Sayaka Kawano

Gender-related alterations in plasma adrenomedullin level and its correlation with body weight gain

Plasma levels of adrenomedullin (AM), a bioactive peptide produced in adipose tissue, have been shown to be higher in obese patients than in non-obese patients, but little is known about gender differences in plasma AM levels. The aims of this study were to clarify gender-related alterations in plasma AM levels and to examine the body weight (BW) gain–plasma AM relationship in the general population. We measured plasma AM levels of 346 local residents (62.0±8.9 years, mean±s.d.) in the Kiyotake area, Japan, who underwent a regular health check-up, by a specific fluorescence immunoassay. Plasma AM levels in the female residents were lower than that in the males, and multiple regression analysis revealed a possible gender difference in plasma AM. The AM levels were significantly correlated with BMI or waist circumference in women, but such a relationship was not seen in men. When the subjects were divided into two groups by results of a questionnaire about BW gain of 10 kg or more since the age of 20 years, the plasma AM level of women with BW gain ≧10 kg was significantly higher than that in those without BW gain, although no difference was noted between the men with and without BW gain. In conclusion, possible gender differences were noted in the plasma AM levels and in the BW gain–plasma AM relationship in the general population. The plasma AM levels in the female residents without BW gain seem partly attributable to the lower AM of women.

Successful treatment of non-Hodgkin’s lymphoma with rituximab and dose-adjusted CHOP therapy in a patient with concomitant end-stage renal disease requiring haemodialysis

Although malignancy is a fatal complication of end-stage renal disease (ESRD) requiring haemodialysis, successful treatment of haematological malignancies has been rarely reported. We describe the case of a 64-year-old man who presented with non-Hodgkin’s lymphoma (NHL; clinical stage, IVB) concomitant with ESRD. Before chemotherapy, haemodialysis was initiated, and one course of dose-adjusted CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) therapy followed by eight courses of rituximab therapy were administered according to the performance status and degree of organ dysfunction. Consequently, the patient was disease free for 27 months. Thus, rituximab plus CHOP combination therapy was effective for NHL concomitant with ESRD.

The Impact of a Humanized CCR4 Antibody (Mogamulizumab) on Patients with Aggressive-Type Adult T-Cell Leukemia-Lymphoma Treated with Allogeneic Hematopoietic Stem Cell Transplantation

Although a humanized CCR4 antibody (mogamulizumab) was reported to be effective for refractory adult T-cell leukemia-lymphoma (ATL), several reports regarding the use of mogamulizumab before allo-hematopoietic stem cell transplantation (HSCT) strongly indicated a high incidence of severe acute graft-versus-host-disease (GVHD) and treatment-related mortality (TRM). We retrospectively analyzed nine aggressive-type ATL patients who underwent allo-HSCT at a single institution in Miyazaki from 2006.1.1 to 2015.7.31. Among nine ATL patients, three had used mogamulizumab before treatment with allo-HSCT because of the poor control of refractory ATL. All three patients were treated with four to eight cycles of mogamulizumab. The interval from last administration of mogamulizumab to allo-HSCT was two to five months. All three patients with prior mogamulizumab treatment developed mild-moderate acute GVHD (grade 2) 28, 34, or 40 days after allo-HSCT. Acute GVHD was controlled by prednisolone treatment. Two patients in complete remission before allo-HSCT exhibited relatively prolonged survival (survival rate, 66%). Moreover, one patient developed human T-cell leukemia virus type 1-associated myelopathy-mimicking myelitis at five months after allo-HSCT. In contrast, two of six ATL patients without a history of mogamulizumab use survived (survival rate 33%). Thus, in cases of mogamulizumab use before treatment with allo-HSCT for refractory ATL, an appropriately long interval from the last administration of mogamulizumab to allo-HSCT may be one of factors to reduce TRM by acute GVHD, and to subsequently enhance graft-versus-tumor effects in ATL cases. Furthermore, caution is needed when administering mogamulizumab before allo-HSCT for severe GVHD and TRM.

