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1.
Roberto Cairoli Alessandro Beghini Mauro Turrini Giambattista Bertani Gianpaolo Nadali Francesco Rodeghiero Carlo Castagnola Francesca Lazzaroni Michele Nichelatti Felicetto Ferrara Giovanni Pizzolo Enrico Pogliani Giuseppe Rossi Giovanni Martinelli Enrica Morra 《American journal of hematology》2013,88(7):594-600
Acute myeloid leukemia (AML) with deranged core‐binding factor beta (CBFβ) is usually associated with a favorable prognosis with 50–70% of patients cured using contemporary treatments. We analyzed the prognostic significance of clinical features on 58 patients with CBFβ‐AML aged ≤60 years. Increasing age was the only predictor for survival (P <0.001), with an optimal cut‐point at 43 years. White blood cells (WBCs) at diagnosis emerged as an independent risk factor for relapse incidence (P = 0.017), with 1.1% increase of hazard for each 1.0 × 109/L WBC increment. KIT mutations lacked prognostic value for survival and showed only a trend for relapse incidence (P = 0.069). Am. J. Hematol. 88:594–600, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
2.
Sylvain P. Chantepie Jean‐Jacques Parienti Véronique Salaun Khaled Benabed Stéphane Cheze Anne‐Claire Gac Hyacinthe Johnson‐Ansah Margaret Macro Gandhi Damaj Jean‐Pierre Vilque Oumedaly Reman 《American journal of hematology》2016,91(6):566-570
In acute myeloid leukemia (AML), new prognostic tools are needed to assess the risk of relapse. Hematogones (HGs) are normal B‐lymphocyte precursors that increase in hematological diseases and may influence remission duration in AML. HG detection was prospectively investigated in 262 AML patients to determine its prognostic value. Flow cytometric HG detection was performed in bone marrow aspiration after intensive chemotherapy at the time of hematological recovery. Patients with HGs in bone marrow samples had a significantly better relapse‐free survival (RFS) and overall survival (OS) than patients without HGs (P = 0.0021, and P = 0.0016). Detectable HGs independently predicted RFS (HR = 0.61, 95%CI: 0.42 ? 0.89, P = 0.012) and OS (HR = 0.59, 95%CI: 0.38 ? 0.92, 0.019) controlling for age, ELN classification, the number of chemotherapy cycles to achieve CR, performance status, secondary AML and flow cytometric minimal residual disease (MRD). In intensively treated AML, individual determination of HGs could be useful to stratify the optimal risk‐adapted therapeutic strategy after induction chemotherapy. Am. J. Hematol. 91:566–570, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
3.
The use of ATG abrogates the antileukemic effect of cytomegalovirus reactivation in patients with acute myeloid leukemia receiving grafts from unrelated donors
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Alessandro Busca Roberto Passera Massimo Pini Francesco Zallio Chiara Dellacasa Ernesta Audisio Luisa Giaccone Enrico Maffini Cristina Costa Rossana Cavallo Benedetto Bruno 《American journal of hematology》2015,90(6):E117-E121
Several studies provided evidence of a consistent antileukemic effect induced by cytomegalovirus (CMV) replication in acute myeloid leukemia (AML) patients receiving allogeneic hematopoietic stem cell transplantation (HSCT), however the use of antithymocyte globulin (ATG) as graft‐versus‐host disease prophylaxis, may potentially abrogate the protective effect of CMV infection. To address this issue, we retrospectively analyzed the risk of relapse in a cohort of 101 patients with AML who received grafts from an unrelated donor after a conditioning regimen including ATG. The cumulative incidence of CMV reactivation, evaluated by RT qPCR, was 59% at 12 months, and 93% of CMV reactivations occurred within the first 100 days post HSCT. The 5‐year cumulative incidence of relapse in patients with CMV reactivation was 29% compared with 37% for patients without CMV reactivation, and the only factor associated with a reduced 5‐year cumulative incidence of relapse was the disease status at HSCT (P < 0.001). In the multivariable model adverse cytogenetics (HR 2.42, 95% CI 1.02‐5.72; P = 0.044) and acute GVHD (HR 3.36, 95% CI 1.32‐8.54; P = 0.011) were independent risk factors for reducing overall survival (OS), while the presence of chronic GVHD was associated with a better OS (HR 0.37, 95% CI 0.15‐0.89; P = 0.027). CMV replication was not an independent risk factor for OS (HR 1.06, 95% CI 0.07‐15.75; P = 0.965). In Conclusion, the results of present study suggest that relapse prevention in patients with AML receiving T‐cell depleted HSCT using ATG do not benefit from CMV reactivation. Am. J. Hematol. 90:E117–E121, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
4.
