[Show abstract][Hide abstract] ABSTRACT: Intestinal transplant-associated microangiopathy (i-TAM) is an important complication after allogeneic hematopoietic SCT. From 1997 to 2006, 87 of 886 patients with diarrhea after transplantation received colonoscopic biopsy. i-TAM, GVHD and CMV colitis were diagnosed histopathologically. The median duration from transplantation to the onset of diarrhea was 32 days (range: 9-130 days) and that from the onset of diarrhea to biopsy was 12 days (range: 0-74 days). The median maximal amount of diarrhea was 2 l/day (range: 130-5600 ml/day). Histopathological diagnosis included i-TAM (n=80), GVHD (n=26), CMV colitis (n=17) and nonspecific findings (n=2) with overlapping. Among 80 patients with i-TAM, abdominal pain was a major symptom, and only 11 patients fulfilled the proposed criteria for systemic TAM. Non-relapse mortality (NRM) among patients without resolution of diarrhea was 72% and i-TAM comprised 57% of NRM. NRM was 25% among patients without intensified immunosuppression, but was 52, 79 and 100% among those with intensified immunosuppression before diarrhea, after diarrhea, and before and after diarrhea, respectively. In conclusion, i-TAM is a major complication presenting massive refractory diarrhea and abdominal pain, which causes NRM. Avoiding intensified immunosuppression that damages vascular endothelium until the resolution of i-TAM may improve transplant outcome.
Bone marrow transplantation 02/2009; 44(1):43-9. · 3.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thrombotic microangiopathy (TMA) is one of the severe complications after stem cell transplantation (SCT) and is associated with graft-versus-host disease (GVHD) prophylaxis including FK506. In this study, we experimented on rats using FK506 to demonstrate the occurrence of intestinal TMA. FK506 was administrated into Wistar/ST rats intraperitoneally for 7 days. Rats were examined histopathologically after FK506 injection using light and electron microscopy and immunohistochemistry. FK506 concentrations in whole blood were measured by enzyme immunoassay. In the acute phase, hemorrhagic lesions with multifocal erosions and crypt loss were found in the small intestines of all treated rats. Capillary vessels were dilated, and a few platelet thrombi were found. Electron microscopy demonstrated degenerative swelling of endothelial cells and platelet aggregates adhering to the vessel walls. In the later phase, epithelial regenerative failure, characterized by crypt ghosts, was found in the affected mucosa. Apoptotic epithelial cells were increased in number. The extent of intestinal injury was proportional to the whole blood levels of FK506. The intestinal lesions in rats were consistent with TMA and induced by the injection of FK506 alone. Apoptotic enteropathy was also observed and similar to intestinal GVHD. In this study, we established an intestinal TMA model induced by immunosuppressant (Tacrolimus) only without irradiation.
Bone Marrow Transplantation 04/2007; 39(6):367-72. · 3.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We used immunohistochemical analysis to investigate 146 bone marrow (BM) clot specimens from patients with fever of unknown origin (FUO) (n = 124) or hemophagocytic syndrome (HPS) (n = 22). Intravascular lymphoma (IVL) primarily involving BM was detected in 12 (8.2%) of the 146 patients. Diagnosis was based on the presence of CD20+ and CD79a+ tumor cells confined within the lumina of sinuses and surrounded by CD34+ endothelial cells. Of the 12 IVL cases, 6 were CD5+; of these 6 CD5+ cases, 5 were positive for vimentin. The finding of a considerably high prevalence of IVL tumor cells in BM from patients with FUO or HPS suggests that immunohistochemical examination of BM may be helpful in the diagnosis of IVL in these patients. Vimentin coexpression in CD5+ IVL might be evidence of origin from a subset of prefollicular B-cells.
