ABSTRACT
Myelodysplastic syndromes (MDS) are a heterogenous group of hematologic malignancies characterized by clonal expansion of BM myeloid cells with impaired differentiation. Of particular interest mutations is the recent recognition that genes involved in the regulation of histone function (EZH2, ASXL1,and UTX) and DNA methylation (DNMT3A,IDH 1/IDH2,TET2) are recurrently mutated in MDS,providing an important link between genetic and epigenetic alterations in this disease. Ongoing analysis of the seminal AZA-001study has taught many important lessons in the use of DNA methyltransferase (DNMT) inhibitors.Improved survival in patients with high-risk MDS treated with azacitidine extends to patients with any International Working Group-defined hematologic response.New information on the impact of DNMT inhibitors on the immune system and on stem cells will likely lead to novel uses of these drugs in MDS and other hematologic and nonhematologic malignancies. The immunomodulating drug thalidomide and its derivative lenalidomide have been used in the treatment of MDS,principally in lower-risk MDS.
ABSTRACT
Objective To explore the incidence and risk factors of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods The clinical data of 72 cases allo-HSCT from Oct 2004 to Dec 2008 were analyzed. Thirteen factors possibly correlated with the development of aGVHD were analyzed. Results aGVHD was developed in 32 cases (44.4 %), in which grades Ⅰ aGVHD was 11.1%, gradesⅡaGVHD was 18.1%, and grades Ⅲ-Ⅳ aGVHD was 15.3 %. The univariate analysis showed that diagnosis, the status of disease, use ATG, conditioning regimen, donor type,ABO blood group disparity between donor and recipient, CD34+ cell number, early engraftment and neutropenic infection, HLA locus were associated with the occurence of aGVHD (P ＜0.1). On the COX regression mode, an increased risk of aGVHD was associated with HLA mismatch (HR =2.58, P ＜0.005), GVHD prophylaxis without ATG (HR =2.94, P ＜ 0.001), and unrelated donor (HR =1.97, P ＜0.01). Conclusion aGVHD is a common complication after allo-HSCT, and HLA mismatch and unrelated donor are independent risk factors for aGVHD.