Missing HLA C group 1 ligand in patients with AML and MDS is associated with reduced risk of relapse and better survival after allogeneic stem cell transplantation with fludarabine and treosulfan reduced toxicity conditioning
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Avichai Shimoni Luca Vago Massimo Bernardi Ronit Yerushalmi Jacopo Peccatori Raffaella Greco Noga Shem‐Tov Alessandro Lo Russo Ivetta Danylesko Arie Apel Chiara Bonini Maria Teresa Lupo Stanghellini Arnon Nagler Fabio Ciceri 《American journal of hematology》2017,92(10):1011-1019
Reduced‐toxicity conditioning with fludarabine and treosulfan is a dose‐intensive regimen with enhanced anti‐leukemia effect and acceptable toxicity in AML/MDS. HLA‐C regulates natural‐killer (NK) cell function by inhibiting Killer immunoglobulin‐like receptors (KIR) and is divided into C1 and C2 epitopes. The missing‐ligand theory suggests that missing recipient KIR ligands drives NK‐alloreactivity after SCT, in the absence of HLA‐mismatch by activating unlicensed donor NK cells. We analyzed SCT outcomes in 203 patients with AML/MDS, median age 58 years, given SCT from matched‐siblings (n = 97) or matched‐unrelated donors (n = 106), using two treosulfan doses (total 36 or 42 g/m2). 34% expressed one HLA‐C group 1 allele (C1C1), 19% one HLA‐C group 2 allele (C2C2), and 48% both KIR ligands (C1C2). Median follow‐up was 48 months. 5‐year relapse, nonrelapse mortality (NRM) and leukemia‐free survival (LFS) rates were 38%, 27%, and 36%, respectively. Relapse rates were 43%, 45%, and 26% in patients expressing C1C1, C1C2, and C2C2 ligands, respectively (P = .03). Multivariate‐analysis identified chemo‐refractory disease (HR 3.1, P = .003), poor cytogenetics (HR 1.7, P = .08), female donor to male recipient (HR 0.4, P = .01) and C2C2 ligands (HR 0.4, P = .04) as independent factors predicting relapse. HLA‐C ligands were not associated with GVHD or NRM. LFS was 33%, 30%, and 46%, respectively (P = .07). Chemorefractory disease (HR 3.1, P = .0004) and C2C2 group ligand (HR 0.6, P = .06) independently predicted LFS. Treosulfan dose did not predict any SCT outcome. In conclusion, missing HLA‐C group 1 ligand is associated with reduced relapse risk, similar NRM and improved LFS, after HLA‐matched SCT with treosulfan conditioning in AML/MDS. 相似文献
5.
Carolina Martínez‐Laperche Leyre Bento Cristina Pascual Mi Kwon Pascual Balsalobre Cristina Muñoz Elena Buces David Serrano Jorge Gayoso Ismael Buño Javier Anguita José Luís Diéz‐Martín 《European journal of haematology》2014,93(3):239-246
Allogeneic stem cell transplantation (allo‐SCT) has become the treatment of choice in patients with intermediate‐risk and high‐risk acute myeloid leukemia (AML). The quality of response to treatment, assessed in terms of detection of minimal residual disease (MRD), has been consistently associated with prognosis and clinical outcome in patients with AML. The aim of the present study was to evaluate the prognostic impact of analyzing MRD in bone marrow using 4‐color multiparametric flow cytometry (MFC) in 29 patients with AML before and after allo‐SCT. Eighteen patients who were shown to be MRD‐negative [≤0.1% leukemia‐associated immunophenotypes (LAIPs)] by MFC at transplantation and underwent allo‐SCT had lower rates of relapse (15% vs. 66%, P = 0.045), better overall 1‐yr survival (83% vs. 52%, P = 0.021) and a lower cumulative incidence of relapse (P = 0.032) than patients who were MRD‐positive (>0.1%). All post‐transplant MRD‐positive patients underwent a therapeutic intervention after transplant (tapering of immunosuppression, donor lymphocyte infusion, or re‐transplant) with the intention of preventing relapse. Disease was controlled and MRD disappeared in five of these patients. Disease recurred in the other seven patients. We can conclude that follow‐up with MFC for the detection of MRD in AML before and after SCT is useful for predicting relapse. In the post‐transplant setting, monitoring of MRD by MFC could be a key preemptive intervention. 相似文献
6.
