45 results on '"Myeloid leukaemia"'
Search Results
2. Granulocyte transfusion during cord blood transplant for relapsed, refractory AML is associated with massive CD8+ T‐cell expansion, significant cytokine release syndrome and induction of disease remission.
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Borrill, Roisin, Poulton, Kay, Kusyk, Laura, Routledge, Amy, Bonney, Denise, Hanasoge‐Nataraj, Ramya, Powys, Madeleine, Mustafa, Omima, Campbell, Helen, Senthil, Srividhya, Dillon, Richard, Jovanovic, Jelena, Morton, Suzy, James, Beki, Rao, Kanchan, Stanworth, Simon, Konkel, Joanne, and Wynn, Robert
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CORD blood transplantation , *CYTOKINE release syndrome , *REMISSION induction , *CORD blood , *T cells , *DISEASE remission - Abstract
Summary: In high‐risk myeloid malignancy, relapse is reduced using cord blood transplant (CBT) but remains the principal cause of treatment failure. We previously described T‐cell expansion in CBT recipients receiving granulocyte transfusions. We now report the safety and tolerability of such transfusions, T‐cell expansion data, immunophenotype, cytokine profiles and clinical response in children with post‐transplant relapsed acute leukaemia who received T‐replete, HLA‐mismatched CBT and pooled granulocytes within a phase I/II trial (ClinicalTrials.Gov NCT05425043). All patients received the transfusion schedule without significant clinical toxicity. Nine of ten patients treated had detectable measurable residual disease (MRD) pre‐transplant. Nine patients achieved haematological remission, and eight became MRD negative. There were five deaths: transplant complications (n = 2), disease (n = 3), including two late relapses. Five patients are alive and in remission with 12.7 months median follow up. Significant T‐cell expansion occurred in nine patients with a greater median lymphocyte count than a historical cohort between days 7–13 (median 1.73 × 109/L vs. 0.1 × 109/L; p < 0.0001). Expanded T‐cells were predominantly CD8+ and effector memory or TEMRA phenotype. They exhibited markers of activation and cytotoxicity with interferon‐gamma production. All patients developed grade 1–3 cytokine release syndrome (CRS) with elevated serum IL‐6 and interferon‐gamma. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Recommendations for laboratory testing of UK patients with acute myeloid leukaemia.
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Mehta, Priyanka, Telford, Nick, Wragg, Chris, Dillon, Richard, Freeman, Sylvie, Finnegan, Damian, Hamblin, Angela, Copland, Mhairi, and Knapper, Steve
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ACUTE myeloid leukemia , *ACUTE promyelocytic leukemia , *TESTING laboratories , *MAST cell disease - Abstract
The new 2022 WHO classification has replaced the category of AML with myelodysplasia-related changes (AML-MRC) with AML-Myelodysplasia Related (AML-MR) and its diagnostic criteria are updated (see Endnote). Keywords: cytogenetics; flow cytometry; leukaemia diagnosis; molecular genetics; myeloid leukaemia EN cytogenetics flow cytometry leukaemia diagnosis molecular genetics myeloid leukaemia 150 159 10 01/16/23 20230115 NES 230115 METHODOLOGY This Good Practice Paper was compiled according to the BSH process (https://b-s-h.org.uk/media/19922/bsh-guidance-development-process-july-2021.pdf). Key changes include removal of morphology alone to make a diagnosis of AML-MR, updating the cytogenetic criteria and introducing the mutation-based diagnosis of AML-MR. INTRODUCTION Making a diagnosis of acute myeloid leukaemia (AML) requires a multi-faceted approach bringing together clinical features of patient presentation with laboratory investigations encompassing morphological, immunophenotypic and genetic evaluation of blood, bone marrow and, when appropriate, cerebrospinal fluid (CSF). [Extracted from the article]
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- 2023
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4. A novel ATRX variant with splicing consequences in myelodysplastic syndrome with acquired alpha thalassaemia.
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Nguyen, Phillip C., Tiong, Ing Soo, Westerman, David A., and Blombery, Piers
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MYELODYSPLASTIC syndromes , *THALASSEMIA , *SOMATIC mutation , *RED blood cell transfusion , *MYELOID leukemia , *CHRONIC leukemia - Abstract
The amount of HbH has been shown to correlate with the size of the I ATRX i clone.[6] In the Oxford ATMDS Registry, one patient demonstrated an I ATRX i clone size of 35% and 1.5% at two different time-points, corresponding to 25% and <1% HbH-containing cells by supravital staining respectively. Keywords: genetic analysis; myeloid leukaemia; red blood cell disorders; somatic mutation; thalassaemia EN genetic analysis myeloid leukaemia red blood cell disorders somatic mutation thalassaemia e13 e16 4 12/22/22 20230101 NES 230101 Acquired -thalassaemia is a rare disorder that can arise in patients with myelodysplastic syndrome ( -thalassaemia myelodysplastic syndrome, ATMDS).[1] In contrast to I cis- i acting variants of the -gene cluster in inherited thalassaemia, ATMDS is caused by somatic variants in the X-linked I ATRX i gene that encodes a I trans- i acting chromatin-associated protein.[[2]] Consistent with this, germline I ATRX i variants cause the inherited ATR-X syndrome characterised by severe mental retardation and mild -thalassaemia in males.[[4]] Despite advances in understanding ATRX protein function, the exact mechanism of -globin gene repression is unknown, and several clinical observations remain unresolved: (1) the haematologic phenotype for a given variant is more severe in ATMDS compared to ATR-X syndrome, (2) the proportion of HbH can fluctuate with time, and (3) the -thalassaemia often resolves after leukaemic transformation. Acquired somatic ATRX mutations in myelodysplastic syndrome associated with alpha thalassemia (ATMDS) convey a more severe hematologic phenotype than germline ATRX mutations. [Extracted from the article]
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- 2023
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5. Development and validation of a prognostic scoring model to risk stratify childhood acute myeloid leukaemia.
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Li, Jun, Liu, Lipeng, Zhang, Ranran, Wan, Yang, Gong, Xiaowen, Zhang, Li, Yang, Wenyu, Chen, Xiaojuan, Zou, Yao, Chen, Yumei, Guo, Ye, Ruan, Min, and Zhu, Xiaofan
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ACUTE myeloid leukemia , *PROGNOSTIC models , *HEMATOPOIETIC stem cell transplantation , *DISEASE risk factors , *RECEIVER operating characteristic curves - Abstract
Summary: To create a personal prognostic model and modify the risk stratification of paediatric acute myeloid leukaemia, we downloaded the clinical data of 597 patients from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database as a training set and included 189 patients from our centre as a validation set. In the training set, age at diagnosis, ‐7/del(7q) or ‐5/del(5q), core binding factor fusion genes, FMS‐like tyrosine kinase 3‐internal tandem duplication (FLT3‐ITD)/nucleophosmin 1 (NPM1) status, Wilms tumour 1 (WT1) mutation, biallelic CCAAT enhancer binding protein alpha (CEBPA) mutation were strongly correlated with overall survival and included to construct the model. The prognostic model demonstrated excellent discriminative ability with the Harrell's concordance index of 0.68, 3‐ and 5‐year area under the receiver operating characteristic curve of 0.71 and 0.72 respectively. The model was validated in the validation set and outperformed existing prognostic systems. Additionally, patients were stratified into three risk groups (low, intermediate and high risk) with significantly distinct prognosis, and the model successfully identified candidates for haematopoietic stem cell transplantation. The newly developed prognostic model showed robust ability and utility in survival prediction and risk stratification, which could be helpful in modifying treatment selection in clinical routine. [ABSTRACT FROM AUTHOR]
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- 2022
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6. Therapy‐related myeloid neoplasms with normal karyotype show distinct genomic and clinical characteristics compared to their counterparts with abnormal karyotype.
