Effect of graft-versus-host disease on the outcome of bone marrow transplantation from an HLA-identical sibling donor using GVHD prophylaxis with cyclosporin A and methotrexate.

The effect of graft-versus-host disease (GVHD) on relapse incidence and survival has been analyzed in several studies, but previous studies included heterogeneous patients. Therefore, we analyzed the data of 2114 patients who received unmanipulated bone marrow graft from an HLA-identical sibling donor with a GVHD prophylaxis using cyclosporin A and methotrexate. Among the 1843 patients who survived without relapse at 60 days after transplantation, 435 (24%) developed grade II-IV acute GVHD. Among the 1566 patients who survived without relapse at 150 days after transplantation, 705 (47%) developed chronic GVHD. The incidence of relapse was significantly lower in patients who developed acute or chronic GVHD, but disease-free survival (DFS) was significantly inferior in patients who developed acute GVHD. A benefit of 'mild' GVHD was only seen in high-risk patients who developed grade I acute GVHD. The strongest association between GVHD and a decreased incidence of relapse was observed in patients with standard-risk acute myelogenous leukemia/myelodysplastic syndrome. In conclusion, the therapeutic window between decreased relapse and increased transplant-related mortality due to the development of GVHD appeared to be very narrow.     

Mutation Analysis of the WT1 Gene in Myelodysplastic Syndromes

The WT1 tumor suppressor gene was examined for mutations in a panel of 44 patients with myelo-dysplastic syndromes (MDS) including acute myelogenous leukemias (AML) secondary to MDS, using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis and sequencing analysis. A WT1 mutation was detected in one out of 17 cases of AML secondary to MDS. This mutation exists upstream of the zinc finger region and is predicted to produce a truncated WT1 protein lacking the zinc finger region. No mutations were detected in 27 MDS patients who had not progressed to AML. This is the first report of analysis for WT1 mutations in a large number of MDS patients, suggesting that WT1 mutations are uncommon in MDS. Abnormalities in this gene may, however, contribute to a small proportion of cases showing progression from MDS into AML.     

Evaluation of syringomyelia with three-dimensional constructive interference in a steady state (CISS) sequence

The purpose of this study was to evaluate a three-dimensional (3D) constructive interference in steady state (CISS) sequence in the assessment of syringomyelia. Eleven patients with syringomyelia were prospectively studied with magnetic resonance imaging. All patients underwent sagittal imaging with T1- and T2-weighted spin-echo (SE), and 3D-CISS sequences. The SE and 3D-CISS images, as well as multiplanar reconstruction (MPR) images of the 3D-CISS sequence, were analyzed with regard to image quality, degree of artifacts, visualization of the extent and internal structure of the syringomyelia, and contrast-to-noise ratio (CNR) of the fluid within the syringomyelia. Contrast between the spinal cord and cerebrospinal fluid (CSF), as well as delineation was significantly poorer for the T1-weighted SE sequence than for the 3D-CISS sequence (P < 0.01), while there was no significant difference between the T2-weighted SE sequence and the 3D-CISS sequence. Artifacts induced by CSF flow were significantly more for the T2-weighted SE sequence than for the 3D-CISS sequence (P < 0.01). Although the extent of syringomyelia was delineated equally among the three sequences in 9 of 11 patients, it was better for the 3D-CISS sequence than for the SE sequences in the remaining two. Septation and communication between the cavities were best detected by the 3D-CISS MPR images. The CNR of the 3D-CISS sequence was significantly higher than that of the SE sequence (P < 0.01). The 3D-CISS sequence demonstrates the extent and internal structures of syringomyelia better than conventional SE sequences and should be added to SE sequences in the evaluation of syringomyelia.     

Postoperative interstitial pneumonia: 2 cases after lobectomy

Two patients with postoperative interstitial pneumonia are reported. Preoperative diagnosis was primary lung cancer without idiopathic interstitial pneumonia (IIP). Within one week after operation acute interstitial pneumonia (AIP) occurred on the nonoperated side and developed. Steroid therapy was performed but one was dead. AIP is a fatal complication after pulmonary resection and steroid therapy may be useful in some cases of postoperative AIP.     

Identification of Ki23819, a highly potent inhibitor of kinase activity of mutant FLT3 receptor tyrosine kinase.

Constitutively active internal tandem duplication (ITD) in the juxtamembrane domain of Fms-like tyrosine kinase 3 (FLT3), a type III receptor tyrosine kinase, is the most common molecular defect associated with acute myeloid leukemia. Its presence confers a poor outcome in patients with acute myeloid leukemia who receive conventional chemotherapy. FLT3-ITD has therefore been considered to be an attractive molecular target for a novel therapeutic modality. We describe here the identification and characterization of Ki23819 as a novel FLT3 inhibitor. Ki23819 suppressed proliferation and induced apoptosis of FLT3-ITD-expressing human leukemia cell lines. The growth-inhibitory effect of Ki23819 on MV4-11 cells was superior to that of SU11248, another FLT3 inhibitor (IC(50)<1 vs 3-10 nM). Ki23819 inhibited the autophosphorylation of FLT3-ITD more efficiently than that of wild-type FLT3. FLT3-ITD-dependent activation of the downstream signaling proteins ERK and STAT5 was also inhibited within similar concentration ranges. Thus, Ki23819 is a potent in vitro inhibitor of FLT3.     

Clinical evaluation of biventriculo-cineangiographic findings in hypertensive left ventricular hypertrophy

In the present study, we demonstrated that hypertensive left ventricular hypertrophy can be divided angiographically into symmetrical (SH) and asymmetrical septal hypertrophy (ASH) groups. In the SH group, the dynamics of the septal wall and the free wall were almost the same as those of the control group. On the other hand, the ASH group rather resembled the HCM group in the thickness and dynamics of the septal wall and the free wall as well as in the septal configuration. The most characteristic difference of the ASH and HCM groups from the SH group was in the significantly greater thickness of the septal wall at end diastole. However, in view of the developmental mechanism of hypertensive heart, it is interesting to note that the more the septal-free wall ratio increases, the more the thickness of the septal wall increases in the SH group.