Long term impact of hyperleukocytosis in newly diagnosed acute myeloid leukemia patients undergoing allogeneic stem cell transplantation: An analysis from the acute leukemia working party of the EBMT
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Jonathan Canaani Myriam Labopin Gerard Socié Anne Nihtinen Anne Huynh Jan Cornelissen Eric Deconinck Tobias Gedde‐Dahl Edouard Forcade Patrice Chevallier Jean H. Bourhis Didier Blaise Mohamad Mohty Arnon Nagler 《American journal of hematology》2017,92(7):653-659
Up to 20% of acute myeloid leukemia (AML) patients present initially with hyperleukocytosis, placing them at increased risk for early mortality during induction. Yet, it is unknown whether hyperleukocytosis still retains prognostic value for AML patients undergoing hematopoietic stem cell transplantation (HSCT). Furthermore, it is unknown whether hyperleukocytosis holds prognostic significance when modern molecular markers such as FLT3‐ITD and NPM1 are accounted for. To determine whether hyperleukocytosis is an independent prognostic factor influencing outcome in transplanted AML patients we performed a retrospective analysis using the registry of the acute leukemia working party of the European Society of Blood and Marrow Transplantation. A cohort of 357 patients with hyperleukocytosis (159 patients with white blood count [WBC] 50 K‐100 K, 198 patients with WBC ≥ 100 K) was compared to 918 patients without hyperleukocytosis. Patients with hyperleukocytosis were younger, had an increased rate of favorable risk cytogenetics, and more likely to be FLT3 and NPM1 mutated. In multivariate analysis, hyperleukocytosis was independently associated with increased relapse incidence (hazard ratio [HR] of 1.55, 95% confidence interval [CI], 1.14‐2.12; P = .004), decreased leukemia‐free survival (HR of 1.38, 95% CI, 1.07‐1.78; P = .013), and inferior overall survival (HR of 1.4, 95% CI, 1.07‐1.84; P = .013). Hyperleukocytosis retains a significant prognostic role for AML patients undergoing HSCT. 相似文献
7.
Mild chronic graft‐versus‐host disease may alleviate poor prognosis associated with FLT3 internal tandem duplication for adult acute myeloid leukemia following allogeneic stem cell transplantation with myeloablative conditioning in first complete remission: a retrospective study
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Barbara Nasilowska‐Adamska Anna Czyz Miroslaw Markiewicz Piotr Rzepecki Beata Piatkowska‐Jakubas Monika Paluszewska Monika Dzierzak‐Mietla Iwona Solarska Katarzyna Borg Monika Prochorec‐Sobieszek Richard Szydlo Krzysztof Lewandowski Aleksander Skotnicki Wieslaw Wiktor Jedrzejczak Slawomira Kyrcz‐Krzemien Mieczyslaw Komarnicki Krzysztof Warzocha 《European journal of haematology》2016,96(3):236-244
Internal tandem duplication (ITD) of the FLT3 gene (Fms‐like tyrosine kinase 3) is the most commonly found mutation in acute myeloid leukemia (AML). The significance of FLT3‐ITD at diagnosis was retrospectively estimated for allo‐HSCT (allogeneic hematopoietic stem cell transplantation) outcomes in 140 patients, median age of 38, undergoing allo‐HSCT after myeloablative conditioning in first complete remission of AML. FLT3‐ITD was detected at AML diagnosis in 42/140 (30%) of included into this study patients. At 3 years, relapse incidence (RI) following allo‐HSCT in AML patients with intermediate or normal karyotype was significantly higher in those FLT3‐ITD positive than FLT3‐ITD negative [52.9 vs. 20.4%, P = 0.002]. Additionally, patients with mild chronic graft‐versus‐host disease (cGvHD) had significantly lower RI compared to patients with moderate or severe grade cGvHD or those not experiencing cGvHD, respectively, 4.8 vs. 36.0 vs. 27.8%, P = 0.032. FLT3‐ITD was harboring a poor prognosis in AML with intermediate or normal karyotype and significantly increased risk of relapse following allo‐HSCT. It appears that allo‐HSCT does not cure patients with FLT3‐ITD, unless they develop symptoms of mild cGvHD and graft versus leukemia, which may decrease RI. 相似文献
8.
Fludarabine and cytarabine versus high‐dose cytarabine in consolidation treatment of t(8; 21) acute myeloid leukemia: A prospective,randomized study
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Ruiqi Li Xiaoxia Hu Libing Wang Hui Cheng Shuqing Lv Weiping Zhang Jianmin Wang Jianmin Yang Xianmin Song 《American journal of hematology》2017,92(1):12-17
Acute myeloid leukemia (AML) patients with t(8;21) aberration often have favorable outcomes, however, relapse still occurs in 30–40% patients, with only 50–60% of patients with t(8;21) AML cured with regimens containing high‐dose cytarabine (HD‐Ara‐C). To evaluate the effects of fludarabine and cytarabine (FA) consolidation therapy for t(8;21) AML patients, a prospective randomized study was performed. A total of 45 patients with t(8;21) AML after achieving complete remission (CR) were randomly assigned to receive four course consolidation with FA (n = 23) or HD‐Ara‐C (n = 22). Our study showed that at 36‐months, relapse‐free survival (RFS) was 81.73% in the FA arm and 50.73% in the HD‐Ara‐C arm (P = 0.04), overall survival (OS) was 91.1% and 48.4% (P = 0.01) in the FA arm and in the HD‐Ara‐C arm respectively; whereas cumulative incidence of relapse (CIR) was 18.27% and 47.39%, in the FA arm and in the HD‐Ara‐C arm respectively (P = 0.05). In our study, treatment with FA, MRD2 status (reduction ≥ 3‐log) and absence of c‐kit mutations were identified as independent prognostic factors for lower risk of relapse, improved RFS and OS. We also found RFS for patients without c‐kit mutations was 100% in FA arm, and 57.8% in HD‐Ara‐C arm at 36 months (P = 0.005); OS of both groups at 36 months was 100% and 51.4%, respectively (P = 0.004), suggesting a benefit of consolidation therapy with FA for t(8;21) AML patients, especially, those without c‐kit mutations (Clinicaltrials.org ID NCT# 02024308). Am. J. Hematol. 92:12–17, 2017. © 2016 Wiley Periodicals, Inc. 相似文献
9.