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Tariq, Hamza, Barnea Slonim, Liron, Coty Fattal, Zachary, Alikhan, Mir B., Segal, Jeremy, Gurbuxani, Sandeep, Helenowski, Irene B., Zhang, Hui, Sukhanova, Madina, Lu, Xinyan, Altman, Jessica K., Chen, Qing C., and Behdad, Amir
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KARYOTYPES , *MYELODYSPLASTIC syndromes , *CANCER chemotherapy , *SURVIVAL analysis (Biometry) , *OVERALL survival - Abstract
Summary: Therapy‐related myeloid neoplasms (t‐MNs) are a complication of treatment with cytotoxic chemotherapy and/or radiation therapy. The majority of t‐MNs show chromosomal abnormalities associated with myelodysplastic syndrome (MDS) or KMT2A rearrangements and are characterized by poor clinical outcomes. A small but substantial subset of patients have normal karyotype (NK) and their clinical characteristics and mutational profiles are not well studied. We retrospectively studied patients diagnosed with t‐MN at three institutions and compared the mutational profile and survival data between t‐MNs with NK and t‐MNs with abnormal karyotype (AK). A total of 204 patients with t‐MN were identified including 158 with AK and 46 with NK. NK t‐MNs, compared to AK, were enriched for mutations in TET2 (p < 0.0001), NPM1 (p < 0.0001), ASXL1 (p = 0.0003), SRSF2 (p < 0.0001), RUNX1 (p = 0.0336) and STAG2 (p = 0.0099) and showed a significantly lower frequency of TP53 mutations (p < 0.0001). Overall survival (OS) was significantly lower in AK t‐MNs as compared to NK cases (p = 0.0094). In our study, NK t‐MNs showed a significantly better OS, a higher prevalence of MN‐associated mutations and a lower frequency of TP53 mutations compared to their AK counterparts. The distinct clinical and mutational profile of NK t‐MNs merits a separate classification. [ABSTRACT FROM AUTHOR]
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- 2022
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7. A novel algorithmic approach to generate consensus treatment guidelines in adult acute myeloid leukaemia.
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Coats, Thomas, Bean, Daniel, Basset, Aymeric, Sirkis, Tamir, Brammeld, Jonathan, Johnson, Sean, Thomas, Ian, Gilkes, Amanda, Raj, Kavita, Dennis, Mike, Knapper, Steve, Mehta, Priyanka, Khwaja, Asim, Hunter, Hannah, Tauro, Sudhir, Bowen, David, Jones, Gail, Dobson, Richard, Russell, Nigel, and Dillon, Richard
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ACUTE myeloid leukemia , *DECISION trees , *MYELOID leukemia - Abstract
Summary: Induction therapy for acute myeloid leukaemia (AML) has changed with the approval of a number of new agents. Clinical guidelines can struggle to keep pace with an evolving treatment and evidence landscape and therefore identifying the most appropriate front‐line treatment is challenging for clinicians. Here, we combined drug eligibility criteria and genetic risk stratification into a digital format, allowing the full range of possible treatment eligibility scenarios to be defined. Using exemplar cases representing each of the 22 identified scenarios, we sought to generate consensus on treatment choice from a panel of nine aUK AML experts. We then analysed >2500 real‐world cases using the same algorithm, confirming the existence of 21/22 of these scenarios and demonstrating that our novel approach could generate a consensus AML induction treatment in 98% of cases. Our approach, driven by the use of decision trees, is an efficient way to develop consensus guidance rapidly and could be applied to other disease areas. It has the potential to be updated frequently to capture changes in eligibility criteria, novel therapies and emerging trial data. An interactive digital version of the consensus guideline is available. [ABSTRACT FROM AUTHOR]
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- 2022
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8. Is the risk of childhood leukaemia associated with socioeconomic measures in Denmark? A nationwide register‐based case‐control study.
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Erdmann, Friederike, Hvidtfeldt, Ulla Arthur, Feychting, Maria, Sørensen, Mette, and Raaschou‐Nielsen, Ole
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LEUKEMIA ,ACUTE myeloid leukemia ,CASE-control method ,MYELOID leukemia - Abstract
The aetiology of childhood leukaemia is poorly understood. Knowledge about differences in risk by socioeconomic status (SES) may enhance etiologic insights. We conducted a nationwide register‐based case‐control study to evaluate socioeconomic differences in the risk of childhood leukaemia in Denmark and to access whether associations varied by different measures of SES, time point of assessment, leukaemia type and age at diagnosis. We identified all cases of leukaemia in children aged 0 to 19 years, born and diagnosed between 1980 and 2013 from the Danish Cancer Registry (N = 1336) and sampled four individually matched controls per case (N = 5330). We used conditional logistic regression models for analysis. Medium and high level of parental education was associated with a higher risk of acute myeloid leukaemia (AML) in the offspring, mainly driven by children diagnosed at ages 0 to 4 years [odds ratio (OR) for high maternal education = 3.07; 95% confidence interval (CI): 1.44‐6.55]. We also observed a modestly increased risk for lymphoid leukaemia (LL) in association with higher level of parental education, but only in children diagnosed at ages 5 to 19 years. Higher parental income was associated with an increased risk of LL but not AML among children aged 5 to 19 years at diagnosis (OR for high maternal income = 2.78; 95% CI: 1.32‐5.89). Results for neighbourhood SES measures indicated null associations. Bias or under‐ascertainment of cases among families with low income or basic education are unlikely to explain the observed socioeconomic differences. Future research addressing explicitly the underlying mechanisms of our results may help to enhance etiologic insights of the disease. What's new? The aetiology of childhood leukaemia is still poorly understood. In this nationwide register‐based case‐control study, the authors found that higher level of parental education was associated with higher risk of childhood leukaemia in Denmark, particularly acute myeloid leukaemia. Higher parental income was also associated with an increased risk of lymphoid leukaemia, but only among children aged 5‐19 years. Bias or under‐ascertainment of cases among families with low income or basic education are unlikely to explain the observed socioeconomic differences. Identifying differences in the risk of childhood leukaemia by socioeconomic group may help to generate new etiologic hypotheses, which are urgently needed for developing prevention strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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9. Response to erythropoiesis‐stimulating agents in patients with WHO‐defined myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN‐RS‐T).
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Antelo, Guadalupe, Mangaonkar, Abhishek A., Coltro, Giacomo, Buradkar, Ajinkya, Lasho, Terra L., Finke, Christy, Carr, Ryan, Binder, Moritz, Gangat, Naseema, Al‐Kali, Aref, Elliott, Michelle A., King, Rebecca L., Howard, Matthew, Melody, Megan E., Hogan, William, Litzow, Mark R, Tefferi, Ayalew, Fernandez‐Zapico, Martin E., Komrokji, Rami, and Patnaik, Mrinal M.
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MYELOFIBROSIS , *MYELODYSPLASTIC syndromes , *LEUKOCYTE count - Abstract
Response to erythropoiesis-stimulating agents in patients with WHO-defined myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) Keywords: MDS/MPN-RS-T; myeloid leukaemia; erythropoiesis stimulating agents; ESA; MDS-RS; sideroblastic anaemia EN MDS/MPN-RS-T myeloid leukaemia erythropoiesis stimulating agents ESA MDS-RS sideroblastic anaemia e104 e108 5 04/30/20 20200501 NES 200501 To the Editor, In the 2016 iteration of the World Health Organisation (WHO) classification of myeloid neoplasms, myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) has been included as a unique entity, defined by the presence of erythroid lineage dysplasia in the presence or absence of multilineage dysplasia and persistent thrombocytosis (platelet count >=450 × 10 SP 9 sp /l), without other disease-defining genetic abnormalities (Arber I et al i ., [1]). We conducted a single institution retrospective study to assess ESA responses among WHO-defined patients with MDS/MPN-RS-T. After Institutional Review Board approval, adult patients with WHO-defined MDS/MPN-RS-T, diagnosed from years 2002 to 2014 at our institution, were included in the study. While ESA therapy has long been used to manage anaemia in MDS/MPN-RS-T, ours is the first study to meticulously document ESA response rates in these patients by using the IWG MDS/MPN overlap syndrome response criteria (Savona I et al i ., [14]). [Extracted from the article]
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- 2020
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10. Peripheral blood blast rate of clearance is an independent predictor of clinical response and outcomes in acute myeloid leukaemia.
