (P = 0·33) differences were observed in the ITT population. In the tandem arm, 26% (n = 47/181) of patients refused a second HDM/ASCT due to non‐medical reasons. A per‐protocol (PP) analysis, including patients who received the intervention (single/tandem HDM/ASCT: n = 156/93) and patients who did not receive a second HDM/ASCT due to medical reasons (12%, n = 22/181), did not yield differences in EFS (P = 0·61) or OS (P = 0·16). In the ITT and PP set of the tandem arm, the rates of complete responses increased from first to second HDM/ASCT (both P = 0·04). Ten‐year OS for the entire ITT was 34% (95% confidence interval: 29–40%). OS after first relapse was significantly shortened in the tandem arm (P = 0·04). In this study single HDM/ASCT was non‐inferior to tandem HDM/ASCT in MM. 相似文献