Inferior outcome after allogeneic transplant in first remission in high‐risk AML patients who required more than two cycles of induction therapy
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Sara J. Lim Matthew J. Lim Anastasios Raptis Jing‐Zhou Hou Rafic Farah Stanley M. Marks Annie Im Kathleen Dorritie Alison Sehgal Mounzer Agha Raymond Felgar Seah H. Lim 《American journal of hematology》2015,90(8):715-718
While some patients with high‐risk acute myeloid leukemia (AML) require one or two cycles of induction chemotherapy to achieve a complete remission (CR), others require more than two cycles. We examined the outcomes of patients with high‐risk AML who received allogeneic HPC transplant in CR1. Forty five consecutive high‐risk AML patients in CR1 were included. All 45 patients had adverse cytogenetics, FLT 3 mutations, or secondary AML. Group A patients (n = 33) received one or two cycles, and Group B (n = 12) three or more cycles of induction chemotherapy. The patients were comparable in age, sex, white cell count at presentation, and time from diagnosis and from last chemotherapy to transplant. The 100‐day mortality rate was higher in Group B patients (50% vs. 9%, P = 0.006). They had a higher non‐relapse mortality (33% vs. 6%, P = 0.035) and a longer length of hospital stay from the day of stem cell infusion (median 21 vs. 20, P = 0.02; third quartile 22 vs. 28, P = 0.02). There was also a trend toward inferior event‐free survival and overall survival. High‐risk AML patients undergoing allogeneic transplant in CR1 after three or more cycles of induction chemotherapy have an inferior outcome and higher mortality when compared to those who only needed one or two cycles of induction chemotherapy. Novel strategies are needed to reduce the transplant‐related mortality in high‐risk AML patients needing more than two cycles of induction chemotherapy prior to allogeneic transplant in CR1. Am. J. Hematol. 90:715–718, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
10.
Outcome of conditioning intensity in acute myeloid leukemia with monosomal karyotype in patients over 45 year‐old: A study from the acute leukemia working party (ALWP) of the European group of blood and marrow transplantation (EBMT)
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Xavier Poiré Myriam Labopin Jan J. Cornelissen Liisa Volin Carlos Richard Espiga J. Hendrik Veelken Noël Milpied Jean‐Yves Cahn Ibrahim Yacoub‐Agha Gustaaf W. van Imhoff Mauricette Michallet Lucienne Michaux Mohamad Mohty 《American journal of hematology》2015,90(8):719-724
Acute myeloid leukemia with monosomal karyotype (MK AML) carries a very poor prognosis, even after allogeneic stem cell transplantation (SCT). However, SCT remains the only curative option in this high‐risk population. Because myeloablative conditioning regimen (MAC) is associated with less relapse, we hypothesized that more intensive conditioning regimen might be beneficial for MK AML patients. We reviewed 303 patients over age 45 diagnosed with either de novo or secondary MK AML. One hundred and five patients received a MAC and 198 a reduced‐intensity conditioning (RIC). The median age at SCT was 57‐year‐old, significantly lower in the MAC (53‐year‐old) than in the RIC group (59‐year‐old). The median follow‐up was 42 months (range, 3 ? 156 months). The 3‐year overall survival (OS), leukemia‐free survival (LFS), and relapse rate (RR) were not significantly different between both groups with overall values of 34%, 29%, and 51%, respectively. On the contrary, the 3‐year nonrelapse mortality (NRM) was significantly higher in MAC recipients (28%) compared with RIC patients (16%, P = 0.004). The incidence of Grades II to IV acute graft‐versus‐host disease (GvHD) was significantly higher after a MAC (30.5%) than after a RIC (19.3%, P = 0.02). That of chronic GvHD was comparable between both groups (35%) and did not impact on LFS. Interestingly, within our MK AML cohort, hypodiploidy was significantly associated with worse outcomes. Due to reduced toxicity and comparable OS, LFS, and RR, RIC appears as a good transplant option in the very high‐risk population, including older patients, diagnosed with MK AML. Am. J. Hematol. 90:719–724, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
11.