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Holtzman, Noa G., El Chaer, Firas, Baer, Maria R., Ali, Omer, Patel, Ameet, Duong, Vu H., Sausville, Edward A., Singh, Zeba N., Koka, Rima, Zou, Ying S., Etemadi, Arash, and Emadi, Ashkan
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LEUKEMIA , *ACUTE myeloid leukemia , *BLOOD , *BONE marrow , *BLASTING - Abstract
Summary: The day 14 bone marrow aspirate and biopsy (D14BM) is regularly used to predict achievement of complete remission (CR) with induction chemotherapy in acute myeloid leukemia (AML), however its utility has been questioned. Clearance of peripheral blood blasts (PBB) may serve as an early measure of chemosensitivity. PBB rate of clearance (PBB‐RC) was calculated for treatment‐naive AML patients (n = 164) undergoing induction with an anthracycline and cytarabine (7+3) and with detectable PBB at diagnosis. PBB‐RC was defined as the percentage of the absolute PBB count on the day of diagnosis that was cleared with each day of therapy, on average, until D14 or day of PBB clearance. Each 5% increase in PBB‐RC approximately doubled the likelihood of D14BM clearance (OR = 1·81; 95% CI: 1·24–2·64, P < 0·005). PBB‐RC was also associated with improved CR rates (OR per 5% = 1·97; 95% CI: 1·27–3·01, P < 0·005) and overall survival (OS) [hazard ratio (HR) per 5% = 0·67; 95% CI: 0·52–0·87]. African American patients had poorer OS adjusted for PBB‐RC (HR = 2·18; 95% CI: 1·13–4·23), while race was not associated with D14BM or CR rate. PBB‐RC during induction chemotherapy is predictive of D14BM clearance, CR, and OS, and can therefore serve as a prognostic marker for clinical outcomes in AML. [ABSTRACT FROM AUTHOR]
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- 2020
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11. Patients aged less than 3 years with acute myeloid leukaemia characterize a molecularly and clinically distinct subgroup.
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Hara, Yusuke, Shiba, Norio, Yamato, Genki, Ohki, Kentaro, Tabuchi, Ken, Sotomatsu, Manabu, Tomizawa, Daisuke, Kinoshita, Akitoshi, Arakawa, Hirokazu, Saito, Akiko M., Kiyokawa, Nobutaka, Tawa, Akio, Horibe, Keizo, Taga, Takashi, Adachi, Souichi, Taki, Tomohiko, and Hayashi, Yasuhide
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LEUKEMIA , *PROGNOSIS , *INFANTS , *PATIENTS , *CANCER chemotherapy - Abstract
Summary: Although infants (age <1 year) with acute myeloid leukaemia (AML) have unique characteristics and are vulnerable to chemotherapy, children aged 1–2 years with AML may have characteristics similar to that of infants. Thus, we analysed 723 paediatric AML patients treated on the Japanese AML99 and AML‐05 trials to identify characteristics of younger children. We identified patients aged <3 years (the younger group) as a distinct subgroup. KMT2A‐rearrangement (KMT2A‐R), CBFA2T3‐GLIS2, CBFB‐MYH11 and NUP98‐KDM5A were frequently found in the younger group. Prognostic analyses revealed poor 5‐year overall survival (OS), event‐free survival (EFS) and cumulative incidence of relapse (CIR) in patients with CBFA2T3‐GLIS2 (42%, 17% and 83%, respectively) and those with NUP98‐KDM5A (33%, 17% and 83%, respectively). Additionally, we identified KMT2A‐R and CBFB‐MYH11 as age‐specific prognostic markers. Regarding KMT2A‐R, the younger group had significantly better OS, EFS and CIR than the older group (aged 3 to <18 years) (P = 0·023, 0·011 and <0·001, respectively). Conversely, concerning CBFB‐MYH11, the younger group had significantly poor EFS and CIR than the older group (each P < 0·001), suggesting that certain molecular markers are linked to different prognoses according to age. Therefore, we characterized patients <3 years as a distinct subgroup of paediatric AML. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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12. Next‐generation sequencing for measurable residual disease detection in acute myeloid leukaemia.
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Ghannam, Jack, Dillon, Laura W., and Hourigan, Christopher S.
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NUCLEOTIDE sequencing , *ACUTE promyelocytic leukemia , *LEUKEMIA , *HEMATOLOGIC malignancies , *SOMATIC mutation - Abstract
Summary: Acute myeloid leukaemia (AML) is a blood cancer characterized by acquired genetic mutations. There is great interest in accurately establishing measurable residual disease (MRD) burden in AML patients in remission after treatment but at risk of relapse. However, inter‐ and intrapatient genetic diversity means that, unlike in the chronic myeloid and acute promyelocytic leukaemias, no single genetic abnormality is pathognomonic for all cases of AML MRD. Next‐generation sequencing offers the opportunity to test broadly and deeply for potential genetic evidence of residual AML, and while not currently accepted for such use clinically, is likely to be increasingly used for AML MRD testing in the future. [ABSTRACT FROM AUTHOR]
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- 2020
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13. How to address second and therapy‐related acute myelogenous leukaemia.
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Oliai, Caspian and Schiller, Gary
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LEUKEMIA , *BISPECIFIC antibodies , *STEM cell transplantation , *CELLULAR therapy , *MULTIDRUG resistance - Abstract
Summary: Secondary acute myelogenous leukaemia (AML), as compared to de novo AML, occurs in the more elderly population, is independently more resistant to cytotoxic chemotherapy, has a higher relapse rate, and a worse prognosis. Secondary AML (sAML) is a heterogeneous disease, both biologically and clinically, even within the World Health Organization subgroups of sAML. Outcomes are the poorest in subgroups with sAML arising from an antecedent haematologic disorder which has been previously treated (ts‐AML), and sAML in patients <55 years of age. This review describes the suboptimal outcomes of contemporary therapy, to support the notion of an unmet need for innovative treatment strategies in sAML. Despite the recent approval of CPX‐351, long‐term outcomes for this high‐risk disease remain dismal. Resistance mechanisms to intensive chemotherapy contribute to relapse. Targeted immune therapy may avoid multidrug resistance mechanisms, but are unlikely to provide long‐term remission due to a complex and rapidly evolving clonal disease profile. Advances for sAML will likely be accomplished by CAR T cell therapy or bispecific antibodies providing a bridge to allogeneic stem cell transplantation. Therefore, focus should be placed on novel strategies that can augment the untargeted effector function of allogeneic grafts. [ABSTRACT FROM AUTHOR]
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- 2020
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14. Anthropometric factors and risk of myeloid leukaemias and myelodysplastic syndromes: a prospective study and meta‐analysis.
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Teras, Lauren R., Patel, Alpa V., Carter, Brian D., Rees‐Punia, Erika, McCullough, Marjorie L., and Gapstur, Susan M.
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MYELODYSPLASTIC syndromes , *CHRONIC myeloid leukemia , *LONGITUDINAL method , *BODY mass index , *BODY weight - Abstract
Summary: There is insufficient evidence linking excess body weight to risk of myeloid malignancies. We investigated this association using data from the Cancer Prevention Study‐II (CPS‐II), and a meta‐analysis of published cohort studies. Among 152 090 CPS‐II participants, 387 acute myeloid leukaemias (AML), 100 chronic myeloid leukaemias (CML) and 170 MDS were identified over 21 years of follow‐up. In CPS‐II, body mass index (BMI) was weakly associated with risk of CML (hazard ratio [HR] = 1·04, 95% confidence interval [CI]: 0·99–1·09 per 1 unit increase in BMI), AML (HR = 1·01, 95% CI: 0·98–1·03) and MDS (HR = 1·03, 95% CI: 0·99–1·07). After controlling for other anthropometric factors, no clear association was observed for height, BMI at age 18 years or weight change. In the meta‐analysis (n = 7117 myeloid leukaemias), BMI 25–29·9 kg/m2 (HRpooled = 1·36, 95% CI: 1·12–1·59) and BMI ≥30 kg/m2 (HRpooled = 1·43, 95% CI: 1·18–1·69) were associated with higher risk of myeloid leukaemia overall, compared to a BMI <25 kg/m2. Likewise, BMI ≥25 kg/m2 was positively associated with both AML and CML risk individually in the meta‐analysis. These results underscore the need for large studies to detect associations with rare cancers, and show a modest, but positive association between excess body weight and myeloid malignancy risk. [ABSTRACT FROM AUTHOR]
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- 2019
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15. Granulocyte transfusion during cord blood transplant for relapsed, refractory AML is associated with massive CD8 + T-cell expansion, significant cytokine release syndrome and induction of disease remission.
