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secondary acute myeloid leukemia

George E Georges, Kris Doney, Rainer Storb
Treatment of severe aplastic anemia has improved significantly over the past 4 decades. This review will summarize the key areas of progress in the use of allogeneic hematopoietic cell transplantation and nontransplant immunosuppressive therapy (IST) for the treatment of aplastic anemia and then summarize the recommendations for first-line treatment. Based on recent data, we argue that guidelines for the initial treatment of patients with newly diagnosed severe aplastic anemia require revision. At the time of diagnosis, before beginning treatment, HLA typing should be done to identify a marrow donor among family members or in the unrelated donor registries, and a marrow transplant should be considered first-line therapy...
August 14, 2018: Blood Advances
Sung-Soo Park, Young-Woo Jeon, Gi June Min, Silvia Park, Seung-Ah Yahng, Jae-Ho Yoon, Seung-Hwan Shin, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Seok Lee, Hee-Je Kim, Chang-Ki Min, Seok-Goo Cho, Jong Wook Lee, Yoo-Jin Kim
Graft-versus-host disease-free, relapse-free survival (GRFS) is a composite endpoint that measures survival free of relapse or significant morbidity following allogeneic hematopoietic stem cell transplantation (HSCT). Consecutive 324 adult patients who received HSCT with fluarabine and busulfan based conditioning for myelodysplastic syndrome (MDS) or secondary acute myeloid leukemia evolved from MDS were retrospectively analyzed. 1-year and 3-year GRFS rates were 47.8% and 34.5%, respectively. Three fixed factors (circulating blast >3%, high cytogenetic risk, and high comorbidity index) and two factors (which is) modifiable by clinicians [myeloablative conditioning and low-dose (<7...
August 10, 2018: Biology of Blood and Marrow Transplantation
G H Lyman, L Yau, R Nakov, A Krendyukov
Background: The use of supportive granulocyte colony-stimulating factor (G-CSF) to reduce the risk of neutropenic complications in high-risk cancer patients is consistently recommended by several clinical practice guidelines. However, in a previous meta-analysis, G-CSF prophylaxis was associated with an increased risk of secondary malignancies while reducing long-term mortality. We present here an updated systematic review and meta-analysis. Materials and methods: A systematic literature search was performed to identify randomized controlled trials of cancer patients receiving conventional-dose chemotherapy, assigned to primary G-CSF support or a control group without initial G-CSF, with at least 2 years of follow-up...
August 7, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Naghmeh Niktoreh, Beate Lerius, Martin Zimmermann, Bernd Gruhn, Gabriele Escherich, Jean-Pierre Bourquin, Michael Dworzak, Lucie Sramkova, Claudia Rossig, Ursula Creutzig, Dirk Reinhardt, Mareike Rasche
Despite intensified salvage treatments, children with relapsed/refractory acute myeloid leukemia have poor survival. We evaluated Gemtuzumab Ozogamicin (CD33-targeted drug) used on compassionate basis in patients diagnosed from 1995 until 2014 within Acute Myeloid Leukemia-Berlin-Frankfurt-Munster studies and identified 76 patients (<18 years) with highly-advanced and pretreated acute myeloid leukemia [refractory de novo acute myeloid leukemia (n=10), de novo acute myeloid leukemia refractory to relapse (1st early: n=41; 1st late: n=10; 2nd or more: n=10), and secondary acute myeloid leukemia (n=5)]...
August 9, 2018: Haematologica
Akanksha Bothale, Kalpana Bothale, Sadhana Mahore, Trupti Dongre
Extramedullary hematopoiesis (EMH) is a compensatory mechanism that occurs when the marrow is unable to maintain sufficient red cell mass. EMH generally occurs in the patients with deficient bone marrow hematopoiesis secondary to either peripheral red cell destruction or marrow replacement. Although EMH is known to occur in agnogenic myeloid metaplasia with myelofibrosis, chronic myelogenous leukemia, thalassemia, and infiltrative disorders, such as lymphomas, it is rare in acute leukemias. EMH is most commonly seen in the liver and spleen as a diffuse lesion...