Daniela Damiani Mario Tiribelli Alessandra Franzoni Angela Michelutti Dora Fabbro Margherita Cavallin Eleonora Toffoletti Erica Simeone Renato Fanin Giuseppe Damante 《American journal of hematology》2013,88(10):848-852
Overexpression of brain and acute leukemia cytoplasmic (BAALC) gene confers poor prognosis in cytogenetically normal acute myeloid leukemia (AML) patients, while less defined is its role in AML with abnormal karyotype. We evaluated the effect of BAALC overexpression on outcome of 175 adult AML patients with different cytogenetic risks. Karyotype was favorable in 13, intermediate in 117 and unfavorable in 45 patients, respectively. Quantitative BAALC expression was determined by real‐time PCR, with cut off value set at 50th percentile. BAALC was overexpressed in 87/175 (50%) patients, without association with cytogenetic status. High BAALC was associated with unmutated NPM (P = 0.006) and CD34 positivity (P < 0.0001). Complete remission (CR) was attained in 111 patients (63%), and was maintained at 5 years in 52 ± 7%. BAALC overexpression had a negative impact on CR achievement (P = 0.04), while did not influence relapse probability. Median survival was 22 months with a 5‐years overall survival (OS) of 35%. Factors with a negative impact on OS were older age (P = 0.0001), unfavorable cytogenetic (P = 0.005), ABCG2 overexpression (P = 0.03) and high BAALC levels (P = 0.01). We observed a worse outcome in patients with high BAALC expression through all cytogenetic risk categories: 5‐years OS was 100% vs. 71% in patients with favorable cytogenetics (P = 0.05), 55% vs. 40% in cases with intermediate karyotype (P = 0.04) and 34% vs. 23% in unfavorable cytogenetic subgroup (P = 0.02). BAALC overexpression identified AML patients with poor prognosis in all cytogenetic groups. Though relatively rare, BAALC positivity in patients with favorable or unfavorable karyotype significantly worsened survival. Am. J. Hematol. 88:848–852, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
12.
Jonathan Canaani Myriam Labopin Xiao‐Jun Huang William Arcese Fabio Ciceri Didier Blaise Giuseppe Irrera Lucia Lopez Corral Benedetto Bruno Stella Santarone Maria Teresa Van Lint Antonin Vitek Jordi Esteve Mohamad Mohty Arnon Nagler 《American journal of hematology》2018,93(6):736-744
Acute myeloid leukemia (AML) patients harboring the FLT3‐ITD mutation are considered a high risk patient subset preferentially allocated for allogeneic stem cell transplantation in first remission. Whether FLT3‐ITD retains a prognostic role in haploidentical stem cell transplantation (haplo‐SCT) is unknown. To analyze the prognostic impact of FLT3‐ITD in haplo‐SCT, we performed a retrospective analysis of the multicenter registry of the acute leukemia working party of the European Society for Blood and Marrow Transplantation. We included all adult AML patients with known FLT3 status who underwent a first T‐cell replete related haplo‐HCT in first complete remission from 2005 to 2016. We evaluated 293 patients of whom 202 were FLT3wt and 91 were FLT3‐ITD mutated. FLT3‐ITD patients were more likely to be NPM1 mutated as well as be in the intermediate risk cytogenetic risk category. In multivariate analysis, patients with FLT3‐ITD had comparable rates of relapse incidence [Hazard ratio (HR) = 1.34, confidence interval (CI) 95%, 0.67‐2.7; P = .9] and leukemia‐free survival (HR = 0.99, CI 95%, 0.62‐1.57; P = .9) to those of FLT3wt patients. Overall survival, the incidence of nonrelapse mortality, and graft versus host disease‐free/relapse‐free survival were not significantly impacted by FLT3‐ITD status. Furthermore, relapse and overall survival were comparable between FLT3‐ITD patients transplanted from various donor pools, namely matched siblings, unrelated donors, haplo‐SCT). Finally, subset analysis of patients with intermediate risk cytogenetics confirmed the absence of a prognostic impact of FLT3‐ITD also for this patient segment. In AML patients undergoing T‐cell replete haplo‐SCT, the FLT3‐ITD mutation possibly does not retain its prognostic significance. 相似文献
13.