International Journal of Hematology 03/2003; 77(2):159-63. · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the relationship between the fetal hemoglobin-containing erythroblasts (F blasts) and apoptosis in myelodysplastic syndromes (MDS), we immunohistochemically assessed F blasts, F cells, and apoptosis in 137 patients with MDS. A marked increase in the number of F blasts in the bone marrow was identified in 116 of 137 patients (84.7%), and the number of F cells was elevated in 54 patients (39.4%). Among the erythroblasts stained by anti-glycophorin C antibody, the mean percentage of F blasts was 14.63 +/- 9.17% in MDS, which was significantly higher than that in non-MDS patients with stress erythropoiesis (4.82 +/- 3.35%, P < 0.01), although there were no significant differences in the number of F cells between these groups. In particular, 62 of the 137 MDS patients (45.3%) had an apparent increase in F blasts but no elevation of F cells. The apoptotic rate was significantly higher in the patients with a F blast/F cell (Fb/Fc) ratio >or=5.0 than in those with a Fb/Fc ratio <1.0 (P < 0.01). The results indicate that F cell precursors are incapable of maturing into functioning end-stage F cells, presumably owing to apoptotic cell death. The measurement of F blasts in the bone marrow is needed for the precise evaluation of fetal-type erythropoiesis in MDS.
[Show abstract][Hide abstract] ABSTRACT: Making a morphologic distinction between hypocellular refractory anemia (hypo RA) and aplastic anemia (AA) is difficult. To investigate the significance of hemoglobin F-containing erythroblasts (F-blasts) and p53 expression in making the distinction between hypo RA and acquired AA, we immunohistochemically assessed F-blasts and p53 in bone marrow specimens from 16 patients with hypo RA, 31 patients with acquired AA, and 15 hematologically normal individuals. F-blast production was elevated in 87.5% (14/16) of patients with hypo RA, but in only 3.2% (1/31) of patients with AA (P < .01). p53 was overexpressed in 75.0% (12/16) of hypo RA patients and in 6.4% (2/31) of AA patients (P < .01). The mean contents of F-blasts and p53-positive cells in patients with hypo RA were 6.31% +/- 3.27% and 7.54% +/- 4.36%, respectively, of all bone marrow cells, which were significantly higher than for patients with AA (0.35% +/- 0.46% and 0.58% +/- 1.29%, P < .01). In conclusion, a high prevalence of elevated F-blast production is noted in hypo RA, suggesting that the assessment of F-blasts in bone marrow can be used as an additional tool for differentiating hypo RA from acquired AA.
International Journal of Hematology 05/2002; 75(3):257-60. · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated whether the anatomic distribution of hematopoietic cells determines the type of hemoglobin produced in patients with extramedullary hematopoiesis (EMH). Fetal hemoglobin (HbF) production is not restricted to fetal erythropoietic organs during EMH. A shift of erythropoiesis to fetal hematopoietic organs in EMH does not necessarily induce HbF synthesis in adulthood.
[Show abstract][Hide abstract] ABSTRACT: To date there are few antibodies available for the detection of fetal hemoglobin (HbF)-containing erythroblasts (F-blasts)
in paraffin-embedded hematopoietic tissues. Recently, we developed a new polyclonal antibody specific to F-blasts by immunization
of a rabbit with synthetic peptides of human HbF. Specificity and reactivity of the antibody were confirmed by enzyme-linked
immunosorbent assay (ELISA) and immunohistochemistry. ELISA confirmed that the antibody showed strong immunoreactivity to
fetal hemoglobin but no reaction to adult hemoglobin. The antibody could detect the presence of fetal blood hemolysates (10
μxg/mL) at a dilution of 10p-5. According to immunohistochemical analysis, there were strong positive reactions to fetal erythroblasts in the liver and
the spleen at 29 weeks of gestation and to erythroblasts from patients with myelodysplastic syndromes and erythroleukemia
but no reactions to normal adult erythroblasts in bone marrow. Fetal erythrocytes in fetal blood vessels of placental tissues
were strictly distinguished from maternal erythrocytes in the same sections by their positive reactions, indicating the presence
of HbF. This new antibody will be a useful tool for studying fetal hemoglobin synthesis and for detecting F-blasts in archival
specimens of various hematological diseases.
International Journal of Hematology 01/2001; 74(3):277-280. · 1.68 Impact Factor