Although stem cell transplantation (SCT) is being used for hematopoietic reconstitution following high-dose chemotherapy for malignancy, it involves certain serious transplant-related complications such as graft-versus-host disease (GVHD). Angiopoietins play important roles in angiogenesis. However, the role of angiopoietins after SCT is poorly understood. In this study, 52 patients underwent SCT; 26 patients received allogeneic SCT, while the remaining 26 received autologous SCT. In 48 of 52 patients, levels of angiopoietins, cytokines, and soluble factors were measured by enzyme-linked immunosorbent assay. Soluble Fas ligand (sFasL) and endothelial cell-derived microparticle (EDMP) exhibited significant elevation in the early phase (2-3 weeks) after SCT. In addition, the elevation of interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and sIL-2 receptor (sIL-2R), which are GVHD markers after allogeneic SCT was observed. The level of angiopoietin (Ang)-2 in allogeneic SCT continued to increase for up to 4 weeks, although the level of Ang-1 did not show significant changes. The patients with high Ang-2 exhibited significant increase of sFasL and EDMP compared with those with low Ang-2. In addition, the patients with high-grade GVHD exhibited a significant increase in Ang-2 compared to patients with low-grade GVHD. In the in vitro experiment using endothelial cells, the suppressive effect of Ang-1 on EDMP generation by TNF-alpha was partially inhibited by the addition of Ang-2. Furthermore, multivariate regression analysis showed that EDMP and sFasL were significant factors in Ang-2 elevation. Our results suggest that Ang-2 generation after allogeneic SCT relates to GVHD.

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Human T-cell lymphotropic virus type II (HTLV-II) is endemic in several ethnic tribes and among intravenous drug users in metropolitan areas. Despite the presence of HTLV-II in these various populations, the association of HTLV-II with disease is sparse and mainly limited to isolated case reports. This study is an extension of an earlier description of an HTLV-II-infected patient with neurologic disease and presents the clinical and immunologic findings of 4 patients with HTLV-II seropositivity and spastic paraparesis. The patients are of African-American origin with 3 of the patients being of Amerindian descent. All of the patients are seronegative for the human immunodeficiency virus (HIV). The patients progressed to a nonambulatory state in less than 5 years. Magnetic resonance imaging studies obtained from 3 of the patients demonstrated white matter disease in the cerebrum and spinal cord. The cerebrospinal fluid and serum contained antibodies to HTLV-II. The presence of proviral HTLV-II was confirmed by polymerase chain reaction analysis of peripheral blood lymphocytes (PBLs). A spinal cord biopsy from 1 patient demonstrated HTLV RNA within a lesion. Immunologic studies on 2 patients demonstrated that spontaneous lymphoproliferation of PBLs was present but decreased relative to HTLV-I-infected patients. The clinical and immunologic findings from these HTLV-II-infected patient resemble those found in HTLV-I-associated myelopathy/tropical spastic paraparesis.

Our findings suggest that endothelial cell activation might be linked to aGVHD, and that rTM might act to prevent aGVHD, at least in part, through its effect on endothelial cells.

No abstract

Prophylactic effect of human T cell leukemia virus type I (HTLV-I) immune globulin (HTLVIG) against milkborne transmission of HTLV-I was investigated in a rabbit model. Four litters (A-D: 7, 5, 7, and 7 offspring, respectively) born to an HTLV-I-infected rabbit were used. Litters A and D were allowed to grow normally as controls, while litters B and C were given weekly intraperitoneal inoculation of HTLVIG four times until weaning at 4.5 weeks of age. Only 1 (8.3%) of the 12 HTLVIG-inoculated rabbits, compared with 6 (42.9%) of the 14 control rabbits, seroconverted for HTLV-I. Gene amplification detected the presence of HTLV-I proviral sequences in all of the seroconverted but in none of the seronegative rabbits. These results suggest that passive immunization is effective in preventing dam-to-offspring transmission of HTLV-I.

The passive immune basophil activation test may help clarify the causal relationship between allergic transfusion reactions and transfused blood, even when patients experience myelosuppression.

Eltrombopag is an oral, nonpeptide, thrombopoietin receptor agonist approved for treatment of chronic immune thrombocytopenia (ITP). The safety, tolerability, and efficacy of eltrombopag for up to 3 years were evaluated in 19 Japanese patients with chronic ITP who had completed a prior 6-month study. Patients received eltrombopag once daily at the last dosage received in the prior study (12.5, 25, or 50 mg). Dose adjustments and treatment interruptions were permitted to maintain platelet counts of 50,000-200,000/μL. Primary evaluations were safety and tolerability of long-term eltrombopag treatment. The median duration of exposure was 27.5 months (range, 9.9-32.3). Adverse events were similar to those reported with short-term use of eltrombopag, and none led to treatment discontinuation. Nine serious adverse events were reported. Median platelet counts began to increase after 1 week of treatment and remained above 50,000/μL for most assessments. Bleeding episodes decreased from 63 % at baseline to 21 % after 2 weeks of treatment and remained below baseline for all assessments. Of 15 patients receiving concomitant baseline ITP medications, 10 permanently discontinued or achieved a sustained reduction of at least one treatment without requiring rescue treatment. Long-term treatment with eltrombopag was safe, well tolerated, and effective in Japanese patients with chronic ITP.