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Borrill R, Poulton K, Kusyk L, Routledge A, Bonney D, Hanasoge-Nataraj R, Powys M, Mustafa O, Campbell H, Senthil S, Dillon R, Jovanovic J, Morton S, James B, Rao K, Stanworth S, Konkel J, and Wynn R
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- Child, Humans, CD8-Positive T-Lymphocytes pathology, Cytokine Release Syndrome etiology, Granulocytes pathology, Interferon-gamma, Neoplasm Recurrence, Local etiology, Remission Induction, Cord Blood Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute therapy
- Abstract
In high-risk myeloid malignancy, relapse is reduced using cord blood transplant (CBT) but remains the principal cause of treatment failure. We previously described T-cell expansion in CBT recipients receiving granulocyte transfusions. We now report the safety and tolerability of such transfusions, T-cell expansion data, immunophenotype, cytokine profiles and clinical response in children with post-transplant relapsed acute leukaemia who received T-replete, HLA-mismatched CBT and pooled granulocytes within a phase I/II trial (ClinicalTrials.Gov NCT05425043). All patients received the transfusion schedule without significant clinical toxicity. Nine of ten patients treated had detectable measurable residual disease (MRD) pre-transplant. Nine patients achieved haematological remission, and eight became MRD negative. There were five deaths: transplant complications (n = 2), disease (n = 3), including two late relapses. Five patients are alive and in remission with 12.7 months median follow up. Significant T-cell expansion occurred in nine patients with a greater median lymphocyte count than a historical cohort between days 7-13 (median 1.73 × 10
9 /L vs. 0.1 × 109 /L; p < 0.0001). Expanded T-cells were predominantly CD8+ and effector memory or TEMRA phenotype. They exhibited markers of activation and cytotoxicity with interferon-gamma production. All patients developed grade 1-3 cytokine release syndrome (CRS) with elevated serum IL-6 and interferon-gamma., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)- Published
- 2023
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16. Clinical spectrum and clonal evolution in germline syndromes with predisposition to myeloid neoplasms.
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Perez Botero, Juliana, Ho, Thanh P., Hogan, William J., Kenderian, Saad, Gangat, Naseema, Tefferi, Ayalew, Abraham, Roshini S., Nguyen, Phuong, Oliveira, Jennifer L., He, Rong, Chen, Dong, Viswanatha, David, Rodriguez, Vilmarie, Khan, Shakila P., and Patnaik, Mrinal M.
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GERM cells , *GENETIC mutation , *MYELOID leukemia , *MYELODYSPLASTIC syndromes , *STEM cell transplantation - Abstract
The article discusses research which examined the adult and pediatric bone marrow failure syndrome database at the Mayo Clinic from 1990-2016 for patients with inherited bone marrow failure syndrome (IBMFS). Topics covered include the analysis of the electronic medical record for germline disorders, the demographic characteristics, clinical correlates, details on myeloid clonal evolution and outcomes, and outcomes of allogeneic stem cell transplantation.
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- 2018
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17. A retrospective review of acute myeloid leukaemia in 35 dogs diagnosed by a combination of morphologic findings, flow cytometric immunophenotyping and cytochemical staining results (2007‐2015).
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Davis, L. L., Hume, K. R., and Stokol, T.
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DOG diseases , *VETERINARY therapeutics , *ACUTE myeloid leukemia diagnosis , *ACUTE myeloid leukemia treatment , *LYMPHADENITIS , *FLOW cytometry , *TACHYPNEA , *IMMUNOPHENOTYPING - Abstract
Acute myeloid leukaemia (AML) is an uncommon, rapidly progressive neoplasm in dogs. The aim of this retrospective study was to characterize the clinical presentation, haematologic findings, diagnostic imaging results, treatment and survival time of a contemporary cohort of dogs with AML. Diagnosis was based on >20% blasts in bone marrow or blood identified as myeloid based on morphologic findings, flow cytometric immunophenotyping and cytochemical staining. Medical records of 35 dogs diagnosed with AML from 2007 to 2015 were included. Most dogs presented with inappetence (66%) and lethargy (57%) and physical examination findings of peripheral lymphadenopathy (74%) and tachypnea (62%). Common haematologic findings were quantifiable circulating blasts (85%; median blast count 35 700/μL; range: 300‐276 500/μL), anaemia (median haematocrit 34%; range: 11%‐52%) and thrombocytopenia (median 57 000/μL; range: 9000‐252 000/μL). Bicytopenia and pancytopenia were each found in 44% of dogs. Follow‐up information was available for 34 dogs. The overall median survival time from diagnosis was 19 days (range: 1‐121 days). Clinical progression in some dogs was not as rapid as previously reported. Haematologic responses to various chemotherapeutics were documented in 3 dogs, with associated survival times of 62, 103 and 121 days. Dogs treated with prednisone or a combination of chemotherapy and prednisone had improved survival compared to dogs that received symptomatic care only (
P < .0001). Our results show canine AML has an overlapping clinical presentation with lymphoma. The prognosis for canine AML remains extremely guarded. Further studies are needed to optimize therapeutic regimens for dogs with AML. [ABSTRACT FROM AUTHOR]- Published
- 2018
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18. Impact of genotype on leukaemic transformation in polycythaemia vera and essential thrombocythaemia.
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Alvarez‐Larrán, Alberto, Senín, Alicia, Fernández‐Rodríguez, Concepción, Pereira, Arturo, Arellano‐Rodrigo, Eduardo, Gómez, Montse, Ferrer‐Marin, Francisca, Martínez‐López, Joaquín, Camacho, Laura, Colomer, Dolors, Angona, Anna, Navarro, Blanca, Cervantes, Francisco, Besses, Carlos, Bellosillo, Beatriz, and Hernández‐Boluda, Juan Carlos
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POLYCYTHEMIA vera , *THROMBOCYTOPENIA , *MYELOID leukemia , *GENOTYPES , *PROGNOSIS - Abstract
The influence of driver mutations on leukaemic transformation was analysed in 1747 patients with polycythaemia vera or essential thrombocythaemia. With a median follow-up of 7·2 years, 349 patients died and 62 progressed to acute leukaemia or myelodysplastic syndrome. Taking death as a competing risk, CALR genotype was associated with a lower risk of transformation [subdistribution hazard ratio (SHR): 0·13, 95% confidence interval (CI): 0·2-0·9, P = 0·039], whereas JAK2 V617F showed borderline significance for higher risk (SHR: 2·05, 95% CI: 0·9-4·6, P = 0·09). Myelofibrotic transformation increased leukaemic risk, except in CALR-mutated patients. Next generation sequencing of 51 genes at the time of transformation showed additional mutations (median number: 3; range: 1-5) in 25 out of 29 (86%) assessable cases. Mutations (median: 1; range: 1-3) were detected in 67% of paired samples from the chronic phase. Leukaemia appeared in a JAK2 V617F negative clone in 17 (58%) cases, eleven of them being previously JAK2 V617F-positive. JAK2 V617F-mutated leukaemia was significantly associated with complex karyotype and acquisition of TP53 mutations, whereas EZH2 and RUNX1 mutations were more frequent in JAK2 V617F-negative leukaemia. Survival was longer in JAK2 V617F-unmutated leukaemia (343 days vs. 95 days, P = 0·003). In conclusion, CALR genotype is associated with a lower risk of leukaemic transformation. Leukaemia arising in a JAK2 V617F-negative clone is TP53 independent and shows better survival. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
19. PHF6 mutations in paediatric acute myeloid leukaemia.
- Author
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Rooij, Jasmijn D. E., Heuvel ‐ Eibrink, Marry M., Rijdt, Nina K. A. M., Verboon, Lonneke J., Haas, Valerie, Trka, Jan, Baruchel, Andre, Reinhardt, Dirk, Pieters, Rob, Fornerod, Maarten, and Zwaan, Christian Michel
- Subjects
- *
MYELOID leukemia , *CHILDHOOD cancer , *PEDIATRICS , *CHROMOSOME abnormalities , *HEMATOLOGY - Abstract
The article discusses PHF6 mutation in pediatric acute myeloid leukemia (AML), a heterogeneous disease marked by the presence of different collaborating cytogenic aberrations. Topics discussed include findings from a study on 318 de novo pediatric AML cases, the prevalence of PHF6 mutations in males, and results of qRT-PCR analysis performed on patients with available RNA.
