[Isolated central nervous system relapse of Philadelphia chromosome-positive acute lymphoblastic leukemia during ponatinib maintenance therapy].

A 65-year-old man was diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia with no initial central nervous system (CNS) involvement. Complete remission was achieved after the induction therapy. However, during consolidation therapy, he developed septic shock and pneumocystis pneumonia, leading to interruption in chemotherapy and allogeneic transplantation. Subsequently, he achieved complete molecular remission and ponatinib maintenance therapy was initiated. Two years later, he developed left leg paralysis and was diagnosed with isolated CNS relapse; however, radiation therapy improved CNS lesions and paralysis. Thus, ponatinib maintenance therapy alone is inadequate in preventing CNS relapse in patients who have not completed systemic chemotherapy for CNS relapse prevention.

[Successful treatment of secondary graft failure after allogeneic stem cell transplantation for aplastic anemia with eltrombopag].

Herein we report a case of successful treatment of secondary graft failure due to poor graft function (PGF) using eltrombopag. A 25-year-old woman with aplastic anemia (stage 3) underwent allogeneic bone marrow transplantation (BMT) from her HLA-matched brother. Neutrophil engraftment was achieved on day 17, but she remained dependent on platelet transfusion. Chimerism analysis showed complete donor type, but she also became dependent on red blood cell transfusion later. Eltrombopag was administered on day 253 after BMT, after which she exhibited hematopoietic recovery, resulting in the withdrawal of transfusion dependency. Blood counts continued to be stable after eltrombopag was discontinued. The use of eltrombopag enabled outpatient treatment and induced hematopoietic recovery without significant side effects. Eltrombopag may be an effective and safe option for PGF after BMT.

Increased SLAMF7high monocytes in myelofibrosis patients harboring JAK2V617F provide a therapeutic target of elotuzumab.

Monocyte-derived fibrocytes recently garnered attention because the novel pathogenesis of myelofibrosis (MF), and suppression of fibrocyte differentiation by serum amyloid P remarkably improved MF. We previously revealed that human fibrocytes highly expressed signaling lymphocytic activation molecule F7 (SLAMF7) compared with macrophages and that SLAMF7high monocytes in the peripheral blood (PB) of MF patients were significantly elevated relative to those in healthy controls (HCs). In this study, we evaluated SLAMF7high monocyte percentage in the PB of HCs, myeloproliferative neoplasm (MPN) patients with MF, and MPN patients without MF by using a cross-sectional approach. We found that MPN patients with MF who harbored JAK2V617F had a significantly elevated SLAMF7high monocyte percentage, which correlated positively with the JAK2V617F allele burden. In addition, the serum concentration of interleukin-1ra (IL-1ra) was significantly correlated with the SLAMF7high monocyte percentage and JAK2V617F allele burden. These findings suggest that both SLAMF7high monocytes and IL-1ra could be useful noninvasive markers of MF onset. Furthermore, the JAK2V617F allele burden of SLAMF7high monocytes was significantly higher than that of SLAMF7low monocytes and could be a potential target of elotuzumab (Elo), an anti-SLAMF7 antibody used for treating multiple myeloma. Elo independently inhibited differentiation of fibrocytes derived not only from HCs but also from MF patients in vitro. Elo also ameliorated MF and splenomegaly induced by romiplostim administration in humanized NOG mice. In conclusion, an increase of SLAMF7high monocytes with higher JAK2V617F allele burden was associated with the onset of MF in MPN patients harboring JAK2V617F, and Elo could be a therapeutic agent for MPN patients with MF who harbor JAK2V617F.

[Spontaneous resolution of refractory ascites in the late phase after cord blood transplantation in acute myeloid leukemia].

Patients with refractory ascites that develops >3 months after allogenic stem cell transplantation typically have a poor prognosis. We present the case of a 61-year-old man who developed refractory massive ascites approximately 3 months after cord blood transplantation (CBT) and showed complete and spontaneous remission from ascites after 18 months. The patient complained of severe bloating and needed weekly paracentesis to manage the fluid levels. Laboratory tests indicated that the ascites was caused by liver fibrosis. After the patient underwent Keisuke-Matsusaki cell-free and concentrated ascites reinfusion therapy (KM-CART), we were able to decrease the frequency of paracentesis treatments. We planned a transjugular liver biopsy, but the patient contracted pneumocystis pneumonia before the procedure could be performed. Although the pneumonia improved, the ascites worsened again. However, weekly paracentesis spontaneously stopped the progression of ascites and eventually resolved it completely, resulting in the patient's survival.

[Bendamustine and rituximab combination therapy for recurrent indolent B-cell lymphomas: a retrospective single-institution study].

