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acute myeloide leukemia relapse

Animesh Pardanani
OVERVIEW: Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in extra-cutaneous organs. DIAGNOSIS: The major criterion is presence of multifocal clusters of abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC CD25 expression, and presence of KITD816V mutation. RISK STRATIFICATION: Establishing SM subtype as per the World Health Organization classification system is an important first step...
December 8, 2018: American Journal of Hematology
Adir Shaulov, Gary Rodin, Gordana Popovic, Valerie B Caraiscos, Lisa W Le, Anne Rydall, Aaron D Schimmer, Camilla Zimmermann
PURPOSE: Acute leukemia (AL) is associated with substantial morbidity and mortality. We assessed the prevalence and correlates of pain in patients with newly diagnosed or relapsed AL. METHODS: Patients with newly diagnosed or relapsed AL admitted to a comprehensive cancer center completed the Memorial Symptom Assessment Scale (MSAS), which assesses prevalence, severity, and distress associated with pain and other symptoms. Factors associated with severe pain were assessed using logistic regression...
December 8, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Yusuke Narita, Tatsuki Uchiyama, Chisaki Mizumoto, Tomoharu Takeoka, Kenjiro Tomo, Masaaki Tsuji, Tatsuharu Ohno
A 44-year-old woman in the first remission phase of mixed-phenotype acute leukemia (T-lymphoid and myeloid lineages) suddenly exhibited thrombocytopenia (1.1×104 /µl) with generalized petechiae approximately 150 days after bone marrow transplantation (BMT) from a one-locus (HLA-B) mismatched unrelated donor. Until then, the donor bone marrow had smoothly engrafted, and the platelet count had promptly normalized. Despite extensively searching for the triggering agent such as GVHD, graft failure, relapsed leukemia, or adverse drug effects, it could not be determined...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Carla Filì, Anna Candoni, Maria Elena Zannier, Jacopo Olivieri, Silvia Imbergamo, Manuela Caizzi, Gianpaolo Nadali, Eros Di Bona, Anna Ermacora, Michele Gottardi, Davide Facchinelli, Rosanna Ciancia, Davide Lazzarotto, Maria Vittoria Dubbini, Gianluca Festini, Filippo Gherlinzoni, Maria Grazia Michieli, Gianpietro Semenzato, Renato Fanin
BACKGROUND: The hypomethylating agent Decitabine (DAC) is a valuable treatment option in acute myeloid leukemia (AML), particularly in elderly patients (pts) not suitable for intensive chemotherapy (CHT). However, limited data are available about efficacy and safety of DAC in clinical practice. PATIENTS AND METHODS: We retrospectively reviewed data of 104 AML pts treated with DAC in eight Italian Hematological Centers from 2015 to 2017. The objective of this study was to evaluate the efficacy and safety of DAC in older AML pts outside of clinical trial...
November 28, 2018: Leukemia Research
Fahrettin Covut, Divya Gupta, Raisa Pinto, Nina Dambrosio, Najla El Jurdi, Howard Meyerson, Masumi Ueda, Merle Kolk, Richard Creger, Leland Metheny, Brenda W Cooper, Paolo F Caimi, Ehsan Malek, Folashade Otegbeye, Hillard M Lazarus, Marcos De Lima, Benjamin K Tomlinson
INTRODUCTION: Induction chemotherapy with cytarabine and an anthracycline (7+3) remains the standard of care for acute myeloid leukemia (AML). PATIENTS AND METHODS: We retrospectively analyzed 183 newly diagnosed AML patients to compare the utility of rapid peripheral blast clearance (PBC), day of peripheral blast disappearance, residual blasts, and cellularity at day 14 bone marrow biopsy (D14BM) in predicting clinical response to 7+3 induction, overall survival (OS), and relapse-free survival (RFS)...
November 12, 2018: Clinical Lymphoma, Myeloma & Leukemia
Beatrice U Mueller, Katja Seipel, Thomas Pabst
Most patients above 60 years with acute myeloid leukemia (AML) will die from their disease. Nevertheless, the treatment concepts in elderly patients with myelodysplastic syndromes (MDS) and AML are rapidly evolving. A number of recent reports have identified better survival rates with intensive induction chemotherapy for patients up to 80 years, with the exception of patients with unfavorable genomic risk abnormalities or with major co-morbidities. Gemtuzumab ozogamicin is increasingly added to induction therapy for AML patients up to 70 years with favorable or intermediate risk profile, and Midostaurin for patients with a FLT3 mutation...
