Levels of cytokines, chemokines, and soluble molecules fluctuate after allogeneic hematopoietic stem cell transplantation. These biomarkers may have diagnostic and prognostic value for transplantation-associated coagulopathy （TAC）. Veno-occlusive disease（VOD）is a clinical syndrome characterized by tender hepatomegaly, jaundice, ascites, fluid retention, unexplained weight gain, and transfusion refractory thrombocytopenia. Several approaches have been evaluated for the treatment of VOD, but none has been uniformly effective. Recombinant thrombomodulin（rTM）is composed of the active, extracellular domain of TM. Similar to membrane-bound TM, rTM binds to thrombin to inactive coagulation, and the thrombin-rTM complex activates protein C to produce active protein C, which in the presence of protein S, inactivates factors VIIIa and Va, thereby inhibiting further thrombin formation. In addition, rTM possesses an anti-inflammatory effect of the lectin domain. One cause of TAC, such as VOD, appears to be pro-inflammatory cytokines including high-mobility group box 1 protein. For this reason, it is thought that the direct anti-inflammatory effect of the lectin domain of rTM plays an important role in the therapeutic mechanism for treatment of TAC.
In allogeneic hematopoietic stem cell transplantation, an HLA-matched unrelated donor is the preferred alternative donor for patients who lack an HLA-identical sibling. However, for patients who have a rare haplotype, or who need immediate transplantation, other alternative donors should be considered. In this case, an HLA 1-antigen-mismatched related donor is the preferred donor, if available. A recent study showed that the use of antithymocyte globulin in HLA 1-antigen-mismatched related donor transplantation could decrease severe acute graft-versus-host disease, and improve survival. If this type of donor is not available, an HLA 1-allele-mismatched donor and an HLA-DR 1-antigen-mismatched unrelated donor are the next candidates. An unrelated cord blood unit with up to 2-antigen mismatches is also a good choice of donor, if it contains adequate total nucleated cells for engraftment. An HLA 2-3-antigen-mismatched related donor is also an attractive alternative donor, and various clinical trials of transplantation using this type of donor are ongoing. The superiority of these donors remains unknown, and should be studied in the future.
Long-term survivors after allogeneic hematopoietic cell transplantation (allo-HCT) are at risk for developing late complications. To assess the feasibility of long-term follow-up (LTFU) system for allo-HCT survivors, we performed a feasibility study at our center. Patients aged 20 or above who received their first allo-HCT at our center were prospectively enrolled. Patients who had recurrent malignancy were not eligible. LTFU visits were scheduled at 1, 3, 6 months and every 1 year after allo-HCT. Regular blood test, performance status, body weight, graft-versus-host disease, pulmonary function, chest X-ray, disease status, thyroid function, bone density and immune recovery were assessed at each visit. Quality of life (QOL) was also assessed using the FACT-BMT and SF-36. Forty-seven patients with a median age of 55 years and a median follow-up of 24 months (range, 3 months to 7 years) were enrolled during the 6-month study period. Proportions of patients who completed scheduled screening tests ranged from 64 to 100%, and 32% of the participants completed all the screening tests. Fifty-seven percent of participants returned the QOL questionnaires. In conclusion, the LTFU system was feasible at our center, although a more systematic ordering system and tools to capture specific problems after allo-HCT are warranted.
We report the case of a 45-year-old male patient who developed human herpesvirus 6 (HHV6)-associated pleurisy after an unrelated cord blood transplantation (CBT) for acute lymphoblastic leukemia. A large amount of pleural effusion accompanied by interstitial pneumonitis was noted on the right side on day 37 posttransplantation. A real-time quantitative PCR (RQ-PCR) assay revealed that the HHV6 viral load was substantially higher in the pleural effusion than in the peripheral blood plasma at the onset of pleurisy, with 2.2 × 102 and 7.9 × 103 copies of HHV6 DNA/mL in the peripheral blood plasma and the supernatant of the pleural effusion, respectively. Moreover, HHV6 DNA was still detected in the pleural effusion after antiviral therapy. Therefore, the pleural cavity may have been the primary site of HHV6 replication in the present case. To our knowledge, the present study is the first detailed report of adult HHV6-associated pleurisy after CBT. HHV6-associated pleurisy should be considered a potential complication when pleural effusion of unknown cause is encountered after CBT, even in the absence of HHV6 DNA in the peripheral blood.