July 2018: Journal of Cytology
Kyriakos P Papadopoulos, Eytan Ben-Ami, Amita Patnaik, Denise Trone, Jianke Li, George D Demetri
BACKGROUND: Quizartinib, an inhibitor of class III receptor tyrosine kinases (RTKs), is currently in phase 3 development for the treatment of acute myeloid leukemia (AML) bearing internal tandem duplications in the FLT3 gene. Aberrant RTK signaling is implicated in the pathogenesis of a variety of solid tumors, suggesting that inhibiting quizartinib-sensitive RTKs may be beneficial in precision cancer therapy. METHODS: This was a phase 1, open-label, modified Fibonacci dose-escalation study of orally administered quizartinib in patients with advanced solid tumors whose disease progressed despite standard therapy or for which there was no available standard treatment...
August 6, 2018: BMC Cancer
Esther Schuler, Natalie Zadrozny, Sabine Blum, Thomas Schroeder, Corinna Strupp, Barbara Hildebrandt, Andrea Kündgen, Norbert Gattermann, Carlo Aul, Mustafa Kondakci, Guido Kobbe, Rainer Haas, Ulrich Germing
Intensive chemotherapy (IC) used to be a common treatment approach for patients with higher-risk myelodysplastic syndromes (MDS) or acute myeloid leukemia after MDS (sAML). We conducted a retrospective analysis of 299 patients, including a matched pair analysis comparing 96 patients receiving IC with 96 patients not undergoing IC, in order to evaluate the impact of IC on overall survival (OS) and to identify factors that influence remission rates and OS. Complete remission (CR) after first induction chemotherapy was reached in 50% of patients...
August 4, 2018: Annals of Hematology
Juliette Lambert, Cécile Pautas, Christine Terré, Emmanuel Raffoux, Pascal Turlure, Denis Caillot, Ollivier Legrand, Xavier Thomas, Claude Gardin, Karïn Gogat-Marchant, Stephen D Rubin, Rebecca J Benner, Pierre Bousset, Claude Preudhomme, Sylvie Chevret, Herve Dombret, Sylvie Castaigne
The randomized, phase 3 ALFA-0701 trial showed that a reduced and fractionated dose of gemtuzumab ozogamicin added to standard front-line chemotherapy significantly improves event-free survival in adults with de novo acute myeloid leukemia. Here we report an independent review of event-free survival, final overall survival, and additional safety results from ALFA-0701. Patients (N=271) aged 50-70 years with de novo acute myeloid leukemia were randomized to receive conventional front-line induction chemotherapy (3+7 daunorubicin+cytarabine) with/without gemtuzumab ozogamicin 3 mg/m2 on days 1, 4, and 7 during induction...
August 3, 2018: Haematologica
Jorge E Cortes, B Douglas Smith, Eunice S Wang, Akil Merchant, Vivian G Oehler, Martha Arellano, Daniel J DeAngelo, Daniel A Pollyea, Mikkael A Sekeres, Tadeusz Robak, Weidong Wendy Ma, Mirjana Zeremski, M Naveed Shaik, A Douglas Laird, Ashleigh O'Connell, Geoffrey Chan, Mark A Schroeder
Glasdegib is a Hedgehog pathway inhibitor. This ongoing, open-label, phase 2 study (NCT01546038) evaluated glasdegib plus cytarabine/daunorubicin in patients with untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS).Patients received glasdegib 100-mg orally, once-daily in continuous 28-day cycles from day -3, with intravenous cytarabine 100 mg/m2 on days 1-7 and daunorubicin 60 mg/m2 on days 1-3. Patients in remission then received consolidation therapy (2-4 cycles of cytarabine 1 g/m2 twice-daily on days 1, 3, 5 of each cycle), followed by maintenance glasdegib (maximum 6 cycles)...
August 3, 2018: American Journal of Hematology
Eva J Schaefer, R Coleman Lindsley
Clonal hematopoiesis as a hallmark of myelodysplastic syndrome (MDS) is mediated by the selective advantage of clonal hematopoietic stem cells in a context-specific manner. Although primary MDS emerges without known predisposing cause and is associated with advanced age, secondary MDS may develop in younger patients with bone marrow failure syndromes or after exposure to chemotherapy, respectively. This article discusses recent advances in the understanding of context-dependent clonal hematopoiesis in MDS with focus on clonal evolution in inherited and acquired bone marrow failure syndromes...