- Published
- 2016
- Full Text
- View/download PDF
20. MAPK8-mediated stabilization of SP1 is essential for RUNX1- RUNX1T1 - driven leukaemia.
- Author
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Maiques‐Diaz, Alba, Hernando, Miriam, Sánchez‐López, Amanda, Rio‐Machin, Ana, Shrestha, Mahesh, Mulloy, James C., Cigudosa, Juan C., and Alvarez, Sara
- Subjects
- *
LEUKEMIA risk factors , *CHIMERIC proteins , *RUNX proteins , *RETROVIRUSES , *GENE expression - Abstract
The article discusses the study on leukaemia that is driven by RUNX1-RUNX1T1 fusion protein. The study reportedly involved transducing of normal CD34+cells with RUNX1-RUNX1T1-expressing retroviruses. The results revealed that MAPK8-mediated stabilization of SP1 is crucial for RUNX1-RUNX1T1-driven leukaemia.
- Published
- 2016
- Full Text
- View/download PDF
21. You have free access to this contentAddition of suberoylanilide hydroxamic acid (Vorinostat) to azacitidine for patients with higher risk myelodysplastic syndromes and azacitidine failure: a phase II add-on study from the Groupe Francophone des Myelodysplasies.
- Author
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Prebet, Thomas, Delaunay, Jacques, Wattel, Eric, Braun, Thorsten, Cony‐Makhoul, Pascale, Dimicoli, Sophie, Wickenhauser, Stephan, Lejeune, Julie, Chevret, Sylvie, Chermat, Fatiha, Fenaux, Pierre, and Vey, Norbert
- Subjects
- *
HYDROXAMIC acids , *AZACITIDINE , *MYELODYSPLASTIC syndromes , *DNA methylation , *HISTONE deacetylase , *GENE silencing , *THERAPEUTICS - Abstract
The article looks at a study regarding the addition of suberoylanilide hydroxamic acid to azacitidine for patients with higher risk myelodysplastic syndromes and azacitidine failure. It mentions DNA methylation and histone deacetylation (HDAC) are synergistic in terms of gene silencing and the combination of inhibitors. It also mentions toxicity and efficacy of new drugs in combination with hypomethylating agents (HMAs).
- Published
- 2018
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22. Stromal CYR61 Confers Resistance to Mitoxantrone via Spleen Tyrosine Kinase Activation in Human Acute Myeloid Leukaemia.
- Author
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Long, Xin, Yu, Yang, Perlaky, Laszlo, Man, Tsz‐Kwong, and Redell, Michele S.
- Subjects
- *
ACUTE myeloid leukemia treatment , *APOPTOSIS inhibition , *CELLULAR signal transduction , *CHEMORECEPTORS , *DRUG resistance , *MITOXANTRONE , *THERAPEUTICS - Abstract
Approximately 50% of children with acute myeloid leukaemia ( AML) relapse, despite aggressive chemotherapy. The bone marrow stromal environment protects leukaemia cells from chemotherapy (i.e., stroma-induced chemoresistance), eventually leading to recurrence. Our goal is to delineate the mechanisms underlying stroma-mediated chemoresistance in AML. We used two human bone marrow stromal cell lines, HS-5 and HS-27A, which are equally effective in protecting AML cells from chemotherapy-induced apoptosis in AML-stromal co-cultures. We found that CYR61 was highly expressed by stromal cells, and was upregulated in AML cells by both stromal cell lines. CYR61 is a secreted matricellular protein and is associated with cell-intrinsic chemoresistance in other malignancies. Here, we show that blocking stromal CYR61 activity, by neutralization or RNAi, increased mitoxantrone-induced apoptosis in AML cells in AML-stromal co-cultures, providing functional evidence for its role in stroma-mediated chemoresistance. Further, we found that spleen tyrosine kinase ( SYK) mediates CYR61 signalling. Exposure to stroma increased SYK expression and activation in AML cells, and this increase required CYR61. SYK inhibition reduced stroma-dependent mitoxantrone resistance in the presence of CYR61, but not in its absence. Therefore, SYK is downstream of CYR61 and contributes to CYR61-mediated mitoxantrone resistance. The CYR61- SYK pathway represents a potential target for reducing stroma-induced chemoresistance. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
23. Targeting of the Hedgehog pathway in myeloid malignancies: still a worthy chase?
- Author
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Khan, Alesia A., Harrison, Claire N., and McLornan, Donal P.
- Subjects
- *
MYELOID leukemia , *LEUKEMIA treatment , *CELLULAR signal transduction , *SMALL molecules , *TARGETED drug delivery , *HEMATOLOGY , *ENZYME inhibitors - Abstract
Deregulated Hedgehog (Hh) signalling activity may be associated with a broad range of cancer types and hence has become an attractive target for therapeutic intervention. Although initial haematological interest focused on the therapeutic targeting of this pathway in chronic myeloid leukaemia), small molecule inhibitors targeting the Hh pathway are now being tested in a range of other myeloid disorders, including myelofibrosis, myelodysplasia and acute myeloid leukaemia. In this review we will evaluate the rationale for targeting of the Hh pathway in myeloid diseases and discuss the novel agents that have entered the clinical arena. We will discuss pre-clinical models, emerging clinical trial data, and suggest how these targeted therapies may address current unmet medical needs. Finally, we will explore potential limitations of these therapies due to the emergence of secondary resistance mechanisms and speculate on future developments within this arena. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
24. The spectrum of somatic mutations in high-risk acute myeloid leukaemia with -7/del(7q).
- Author
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McNerney, Megan E., Brown, Christopher D., Peterson, April L., Banerjee, Mekhala, Larson, Richard A., Anastasi, John, Le Beau, Michelle M., and White, Kevin P.
- Subjects
- *
SOMATIC mutation , *DNA methylation , *LEUKEMIA treatment , *MYELOID leukemia , *TRANSCRIPTION factors , *TUMOR treatment - Abstract
-7/del(7q) occurs in half of myeloid malignancies with adverse-risk cytogenetic features and is associated with poor survival. We identified the spectrum of mutations that co-occur with -7/del(7q) in 40 patients with de novo or therapy-related myeloid neoplasms. -7/del(7q) leukaemias have a distinct mutational profile characterized by low frequencies of alterations in genes encoding transcription factors, cohesin and DNA-methylation-related proteins. In contrast, RAS pathway activating mutations occurred in 50% of cases, a significantly higher frequency than other acute myeloid leukaemias and higher than previously reported. Our data provide guidance for which pathways may be most relevant in the treatment of adverse-risk myeloid leukaemia. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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25. Prognostic factors for acute myeloid leukaemia in adults - biological significance and clinical use.
