Effects of recombinant thrombomodulin on long-term prognosis after allogeneic hematopoietic stem cell transplantation.

We investigated the effects of early recombinant thrombomodulin (rTM) treatment on long-term prognosis after hematopoietic stem cell transplantation (HSCT). Subjects included 300 patients who underwent allogeneic HSCT (131 in the rTM(+) group and 169 in the rTM(-) group). The control group received heparin or no anti-coagulation therapy. When we examined patients with confirmed complications (day 1-100), the frequencies of acute graft-versus-host disease (aGVHD) and thrombotic microangiopathy (TMA) were significantly lower in the rTM(+) group, while the frequencies of veno-occlusive disease did not show such differences. rTM administration was associated with significant differences in the cumulative incidence of aGVHD (any grade and II-IV grades) and TMA. The cumulative overall survival probability was significantly higher in the rTM(+) group (42.3% versus 26.2%, p = .037). Therefore, some causes of a poor prognosis included aGVHD and TMA. The present findings suggest that rTM plays a preventive role in transplant-related complications, such as aGVHD and TMA, after allogeneic HSCT.

Role of alternative donor allogeneic hematopoietic stem cell transplantation in patients with intermediate- or poor-risk acute myeloid leukemia in first complete remission.

Allogeneic hematopoietic stem cell transplantation (HCT) offers the most effective prevention of relapse and has significant overall survival (OS) benefits for patients with acute myeloid leukemia (AML) in first complete remission (CR1). We conducted a retrospective analysis of a cohort of patients with intermediate- or poor-risk AML. The purpose of the present study was to investigate the role of alternative donors for AML in CR1. We analyzed 1561 patients who underwent HCT from an HLA-matched related donor (MRD), HLA 8/8-matched unrelated donor (MUD), or umbilical cord blood (UCB). The results of a multivariate analysis showed that HCT from UCB (HR = 1.28, 95% CI: 1.07-1.52), age ≥50 years (HR = 1.36, 95% CI: 1.14-1.62), male (HR = 1.42, 95% CI: 1.21-1.66), PS > 1 (HR = 1.68, 95% CI: 1.17-2.42), and poor-risk cytogenetics (HR = 1.53, 95% CI: 1.29-1.81) had an inferior prognostic impact on OS. We conclude that an MUD is the best alternative to an HLA identical MRD for patients with AML in CR1. UCB is an alternative option if neither MRD nor MUD are available, or when patients need to receive urgent HCT for poor-risk AML in CR1.

Additional Cytogenetic Abnormalities with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia on Allogeneic Stem Cell Transplantation in the Tyrosine Kinase Inhibitor Era.

Cytogenetic abnormalities are well known and powerful independent prognostic factors for various hematologic disorders. Although the combination of chemotherapy with tyrosine kinase inhibitor (TKI) is now considered the standard of care in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia, little is known about the impact of additional cytogenetic abnormalities (ACAs). Therefore, we retrospectively evaluated 1375 adult patients who underwent their first allogeneic hematopoietic stem cell transplantation in the TKI era. In this study, 224 patients had ACAs (16.3%). The ACAs that were seen in more than 20 cases (1.5%) were as follows: -7, der(22), der(9), +8, and +X. Overall survival at 4 years was 56.9% (95% confidence interval [CI], 49.4% to 63.7%) in the group with ACAs and 60.5% (95% CI, 57.3% to 63.5%) in the group without ACAs (P = .266). The cumulative incidence of relapse at 4 years was 28.9% (95% CI, 22.6% to 35.6%) in the group with ACAs and 21.9% (95% CI, 19.4% to 24.6%) in the group with Ph alone (P = .051). In multivariate analyses there were no statistically significant differences in the risk of overall mortality or risk of relapse between the groups with and without ACAs. In the subgroup analyses of specific ACAs, although the presence of +8 was associated with a higher relapse rate in univariate and multivariate analyses, no specific ACA was associated with poor overall survival. Further studies will be needed to verify the impact of specific ACAs on transplantation outcomes.

A Multicenter Retrospective Study of Mogamulizumab Efficacy in Adult T-Cell Leukemia/Lymphoma.