Clinical effect of rituximab as early administration for refractory thrombotic thrombocytopenic purpura associated with connective tissue diseases

Abstract As previous reports regarding rituximab usage for refractory thrombotic thrombocytopenic purpura (TTP) patients with connective tissue diseases (CTD) are limited, it is essential to clarify the clinical effect of early rituximab administration for refractory TTP with CTD in clinical practice. We retrospectively analysed three refractory TTP patients with CTD (plasma exchange [PE]-refractory case (case 2) or cases (case 1 and case 3) with high titers of von Willebrand factor-cleaving protease [ADAMTS13] inhibitor) in a single institution during 2012–2015. The patients were treated with PE/plasma infusion, steroids, and off-label use of rituximab treatment as early administration, at a dosage of 375 mg/m2 weekly with four or eight repeats. Owing to the early diagnosis of refractory TTP with ADAMTS13 activity-deficiency and presence of ADAMTS13 inhibitors (case 1: 2.5, case 2: 1.0, case 3: 6.6), and the subsequent early rituximab treatment combined with PE (case 1: day 1, case 2: day 12, case 3: day 1), all three patients achieved early complete remission and survived without relapse to 779, 498 and 388 days, respectively. In all three cases, the recovery of platelet counts (>50 × 109/L) was achieved within three weeks of rituximab administration. The adverse effect (only an infusion reaction) was safe and tolerable. In contrast to previous reports regarding rituximab treatment for TTP in CTD patients, in our case series study, it’s to the credit that we described the detailed clinical course and short- and long-term effect of early rituximab administration at refractory TTP patients with CTD in clinical practice.

The clinical impact of human T-lymphotrophic virus type 1 (HTLV-1) infection on the development of adult T-cell leukemia-lymphoma (ATL) or HTLV-1–associated myelopathy (HAM) / atypical HAM after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and renal transplantation

Because there are limited clinical reports on the impact of human T-lymphotropic virus type 1 (HTLV-1) on organ transplantation, its effects on the development of adult T-cell leukemia-lymphoma (ATL), post-transplantation lymphoproliferative disorder (PTLD) and HTLV-1–associated myelopathy (HAM) or atypical HAM after organ transplantation remain unclear. We retrospectively analyzed the impact of HTLV-1 in 54 allogeneic hematopoietic stem cell transplantation (allo-HSCT) cases and 31 renal transplantation cases between January 2006 and December 2016. Among the 54 allo-HSCT cases, nine recipients with ATL tested positive for HTLV-1, and one was found to be an HTLV-1 carrier. All donors tested negative for HTLV-1. Only one HTLV-1 carrier did not present with ATL or HAM development after allo-HSCT. Among nine ATL cases after allo-HSCT, four eventually relapsed due to proliferation of recipient-derived ATL cells. However, in one ATL case, atypical HAM developed rapidly at 5 months after allo-HSCT. Among the 31 renal transplantation cases, all donors tested negative for HTLV-1, and only recipients tested positive. Only one HTLV-1 carrier recipient did not present with ATL or HAM development after renal transplantation. However, one HTLV-1-negative recipient developed PTLD in the brain 10 years after renal transplantation. In clinical practice, careful follow-up of HTLV-1 infected recipients after organ transplantation is important because atypical HAM can develop in ATL patients after allo-HSCT. Furthermore, to clarify the risk of ATL or HAM development in HTLV-1 infected recipients, we prospectively followed up our cohort.

Clinical Features and Treatment Outcomes of 51 Patients with Chronic Myeloid Leukemia Treated with a Tyrosine Kinase Inhibitor at a Single Institution from 2002 to 2014.

Although clinical trials of first- and second-generation tyrosine kinase inhibitors (TKIs) have been shown to improve the prognosis of chronic myeloid leukemia (CML), there is still uncertainty about the clinical features, treatment outcomes, adverse effects, and other possible problems of their use in the clinical setting. We retrospectively analyzed 51 CML patients treated with TKIs at a single institution between 2002 and 2014. The patients (median age: 53.8 years) were classified as having chronic (n = 48), accelerated (n = 2), or blastic phase (n = 1) CML. Our treatments included both 1st generation TKIs (60.8%) and 2nd generation TKIs (39.2%). We found that the overall response rates of complete cytogenetic response (CCyR), major molecular response (MMR), and MR4 (molecular response 4) were 90.2%, 78.4%, and 64.7%, respectively. Second line 2nd generation TKIs had response rates equivalent to those of 1st line 1st generation TKIs. Moreover, 1st line 2nd generation TKIs tended to achieve an early response rate. Overall survival (OS) at 5 years was 93.2%. Sudden blastic crisis (BC) occurred in 2 CML patients receiving TKI with CCyR status. Hematopoietic stem cell transplantation was performed for BC (n = 1) and sudden BC (n = 2). Side effects of all grades (1-3) and grade 3 alone were 64.7% and 11.8%, respectively. Dose reduction, replacement with another TKI, or low dose TKI treatment may be useful methods to control side effects. Further reasons of TKI discontinuation were economic problems (n = 3) and pregnancy (n = 1). Consequently, our treatment strategy for CML demonstrated good response rate and OS. Currently, treatment discontinuation due to intolerance, resistance, economic problems, pregnancy, and sudden BC remains a concern in clinical practice.