August 2018: Hematology/oncology Clinics of North America
Amir T Fathi, Harry P Erba, Jeffrey E Lancet, Eytan M Stein, Farhad Ravandi, Stefan Faderl, Roland B Walter, Anjali S Advani, Daniel J DeAngelo, Tibor J Kovacsovics, Anand Jillella, Dale Bixby, Moshe Y Levy, Megan M O'Meara, Phoenix A Ho, Jenna Voellinger, Anthony S Stein
Treatment of acute myeloid leukemia (AML) among the elderly is challenging due to intolerance of intensive therapy and therapy-resistant biology. Hypomethylating agents (HMAs) are commonly used, with suboptimal outcomes. Vadastuximab talirine is a CD33 directed antibody conjugated to pyrrolobenzodiazepine (PBD) dimers. Preclinically, HMA followed by vadastuximab talirine produced upregulated CD33 expression, increased DNA incorporation by PBD, and enhanced cytotoxicity. A combination cohort in a phase 1 study (NCT01902329) assessed safety, tolerability, and activity of vadastuximab talirine with HMA...
July 25, 2018: Blood
Kensuke Usuki, Toru Sakura, Yukio Kobayashi, Toshihiro Miyamoto, Hiroatsu Iida, Satoshi Morita, Erkut Bahceci, Masahito Kaneko, Mikiko Kusano, Shunsuke Yamada, Shigeru Takeshita, Shuichi Miyawaki, Tomoki Naoe
Gilteritinib, a novel, highly specific, potent fms-like tyrosine kinase 3/AXL inhibitor, demonstrated antileukemic activity in patients with relapsed/refractory acute myeloid leukemia. In this open-label, Phase 1 study (NCT02181660), Japanese patients (aged ≥18 years) with relapsed/refractory acute myeloid leukemia received once-daily gilteritinib escalating from 20 mg/day to 300 mg/day. Primary endpoints were safety/tolerability including the maximum tolerated dose and recommended dose; secondary endpoints were antileukemic activity and pharmacokinetics...
July 24, 2018: Cancer Science
Jeffrey E Lancet, Geoffrey L Uy, Jorge E Cortes, Laura F Newell, Tara L Lin, Ellen K Ritchie, Robert K Stuart, Stephen A Strickland, Donna Hogge, Scott R Solomon, Richard M Stone, Dale L Bixby, Jonathan E Kolitz, Gary J Schiller, Matthew J Wieduwilt, Daniel H Ryan, Antje Hoering, Kamalika Banerjee, Michael Chiarella, Arthur C Louie, Bruno C Medeiros
Purpose CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic 5:1 drug ratio into leukemia cells to a greater extent than normal bone marrow cells. Prior clinical studies demonstrated a sustained drug ratio and exposure in vivo and prolonged survival versus standard-of-care cytarabine plus daunorubicin chemotherapy (7+3 regimen) in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). Patients and Methods In this open-label, randomized, phase III trial, 309 patients age 60 to 75 years with newly diagnosed high-risk/sAML received one to two induction cycles of CPX-351 or 7+3 followed by consolidation therapy with a similar regimen...
July 19, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Marlijn Hoeks, Marit van der Pol, Rutger Middelburg, Dorothea Evers, Marian van Kraaij, Jaap Jan Zwaginga
OBJECTIVES: Secondary iron overload due to red blood cell transfusions (RBCT) is associated with increased morbidity and mortality. However, attention for secondary iron overload and its side effects in patients with hematological malignancies may need improvement. The aim of this study was to determine the number of transfused RBCT needed to reach a maximum bone marrow iron score (BMIS). METHODS: BMIS was independently assessed by two researchers on consecutive bone marrow samples of 35 acute myeloid leukemia (AML) patients...
July 17, 2018: European Journal of Haematology
Kun Li, Kun Yang, Lifang Zheng, Yuanyuan Li, Qi Wang, Ruili Lin, Dian He
2-Chloro-3-alkyl-1,4-naphthoquinone derivatives were synthesized and tested as the anti-acute myeloid leukaemia agents. The compound 9b (2-chloro-3-ethyl-5,6,7-trimethoxy-1,4-naphthoquinone) was the most potent toward HL-60 leukaemia cells. In mechanistic study for 9b, the protein levels of mtDNA-specific DNA polymerase γ (poly-γ) and mtDNA transcription factor A (mt-TFA) were decreased after the 24 h treatment, showing the occurrence of mtDNA damage. And 9b triggered cell cycle arrest at S phase accompanied by a secondary block in G2/M phase which had a direct link to the process of mtDNA damage...