BACKGROUND: Mogamulizumab, a defucosylated humanized monoclonal antibody targeting C-C chemokine receptor 4, recently became available for the treatment of adult T-cell leukemia/lymphoma (ATL). We conducted a multicenter retrospective study of the efficacy of mogamulizumab in ATL treatment in patients on Hokkaido Island, Japan. MATERIALS AND METHODS: A total of 125 patients with ATL treated from January 2010 to December 2014 in 20 hospitals affiliated with the Hokkaido Hematology Study Group were enrolled in the present retrospective study. RESULTS: Of the 125 ATL patients, 62 (46.6%) presented with the acute type, 51 (38.3%) with the lymphoma type, and 12 (9.0%) with the chronic type; the latter group included 7 unfavorable chronic cases. The median age at diagnosis was 68 years (range, 35-86 years). The median survival for those with acute, lymphoma, and unfavorable chronic types was 302, 279, and 921 days, respectively. Advanced age, high lactate dehydrogenase level, poor performance status (3-4), and the existence of B symptoms were unfavorable prognostic factors for overall survival (OS). Survival rate calculated from the day of diagnosis was significantly higher in patients treated with mogamulizumab. The OS of individuals receiving hematopoietic stem cell transplantation (HSCT) was superior to that of the non-HSCT group. The median interval between the last mogamulizumab dose and allogeneic HSCT was 38 days (range, 21-53 days). Of the 22 HSCT recipients who were not treated with mogamulizumab, overall acute graft-versus-host disease (aGVHD) and grade III-IV aGVHD occurred in 12 (54.5%) and 3 (13.6%) patients, respectively. However, overall aGVHD and grade III-IV aGVHD developed in 8 (88.9%) and 3 (33.3%) of the 9 HSCT recipients treated with mogamulizumab, respectively. CONCLUSION: Mogamulizumab improves OS in patients with ATL, although its use in HSCT patients might trigger severe GVHD. Determining the optimal pre-HSCT mogamulizumab treatment regimen is thus a priority.

Prospective registry for laparoscopic liver resection.

INTRODUCTION: Laparoscopic liver resection (LLR) has been widely performed throughout the world. Although prospective registry studies to clarify the safety of LLR have been feasible, no prior multicenter prospective study has addressed this issue. We have conducted a multicenter prospective cohort study to reveal the current status of LLR in Japan. METHODS: From April 2015 to March 2016, candidates for LLR were preoperatively enrolled at 12 institutions. The primary end-point was surgical safety, which was evaluated based on surgical factors and on short-term and midterm outcomes. RESULTS: A total of 102 patients were enrolled. Planned laparoscopic procedures included 96 pure laparoscopies, 1 hand-assisted laparoscopy, and 5 hybrid techniques. Non-anatomical partial resection or left lateral sectionectomy were performed in almost all cases. The median duration of surgery was 221 min. The median blood loss was 80.5 mL. Conversion was required for four patients (3.9%). The 90-day postoperative morbidities with grades more severe than II in the Clavien-Dindo classification were observed in six patients (5.9%). The median postoperative hospital stay was 9.5 days. No cases involved reoperation or mortality. CONCLUSION: Minor resection of LLR has been performed safely. To ensure the safe dissemination of LLR, including for major resection, a larger multicenter prospective study is required.

Plural light chains in a single plasma cell of a monoclonal gammopathy undetermined significance case: an ultrastructural study.

A 44-year-old man was found to have M-proteins of IgG consisting of kappa- and lambda-chains in serum without lymphadenopathy or splenomegaly. The serum concentrations of IgG, IgA and IgM were within normal limits. Bone marrow examination showed normal cellular marrow containing 6.3% of plasma cells with no abnormal features. No chromosomal abnormality was observed at all. The patient was diagnosed as having monoclonal gammopathy of undetermined significance. The bone marrow plasma cells possessed free kappa- and lambda-chains in Golgi apparatus, rough endoplasmic reticula and cytoplasmic matrices. Plural light chains were simultaneously produced with the same heavy chain in a plasma cell by immunoelectron microscopy. This is the first report in the world of a monoclonal gammopathy of undetermined significance producing plural light chains with the same heavy chain.

Magnetic resonance imaging of prostate carcinoma using phased-array coils: therapeutic effect and recurrence.

Magnetic resonance imaging with phased-array coils was performed in patients with prostate carcinoma before and after hormonal therapy, radiation therapy or radical prostatectomy to evaluate therapeutic effect and recurrence. After hormonal therapy, the prostate gland, seminal vesicle and primary site of tumor usually decrease in size with variable T2 hypointensity. Recurrent or residual tumors after hormonal therapy usually represent T2 hyperintense lesions compared to the hypointensity of the surrounding tissues. Changes of metastatic sites after therapy were also demonstrated.

Analysis of T-cell repertoire and mixed chimaerism in a patient with aplastic anaemia after allogeneic bone marrow transplantation.

We analysed 26 T-cell receptor (TCR) beta chain subfamilies (VB) of a patient with aplastic anaemia (AA) who underwent allogeneic bone marrow transplantation (allo-BMT). The patient developed pancytopenia at d 80. The patient's T cells were skewed in 10 of 26 TCR-VB on d 83. These TCR-VB, especially VB15, which were almost entirely CD8-positive cells, were skewed throughout her clinical course. Chimaerism analysis of the CD8-positive cells indicated that they were of recipient origin. Therefore, some immune responses induced by the recipient CD8-positive T cells had an important role in pancytopenia in AA patients after allo-BMT.