- Author
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Liersch, Ruediger, Müller‐Tidow, Carsten, Berdel, Wolfgang E., and Krug, Utz
- Subjects
- *
ACUTE myeloid leukemia , *CHROMOSOME abnormalities , *GENETIC mutation , *MYELODYSPLASTIC syndromes , *GENE expression , *DECISION making in clinical medicine , *PROGNOSIS - Abstract
Acute myeloid leukaemia ( AML) is a heterogenous disease. Prognosis of AML is influenced both by patient-specific as well as disease-specific factors. Age is the most prominent patient-specific risk factor, while chromosomal aberrations are the strongest disease-specific risk factors. For patients with cytogenetically normal AML, prognosis can be specified by mutational status of the genes NPM1, FLT3 and CEBPA. A growing number of recurrent mutations in additional genes have recently been identified, for which the prognostic effect yet has to be determined. Performance status, geriatric assessment, secondary leukaemia following myelodysplastic syndrome or cytotoxic treatment, common laboratory parameters, leukaemic stem cell frequency, bone marrow microenvironment, gene expression levels, epigenetic changes, micro- RNA's as well as kinetics and depth of response to treatment influence prognosis of AML patients. Despite the high number of established risk factors, only few predictive markers exist which can truly aid therapy decisions in patients with AML. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
26. Subsequent leukaemia in autoimmune disease patients.
- Author
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Hemminki, Kari, Liu, Xiangdong, Försti, Asta, Ji, Jianguang, Sundquist, Jan, and Sundquist, Kristina
- Subjects
- *
LEUKEMIA risk factors , *AUTOIMMUNE diseases , *HOSPITAL care , *MYELOFIBROSIS , *RHEUMATOID arthritis , *PROPORTIONAL hazards models - Abstract
Previous studies have shown that patients diagnosed with some autoimmune ( AI) diseases are at an increased risk of leukaemia but limited data are available on survival. We systematically analysed the risks (standardized incidence ratio, SIR) and survival (hazard ratio, HR) in nine types of leukaemia among 402 462 patients hospitalized for any of 33 AI diseases and compared to persons not hospitalized for AI diseases. Risk for all leukaemia was increased after 13 AI diseases and survival was decreased after six AI diseases. SIRs were increased after all AI diseases for seven types of leukaemia, including SIR 1·69 (95% confidence interval ( CI): 1·29-2·19) for acute lymphoblastic leukaemia ( ALL), 1·85 (95% CI: 1·65-2·07) for acute myeloid leukaemia, 1·68 (95% CI: 1·37-2·04) for chronic myeloid leukaemia, 2·20 (95% CI: 1·69-2·81) for 'other myeloid leukaemia', 2·45 (95% 1·99-2·98) for 'other and unspecified leukaemia', 1·81 (95% CI: 1·11-2·81) for monocytic leukaemia, and 1·36 (95% CI: 1·08-1·69) for myelofibrosis. The HRs were increased for four types of leukaemia, most for myelofibrosis (1·74, 95% CI: 1·33-2·29) and ALL (1·42, 95% CI: 1·03-1·95). Some AI diseases, including rheumatoid arthritis, were associated with increased SIRs and HRs in many types of leukaemia. The present data showed increases in risk and decreases in survival for many types of leukaemia after various AI diseases. Leukaemia is a rare complication in AI disease but findings about this comorbidity at the time of leukaemia diagnosis may help to optimize the treatment and improve survival. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
27. Flow cytometry thresholds of myeloperoxidase detection to discriminate between acute lymphoblastic or myeloblastic leukaemia.
- Author
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Guy, Julien, Antony‐Debré, Iléana, Benayoun, Emmanuel, Arnoux, Isabelle, Fossat, Chantal, Garff‐Tavernier, Magali, Raimbault, Anna, Imbert, Michèle, Maynadié, Marc, Lacombe, Francis, Béné, Marie C, and Wagner‐Ballon, Orianne
- Subjects
- *
LYMPHOBLASTIC leukemia diagnosis , *MYELOPEROXIDASE , *FLOW cytometry , *NOSOLOGY , *CYTOCHEMISTRY - Abstract
The World Health Organization 2008 Classification emphasizes myeloperoxidase ( MPO) detection as sufficient for assigning a blast population to the myeloid lineage. Published MPO positivity thresholds are 10% for flow cytometry ( FCM) but 3% for cytochemistry. Here we re-evaluated the FCM- MPO threshold by comparing retrospectively 128 acute lymphoblastic leukaemias and 75 acute myeloid leukaemias without maturation, all assessed by benzidine-based cytochemistry. A 13% threshold was found to be relevant using an isotype control as background-reference (sensitivity 95·1%, specificity 91·7%). Residual normal lymphocytes proved to be an advantageous alternative reference, a threshold of 28% yielding improved 97·4% sensitivity and 96·1% specificity. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
28. Poor prognosis in familial acute myeloid leukaemia with combined biallelic CEBPA mutations and downstream events affecting the ATM, FLT3 and CDX2 genes.
- Author
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Carmichael, Catherine L., Wilkins, Ella J., Bengtsson, Henrik, Horwitz, Marshall S., Speed, Terence P., Vincent, Paul C., Young, Graham, Hahn, Christopher N., Escher, Robert, and Scott, Hamish S.
- Subjects
- *
LETTERS to the editor , *MYELOID leukemia - Abstract
A letter to the editor is presented related to loss of CEBPA gene function in patients with acute myeloid leukaemia due to biallelic point mutation.
- Published
- 2010
- Full Text
- View/download PDF
29. Current status of gene expression profiling in the diagnosis and management of acute leukaemia.
- Author
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Bacher, Ulrike, Kohlmann, Alexander, and Haferlach, Torsten
- Subjects
- *
LEUKEMIA diagnosis , *GENE expression , *ACUTE myeloid leukemia , *LYMPHOBLASTIC leukemia , *KARYOTYPES , *HUMAN cytogenetics - Abstract
Gene expression profiling (GEP) enables the simultaneous investigation of the expression of tens of thousands of genes and was successfully introduced in leukaemia research a decade ago. Aiming to better understand the diversity of genetic aberrations in acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL), pioneer studies investigated and confirmed the predictability of many cytogenetic and molecular subclasses in AML and ALL. In addition, GEP can define new prognostic subclasses within distinct leukaemia subgroups, as illustrated in AML with normal karyotype. Another approach is the development of treatment-specific sensitivity assays, which might contribute to targeted therapy studies. Finally, GEP might enable the detection of new molecular targets for therapy in patients with acute leukaemia. Meanwhile, large multicentre studies, e.g. the Microarray Innovations in LEukaemia (MILE) study, prepare for a standardised introduction of GEP in leukaemia diagnostic algorithms, aiming to translate this novel methodology into clinical routine for the benefit of patients with the complex disorders of AML and ALL. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
30. In vitro anti-leukaemia activity of sphingosine kinase inhibitor.
- Author
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Ricci, Clara, Onida, Francesco, Servida, Federica, Radaelli, Franca, Saporiti, Giorgia, Todoerti, Katia, Deliliers, Giorgio Lambertenghi, and Ghidoni, Riccardo
- Subjects
- *
MYELOID leukemia , *ENZYME inhibitors , *SPHINGOSINE , *IMATINIB , *METHANESULFONATES - Abstract
Compelling evidence indicates the role of sphingosine kinase 1 (SPHK1) deregulation in the processes of carcinogenesis and acquisition of drug resistance, providing the rationale for an effective anti-cancer therapy. However, no highly selective inhibitors of SPHK1 are available for in vitro and in vivo studies, except for the newly discovered ‘SK inhibitor’ (SKI). The present study showed that, in a panel of myeloid leukaemia cell lines, basal level of SPHK1 correlated with the degree of kinase inhibition by SKI. Exposure to SKI caused variable anti-proliferative, cytotoxic effects in all cell lines. In particular, SKI induced an early, significant inhibition of SPHK1 activity, impaired cell cycle progression and triggered apoptosis in K562 cells. Moreover, SKI acted synergistically with imatinib mesylate (IM) to inhibit cell growth and survival. Finally, the inhibitor affected the clonogenic potential and viability of primary cells from chronic myeloid leukaemia (CML) patients, including one harbouring the IM-insensitive Abl kinase domain mutation T315I. Due to the fact that the phenomenon of resistance to IM remains a major issue in the treatment of patients with CML, the identification of alternative targets and new drugs may be of clinical relevance. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
31. t(14;22)(q32;q11) in non-Hodgkin lymphoma and myeloid leukaemia: molecular cytogenetic investigations.
