1,441 results match your criteria therapy-related myeloid


Allogeneic hematopoietic stem cell transplantation overcomes the poor prognosis in MLL-rearranged solid tumor therapy related-acute myeloid leukemia.

Am J Cancer Res 2021 15;11(4):1683-1696. Epub 2021 Apr 15.

Department of Hematology, Nanfang Hospital, Southern Medical University Guangzhou, China.

MLL rearrangement is very common in solid tumor therapy-related acute myeloid leukemia (t-AML). To investigated the prognosis of solid tumor MLL t-AML, 157 patients were divided into 3 groups: non-MLL t-AML (n=41), MLL t-AML (n=18) and MLL de novo AML (n=98). Of the 150 patients underwent anti-leukemia therapy, the complete remission (CR) was similar in MLL t-AML, non-MLL t-AML and MLL de novo AML (P=0. Read More

View Article and Full-Text PDF

Clinical and Pathologic Spectrum of DDX41-Mutated Hematolymphoid Neoplasms.

Am J Clin Pathol 2021 Apr 30. Epub 2021 Apr 30.

Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.

Objectives: This study seeks to further characterize the clinicopathologic spectrum of DDX41-mutated hematolymphoid malignancies.

Methods: We identified DDX41 mutations from a cohort of known or suspected hematologic disorders and reviewed the corresponding clinical, genetic, phenotypic, and morphologic findings.

Results: DDX41 mutations were identified in 20 (1. Read More

View Article and Full-Text PDF

Flexible Modeling of Net Survival and Cure by AML Subtype and Age: A French Population-Based Study from FRANCIM.

J Clin Med 2021 Apr 13;10(8). Epub 2021 Apr 13.

Dijon-Bourgogne University Hospital, Registre Bourguignon des Cancers Digestifs, F-21000 Dijon, France.

With improvements in acute myeloid leukemia (AML) diagnosis and treatment, more patients are surviving for longer periods. A French population of 9453 AML patients aged ≥15 years diagnosed from 1995 to 2015 was studied to quantify the proportion cured (P), time to cure (TTC) and median survival of patients who are not cured (MedS). Net survival (NS) was estimated using a flexible model adjusted for age and sex in sixteen AML subtypes. Read More

View Article and Full-Text PDF

What's new in the pathogenesis and treatment of therapy-related myeloid neoplasms.

Blood 2021 Apr 19. Epub 2021 Apr 19.

2Saint Camillus International University of Health Sciences, Italy.

Therapy-related myeloid neoplasms (t-MN) include diseases onsetting in patients treated with chemo- and/or radiotherapy for a primary cancer, or an autoimmune disorder. Genomic variants, in particular in familial cancer genes, may play a predisposing role. Recent advances in deep sequencing techniques have shed light on the pathogenesis of t-MN, identifying clonal hematopoiesis of indeterminate potential (CHIP) as a frequent first step in the multi-hit model of t-MN. Read More

View Article and Full-Text PDF

Targeted gene panels identify a high frequency of pathogenic germline variants in patients diagnosed with a hematological malignancy and at least one other independent cancer.

Leukemia 2021 Apr 13. Epub 2021 Apr 13.

Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.

The majority of studies assessing the contribution of pathogenic germline variants (PGVs) to cancer predisposition have focused on patients with single cancers. We analyzed 45 known cancer predisposition genes (CPGs) in germline samples of 202 patients with hematological malignancies (HMs) plus one or more other independent cancer managed at major tertiary medical centers on two different continents. This included 120 patients with therapy-related myeloid neoplasms (t-MNs), where the HM occurred after cytotoxic treatment for a first malignancy, and 82 patients with multiple cancers in which the HM was not preceded by cytotoxic therapy (MC-HM). Read More

View Article and Full-Text PDF

Therapy-related Myeloid Leukemia With the Translocation t(8;19)(p11;q13) Leading to a Fusion Gene.

Anticancer Res 2021 Apr;41(4):1753-1760

Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.

Background/aim: The chromosome translocation t(8;19)(p11;q13) has been reported in only six acute myeloid leukemia (AML) patients. We here present the genetic and clinical features of the seventh AML case with this aberration.

Materials And Methods: Cytogenetic and molecular genetic investigations were performed on leukemic bone marrow cells from a patient with therapy-related AML. Read More

View Article and Full-Text PDF

Allogeneic hematopoietic stem cell transplantation for therapy-related myeloid neoplasms following treatment of a lymphoid malignancy.

