improved. The overall and event-free survival rates of the +8 patients with and without increased GPI-AP -cells at five years were 100% and 100% and 59% and 57%, respectively. Examining the peripheral blood for the presence of increased GPI-AP -cells may thus be helpful for choosing the optimal 4 treatment for +8 patients with AA or low-risk MDS.
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Myelodysplastic SyndromesAlthough myelodysplastic syndromes are heterogeneous disorders comprising a benign subset of bone marrow failure similar to aplastic anemia, no laboratory test has been established to distinguish it from bone marrow failures that can evolve into acute myeloid leukemia. Plasma thrombopoietin levels were measured in 120 patients who had myelodysplastic syndrome with thrombocytopenia (< 100 x 10 9 /L) to determine any correlation to markers associated with immune pathophysiology and outcome. Thrombopoietin levels were consistently low for patients with refractory anemia with excess of blasts, while patients with other myelodysplatic syndrome subsets had more variable results. Patients with thrombopoietin levels of 320 pg/mL and over had increased glycosylphosphatidylinositol-anchored protein-deficient blood cells (49.1% vs. 0%), were more likely to have a low International Prognostic Scoring System (IPSS) score (≤1.0, 100% vs. 65.5%), a higher response rate to immunosuppressive therapy (84.2% vs. 14.3%), and a better 5-year progression-free survival rate (94.1% vs. 63.6% for refractory cytopenia with unilineage dysplasia; 100.0% vs. 44.4% for refractory cytopenia with multilineage dysplasia). In conclusion, increased plasma thrombopoietin levels were associated with a favorable prognosis of bone marrow failure and could, therefore, represent a reliable marker for a benign subset of myelodysplastic syndrome.
Increased plasma thrombopoietin levels in patients with
SummaryPatients with mild hypomegakaryocytic thrombocytopenia (HMT) that does not meet the diagnostic criteria for a definite disease entity may potentially progress to aplastic anaemia (AA) refractory to therapy. To clarify the clinical pictures of HMT, we prospectively followed 25 HMT patients that fulfilled 2 the following criteria: a WBC count of >3.0x10 9 /l, an Hb level of >10g/dl, and a platelet count of <100.0x10 9 /l in the absence of morphological and karyotypic abnormalities in the bone marrow.Glycosylphosphatidylinositol-anchored protein-deficient blood cells (PNH-type cells) were detected in 7 of the 25 (28%) patients and elevated plasma thrombopoietin (TPO) levels (>320 pg/ml) were observed in 11 (44%) patients. Five (four PNH+ and one PNH-) of six TPO high patients who were treated with cyclosoporine (CsA) showed improvement. Among the 21 patients who were followed without treatment, thrombocytopenia progressed in four of ten TPO low patients and four of 11 TPO high patients. The three-year failure-free survival rate of the TPO high patients who were treated with CsA (100%) was significantly higher than that of the untreated TPO high patients (20%). These results suggest that a significant population of HMT patients has an immune pathophysiology that is similar to AA and may be improved by early therapeutic intervention with CsA.
Sixty-six adult patients with hematologic malignancies underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) without T cell depletion. The patients were preconditioned with a reduced intensity regimen, and tacrolimus was used for graft-versus-host disease (GVHD) prophylaxis. Successful engraftment occurred in 60 patients (90.1%) and graft rejection in only 4 patients (6.1%). Among the 60 engrafted patients, only 5 developed severe (grade III or IV) acute GVHD. Twenty patients, including 19 relapse-free patients were alive at a median follow-up of 48 months (range 6-77 months). The overall survival (OS) at 6 years was 29.3%. The OS of 45 patients < 60 years of age was 43.6%, which was superior to that of 21 patients who were 60 years of age and older (9.5%) (P < 0.01). The OS of 11 patients from human leukocyte antigen (HLA) 1 locus-mismatched donors (63.6%) was higher than that of 28 patients from HLA 3 loci-mismatched donors (12.5%) (P < 0.01). Organ injury and infection were the main causes of mortality. Notably, immunosuppressive therapy could be successfully stopped in 9 patients transplanted from HLA 2 or 3 loci-mismatched donors with a median duration of 45 months (range 5-71 months). These data suggest that haplo-HSCT is a promising treatment for patients who need urgent allogeneic transplantation but lack HLA-identical family donors.
Excessive intake of purine-rich foods elevates serum uric acid levels, making it a risk factor for hyperuricemia. We hypothesized that lactic acid bacteria ingested with food might utilize purines and contribute to their decreased absorption in the intestines, thereby preventing hyperuricemia. We previously reported that Lactobacillus gasseri PA-3 (PA-3) incorporates adenosine/inosine and related purines and that oral ingestion of PA-3 reduced the absorption of these purines in rats. However, it is unclear whether PA-3 also decreases the absorption of other purines, such as guanosine 5'-monophosphate (GMP) and guanosine. This study investigated whether PA-3 incorporates GMP and guanosine and reduces their absorption in rats. PA-3 incorporated both purines, with C-GMP uptake being greater than that ofC-guanosine. Radioactivity in rat blood was significantly lower 30, 45, and 60 minutes after administration of C-GMP plus PA-3 than after administration ofC-GMP alone and was significantly lower 15 minutes after administration of C-guanosine plus PA-3 than after administration ofC-guanosine alone. PA-3 incorporates GMP and guanosine in vitro. Oral administration of PA-3 with GMP and guanosine reduces the intestinal absorption of these purines in vivo. These findings, together with those of previous studies, indicate that PA-3 reduces the absorption of major purines contained in foods. PA-3 may also attenuate the excessive absorption of dietary purines in humans, protecting these individuals against hyperuricemia.
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