Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HLA disparity has a negative impact on the outcomes of hematopoietic cell transplantation (HCT). We studied the independent impact of amino acid substitution (AAS) at peptide-binding positions 9, 99, 116, and 156, and killer immunoglobulin-like receptor binding position 77 of HLA-A, B, or C, on the risks for grade 3-4 acute graft-versus-host disease (GVHD), chronic GVHD, treatment-related mortality (TRM), relapse, and overall survival. In multivariate analysis, a mismatch at HLA-C position 116 was associated with increased risk for severe acute GVHD (hazard ratio [HR] = 1.45, 95% confidence interval [CI] = 1.15-1.82, P = .0016). Mismatch at HLA-C position 99 was associated with increased transplant-related mortality (HR = 1.37, 95% CI = 1.1-1.69, P = .0038). Mismatch at HLA-B position 9 was associated with increased chronic GVHD (HR = 2.28, 95% CI = 1.36-3.82, P = .0018). No AAS were significantly associated with outcome at HLA-A. Specific AAS pair combinations with a frequency >30 were tested for association with HCT outcomes. Cysteine to tyrosine substitution at position 99 of HLA-C was associated with increased TRM (HR = 1.78, 95% = CI 1.27-2.51, P = .0009). These results demonstrate that donor-recipient mismatch for certain peptide-binding residues of the HLA class I molecule is associated with increased risk for acute and chronic GVHD and death.
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PMID:Amino acid substitution at peptide-binding pockets of HLA class I molecules increases risk of severe acute GVHD and mortality. 2426 56

Bruton tyrosine kinase signaling (BTK) is critical step for B-cell development and immunoglobulin synthesis. Ibrutinib is an orally bioavailable bruton tyrosine kinase inhibitor (BTKi) and forms an irreversible covalent bound to BTK at the Cysteine-481 residue. Ibrutinib has been approved by FDA for the treatment of mantle cell lymphoma, chronic lymphocytic leukemia, Waldenstrom's macroglobulinemia, marginal zone lymphoma and chronic graft-versus-host disease in allogeneic stem cell transplantation. Ibrutinib is generally well tolerated drug with rapid and durable responses but has some side events. The most common side effects are diarrhea, upper respiratory tract infection, bleeding, fatigue and cardiac side effects. These events are generally mild (grade I-II). However atrial fibrillation (AF) and bleeding are important and may be grade III or higher side effects require strict monitoring. Here side effects of ibrutinib have been summarized and important considerations in the management of these adverse events have been reviewed.
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PMID:Management of adverse effects/toxicity of ibrutinib. 3087 29