Leuk Lymphoma 2021 Mar 29:1-10. Epub 2021 Mar 29.

Department of Medicine A, Hematology and Oncology, University Hospital Muenster, Muenster, Germany.

Advances in lymphoma treatment lead to increasing numbers of long-term survivors. Thus, secondary therapy-related myeloid neoplasms (t-MN) gain clinical relevance. We analyzed 38 t-MN patients receiving an allogeneic stem cell transplantation (SCT) after successful cytotoxic treatment of Hodgkin lymphoma ( = 9), non-Hodgkin lymphoma ( = 24), and multiple myeloma ( = 5), who had developed t-AML ( = 20) or t-MDS ( = 18). Read More

View Article and Full-Text PDF

Predictors of outcomes of therapy-related acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation.

Hematol Oncol Stem Cell Ther 2021 Mar 19. Epub 2021 Mar 19.

Hans Messner Allogeneic Blood and Marrow Transplantation Program, Princess Margaret Cancer Center, University of Toronto, Toronto, ON, Canada. Electronic address:

Background/objective: Existing literature on allogeneic hematopoietic stem cell transplantation (allo-HSCT) in therapy-related acute myeloid leukemia (t-AML) is confounded by the inclusion of patients with secondary AML and t-MDS. We aim to report our 20-year experience of HSCT in t-AML.

Methods: We retrospectively reviewed patients with t-AML who underwent HSCT. Read More

View Article and Full-Text PDF

New Treatment Options for Older Patients with Acute Myeloid Leukemia.

Curr Treat Options Oncol 2021 Mar 20;22(5):39. Epub 2021 Mar 20.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 428, Houston, TX, 77030, USA.

Opinion Statement: The treatment of acute myeloid leukemia (AML) has evolved considerably over the past several years. Advances in the field have historically benefited younger patients; however, a growing understanding of the molecular basis of leukemogenesis has brought multiple targeted agents to the clinic for patients of all ages. These therapies have expanded the therapeutic landscape for elderly patients from more than best supportive care and low-intensity monotherapy. Read More

View Article and Full-Text PDF

Incidence of myelodysplastic syndrome and acute myeloid leukemia in patients receiving poly-ADP ribose polymerase inhibitors for the treatment of solid tumors: A meta-analysis of randomized trials.

Gynecol Oncol 2021 Mar 15. Epub 2021 Mar 15.

Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America. Electronic address:

Background: Clinical trials demonstrated that PARPi (poly [adenosine diphosphate-ribose]-ADP polymerase inhibitor) therapy is effective in solid tumors. However, long term effects such as therapy-related myelodysplastic syndrome or acute myeloid leukemia (MDS/AML) are poorly described. We sought to quantify whether PARPi therapy is associated with the development of MDS/AML. Read More

View Article and Full-Text PDF

Acute myeloid leukemia: Treatment and research outlook for 2021 and the MD Anderson approach.

Cancer 2021 Apr 18;127(8):1186-1207. Epub 2021 Mar 18.

Department of Leukemia, MD Anderson Cancer Center, Houston, Texas.

The unraveling of the pathophysiology of acute myeloid leukemia (AML) has resulted in rapid translation of the information into clinical practice. After more than 40 years of slow progress in AML research, the US Food and Drug Administration has approved nine agents for different AML treatment indications since 2017. In this review, we detail the progress that has been made in the research and treatment of AML, citing key publications related to AML research and therapy in the English literature since 2000. Read More

View Article and Full-Text PDF

Older adults with newly diagnosed high-risk/secondary AML who achieved remission with CPX-351: phase 3 post hoc analyses.

Blood Adv 2021 Mar;5(6):1719-1728

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL.

CPX-351, a dual-drug liposomal encapsulation of daunorubicin/cytarabine in a synergistic 1:5 molar ratio, is approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (AML-MRC). In a pivotal phase 3 study, patients aged 60 to 75 years with newly diagnosed, high-risk/secondary AML were randomized to receive CPX-351 or conventional 7+3 chemotherapy. In the primary endpoint analysis, CPX-351 demonstrated significantly prolonged median overall survival (OS) vs 7+3. Read More

View Article and Full-Text PDF

Treatment of therapy-related acute myeloid leukemia and underlying multiple myeloma with decitabine/venetoclax and daratumumab.

Ann Hematol 2021 Mar 13. Epub 2021 Mar 13.

Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetterstr. 53, 79106, Freiburg, Germany.

View Article and Full-Text PDF

Reducing treatment toxicity in Waldenström macroglobulinemia.

Expert Opin Drug Saf 2021 Mar 8:1-8. Epub 2021 Mar 8.

Harvard Medical School, Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA.

: Waldenström macroglobulinemia (WM) is a rare subtype of non-Hodgkin lymphoma characterized by the presence of IgM-secreting clonal lymphocytes, plasma cells, and lymphoplasmacytic cells. Many well-established treatment options are available for patients with WM. However, a unique array of side effects may occur in patients during therapy related to the underlying disease, as well as the chosen treatment regimen. Read More

View Article and Full-Text PDF

Mutations in Acute Myeloid Leukemia: Still a Daunting Challenge?

Front Oncol 2020 8;10:610820. Epub 2021 Feb 8.

Haematology Unit, S. Eugenio Hospital, ASL Roma 2, Rome, Italy.

is a key tumor suppressor gene with protean functions associated with preservation of genomic balance, including regulation of cellular senescence, apoptotic pathways, metabolism functions, and DNA repair. The vast majority of acute myeloid leukemia (AML) present unaltered alleles. However, mutations are frequently detected in AML related to an increased genomic instability, such as therapy-related (t-AML) or AML with myelodysplasia-related changes. Read More

View Article and Full-Text PDF
February 2021

Therapy-related Myeloid Neoplasms in Children: A Single-institute Study.

J Pediatr Hematol Oncol 2021 Mar 31. Epub 2021 Mar 31.

Department of Pathology and Laboratory Medicine, Children's of Alabama Department of Pediatrics, Division of Hematology and Oncology Departments of Pathology Genetics, University of Alabama at Birmingham, Birmingham, AL.

Therapy-related myeloid neoplasm (t-MN) in the pediatric population is not well characterized. We studied 12 pediatric patients diagnosed with t-MN in our institution since 2006. The median age at the t-MN diagnoses was 14. Read More

View Article and Full-Text PDF

Protein phosphatase, Mg/Mn-dependent 1D (PPM1D) mutations in haematological cancer.

Br J Haematol 2021 Feb 8;192(4):697-705. Epub 2020 Dec 8.

Department of Haematology, Rigshospitalet, Copenhagen, Denmark.

Until recently, the protein phosphatase, Mg/Mn-dependent 1D (PPM1D) gene had not been examined in haematological cancer, but several studies have now explored the functional role of this gene and its aberrations. It is often mutated in the context of clonal haemopoiesis (including in patients with lymphoma, myeloproliferative neoplasms and myelodysplastic syndrome) and mutations have been associated with exposure to cytotoxic and radiation therapy, development of therapy-related neoplasms and inferior survival. The vast majority of PPM1D mutations found in haematopoietic cells are of the nonsense or frameshift type and located within terminal exon 6. Read More

View Article and Full-Text PDF
February 2021

Secondary AML Emerging After Therapy with Hypomethylating Agents: Outcomes, Prognostic Factors, and Treatment Options.

Curr Hematol Malig Rep 2021 Feb 20;16(1):97-111. Epub 2021 Feb 20.

Lineberger Comprehensive Cancer Center, University of North Carolina, Houpt Building, Chapel Hill, NC, #7305, USA.

Purpose Of Review: Secondary AML (s-AML) encompasses a distinct subgroup of AML with either therapy-related AML or AML arising from preexisting myeloid neoplasms. Despite recent advances in the treatment armamentarium of AML, outcomes remain poor in s-AML. The purpose of this review is to highlight distinct characteristics, prognostic factors, and treatment options for patients with s-AML. Read More

View Article and Full-Text PDF
February 2021

Kmt2c mutations enhance HSC self-renewal capacity and convey a selective advantage after chemotherapy.

Cell Rep 2021 Feb;34(7):108751

Department of Pediatrics, Division of Hematology and Oncology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA; Department of Genetics, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA. Electronic address:

The myeloid tumor suppressor KMT2C is recurrently deleted in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), particularly therapy-related MDS/AML (t-MDS/t-AML), as part of larger chromosome 7 deletions. Here, we show that KMT2C deletions convey a selective advantage to hematopoietic stem cells (HSCs) after chemotherapy treatment that may precipitate t-MDS/t-AML. Kmt2c deletions markedly enhance murine HSC self-renewal capacity without altering proliferation rates. Read More

View Article and Full-Text PDF
February 2021

Sequential intensive chemotherapy followed by autologous or allogeneic transplantation for refractory lymphoma.