This retrospective study evaluated the outcomes of patients treated with combination of bendamustine and rituximab (BR) for recurrent indolent B-cell lymphoma from January 2011 to February 2018 in our department. The cohort included 36 males and 27 females, and majority of the patients (59%) were between 51 and 70 years of age. The disease types were follicular lymphoma (FL) and mantle-cell lymphoma in 42 (67%) and 15 (24%) patients, respectively. Median progression-free survival (PFS) was not reached in patients with FL who completed BR therapy. The analysis of patients who received BR therapy revealed that the number of CD4-positive lymphocytes remained around 200/µl even five years after the end of treatment. BR therapy was a useful treatment option for recurrent indolent B-cell lymphoma, especially in patients with FL, and completion of BR therapy appeared to be important for improved PFS. Furthermore, attention should be paid for potential infections for at least five years after BR therapy because cell-mediated immunodeficiency may become apparent after treatment.

Simultaneous evaluation of articular cartilage and subchondral bone from immobilized knee in rats by photoacoustic imaging system.

BACKGROUND: Osteoarthritis is not only a disease of articular cartilage, but also of subchondral bone. It is difficult for ultrasound to evaluate subchondral bone because of permeability. This study aimed to evaluate sequential osteoarthritic changes of articular cartilage and subchondral bone from immobilized knees in rats with a photoacoustic (PA) imaging system. METHODS: The unilateral knee joints of adult male rats were immobilized with an internal fixator (IM group) for 4 and 8 weeks. Sham operated animals had holes drilled in the femur and tibia and screws inserted without a plate (control group). A whole proximal third of the tibia was obtained. The specimens were immersed in normal saline and scanned by the PA imaging system, which can create both ultrasound (US) and PA imaging. After the scanning, specimens were fixed with paraformaldehyde, decalcified and embedded in paraffin. Thinly sliced tissues were prepared for histological evaluation. PA signals from the articular cartilage and subchondral bone were independently evaluated. RESULTS: Gross observations showed that fibrillation occurred in the superficial layers and permeability of the articular cartilage increased. Histological observations showed that the articular cartilage became thicker and the bone marrow space expanded during immobilization. US images by the PA imaging system could evaluate the articular cartilage. PA signals from the articular cartilage and subchondral bone increased with the duration of immobilization and the difference, compared to the control group, was significant. CONCLUSIONS: The PA imaging system could evaluate articular cartilage and subchondral bone simultaneously.

Clinical Utility of Flow Cytometry for Detection of Anti-Jkb IgM in Acute Haemolytic Transfusion Reaction: A Case Report.

Acute hemolytic transfusion reaction (AHTR) is a rare but life-threatening complication of transfusion. We herein report a case of anti-Jkb IgM-related AHTR. Two hours after an 80-year-old man with myelodysplastic syndrome received a packed red blood cell (RBC) A+/Rh-/Jkb+/c- transfusion, he developed acute respiratory failure and a fever. Although he had tested negative in routine screening tests, the 37 °C normal saline test was weakly positive for Jkb. We confirmed the presence of anti-Jkb IgM in the patient's serum by flow cytometry. This case demonstrates the potential utility of flow cytometry for IgM detection.

The effect of recycling bin design on PET bottle collection performance.

Many municipalities in Japan have collected PET bottles as recyclable waste since 1980s. When caps are removed from bottles, it reduces collection and transportation costs because bottles can be easily compressed by collection trucks. However, PET bottles collected from recycling bins are usually capped and include other materials. This study designed 10 recycling bins for PET bottle to investigate the effect of design on cap removal efficiency and recycling contamination (foreign waste mixture). Recycling bins for PET bottle were designed focusing on four design items. They are (1) individual recycling bins specifically for bottles and caps or all-in-one recycling bin for both bottle and cap collections, (2) inside-visibility (see-through), (3) signage (wording like "Bottle" and "Cap") near insert slot and (4) insert slot shape. PET bottle collection performance of designed recycling bins was monitored in Suzukakedai campus of Tokyo Tech. Perceptive preferences of recycling bin designs and insert slot shapes were measured by online surveys. Experimental results indicate that insert slot with round shape contributed to significantly lower recycling contamination than bottle-like shape although perceptive preference of insert slots with bottle-like shape was higher than that of the round shape. Signage and all-in-one design is significantly effective to promote cap removal only when it was set with other recycling bins. On the other hand, signage is effective to decrease recycling contamination in a single setting. This study found that design effect depended on the setting condition of recycling bins in terms of cap removal and foreign waste disposal.

Ultrasonic and photoacoustic imaging of knee joints in normal and osteoarthritis rats.

Osteoarthritis (OA) is a common joint disorder and estimated to cause symptoms in 20-40% of the elderly population. 532 nm laser is much absorbed in developed vascular network in the spongy bone which is one of the main characteristics of OA. In this study, a photoacoustic (PA) imaging system with 532 nm laser and 50 MHz US (ultrasound) transducer was developed. Normal and OA knee joints were observed by US and PA imaging. PA signal from the spongy bone was strong where US reflection was very weak. PA signal from the spongy bone was significantly strong in OA compared with that in normal knee while US showed similar low intensity echo in normal and OA. Detailed structure and information on vascular density of spongy bone in rat knee joint were successfully obtained with US / PA combined imaging. US / PA imaging should be useful for early diagnosis of OA.