Lukas Gaksch Karl Kashofer Ellen Heitzer Franz Quehenberger Shruti Daga Sybille Hofer Iris Halbwedl Ricarda Graf Nina Krisper Gerald Hoefler Armin Zebisch Heinz Sill Albert Wölfler 《American journal of hematology》2018,93(1):23-30
Despite achieving complete remission after intensive therapy, most patients with cytogenetically normal (CN) AML relapse due to the persistence of submicroscopic residual disease. In this pilot study, we hypothesized that detection of leukemia‐specific mutations following consolidation treatment using a targeted parallel sequencing approach predicts relapse. We included 34 AML patients of whom diagnostic material and remission bone marrow slides after at least one cycle of consolidation were available. Isolated DNA was screened for mutations in 19 genes using an Ion Torrent sequencing platform. Furthermore, the variant allelic frequency of distinct mutations was validated by digital PCR and sequencing using a barcoding approach. Twenty‐seven out of 34 patients could be analyzed for mutation clearance. We identified 68 somatic mutations at diagnosis (median, 3 mutations per patient; range 1‐5) and 22 of these were still detected in 16 patients after consolidation therapy with a reliable sensitivity of 0.5% (median, 1 mutation; range 0‐3). The most frequent noncleared mutations were found in DNMT3A. However, as persistence of these mutations has recently been shown to be without any impact on relapse risk, we performed survival and relapse risk analysis excluding DNMT3A mutations. Importantly, persistence of non‐DNMT3A mutations was associated with a higher risk of AML relapse (7/8 pts versus 6/19 pts; P = .013) and with a shorter relapse‐free survival (333 days vs. not reached; log‐rank P = .0219). Detection of residual disease by routine targeted parallel sequencing proved feasible and effective as persistence of somatic mutations other than DNMT3A were prognostic for relapse in CN AML. 相似文献
14.
Predictive factors for latency period and a prognostic model for survival in patients with therapy‐related acute myeloid leukemia
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Moshe C. Ornstein Sudipto Mukherjee Sanjay Mohan Paul Elson Ramon V. Tiu Yogenthiran Saunthararajah Cassie Kendeigh Anjali Advani Matt Kalaycio Jaroslaw P. Maciejewski Mikkael A. Sekeres 《American journal of hematology》2014,89(2):168-173
Therapy‐related acute myeloid leukemia (t‐AML) is an increasingly recognized sequela in patients receiving chemotherapy or radiotherapy for a primary malignancy or autoimmune disease. This study assessed factors related to the latency period (LP) between the antecedent disorder (AD) and t‐AML diagnosis and developed a comprehensive prognostic model to predict overall survival (OS). We evaluated a cohort of newly diagnosed t‐AML patients treated with cytarabine‐based induction therapy from 2001 to 2011. Multivariable linear and proportional hazards models were used to assess the impact of different classes of chemotherapy on the LP and to identify independent prognostic factors for OS. Of 730 treated AML patients, 58 (7.9%) had t‐AML. Median LP to t‐AML was 5.6 years (range, 0.5–38.4). 64% of patients achieved CR and median OS was 10.7 months. Independent prognostic factors of short LP were age at AD (P < 0.0001) and prior treatment with mitotic inhibitors (P = 0.05). Unfavorable cytogenetics (P = 0.004), antecedent hematologic or autoimmune disease (P = 0.01), age >60 (P = 0.03), and platelet count <30,000 μL (P = 0.04) at the time of t‐AML diagnosis were prognostic for inferior OS. A prognostic model using these factors was developed that risk stratified t‐AML patients into two groups: favorable and unfavorable. Patients in the favorable group had a median OS of 37.6 months compared with 6.4 months in patients comprising the unfavorable group (P < 0.0001). Multicomponent prognostic models integrating disease or treatment‐related covariates can help better understand how t‐AML evolves; and can be clinically useful in risk stratifying t‐AML patients undergoing induction therapy. Am. J. Hematol. 89:168–173, 2014. © 2013 Wiley Periodicals, Inc. 相似文献
15.
Characteristics of acute myeloid leukemia with myelodysplasia‐related changes: A retrospective analysis in a cohort of Chinese patients
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Xiao‐Qian Xu Jian‐Min Wang Lei Gao Hui‐Ying Qiu Li Chen Lin Jia Xiao‐Xia Hu Jian‐Min Yang Xiong Ni Jie Chen Shu‐Qing Lü Wei‐Ping Zhang Xian‐Min Song 《American journal of hematology》2014,89(9):874-881
We retrospectively analyzed 449 patients with AML under the WHO classification of AML 2008 and probed implications of this classification in diagnosis and treatment of acute myeloid leukemia with myelodysplasia‐related changes (AML‐MRC) among them. The clinical presentations, biological features, treatments, and prognosis of patients diagnosed with AML‐MRC were analyzed and compared with those of AML not otherwise specified (AML‐NOS). In all patients, 115 (25.6%) were diagnosed as AML‐MRC including 64 males and 51 females with median onset age of 48 years (range from 17 to 78). Their complete remission (CR) rate was 60.9% and relapse rate was 57.1%. The observed median overall survival (OS) and disease‐free survival (DFS) were 10 and 5 months, respectively, which was significantly shorter than those of AML‐NOS patients (P < 0.05). The prognosis of AML‐MRC patients with myelodysplastic syndrome (MDS)‐related cytogenetics sole was similar to those with history of MDS or myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Patients with MDS‐related cytogenetic abnormalities and/or history of MDS or MDS/MPN predisposed significantly shortened CR, OS, and DFS than AML‐MRC patients with only multilineage dysplasia (MLD) and AML‐NOS patients (P < 0.05). Multivariate analysis showed that age, cytogenetics, and history of MDS or MDS/MPN were independent prognostic factors. Patient diagnosed as AML‐MRC presented distinctive clinical and biological features. Presence of MLD does not change the prognosis. Am. J. Hematol. 89:874–881, 2014. © 2014 Wiley Periodicals, Inc. 相似文献
16.