July 7, 2018: Bioorganic & Medicinal Chemistry
Anne Bouvier, Bénédicte Ribourtout, Sylvie François, Corentin Orvain, Damien Luque Paz, Annaëlle Beucher, Alexandre Guérard, Philippe Guardiola, Valérie Ugo, Odile Blanchet, Franck Geneviève, Aline Schmidt, Mathilde Hunault-Berger
Allogeneic hematopoietic stem cell transplantation (HSCT) is the one of treatment known to cure acute myeloid leukemia (AML). Relapse of AML remains the major cause of treatment failure in patients after HSCT. In rare cases, secondary leukemia is derived from donor cells, designated as donor cell leukemia (DCL) This article is protected by copyright. All rights reserved.
July 14, 2018: European Journal of Haematology
Cristina Mambet, Mihaela Chivu-Economescu, Lilia Matei, Laura Georgiana Necula, Denisa Laura Dragu, Coralia Bleotu, Carmen Cristina Diaconu
Acute myeloid leukemia (AML) is an aggressive malignant disease defined by abnormal expansion of myeloid blasts. Despite recent advances in understanding AML pathogenesis and identifying their molecular subtypes based on somatic mutations, AML is still characterized by poor outcomes, with a 5-year survival rate of only 30%-40%, the majority of the patients dying due to AML relapse. Leukemia stem cells (LSC) are considered to be at the root of chemotherapeutic resistance and AML relapse. Although numerous studies have tried to better characterize LSCs in terms of surface and molecular markers, a specific marker of LSC has not been found, and still the most universally accepted phenotypic signature remains the surface antigens CD34+CD38- that is shared with normal hematopoietic stem cells...
June 26, 2018: World Journal of Stem Cells
Wenwen Ding, Danni Li, Chao Zhuang, Pingping Wei, Wenfeng Mou, Lei Zhang, Hui Liang, Yong Liu
RATIONALE: The JAK2 V617F mutation is frequently found in ET, while it is rare in de novo AML. ET has a low frequency of leukemic transformation. Both secondary AML (sAML) from ET and AML with JAK2 V617F mutation have poor prognoses. Because of the low incidence of JAK2 mutation in acute myeloid leukemia (AML), the clinical features of AML with JAK2 mutation are rarely reported so far, either transformed from essential thrombocythemia (ET) or de novo AML. PATIENT CONCERNS: In this article, we present a pediatric AML patient with the JAK2 V617F mutation...
July 2018: Medicine (Baltimore)
Antoine Ponard, Nicole Ferreira-Maldent, Marjan Ertault, Martine Delain, Kamel Amraoui, Sandra Regina, Annie-Pierre Jonville-Béra, Olivier Hérault, Philippe Colombat, Emmanuel Gyan
BACKGROUND: Diabetes and myelodysplastic syndrome are two conditions that may coexist in a single patient, since both diseases are prevalent in the elderly. The pathophysiology of myelodysplastic syndrome involves recurrent genetic mutations, especially in genes controlling epigenetic regulation. Although the pathophysiology of diabetes is not well understood, several studies suggest a role of epigenetics in type 2 diabetes. CASE PRESENTATION: We report here for the first time the case of a 75-year-old Caucasian man who was treated for both diabetes and acute myeloid leukemia secondary to myelodysplastic syndrome, with a temporal association between glycemic dysregulation and the intake of 5-azacitidine...
July 3, 2018: Journal of Medical Case Reports
Raffaele Longo, Véronique Dorvaux, Eric Chatelain, Philippe Quétin, Francesca Plastino, Nada Eid, Nathalie Marcon, Laurent Hennequin, Marco Campitiello
BACKGROUND Myeloid sarcoma is a rare extramedullary soft tissue neoplasm composed of myeloblastic cells, usually associated to hematologic tumor disorders and a poor prognosis. Its diagnosis is very difficult as radiological images are not specific. Histology and immunohistochemistry are necessary for an accurate diagnosis. CASE REPORT We report the case of 46-year-old, Caucasian, non-smoker male, treated in 2014 by orchiectomy and systemic chemotherapy for a stage IIB testicular seminoma. Considering the rapid increase of lactate dehydrogenase (LDH) levels without any evident medical reason, a computed tomography/positron emission tomography (CT/PET) scan was performed and revealing a diffuse, nodular, peritoneal tumor infiltration associated with multiple mesenteric and mediastinal adenopathies...
June 29, 2018: American Journal of Case Reports
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