Leuk Lymphoma 2021 Feb 13:1-15. Epub 2021 Feb 13.

Weill Cornell Medicine/New York-Presbyterian Hospital, New York, NY, USA.

We evaluate the safety of bendamustine as a bridge to stem cell transplantation (SCT) in patients with relapsed/refractory lymphoma and residual disease after salvage therapy. Thirty-four subjects without complete responses (CR) received bendamustine 200 mg/m/day for 2 days followed 14 days later by SCT. Sixteen subjects in partial remission (PR) with maximal FDG-PET SUVs ≤8 prior to bendamustine received autologous SCT, while 13 with suboptimal responses were allografted. Read More

View Article and Full-Text PDF
February 2021

The acquisition of molecular drivers in pediatric therapy-related myeloid neoplasms.

Nat Commun 2021 02 12;12(1):985. Epub 2021 Feb 12.

St. Jude Children's Research Hospital, Department of Pathology, Memphis, TN, US.

Pediatric therapy-related myeloid neoplasms (tMN) occur in children after exposure to cytotoxic therapy and have a dismal prognosis. The somatic and germline genomic alterations that drive these myeloid neoplasms in children and how they arise have yet to be comprehensively described. We use whole exome, whole genome, and/or RNA sequencing to characterize the genomic profile of 84 pediatric tMN cases (tMDS: n = 28, tAML: n = 56). Read More

View Article and Full-Text PDF
February 2021

Real-life experience with CPX-351 and impact on the outcome of high-risk AML patients: a multicentric French cohort.

Blood Adv 2021 01;5(1):176-184

Cote d'Azur University, Hematology Department, Centre Hospitalier Universitaire de Nice, Nice, France.

CPX-351 is a liposomal formulation of cytarabine and daunorubicin approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (MRC-AML). We retrospectively analyzed the efficacy and safety of CPX-351 in a real-world setting in 103 patients from 12 French centers, including the evaluation of molecular abnormalities at baseline and minimal residual disease (MRD) in responding patients, compared with a historical data set from Bordeaux-Toulouse DATAML registry. A favorable safety profile was observed, with a low frequency of alopecia (11%) and gastrointestinal toxicity (50%). Read More

View Article and Full-Text PDF
January 2021

From Clonal Hematopoiesis to Therapy-Related Myeloid Neoplasms: The Silent Way of Cancer Progression.

Biology (Basel) 2021 Feb 6;10(2). Epub 2021 Feb 6.

Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy.

Clonal hematopoiesis (CH) has been recognized as a predisposing factor for the development of myeloid malignancies. Its detection has been reported at different frequencies across studies, based on the type of genome scanning approach used and the population studied, but the latest insights recognize its virtual ubiquitous presence in older individuals. The discovery of CH in recent years paved the way for a shift in the paradigm of our understanding of the biology of therapy-related myeloid malignancies (t-MNs). Read More

View Article and Full-Text PDF
February 2021

Characteristics and outcome of patients with acute myeloid leukaemia and t(8;16)(p11;p13): results from an International Collaborative Study.

Br J Haematol 2021 Mar 2;192(5):832-842. Epub 2021 Feb 2.

NCT Trial Center, National Center of Tumor Diseases, German Cancer Research Center (DKFZ), Heidelberg, Germany.

In acute myeloid leukaemia (AML) t(8;16)(p11;p13)/MYST3-CREBBP is a very rare abnormality. Previous small series suggested poor outcome. We report on 59 patients with t(8;16) within an international, collaborative study. Read More

View Article and Full-Text PDF

Therapy-related acute myeloid leukemia and its prevention.

Am J Blood Res 2020 15;10(6):416-433. Epub 2020 Dec 15.

Department of Chemical Carcinogenesis, Blokhin National Medical Research Center of Oncology, Ministry of Health of Russian Federation Moscow 115478, Russia.

Background: Secondary tumors, including therapy-related acute myeloid leukemia (t-AML), represent one of the most undesirable side effects of chemotherapy, which arise several years after primary cancer treatment. This review aims to analyze the current data on molecular pathogenesis of t-AML revealing potential criteria for predicting predisposition to the disease. Another objective is to analyze the information on promising approaches for t-AML prevention. Read More

View Article and Full-Text PDF
December 2020