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Replication and validation of genetic polymorphisms associated with survival after allogeneic blood or marrow transplant

Multiple candidate gene-association studies of non-HLA single-nucleotide polymorphisms (SNPs) and outcomes after blood or marrow transplant (BMT) have been conducted. We identified 70 publications reporting 45 SNPs in 36 genes significantly associated with disease-related mortality, progression-free survival, transplant-related mortality, and/or overall survival after BMT. Replication and validation of these SNP associations were performed using DISCOVeRY-BMT (Determining the Influence of Susceptibility COnveying Variants Related to one-Year mortality after BMT), a well-powered genome-wide association study consisting of 2 cohorts, totaling 2888 BMT recipients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome, and their HLA-matched unrelated donors, reported to the Center for International Blood and Marrow Transplant Research. Gene-based tests were used to assess the aggregate effect of SNPs on outcome. None of the previously reported significant SNPs replicated at P
Source: Blood - Category: Hematology Authors: Tags: Transplantation Source Type: research

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AbstractImmunocompromised patients are at high risk of invasive fungal infections (IFI), in particular those with haematological malignancies undergoing remission-induction chemotherapy for acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) and recipients of allogeneic haematopoietic stem cell transplants (HSCT). Despite the development of new treatment options in the past decades, IFI remains a concern due to substantial morbidity and mortality in these patient populations. In addition, the increasing use of new immune modulating drugs in cancer therapy has opened an entirely new spectrum of at risk periods. ...
Source: Annals of Hematology - Category: Hematology Source Type: research
Hematopoietic cell transplantation (HCT) is a potentially curative treatment for patients with high-risk hematologic malignancies [1,2]. Common indications for HCT in adults include acute myelogenous leukemia, myeloproliferative neoplasms, myelodysplastic syndromes, chronic myelogenous leukemia, chronic lymphocytic leukemia, acute lymphoblastic leukemia, lymphoma, multiple myeloma, Hodgkin lymphoma, non-Hodgkin lymphoma, and certain solid tumors [2].
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
AbstractPurpose of ReviewAcute leukemia is the most common cancer of childhood. The pathogenesis of childhood leukemia is multifactorial, and most cases occur sporadically. Although the majority of genetic changes are acquired somatic mutations, recent discoveries have revealed that inherited germline mutations are present in an increasing proportion of children, predisposing them to leukemia.Recent FindingsRecently described germline mutations inETV6,SH2B3, andPAX5 have been associated with increased risks of acute lymphoblastic leukemia (ALL). A high incidence of germline mutations inGATA2 is seen in pediatric myelodyspl...
Source: Current Genetic Medicine Reports - Category: Genetics & Stem Cells Source Type: research
CONCLUSIONSIn the absence of RD transplantation, 8/8 URD transplantation is a viable alternative with similar survival outcomes, whereas 7/8 URD transplantation is associated with poorer overall survival. Cancer 2017. © 2017 American Cancer Society.
Source: Cancer - Category: Cancer & Oncology Authors: Tags: Original Article Source Type: research
Conditions:   Acute Lymphoblastic Leukemia in Remission;   Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome;   Acute Myeloid Leukemia in Remission;   CD45-Positive Neoplastic Cells Present;   Chronic Myelomonocytic Leukemia;   Myelodysplastic Syndrome With Excess Bla sts;   Recurrent Adult Acute Myeloid Leukemia;   Refractory Adult Acute Lymphoblastic Leukemia Interventions:   Drug: Cyclosporine;   Drug: Fludarabine ...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conclusion SDF-1/CXCR4 axis plays a crucial role in engraftment; however, more studies are warranted to assess their expression post-transplant. Evaluating the ligand (chemokine, SDF-1) or its receptor (CXCR4) may serve as potential surrogate markers for assessment of engraftment.
Source: Hematology Oncology and Stem Cell Therapy - Category: Cancer & Oncology Source Type: research
We report a case of myelodysplastic syndrome progressing to AML with calreticulin driver mutation in an adult male with TAR syndrome who was successfully treated with hematopoietic allogeneic stem cell transplantation.
Source: Hematology Oncology and Stem Cell Therapy - Category: Cancer & Oncology Source Type: research
Conclusions 11q23+/MLL– occurs rarely, involving different partner chromosomes and showing clinical and pathological features and disease subtypes different from those cases with MLL rearrangement. 11q23+/MLL– appears to be associated with clonal evolution/disease progression in acute leukaemia, a high risk for AML progression in MDS/CMML and a high incidence of disease relapse.
Source: Journal of Clinical Pathology - Category: Pathology Authors: Tags: Original article Source Type: research
HLA mismatches are associated with worse clinical outcomes in unrelated hematopoietic cell transplantation (HCT) [1,2]. Reports of the clinical relevance of mismatches at other polymorphic genetic loci, such as the MHC Class I Chain-Related Gene A (MICA) gene have been contradictory. At least 2 single-center studies have reported significant associations between MICA mismatches and increased risk of severe acute graft-versus-host disease (GVHD; grades III and IV), whereas 1 registry study did not find an association [3-5].
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Single-center studies have reported an association between early (before day 100) cytomegalovirus (CMV) reactivation and decreased incidence of relapse for acute myeloid leukemia (AML) following allogeneic hematopoietic cell transplantation. To substantiate these preliminary findings, the Center for International Blood and Marrow Transplant Research (CIBMTR) Database was interrogated to analyze the impact of CMV reactivation on hematologic disease relapse in the current era. Data from 9469 patients transplanted with bone marrow or peripheral blood between 2003 and 2010 were analyzed according to 4 disease categories: AML (...
Source: Blood - Category: Hematology Authors: Tags: Immunobiology, Transplantation, Free Research Articles, Clinical Trials and Observations Source Type: research
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