Crawford J. Strunk Uwe Platzbecker Christian Thiede Markus Schaich Thomas Illmer Zizhen Kang Patrick Leahy Chunbiao Li Xiuyan Xie Mary J. Laughlin Hillard M. Lazarus Stanton L. Gerson Kevin D. Bunting Gerhard Ehninger William Tse 《American journal of hematology》2009,84(5):308-309
Nearly half of the patients with newly diagnosed acute myeloid leukemia have normal cytogenetics (NC‐AML) and are classified as intermediate risk, but their 5‐year overall survival (OS) ranges from 24 to 42%. Therefore, molecular biomarkers to identify poor‐risk patients are needed. Elevated AF1q expression in the absence of specific poor cytogenetics is associated with poor outcomes in pediatric patients with AML and adult patients with myelodysplastic syndrome. We examined AF1q expression in 290 patients with NC‐AML. We found that patients with low AF1q (n = 73) expression (AF1qlow) have better OS (P = 0.026), disease‐free survival (P = 0.1), and complete remission rate (P = 0.06) when compared with patients with high AF1q expression (AF1qhigh n = 217). The patients with AF1qhigh had significantly greater incidence of concurrent tyrosine kinase3 internal tandem duplication. A subgroup of the patients with AF1qhigh who received allogeneic stem cell transplantation (SCT) had a significant better relapse‐free survival when compared with patients who received chemotherapy/autologous SCT (P = 0.04). This study suggests that high AF1q expression is a poor prognostic marker for adult patients with NC‐AML. 相似文献
17.
Ehab Atallah Judith Abrams Lois Ayash Gail Bentley Muneer Abidi Voravit Ratanatharathorn Joseph Uberti 《American journal of hematology》2010,85(8):579-583
We report here the 10‐year follow‐up of 86 patients who underwent allogeneic stem cell transplantation (ASCT) for myelodysplastic syndrome (MDS). All patients received the busulfan, cytosine arabinoside, and cyclophosphamide (BAC) preparative regimen which consisted of busulfan 16 mg/kg, cytosine arabinoside 8 g/m2 IV, and cyclophosphamide 120 mg/kg IV. Fifty‐nine patients (69%) had de novo MDS; 26 (30%) had secondary MDS (treatment related), and one had a preceding aplastic anemia which progressed to MDS before transplant. Cytogenetics (80 patients) was classified as good (34%), intermediate (17%), or poor (42%). With a median follow‐up for survivors of 124 months, the 10‐year Kaplan‐Meier estimates for overall survival (OS) was 43% (95% confidence interval [CI]: 31–53%). Cumulative nonrelapse mortality (NRM) and relapse was 43% (95% CI: 32–54%) and 19% (95% CI: 11–27%), respectively. No patient relapsed after 2 years. In patients with RAEB‐T/AML, 10‐year relapse‐free survival (RFS), relapse, and NRM was 36%, 36%, and 27%, respectively. Younger age (P = 0.05), human leukocyte antigen (HLA) match (P = 0.002), good risk cytogenetics (P = 0.008), and having a related donor (P = 0.03) significantly improved overall and RFS in the multivariable analysis. The long‐term follow‐up of patients receiving the BAC regimen with ASCT in this study indicated durable relapse‐free and OS with acceptable toxicity in this group of patients with high‐risk features. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc. 相似文献
18.