December 2018: European Journal of Internal Medicine
Wenbin Xiao, Aaron D Goldberg, Christopher Famulare, Sean Devlin, Nghia Nguyen, Sinnifer Sim, Charlene C Kabel, Mina A Patel, Erin McGovern, Akshar Patel, Jessica Schulman, Andrew Dunbar, Zachary D Epstein-Peterson, Kamal Menghrajani, Bartlomiej M Getta, Sheng F Cai, Mark B Geyer, Jacob Glass, Justin Taylor, Aaron D Viny, Ross L Levine, Yanming Zhang, Sergio Giralt, Virginia Klimek, Martin S Tallman, Mikhail Roshal
Measurable residual disease is associated with inferior outcomes in patients with acute myeloid leukemia. Measurable residual disease monitoring enhances risk stratification and may guide therapeutic intervention. European LeukemiaNet working party recently came to a consensus recommendation incorporating leukemia associated immunophenotype-based different from normal approach by multi-color flow cytometry for measurable residual disease evaluation. However, the analytical approach is highly expertise-dependent and difficult to standardize...
December 6, 2018: Haematologica
Li Wang, Jun Xu, Xiaolong Tian, Tingting Lv, Guolin Yuan
BACKGROUND/AIMS: The aim of this work was to investigate the efficacy and predictive factors of CLAG treatment in refractory or relapsed (R/R) acute myeloid leukemia (AML) patients. METHODS: Sixty-seven R/R AML patients were enrolled in this prospective cohort study and treated by a CLAG regimen: 5 mg/m2/day cladribine (days 1-5), 2 g/m2/day cytarabine (days 1-5), and 300 μg/day filgrastim (days 0-5). The median follow-up duration was 10 months. RESULTS: A total of 57 out of 67 patients were evaluable for remission after CLAG therapy, of whom 57...
December 5, 2018: Acta Haematologica
Zhen-Tang Lao, Ling Wen Ding, Omer An, Norimichi Hattori, Qiao-Yang Sun, Kar-Tong Tan, Anand Mayakonda, Wong Gee Chuan, Vikas Madan, De-Chen Lin, Henry Yang, H Phillip Koeffler
Acute leukemia of ambiguous lineage (ALAL) is a rare group of blood cancers that cannot be clearly classified into either myeloid or lymphoid lineage through traditional immunophenotyping (2016 World Health Organization classification). In this study, we performed exome and transcriptome sequencing of 15 diagnosis/relapse samples to identify mutations of this disease. Remarkably, genes involved in DNA repair pathway were frequently mutated and occurred in 80% of the samples. In addition, well known mutations of hematopoietic neoplasms were found in these samples, such as DNMT3A, RUNX1, NOTCH1 and NRAS...
December 4, 2018: Haematologica
Jing Liu, Xiao-Su Zhao, Yan-Rong Liu, Lan-Ping Xu, Xiao-Hui Zhang, Huan Chen, Yu-Hong Chen, Feng-Rong Wang, Wei Han, Yu-Qian Sun, Chen-Hua Yan, Fei-Fei Tang, Xiao-Dong Mo, Kai-Yan Liu, Qiao-Zhen Fan, Xiao-Jun Huang, Ying-Jun Chang
Background: Several studies have shown that detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) is an independent prognostic factor. This study aimed to evaluate the significance of dynamic MRD pretransplantation on outcome of AML patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: We retrospectively analyzed 145 consecutive AML patients undergoing allo-HSCT in complete remission status between June 2013 and June 2016...
