Myelodysplastic Syndromes: How to Recognize Risk and Avoid Acute Myeloid Leukemia Transformation

AbstractPurpose of ReviewTo understand how myelodysplastic syndromes (MDS) transform to AML and to describe how transformation can be predicted and prevented.Recent FindingsRecent genomic analyses have shown that MDS progression to AML is associated with clonal expansion and clonal evolution. Mutation profiles of MDS change during progression and new mutations in signaling genes and transcription factors emerge. AML transformation can be predicted by several parameters including International Prognostic Scoring System IPSS risk category and transfusion requirements. The prognostic relevance of the acquisition of some gene mutations (i.e., IDH1 and 2, CBL, FT3, RAS, NPM1, TP53, and ASXL1) has to be prospectively validated. The most effective preventive therapy for AML transformation is allogeneic stem cell transplantation. Hypomethylating agents have been associated with prolonged time to AML transformation even in patients who did not achieve an objective response.SummaryThe recent progress in the understanding of the molecular events leading to transformation and the event of new effective therapies open new avenues for a better prediction and prevention of AML transformation in patients with MDS.
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research

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Pediatric myelodysplastic syndromes (MDS) represent a spectrum of rare hematopoietic stem cell disorders characterized by cytopenias, ineffective hematopoiesis, marrow dysplasia and risk for leukemic transformation. While some cases are likely acquired due to de novo transformation, germline mutations in DNA repair pathways, ribosomal pathways, the telomere complex or in hematopoietic transcription factors (e.g., CEBPA, RUNX1, GATA2 and ETV6) are predisposition syndromes underlying many pediatric cases of MDS and acute myeloid leukemia (AML).
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Authors: Gorshein E, Weber UM, Gore S Abstract Introduction: Myelodysplastic Syndrome (MDS) represents a group of cancers characterized by abnormal blood cell formation and maturation, leading to various degrees of cytopenias and potential transformation to acute myeloid leukemia. Deletion of the long arm of chromosome 5 (del(5q)) is the most common clonal chromosomal anomaly in MDS, yet the population in this disease subtype is quite heterogeneous. This manuscript analyzes literature on high-risk MDS with del(5q) abnormalities.Areas covered: The paper will review outcomes with lenalidomide among high-risk MDS pati...
Source: Expert Review of Hematology - Category: Hematology Tags: Expert Rev Hematol Source Type: research
Allogeneic stem cell transplantation (allo-SCT) is the only curative treatment option for many hematological diseases, including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Outcomes of allo-SCT have improved with better supportive care, reduced intensity conditioning regimens, and use of alternative stem cell donor sources. [1] However, relapsed disease after allo-SCT remains a major cause of treatment failure, occurring in approximately 40% of AML cases, most of which occur within the first year.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
For patients with refractory or high-risk hematologic malignancies, like acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplant (Allo-HSCT) is a potentially curative approach. Morbidities and mortality associated with current conditioning regimens limit the use of this curative procedure. As a result, many eligible patients do not consider transplant and 2/3 of those transplanted are only able to tolerate a reduced intensity conditioning regimen, which is associated with increased relapse rates (Scott, J Clin Onc 2017).
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 128 Source Type: research
Relapsed acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) following an allogeneic stem cell transplant has a bleak prognosis with no standard for treatment identified. Current literature suggests combining hypomethylating agents (HMA) with a donor lymphocyte infusion (DLI) as salvage therapy to reduce disease burden and induce a graft versus leukemia (GVL) effect. At our institution, this salvage therapy option is being used for this population, peaking interest in our experience to date.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 608 Source Type: research
Genetic abnormalities can predispose patients to develop acute myeloid leukemia (AML), aplastic anemia (AA) and myelodysplastic syndrome (MDS). These mutations are more often seen in pediatric patients so genetic screening is more routinely performed in that population. Recent algorithms propose screening in adolescent and young adults (AYAs) with AML/AA/MDS. However, this is not routine practice in community hospitals where most AYAs are treated. Discovery of familial genetic abnormalities can impact donor choice in patients undergoing allogeneic stem cell transplant and treatment/screening in family members.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 145 Source Type: research
Hematopoietic stem cell transplantation (HSCT) is often indicated and formal transplant referral guidelines exist for pts with AML and HR MDS. However, the proportion of transplant-eligible pts not referred is largely unknown. We therefore assessed HSCT referral patterns, including potential barriers to referral, in pts with ND MDS and AML enrolled in the Connect ® MDS/AML Disease Registry (NCT01688011), a large, US, multicenter, prospective observational cohort study of pts with ND AML (aged ≥ 55 years) or MDS (aged ≥ 18 years).
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 131 Source Type: research
Relapse after allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remains a major cause of treatment failure with associated poor prognosis. Low-dose post-HSCT maintenance azacitidine (AZA) has proved to be beneficial in preventing relapses (de Lima et al. Cancer 2010). Herein, we retrospectively evaluated outcomes of patients (pts) treated with low-dose AZA post-HSCT.
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 175 Source Type: research
Retrospective studies indicate that the use of unrelated hematopoietic stem cell donors with Killer Ig-like Receptor (KIR) genotypes resulting in low inhibitory interactions with recipient HLA are associated with lower relapse and higher survival in patients with myeloid neoplasia undergoing allogeneic hematopoietic cell transplantation (allo HCT). To validate these findings in a prospective fashion and to determine if advantageous KIR donors can readily be identified for patients with myeloid neoplasia, we prospectively KIR genotyped and provided KIR/HLA-based ranking for unrelated donors (URD) evaluated for patients with...
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Tags: 172 Source Type: research
Rationale: The success of tyrosine kinase inhibitor (TKI) therapy has greatly prolonged the survival time of patients with chronic myeloid leukemia (CML), harboring the characteristic Philadelphia (Ph) chromosome. However, a fraction of patients, achieving complete cytogenetic response after TKI therapy, develop a myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with additional clonal chromosomal abnormalities in Philadelphia-negative cells (CCA/Ph–). Patient concerns: A 56-year-old woman with AML, developing from Philadelphia-negative CML after TKI therapy. She showed 6 kinds of somatic variants&m...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
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