Daniela Damiani Mario Tiribelli Antonella Geromin Angela Michelutti Margherita Cavallin Alessandra Sperotto Renato Fanin 《American journal of hematology》2015,90(9):784-789
ABGG2 protein overexpression in acute myeloid leukemia (AML) has been associated with poor response to conventional chemotherapy and increased relapse risk. No data are available on the role of allogeneic stem cell transplantation (SCT) in reversing its negative prognostic role. We have reviewed the outcome of 142 patients with high risk AML who underwent allogeneic SCT in complete remission (n = 94) or with active disease (n = 48). Patients with ABCG2 overexpression at AML diagnosis have lower leukemia free survival (LFS) and increased cumulative incidence of relapse (CIR) compared with ABCG2? patients (5‐year LFS 50% vs. 65%, P = 0.01; 5‐year CIR 46% vs. 27%, P = 0.003). Five‐year overall survival was not significantly different between ABCG2+ and ABCG2? patients (39% vs. 51%, P = 0.1). However, if we consider only disease‐related deaths, ABCG2 maintains its negative role (64% vs. 78%, P = 0.018). The negative impact of ABCG2 overexpression was higher in patients undergoing SCT in CR compared with patients receiving transplant with active disease. Conditioning regimen did not abrogate the effect of ABCG2 overexpression, as CIR was higher in ABCG2+ patients receiving both myeloablative (44% vs. 22%, P = 0.018) or reduced intensity conditioning (50% vs. 32%, P = 0.03). In conclusion, ABCG2 overexpression at AML diagnosis identifies a subset of patients with poor outcome also after allogeneic SCT, mainly in terms of higher relapse rates. Prospective studies employing conditioning drugs or post‐transplant strategies able to target ABCG2 are needed to maximize the curative potential of stem cell transplantation.Am. J. Hematol. 90:784–789, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
19.
Hemmati PG Terwey TH le Coutre P Vuong LG Massenkeil G Dörken B Arnold R 《European journal of haematology》2011,86(4):305-316
The systematic and standardized pretransplant risk assessment represents an important tool to predict the outcome of patients undergoing allogeneic stem cell transplantation (alloSCT). To investigate the capacity of a modified European group for blood and marrow transplantation (mEBMT) risk score to predict the outcome of patients with acute myeloid leukemia (AML) receiving allogeneic stem cell transplants, we retrospectively analyzed 214 patients transplanted at our center between 1995 and 2008. Overall survival (OS) of the whole cohort at 1, 3, and 5 yr was 62%, 48%, and 45%, whereas the cumulative incidence of relapse or non‐relapse mortality (NRM) was 26%, 33%, and 33% or 19%, 21%, and 22%. In univariate analysis, a higher mEBMT risk score was associated with an inferior OS ranging from 69% for patients with a score of 0/1 to 26% for patients with a score of 5/6 at 5 yr (P < 0.0001) and steadily increasing hazard ratios for each additional score point. Likewise, a higher mEBMT risk score was associated with an increased incidence of relapse (P = 0.049). Importantly, the prognostic value of the mEBMT risk score in terms of OS and relapse was maintained in multivariate analysis. Taken together, this indicates that a mEBMT risk score may be used to predict the outcome of patients with AML following alloSCT. 相似文献
20.
De novo acute myeloid leukemia with 20–29% blasts is less aggressive than acute myeloid leukemia with ≥30% blasts in older adults: a Bone Marrow Pathology Group study
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Robert Paul Hasserjian Federico Campigotto Veronica Klepeis Bin Fu Sa A. Wang Carlos Bueso‐Ramos Michael Joseph Cascio Heesun Joyce Rogers Eric Darryl Hsi Craig Soderquist Adam Bagg Jiong Yan Rachel Ochs Attilio Orazi Frank Moore Amer Mahmoud Tracy Irene George Kathryn Foucar Jamie Odem Cassie Booth William Morice Daniel J. DeAngelo David Steensma Richard Maury Stone Donna Neuberg Daniel Alan Arber 《American journal of hematology》2014,89(11):E193-E199
It is controversial whether acute myeloid leukemia (AML) patients with 20–29% bone marrow (BM) blasts, formerly referred to as refractory anemia with excess blasts in transformation (RAEBT), should be considered AML or myelodysplastic syndrome (MDS) for the purposes of treatment and prognostication. We retrospectively studied 571 de novo AML in patients aged > 50 years, including 142 RAEBT and 429 with ≥30% blasts (AML30), as well as 151 patients with 10–19% BM blasts (RAEB2). RAEBT patients were older and had lower white blood count, but higher hemoglobin, platelet count, and karyotype risk scores compared to AML30, while these features were similar to RAEB2. FLT3 and NPM1 mutations and monocytic morphology occurred more commonly in AML30 than in RAEBT. RAEBT patients were treated less often with induction therapy than AML30, whereas allogeneic stem cell transplant frequency was similar. The median and 4‐year OS of RAEBT patients were longer than those of AML30 patients (20.5 vs 12.0 months and 28.6% vs 20.4%, respectively, P = 0.003); this difference in OS was manifested in patients in the intermediate UKMRC karyotype risk group, whereas OS of RAEBT patients and AML30 patients in the adverse karyotype risk group were not significantly different. Multivariable analysis showed that RAEBT (P < 0.0001), hemoglobin (P = 0.005), UKMRC karyotype risk group (P = 0.002), normal BM karyotype (P = 0.004), treatment with induction therapy (P < 0.0001), and stem cell transplant (P < 0.0001) were associated with longer OS. Our findings favor considering de novo RAEBT as a favorable prognostic subgroup of AML. Am. J. Hematol. 89:E193–E199, 2014. © 2014 Wiley Periodicals, Inc. 相似文献