December 5, 2018: Chinese Medical Journal
Takayoshi Tachibana, Satoshi Koyama, Taiki Andou, Yasufumi Ishiyama, Masatsugu Tanaka, Hideaki Nakajima, Heiwa Kanamori
A single-center retrospective study was performed with consecutive patients who received salvage therapy using ponatinib for the aim of allogeneic hematopoietic cell transplantation (HCT) for relapsed or refractory Ph-leukemia between January 2017 and July 2018. A total of ten patients-seven with Ph-acute lymphoblastic leukemia (ALL) and three with chronic phase (CP)/accelerated phase chronic myeloid leukemia (CML)-were eligible. Eight patients had a history of a single tyrosine kinase inhibitor (TKI) use prior to ponatinib...
December 3, 2018: International Journal of Hematology
Eytan M Stein, Courtney D DiNardo, Amir T Fathi, Daniel A Pollyea, Richard M Stone, Jessica K Altman, Gail J Roboz, Manish R Patel, Robert Collins, Ian W Flinn, Mikkael A Sekeres, Anthony S Stein, Hagop M Kantarjian, Ross L Levine, Paresh Vyas, Kyle J MacBeth, Alessandra Tosolini, Jason VanOostendorp, Qiang Xu, Ira Gupta, Thomas Lila, Alberto Risueno, Katharine E Yen, Bin Wu, Eyal C Attar, Martin S Tallman, Stéphane de Botton
Approximately 8-19% of patients with acute myeloid leukemia (AML) have isocitrate dehydrogenase-2 ( IDH2 ) mutations, which occur at active site arginine residues, R140 and R172. IDH2 mutations produce an oncometabolite, 2-hydroxyglutarate (2-HG), that leads to DNA and histone hypermethylation and impaired hematopoietic differentiation. Enasidenib is an oral inhibitor of mutant-IDH2 proteins. This first-in-human phase I/II study evaluated enasidenib doses of 50-650 mg/day, administered in continuous 28-day cycles, in patients with mutant- IDH2 hematologic malignancies (ClinicalTrials...
December 3, 2018: Blood
Robyn M Scherber, Ruben A Mesa
Myelofibrosis (MF) is the most aggressive form of Philadelphia chromosome-negative myeloproliferative neoplasm, and it is complicated by severe symptom burden, thrombotic events, infections, cytopenias, and transformation to acute myeloid leukemia (AML). Ruxolitinib, the first-line therapy for symptomatic or intermediate- and high-prognostic risk MF, has improved overall survival for this population. However, approximately one-half of MF patients will discontinue ruxolitinib by the first few years of therapy due to a spectrum of resistance, intolerance, relapse, or progression to blast phase disease...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
Laura C Michaelis
Given the recent approvals of new agents for acute myeloid leukemia (AML), a clinical trial pipeline stocked with novel therapies, and the rapid integration of imaginative approaches in diseases like acute lymphocytic leukemia and chronic lymphocytic leukemia, it is reasonable to ask whether treatment of AML might finally depart from the classical cytotoxic induction therapy that has been employed since the 1970s. However, for better or worse, in 2018, cytotoxic induction regimens remain the standard of care for most patients...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
Gregory W Roloff, Elizabeth A Griffiths
Mutational profiling has fundamentally changed our approach to patients with acute myeloid leukemia (AML). Patients with AML are routinely profiled for the presence of mutations in FLT3 , NPM1 , CEBPA , and, more recently, TP53 In this chapter, we review the role of mutational profiling to help define disease biology in AML, particularly among patients with putatively intermediate-risk disease. We describe the body of evidence supporting the utility of mutational profiling when performed at the time of diagnosis (to identify prognostic and targetable mutations), at the time of complete remission (to assess minimal residual disease as a marker for relapse), and at the time of relapse (to identify therapeutic targets and eligibility for clinical trials)...
