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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z M, Alousi A, Couriel D, Pidala J, Arora M, Cutler C Abstract Upper gastrointestinal acute graft-versus-host disease is reported in approximately 30% of hematopoietic stem cell transplant recipients developing acute graft-versus-host disease. Currently classified as Grade II in Consensus criteria, upper gastrointestinal acute graft-versus-host disease is often treated with systemic immunosuppression. We reviewed the Center for International Blood and Marrow Transplant Research database to assess prognostic implications of upper gastrointestinal acute graft-versus-host disease in isolation or with other acute graf...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica 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
We recently conducted a randomized double-blind study in which we demonstrated that moderate/severe chronic graft-versus-host disease (cGVHD) but not cGVHD-free survival was reduced in patients receiving anti-T lymphocyte globulin (ATLG) versus placebo. In a companion study we performed immunophenotypic analysis to determine the impact of ATLG on immune reconstitution (IR) and to correlate IR with clinical outcomes. The randomized study (n  = 254) included patients (aged 18 to 65 years) who underwent myeloablative transplants for acute myeloid leukemia, myelodysplastic syndrome, or acute lymphoblastic leukemia from HLA...
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: 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
This study includes 2473 patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome and 2221 10/10 HLA-matched donors treated from 2000 to 2011. Single-variant and gene-level analyses were performed on overall survival (OS), transplantation-related mortality (TRM), and disease-related mortality (DRM). Genotype mismatches between recipients and donors in a rare nonsynonymous variant of testis-expressed gene TEX38 significantly increased risk of TRM, which was more dramatic when either the recipient or donor was female. Using the SKAT-O test to evaluate gene-level effects, variant genotyp...
Source: Blood - Category: Hematology Authors: Tags: Transplantation Source Type: research
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
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