- Author
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Aamot, Hege Vangstein, Bjørnslett, Merete, Delabie, Jan, and Heim, Sverre
- Subjects
- *
LYMPHOMAS , *CHRONIC lymphocytic leukemia , *HUMAN cytogenetics , *FLUORESCENCE in situ hybridization , *HUMAN chromosome abnormalities ,LEUKEMIA genetics - Abstract
Two non-Hodgkin lymphomas (NHL), one chronic lymphocytic leukaemia/small lymphocytic lymphoma and one diffuse large B-cell lymphoma and three cases of myeloid leukaemia, two chronic (CML) and one acute (AML), showed, by G-banding analysis, apparently identical chromosomal translocations t(14;22)(q32;q11), in three of the cases as the sole abnormality. Fluorescence in situ hybridisation (FISH) analysis with locus-specific probes for ABL at 9q34 [bacterial artificial chromosomes (BACs) 835J22 and 1132H12], IGH at 14q32 [P1 artificial chromosome (PAC) 998D24] and IGL (PAC 1019H10) and BCR (BAC 74M14) at 22q11, as well as multicolour in situ hybridisation (M-FISH) analyses were performed. A three-way variant translocation of the classical t(9;22)(q34;q11), t(9;22;14)(q34;q11;q32), involving both BCR and ABL, was unravelled by the molecular cytogenetic investigations in the three myeloid leukaemia cases; a similar variant translocation has previously been reported in seven CML. The two cases of NHL (one NHL with a similar 14;22-translocation has been reported previously) had no involvement of BCR or ABL, but instead the IGH and IGL genes were shown to be juxtaposed by the t(14;22)(q32;q11). How such a rearrangement with recombination of IGH and IGL might elicit a pathogenetic effect is completely unknown. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
32. Expression of co-stimulatory molecules on acute myeloid leukaemia blasts may effect duration of first remission.
- Author
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Whiteway, Alastair, Corbett, Tim, Anderson, Robert, Macdonald, Ian, and Prentice, H. Grant
- Subjects
- *
MYELOID leukemia , *LEUKEMIA - Abstract
Summary. Many solid tumours have been shown to lack expression of either of the immune co-stimulatory molecules CD80 (B7·1) or CD86 (B7·2), which is thought to be one of the ways in which tumours may escape immune recognition. We have examined the surface expression of CD80, CD86, human leucocyte antigen (HLA) class I and II, CD11a, CD54, and CD58 on the blast cells from patients with acute myeloid leukaemia (AML) at presentation. CD80 was only rarely expressed on AML blasts and, in those leukaemic cells expressing CD80, the level of expression was low. In contrast, expression of CD86 was detected on the AML blasts in more than half of the samples tested and, in some cases, the level of expression was equivalent to that of mature monocytes and activated B lymphocytes. The percentage of leukaemic blasts expressing CD86 was higher in the M4 and M5 French–American–British (FAB) types, and expression of CD11a and HLA class II was higher in the M4 FAB type. There was no difference in expression of CD80, CD54, CD58, or HLA Class I between different FAB subgroups. There was no significant difference in duration of first remission with expression of CD80, CD86, CD11a, CD54 or HLA class II. However, when expression of CD80 and CD86 were considered together, a significantly longer duration of remission was found. We suggest that these molecules may play a role in immunosurveillance, resulting in prolonged remission in some patients treated for AML. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
33. The leukaemia-associated transcription factors EVI-1 and MDS1/EVI1 repress transcription and interact with histone deacetylase.
- Author
-
Vinatzer, Ursula, Taplick, Jan, Seiser, Christian, Fonatsch, Christa, and Wieser, Rotraud
- Subjects
- *
TRANSCRIPTION factors , *HISTONE deacetylase ,LEUKEMIA genetics - Abstract
EVI-1 and its variant form, MDS1/EVI1, have been reported to act in an antagonistic manner and be differentially regulated in samples from patients with acute myeloid leukaemia and rearrangements of the long arm of chromosome 3. Here, we show that both EVI-1 and MDS1/EVI1 can repress transcription from a reporter construct containing EVI-1 binding sites and interact with histone deacetylase in mammalian cells. This interaction can be recapitulated in vitro and is mediated by a previously characterized transcription repression domain, whose activity is alleviated by the histone deacetylase inhibitor trichostatin A. [ABSTRACT FROM AUTHOR]
- Published
- 2001
- Full Text
- View/download PDF
34. Fludarabine-containing regimens severely impair peripheral blood stem cells mobilization and collection in acute myeloid leukaemia patients.
- Author
-
Visani, Lemoli, Tosi, Martinelli, Testoni, Ricci, Piccaluga, Pastano, Leopardi, Dizdari, Motta, Rizzi, Tura, and Visani, Giuseppe
- Subjects
- *
ACUTE myeloid leukemia , *STEM cells , *PERIPHERAL circulation , *GRANULOCYTE-colony stimulating factor , *AUTOTRANSPLANTATION , *PHYSIOLOGY , *PATIENTS - Abstract
We studied the effects of an intensified induction/consolidation treatment containing fludarabine (ICE/FLAN/FLAN) on the mobilization and collection of peripheral blood stem cells (PBSC) in 31 consecutive untreated acute myeloid leukaemia (AML) patients. The complete remission (CR) rate was comparable to classic inductions (68% after ICE; 84% after ICE-FLAN I). To mobilize PBSC, 19 patients received 10 μg/kg/d of granulocyte-colony stimulating factor (G-CSF) starting at day 13 after FLAN, 13 (69%) of whom were found to be nonmobilizers. When a second G-CSF administration was performed in 10/13 patients mobilization was either not achieved (8/10) or was considered insufficient (<1 × 106 CD34+ cells/kg) (2/10) and all 13 were subsequently submitted to bone marrow harvest. The harvest was considered adequate in 12/13 (92%) patients and autologous BMT (ABMT) has so far been performed in 10/12 cases with a mean of 8.6 × 108/kg nucleated reinfused cells. The median times to neutrophil and platelet recovery after ABMT did not significantly differ from those of two previous series of patients treated with ABMT without fludarabine-containing regimens. Adequate amounts of PBSC were obtained in 6/19 (31%) patients, who were then reinfused. Median times for platelet recovery were significantly longer than in a previous series of 26 AML cases reinfused with PBSC after treatment with the ICE-NOVIA induction/consolidation regimen (125 v 20 d to 20 × 109 plt/l, P < 0.02; 218 v 37 d to 50 × 109 plt/l, P < 0.02). In addition, times for platelet recovery after ICE/FLAN/FLAN were not significantly different from those in a previous group treated with ABMT performed after ICE/NOVIA,without fludarabine. We conclude that fludarabine-containing regimens severely impair mobilization and collection of PBSC in AML patients and seem unsuitable when PBSC autotransplantation is programmed. [ABSTRACT FROM AUTHOR]
- Published
- 1999
- Full Text
- View/download PDF
35. Butyrate-stable monosaccharide derivatives induce maturation and apoptosis in human acute myeloid leukaemia cells.
- Author
-
Santini, Scappini, Gozzini, Grossi, Villa, Ronco, Douillet, Pouillart, Bernabei, Rossi Ferrini, and Santini
- Subjects
- *
ACUTE myeloid leukemia , *APOPTOSIS , *BUTYRIC acid - Abstract
The rapid degradation and subsequent lack of efficacy of n-butyric acid in vivo has been improved by the synthesis of monosaccharide stable pro-drugs of butyric acid. We studied the effects of D1 (O-n-butanoyl-2,3-O-isopropylidene-alpha-D-mannofuranoside), G1 (1-O-n-butanoyl-D,L-xylitol), and F1 (1-O-n-butanoyl 2,3-O-isopropylidene-D,L-xylitol) on the maturation and proliferation of AML cell lines HL 60 and FLG 29.1 and of purified blast cells from 10 cases of de novo acute myeloid leukaemia (AML). AML cell maturation was measured by surface antigen expression, morphology and cytochemistry. Toxicology in mice was also evaluated (DL50 1000 mg/kg). In HL 60 cells G1 and D1 increased the expression of CD15 and CD11a (presenting 62% of promyelo-metamyelocytes), and in 7/10 cases of primary AMLs that of CD11a, CD11b, CD15, and myeloperoxidase. D1, G1 and F1 induced a dose-dependent inhibition of tritiated thymidine uptake. Apoptosis (evaluated by flow cytometry and agarose gel electrophoresis) was induced in AML blasts by D1 and F1 (79% and 94% respectively for HL 60 cells) and, with less effect, by G1 (27%). The persistence of maturative and apoptotic activity in these new pro-drugs of butyric acid, hydrolysed only inside the tumour cell, suggests a possible use in differentiation therapy of myelodysplastic syndromes and AMLs. [ABSTRACT FROM AUTHOR]
- Published
- 1998
- Full Text
- View/download PDF
36. Toll-like Receptors (TLRs) are expressed by myeloid leukaemia cell lines, but fail to trigger differentiation in response to the respective TLR ligands.
