Acute graft-versus-host disease (aGVHD) is one of the most frequent complications after allogeneic hematopoietic stem cell transplantation (HSCT). First-line therapy for aGVHD usually consists of corticosteroids, but almost half of patients fail to respond, and more than 60% eventually die. Although several treatment options have been developed as second-line therapy, currently, no established strategy for steroid-refractory (SR) aGVHD is available. Mesenchymal stem cells (MSCs) have unique immunoregulatory properties that make them attractive for use in salvage therapy for SR-aGVHD. Following the striking clinical course reported by Le Blanc’s group, many clinical trials have shown favorable results of MSC infusions for SR-aGVHD. In Japan, two clinical trials were performed. Following the favorable results of clinical studies, MSCs have become the first approved stem cell drug for SR-aGVHD. This therapy is called TEMCELL. In this review, we briefly summarize the current status and problems with MSCs in Japan. Now that this cell drug is available to all eligible patients, a post-marketing study is needed to answer crucial clinical questions.
Peripheral blood stem cell transplantation (PBSCT) from HLA-identical sibling donors has been associated with poorer survival outcomes than bone marrow transplantation (BMT), suggesting increased non-relapse mortality (NRM) due to acute or chronic graft-versus-host disease (GVHD). This retrospective study compared the outcomes of tacrolimus versus cyclosporine for GVHD prophylaxis in patients receiving PBSCT from HLA-identical sibling donors. The medical records of 59 adult patients with hematologic malignancies who received their first PBSCT between January 2005 and August 2014 were retrospectively analyzed. The adjusted multivariate analyses showed significant reductions in grade Ⅱ-Ⅳ acute GVHD (hazard ratio [HR], 0.16) and all-grade chronic GVHD (HR, 0.42) with tacrolimus. In contrast, no significant reductions in grade Ⅲ-Ⅳ acute GVHD, intermediate to severe chronic GVHD, or non-relapse mortality were observed. Our results supported the superiority of tacrolimus in acute and chronic GVHD prophylaxis but failed to show survival benefit. This suggests that conditions besides GVHD might be contributing to inferior outcomes with PBSCT or that GVHD prophylaxis with tacrolimus is not sufficiently intensive to prevent lethal GVHD. Randomized prospective trials are necessary to validate the superiority of tacrolimus in PBSCT from HLA-identical sibling donors.
Patients with resolved Hepatitis B virus (HBV) infections are at a high risk of HBV reactivation and de novo HBV infection after allogeneic stem cell transplantation; therefore, it is important to carefully monitor HBV serological markers in these patients.
A 39-year-old man diagnosed with myelodysplastic syndrome and refractory anemia with excess blasts (RAEB-1), received a peripheral blood stem cell transplant from an HLA-matched sibling. The patient had latent HBV infection, while his donor had no history of HBV infection. Twelve months after the transplant, the patient tested negative for HBsAb and he received entecavir (ETV) as prophylaxis for HBV recurrence. Cyclosporine was discontinued 15 months after transplantation. ETV was discontinued after 10 months of treatment because serum HBV-DNA was not detected. Moreover, 2 years after the transplant, the patient underwent HBV vaccination. However, HBV reactivation occurred 29 months post-transplantation, and ETV was readministered. Two months after starting ETV treatment, HBV-DNA was not detected but 4 months later, re-seroconversion occurred and the patient tested positive for HBsAb.
This case suggests that serological HBV markers should be monitored carefully in patients with resolved HBV infections who received allogeneic stem cell transplants. HBV vaccination is recommended for these patients after immunosuppressive medication is discontinued.