MEK/ERK経路とPI3K/AKT経路の阻害は血管周囲炎や細気管支炎を抑制し、肺GVHDの発症を抑制する

京都大学新制・課程博士博士(医学)甲第24513号医博第4955号新制||医||1064(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 平井 豊博, 教授 渡邊 直樹, 教授 松村 由美学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Bortezomib-cyclophosphamide-dexamethasone induction/consolidation and bortezomib maintenance for transplant-eligible newly diagnosed multiple myeloma: phase 2 multicenter trial

[Objectives:] We conducted a phase II trial to prospectively evaluate the efficacy and safety of bortezomib-cyclophosphamide-dexamethasone (VCD) induction, autologous stem cell transplantation (ASCT), VCD consolidation, and bortezomib maintenance in transplant-eligible newly diagnosed multiple myeloma (NDMM) patients in Japan (UMIN000010542). [Methods:] From 2013 to 2016, 42 patients with a median age of 58 (range 42–65) years with NDMM were enrolled in 15 centers. The primary endpoint was the complete response (CR) /stringent CR (sCR) rate after transplantation, and overall/progression-free survival rates were also evaluated. [Results:] Following induction therapy, the overall response rate was obtained in 71% of patients, including a CR/sCR of 10% and a very good partial response (VGPR) of 26%. Twenty-six of the 42 patients completed ASCT following the protocol and CR/sCR and VGPR rate 100 days after ASCT was 26% and 17%, respectively. During consolidation therapy, 3 of the 24 patients achieved deeper responses. Eight of the 18 patients completed 2-year bortezomib maintenance without disease progression and grade 3/4 toxicities. Five patients were VGPR or partial response after ASCT but maintained response with 2-year bortezomib maintenance. Two-year overall and progression-free survival rates were 92.5% (95% confidence interval [CI]: 78.5%−97.5%) and 62.6% (95% CI: 45.8%−75.5%), respectively. Grade 3/4 toxicities (≥ 10%) included neutropenia (19%) and anemia (17%) in induction, and thrombocytopenia (29%) in consolidation. [Conclusion:] VCD induction/consolidation and bortezomib maintenance with ASCT for NDMM resulted in a high CR/sCR rate and provided good overall/progression-free survival in Japan

Drug monitoring for mycophenolic acid in graft-vs-host disease prophylaxis in cord blood transplantation

[Aims] We performed the retrospective analysis to clarify the significance of drug monitoring for mycophenolic acid (MPA), the active form of mycophenolate mofetil (MMF), in prophylaxis for graft‐vs‐host disease (GVHD) in cord blood transplantation. [Methods] We retrospectively analysed the data of 46 patients who underwent first cord blood transplantation and received GVHD prophylaxis with tacrolimus plus MMF. MPA levels were measured on days 7 and 21, and 24‐hour areas under the curve (AUC0–24) were estimated. [Results] The engraftment and 3‐year overall survival rates of all patients were 94% and 78%, respectively. The cumulative incidence of sepsis before engraftment was higher in patients with AUC0–24 on day 7 of >60 μg h/mL than in other patients (33 vs 6%, P = .02). The cumulative incidence of grade II–IV acute GVHD was higher in patients with AUC0–24 on day 21 of ≤30 μg h/mL than in other patients (80 vs 50%, P = .04). The cumulative incidence of human herpesvirus 6 reactivation was higher in patients with AUC0–24 on day 21 of ≤48 μg h/mL (median) than in other patients (50 vs 19%, P = .03). [Conclusion Blood level of MPA was associated with risk of acute GVHD and infection. A prospective trial evaluating the benefit of personalized MMF dosing using MPA levels is needed

Determination of molecular mass of acidic polysaccharides by capillary electrophoresis

We developed a method for the determination of molecular mass of acidic polysaccharides based on their high-resolution separation by capillary electrophoresis. Polymers of N-acetylneuraminic acid (NeuAc) and polysulfated hyaluronic acid were separated into their molecular species up to 100 mono- and 20 disaccharide units, respectively. The relationship between the molecular mass of NeuAc-polymer and their electrophoretic mobilities showed good linearity, and was applied to the determination of molecular masses of larger NeuAc species unresolved by capillary electrophoresis under the same conditions. In the first step, the standard curve for the determination of molecular mass was constructed from the relationship between electrophoretic mobility and molecular mass. Subsequently, the mobility was extrapolated to the standard curve, and the molecular mass was calculated. Five different preparations of NeuAc polymers having different molecular masses showed smaller values than those determined by conventional chromatographic techniques. Further, molecular mass determined by the present method correlated with number-average molecular mass. The methodology presented here was applied to the determination of molecular mass of polysulfated hyaluronic acid. The data indicated that native hyaluronic acid was extensively degraded during sulfonation reaction

Successful hepatectomy for hepatic abscess with chronic granulomatous disease: a case report

Abstract Background Chronic granulomatous disease (CGD), a rare inherited disorder, is characterized by impaired ability of phagocytic cells to kill certain bacteria and fungi. Although liver abscess is a common manifestation of CGD, its optimal management in these patients is unknown. Here, we present a case of successful hepatectomy for hepatic abscess in a patient with CGD. Case presentation An adolescent patient with previously diagnosed CGD presented to the pediatrics department of our institution with fever. Blood tests showed high concentrations of inflammatory markers. A computed tomography (CT) scan showed a multilocular mass measuring 52 mm × 34 mm in hepatic segment 4 (S4). Blood cultures were negative. Despite administration of antibiotics and γ-globulin, his fever and high concentrations of inflammatory markers persisted and the mass did not change on CT scan images. Because the medications had proved ineffective and percutaneous drainage would have been difficult because of the honeycombing in the abscess, we performed hepatic S4a + S5 anatomic resection and cholecystectomy. Culture of the excised specimen was negative. The patient’s postoperative course was uneventful. On day 62, CT showed no abscess around the resection stump. On day 81, he was transferred to undergo bone marrow transplantation. Conclusions Surgical treatment for hepatic abscess can be effective when medical treatment has failed