November 30, 2018: Hematology—the Education Program of the American Society of Hematology
Patrick Williams, Sreyashi Basu, Guillermo Garcia-Manero, Christopher S Hourigan, Karolyn A Oetjen, Jorge E Cortes, Farhad Ravandi, Elias J Jabbour, Zainab Al-Hamal, Marina Konopleva, Jing Ning, Lianchun Xiao, Juliana Hidalgo Lopez, Steve M Kornblau, Michael Andreeff, Wilmer Flores, Carlos Bueso-Ramos, Jorge Blando, Pallavi Galera, Katherine R Calvo, Gheath Al-Atrash, James P Allison, Hagop M Kantarjian, Padmanee Sharma, Naval G Daver
BACKGROUND: Phenotypic characterization of immune cells in the bone marrow (BM) of patients with acute myeloid leukemia (AML) is lacking. METHODS: T-cell infiltration was quantified on BM biopsies from 13 patients with AML, and flow cytometry was performed on BM aspirates (BMAs) from 107 patients with AML who received treatment at The University of Texas MD Anderson Cancer Center. The authors evaluated the expression of inhibitory receptors (programmed cell death protein 1 [PD1], cytotoxic T-lymphocyte antigen 4 [CTLA4], lymphocyte-activation gene 3 [LAG3], T-cell immunoglobulin and mucin-domain containing-3 [TIM3]) and stimulatory receptors (glucocorticoid-induced tumor necrosis factor receptor-related protein [GITR], OX40, 41BB [a type 2 transmembrane glycoprotein receptor], inducible T-cell costimulatory [ICOS]) on T-cell subsets and the expression of their ligands (41BBL, B7-1, B7-2, ICOSL, PD-L1, PD-L2, and OX40L) on AML blasts...
November 30, 2018: Cancer
Matthew Mei, Ibrahim Aldoss, Guido Marcucci, Vinod Pullarkat
One of the most promising developments in therapy for acute myeloid leukemia (AML) in recent years has been the combination of hypomethylating agents (HMA, either decitabine or 5-azacytidine) with the Bcl-2 inhibitor venetoclax (VEN). Although both classes of drugs have single-agent activity in AML, the combination has resulted in high rates of complete remission both in the frontline and relapsed settings suggesting synergy between these two agents. Recent data have suggested that complete remission (CR) + CR with incomplete count recovery rate may exceed 70% for frontline VEN-HMA...
November 30, 2018: American Journal of Hematology
Yimin Shi, Lillia Dincheva-Vogel, Charles E Ayemoba, Jeffrey P Fung, Cristina Bergamaschi, George N Pavlakis, Farzin Farzaneh, Karin M L Gaensler
Engineered autologous acute myeloid leukemia (AML) cells present multiple leukemia-associated and patient-specific antigens and as such hold promise as immunotherapeutic vaccines. However, prior vaccines have not reliably induced effective antileukemic immunity, in part because AML blasts have immune inhibitory effects and lack expression of the critical costimulatory molecule CD80. To enhance induction of leukemia-specific cytolytic activity, 32Dp210 murine AML cells were engineered to express either CD80 alone, or the immunostimulatory cytokine interleukin-15 (IL-15) with its receptor α (IL-15Rα), or heterodimeric IL-15/IL-15Rα together with CD80 and tested as irradiated cell vaccines...
November 27, 2018: Blood Advances
Bruno C Medeiros
Despite advances in treatment for acute myeloid leukemia (AML), the prognosis for patients with relapsed disease is extremely poor. The median overall survival for patients with relapsed AML ranges from 4-6 months and long-term survival from the time of relapse ranges from 5%-20%. Much of the difficulty in establishing a standard of care for relapsed AML is that the disease is clinically and genomically diverse. Nevertheless, significant progress has been made over the past 12 months with the approval of several agents, and the expectation is that additional therapies will be available soon...
December 2018: Best Practice & Research. Clinical Haematology
Kaito Harada, Masamitsu Yanada, Shinichiro Machida, Heiwa Kanamori, Makoto Onizuka, Yukiyasu Ozawa, Hikaru Kobayashi, Masashi Sawa, Yuta Katayama, Kazuteru Ohashi, Junya Kanda, Tatsuo Ichinohe, Yoshiko Atsuta, Shingo Yano
To evaluate the prognostic impact of melphalan dose and total body irradiation (TBI) use in acute myeloid leukemia patients undergoing reduced-intensity allogeneic transplantation, we retrospectively compared outcomes of patients receiving a higher-dose (120-140 mg/m2 , n = 379) or lower-dose melphalan (80-110 mg/m2 , n = 128) with or without TBI of ≤4 Gy. At 3 years, overall survival was 48.9% in the higher-dose group versus 40.3% in the lower-dose group (p = .013). This survival benefit was attributed to lower tumor-related mortality (23...
November 20, 2018: Leukemia & Lymphoma
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