No abstract

No abstract

All of the risk factors previously reported to predict severe aGVHD were obtained only during, but not after, HSCT. Our study suggests that the reactivation of HHV6 (≥ 87 copies/mL) at 30 days after HSCT is a possible predictive marker for grade 2-4 aGVHD on or after post-HSCT day 30.

No abstract

No abstract

Graft failure (GF) remains a major problem in cord blood transplantation (CBT). In 36 adult patients undergoing CBT at our hospital between July 2003 and December 2009, six patients developed GF (primary, n = 5; secondary, n = 1). All six patients underwent second stem cell transplantation (SCT). Three patients had acute myeloid leukemia, one had acute lymphoblastic leukemia, one had chronic myeloid leukemia, and one had aplastic anemia. Five patients were complicated with sepsis before the second SCT. The median elapsed time from first CBT to the diagnosis of primary GF was 27 days. Secondary GF was diagnosed on day 567. The median elapsed time from primary GF to second SCT was 9 days. In the patient with secondary GF, the elapsed time was 35 days. Cord blood grafts were used in 5 patients and a matched sibling donor in one patient. All 6 patients underwent second transplantation following a modified '1-day'-based preparative regimen consisting of fludarabine (30 mg/m(2), 1 day, n = 2; 2 days, n = 1; 3 days, n = 3), cyclophosphamide (2 g/m(2)), and total body irradiation (2 Gy). All patients achieved neutrophil engraftment, and the median elapsed time from second SCT to engraftment was 35 days. Four patients remain alive between 5 and 38 months after second SCT. '1-day'-based short-term conditioning may be a promising salvage regimen.

Recent studies have demonstrated that exosomal microRNAs (miRNAs) have the potential of facilitating molecular diagnosis. Currently, little is known about the underlying mechanism behind late-onset acute graft-versus-host disease (LA GVHD). Identifying differentially expressed miRNAs in exosomes should be useful for understanding the role of miRNAs in this disease. This study was established to investigate the relevance of miRNAs in exosomes derived from patients developing LA GVHD after allogeneic hematopoietic stem cell transplantation (HSCT). Plasma samples were collected from patients with LA GVHD (n = 5), non-GVHD (n = 5), and controls (n = 8) for exosomal miRNA expression profiling using a TaqMan low-density array; the results were validated by quantitative reverse transcription polymerase chain reaction (RT-PCR). We analyzed exosomal miRNAs differentially expressed among these three groups. MirTarBase was employed to predict potential target genes of the miRNAs specific for LA GVHD. We detected 55 miRNAs that were differentially expressed with a significant change >2.0-fold between LA GVHD and non-GVHD. Of these, we selected the 10 miRNAs (miR-423-5p, miR-19a, miR-142-3p, miR-128, miR-193b, miR-30c, miR-193a, miR-191, miR-125b, and miR-574-3p) with the most significant differential expression. Using quantitative RT-PCR, we further identified that miR-128 was significantly upregulated at the onset of LA GVHD compared with that in normal controls and is a promising diagnostic marker of LA GVHD, with an area under the curve (AUC) value of 0.975. MirTarBase analysis revealed that the predicted target genes of miR-128 are involved in the immune system and inflammation. Increased expression of miR-128 may serve as a novel, noninvasive biomarker for early LA GVHD diagnosis.

Dasatinib is an ATP-competitive, multi-targeted SRC and ABL kinase inhibitor that can bind BCR-ABL in both the active and inactive conformations. From a clinical standpoint, dasatinib is particularly attractive because it has been shown to induce hematologic and cytogenetic responses in imatinib-resistant chronic myeloid leukemia patients. The fact because the combination of imatinib and dasatinib shows the additive/synergistic growth inhibition on wild-type p210 BCR-ABL-expressing cells, we reasoned that these ABL kinase inhibitors might induce the different molecular pathways. To address this question, we used DNA microarrays to identify genes whose transcription was altered by imatinib and dasatinib. K562 cells were cultured with imatinib or dasatinib for 16 h, and gene expression data were obtained from three independent microarray hybridizations. Almost all of the imatinib-and dasatinib-responsive genes appeared to be similarly increased or decreased in K562 cells; however, small subsets of genes were identified as selectively altered expression by either imatinib or dasatinib. The distinct genes that are selectively modulated by dasatinib are cyclin-dependent kinase 2 (CDK2) and CDK8, which had a maximal reduction of o5-fold in microarray screen. To assess the functional importance of dasatinib regulated genes, we used RNA interference to determine whether reduction of CDK2 and CDK8 affected the growth inhibition. K562 and TF-1BCR-ABL cells, pretreated with CDK2 or CDK8 small interfering RNA, showed additive growth inhibition with imatinib, but not with dasatinib. These findings demonstrate that the additive/ synergistic growth inhibition by imatinib and dasatinib may be mediated in part by CDK2 and CDK8.