The human gut harbours diverse microorganisms, and gut dysbiosis has recently attracted attention because of its possible involvement in various diseases. In particular, the lack of diversity in the gut microbiota has been associated with complications of haematopoietic stem cell transplantation (HSCT), such as infections, acute graft-versus-host disease and relapse of primary disease, which lead to a poor prognosis. However, few studies have serially examined the composition of the intestinal microbiota after HSCT.In this study, we demonstrated, using next-generation sequencing of the bacterial 16S ribosomal RNA gene, combined with uniFrac distance analysis, that the intestinal microbiota of patients undergoing allogeneic HSCT substantially differed from that of healthy controls and recipients of autologous transplants. Faecal samples were obtained daily throughout the clinical course, before and after transplantation. Notably, the proportions of Bifidobacterium and genera categorized as butyrate-producing bacteria were significantly lower in patients with allogeneic HSCT than in healthy controls. Furthermore, among allogeneic transplant recipients, a subgroup with a preserved microbiota composition showed a benign course, whereas patients with a skewed microbiota showed a high frequency of complications and mortality after transplantation. Thus, we conclude that the stability of intestinal microbiota is critically involved in outcomes of HSCT.

We investigated the effect of laughter on salivary endocrinological stress marker chromogranin A (CgA). In saliva samples collected from 11 healthy males before and after watching a comic film or a non-humorous control film, salivary CgA levels were determined by enzyme-linked immunosorbent assay (ELISA). Samples taken after watching the comic film showed increased levels of CgA. This tendency was more pronounced in individuals with lower initial levels of stress. The control samples showed no significant change in CgA levels. Stress score, subjectively evaluated using a visual analog scale, decreased significantly after watching the comic film. These findings suggest that, in addition to a stress relief effect, laughter can bring about feeling uplifted or fulfilled.

To evaluate the safety and efficacy of donor lymphocyte infusion (DLI), we retrospectively analyzed 414 recipients who received unrelated DLI (UDLI) for the treatment of relapsed hematological malignancy after unrelated bone marrow transplantation (BMT). UDLI was administered for acute myelogenous leukemia (n = 184), myelodysplastic syndrome (n = 69), acute lymphocytic leukemia (n = 57), chronic myelogenous leukemia (CML, n = 36), lymphoid neoplasms (n = 38), adult T cell leukemia/lymphoma (n = 18), and multiple myeloma (n = 12). Sixty-five patients (16%) were in cytogenetic/molecular relapse and 349 (84%) were in hematological relapse after BMT. In total, 266 out of 414 (64%) patients received chemotherapy and/or molecular-targeted agents in combination with UDLI. The median time from BMT to UDLI was 244 days. The median number of infused CD3 cells was 3.51 × 10/kg. Response and survival rates were evaluated at 100 days after UDLI. Complete response was obtained in 37 (57%) of 65 patients with cytogenetic/molecular relapse and in 69 (20%) of 349 patients with hematological relapse (P < .001). Two hundred forty-seven patients (60%) were alive, whereas 110 (26%) had died because of disease progression, 26 (6%) because of infections, 12 (3%) because of graft-versus-host disease (GVHD), and 13 (3%) because of organ failure. Multivariate analysis identified molecular/cytogenetic relapse, GVHD after UDLI, and CML but not combination with chemotherapy as significant prognostic factors. These results indicate that UDLI may have efficacy in relapsed patients with CML, low tumor burden, or occurrence of GVHD after UDLI.

We report a case of a 40-year-old female who developed progressive multifocal leukoencephalopathy (PML), which is associated with JC virus reactivation, after allogeneic hematopoietic cell transplantation. As she had been suffering from graft-versus-host disease and lung damage after pneumocystis pneumonia, the administration of calcineurin inhibitor and steroid could not be discontinued. However, she showed a favorable improvement in clinical symptoms and imaging findings after treatment with the anti-malarial drug, mefloquine and a serotonin receptor blocker, mirtazapine. Continuation of the treatment for eight months finally led to the clearance of the JC virus from her cerebrospinal fluid. She currently shows no neurological disturbance and has resumed her daily activities. PML due to the severe immunosuppressive condition has been reported as a fatal complication after allo-SCT. Our case suggests that combination treatment with mefloquine and mirtazapine may be of great value for the treatment for PML patients in the post allo-SCT setting, although it is difficult to say whether the combination treatment alone led to improvement. Further clinical study is needed to clarify the efficacy of these drugs for the treatment of PML.

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