- Author
-
Okamoto, Masashi, Hirai, Hideyo, Taniguchi, Kyoko, Shimura, Kazuho, Inaba, Tohru, Shimazaki, Chihiro, Taniwaki, Masafumi, and Imanishi, Jiro
- Subjects
- *
CELL lines , *MYELOID leukemia , *LIGANDS (Biochemistry) , *POLYMERASE chain reaction , *CELL proliferation , *MESSENGER RNA , *PHYSIOLOGY - Abstract
The article presents a study which investigates if human leukaemic cells can express toll-like receptors (TLRs) and if TLR ligands induce myeloid differentiation of such cells. A reverse transcription polymerase chain reaction (PCR) was used to examine mRNA expression of TLRs by myeloid leukemia cell lines. However, imiquimod, which significantly delays cell proliferation, is the only TLR ligands tested to observe the acceleration or deceleration of the proliferation of the cell lines.
- Published
- 2009
- Full Text
- View/download PDF
37. Comparison of the survival implications of tumour-associated versus cancer-testis antigen expression in acute myeloid leukaemia.
- Author
-
Guinn, Barbara-ann, Tobal, Khalid, and Mills, Ken I.
- Subjects
- *
TUMORS , *ANTIGENS , *IMMUNOGLOBULINS , *EPITOPES , *THERAPEUTICS , *ONCOLOGY - Abstract
The article informs that a large number of tumor-associated antigens (TAA) have been identified in acute myeloid leukemia, some of which have been shown to play a predictive role in the monitoring of minimal residual disease (MRD). Furthermore, better definition of the relevance of these distinctly high TAA expressing patients may aid the future use of these markers in prognosis and MRD.
- Published
- 2007
- Full Text
- View/download PDF
38. Myeloid sarcoma of the uterus presenting as vaginal bleeding.
- Author
-
Pitz, M. W., Maslyak, O., Morales, C., and Seftel, M. D.
- Subjects
- *
MYELOID leukemia , *CANCER relapse , *UTERUS , *SARCOMA , *HEMORRHAGE - Abstract
Extramedullary relapse of acute myeloid leukaemia may occur in sites such as the central nervous system, testes, and skin. Presentations in the female genital tract are uncommon and usually asymptomatic. In contrast, symptomatic uterine myeloid sarcoma is very rare. Treatment of this is generally unsuccessful, but is improved when systemic therapies are used. We study a case of a uterine relapse of acute myeloid leukaemia presenting as vaginal bleeding and successfully managed by local irradiation. The mechanism of preferential infiltration of uterine tissue requires further study. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
39. Leukaemoid monocytosis in M4 AML following chemotherapy and G-CSF.
- Author
-
RANAGHAN, DRAKE, HUMPHREYS, MORRIS, and Morris
- Subjects
- *
LEUKEMIA treatment , *MYELOID leukemia , *MONOCYTOSIS , *GRANULOCYTE-colony stimulating factor , *THERAPEUTICS - Abstract
We describe a patient with M4 AML treated with standard chemotherapy followed by G-CSF who developed marked monocytosis on day 8 of G-CSF therapy. Fourteen days after discontinuation of G-CSF therapy his monocyte counts returned to normal levels and a marrow aspirate showed a reduction in blast cells. He received further chemotherapy without G-CSF and without any recurrence of the raised leucocyte count but failed to achieve full remission. Although this G-CSF-driven leucocytosis was alarming it did not appear to have adversely affected the patient’s prognosis. [ABSTRACT FROM AUTHOR]
- Published
- 1998
- Full Text
- View/download PDF
40. Acute Myeloid Leukaemia, Mixed Phenotype Acute Leukaemia, The Myelodysplastic Syndromes and Histiocytic Neoplasms
- Author
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Barbara J. Bain, David M. Clark, and Bridget S. Wilkins
- Subjects
business.industry ,Myelodysplastic syndromes ,Cancer research ,Medicine ,Myeloid leukaemia ,business ,medicine.disease ,Mixed phenotype acute leukaemia ,Histiocyte - Published
- 2009
41. Addition of suberoylanilide hydroxamic acid (Vorinostat) to azacitidine for patients with higher risk myelodysplastic syndromes and azacitidine failure: a phase II add-on study from the Groupe Francophone des Myelodysplasies.
- Author
-
Prebet T, Delaunay J, Wattel E, Braun T, Cony-Makhoul P, Dimicoli S, Wickenhauser S, Lejeune J, Chevret S, Chermat F, Fenaux P, and Vey N
- Subjects
- Aged, Azacitidine administration & dosage, Disease-Free Survival, Humans, Kaplan-Meier Estimate, Myelodysplastic Syndromes mortality, Risk Factors, Treatment Outcome, Vorinostat administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Myelodysplastic Syndromes drug therapy
- Published
- 2018
- Full Text
- View/download PDF
42. The absence of CDKN1C (p57KIP2) promoter methylation in myeloid malignancies also characterizes plasma cell neoplasms.
- Author
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Hatzimichael, Eleftheria, Dasoula, Aggeliki, Benetatos, Leonidas, Makis, Alexandros, Stebbing, Justin, Crook, Tim, Syrrou, Maria, and Bourantas, Konstantinos L.
- Subjects
- *
METHYLATION , *MYELOID leukemia , *ALKYLATION , *CASE studies , *TUMORS - Abstract
The article focuses on a case study that was conducted to determine whether CDKN1C methylation is a frequent event in myeloid leukemia and plasma cell neoplasms. Thirty-six multiple myeloma (MM) patients were included in the study. The Durie-Salmon staging system and the International Prognostic Index (IPI) were used for clinical and prognostic discrimination of patients. The study showed that CDKN1C methylation is not a frequent event in myeloid and plasma cell neoplasms.
- Published
- 2008
- Full Text
- View/download PDF
43. The tumour antigens RAGE-1 and MGEA6 are expressed more frequently in the less lineage restricted subgroups of presentation acute myeloid leukaemia.
- Author
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Guinn, Barbara-ann, Gilkes, Amanda F., Mufti, Ghulam J., Burnett, Alan K., and Mills, Ken I.
- Subjects
- *
LETTERS to the editor , *TUMOR antigens - Abstract
A letter to the editor is presented in response to the previously published article about tumor antigens.
- Published
- 2006
- Full Text
- View/download PDF
44. PHF6 mutations in paediatric acute myeloid leukaemia.
- Author
-
de Rooij JD, van den Heuvel-Eibrink MM, van de Rijdt NK, Verboon LJ, de Haas V, Trka J, Baruchel A, Reinhardt D, Pieters R, Fornerod M, and Zwaan CM
- Subjects
- Adolescent, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Leukemia, Myeloid, Acute genetics, Male, Mutation, Repressor Proteins, Carrier Proteins genetics
- Published
- 2016
- Full Text
- View/download PDF
45. LACK OF CONFIRMATION OF AN ASSOCIATION BETWEEN HTLV-I INFECTION AND MYELODYSPLASTIC SYNDROME.
- Author
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M, M, L, M, B, P, D, M, T, P, C, D, L, F, T, R, M, R, L, G, E, G, and T, G
- Subjects
- *
HTLV diseases , *MYELODYSPLASTIC syndromes , *HTLV - Abstract
Presents a study which examined the association of human T cell lymphotropic virus (HTLV)-1 infection with myelodysplastic syndrome. Methodology; Investigation on the involvement of HTLV-1 infection in human diseases in non-endemic areas; Results and discussion.
- Published
- 1999
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