Search

The article reports on a study that explored the origin and evolutionary process of the sequential relationship between Langerhans cell histiocytosis (LCH) and acute lymphoblastic leukemia (ALL). Topics discussed include the comprehensive genomic analysis of the dynamics of clonal architecture for one case and the genomic analysis performed for another 2 ALL cases that subsequently developed LCH. The derivation of LCH from a founding clone with genomic alterations common to ALL is mentioned.

Background: Previous studies have demonstrated an association between prostate-specific antigen (PSA) kinetics and predictive value for treatment outcomes. Abiraterone acetate (AA) is a newly approved cytochrome-P450C17 inhibitor for treatment of metastatic castration-resistant prostate cancer (mCRPC), and few studies have evaluated PSA kinetics using AA so far. Results of a study evaluating PSA kinetics in the beginning of AA and enzalutamide responded chemotherapy-treated patients suggested different trends between the drugs. PSA kinetics of AA-treated patients has been reported using large datasets; however, no studies which have fully evaluated PSA kinetics in the beginning treatment. The present study aimed to assess the PSA kinetics and relationship between the PSA kinetics and PSA progression in chemotherapy-naïve and chemotherapy-treated mCRPC patients receiving AA.Methods: We used two Japanese phase II trial datasets: JPN-201, chemotherapy-naïve mCRPC (n = 48) and JPN-202, chemotherapy-treated mCRPC (n = 46). PSA kinetic parameters were calculated using actual PSA values measured every 4 weeks, and a subgroup analysis was performed to evaluate the influence of early PSA response on time to PSA progression (TTPP). In addition, we used a Cox proportional hazard model to investigate the influence of variables on TTPP.Results: PSA declined from week 4 but took more time to achieve nadir. PSA kinetic parameters were different between the datasets, mean time to PSA nadir was 5.3 ± 5.6 and 2.0 ± 3.4 months, and TTPP was 9.5 ± 7.4 and 3.8 ± 4.8 months in JPN-201 and JPN-202, respectively. In the subgroup analysis of week 4 PSA decline status, Kaplan-Meier curves for TTPP were similar between early responders and non-progression patients in JPN-201 (median, 9.2 vs. 6.5 months, respectively) but separated in JPN-202 (median, 3.7 vs. 1.9 months, respectively). According to univariate Cox regression analysis, achievement of PSA response (≥50 %) at week 12 was associated with TTPP in the both trials, but the hazard ratio of PSA decline (≥30 %) at week 4 was not significant in JPN-201.Conclusions: Our results suggest that PSA kinetics were not comparable and early PSA response showed different association to TTPP according to prior history of chemotherapy.Trial Registration: The original trials are registered at ClinicalTrials.gov. The identifiers are; JNJ-212082-JPN-201 , registered 20 December 2012 and JNJ-212082-JPN-202 , registered 30January 2013. [ABSTRACT FROM AUTHOR]

Papillary fibroelastoma (PFE) is a benign tumor that arises mostly from left-sided valves. PFE can cause stroke, and surgical resection may be needed. Lambl's excrescence (LE) is a filiform valvular lesion and is considered a possible cause of stroke. A 79-year-old man with light-headedness and left-sided hemiparesis was diagnosed with stroke. Transesophageal echocardiography (TEE) revealed a round-shaped mobile mass in the left ventricular outflow tract (LVOT), which was considered the cause of the stroke. Surgical resection was performed transaortically, and during surgery, a mass was incidentally detected on the noncoronary cusp (NCC), which was also resected followed by aortic valve replacement. Pathology confirmed that the mass in the LVOT was a PFE and that the filiform mass on the NCC was LE. We herein report a rare case of PFE in the LVOT and coexisting LE on the NCC. A careful examination via TEE helps to identify other possible causes of stroke hidden behind the obvious cause.

Central nervous system (CNS) involvement in anaplastic large cell lymphoma (ALCL) is uncommon. CNS prophylaxis is not regularly included in second-line treatments for patients who develop CNS-negative relapses. We report a pediatric case of recurrent ALK-negative ALCL who developed isolated CNS progression during the treatment with brentuximab vedotin monotherapy. The patient achieved CNS remission after receiving the CNS-directed treatments including craniospinal irradiation. There is no evidence regarding whether brentuximab vedotin can cross the blood-brain barrier. CNS prophylaxis should be considered in high-risk patients with relapsed ALCL who receive second-line treatments containing agents with limited CNS penetration., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Clofarabine, one of the key treatment agents for refractory and relapsed acute lymphoblastic leukemia (ALL), achieves a remission rate of approximately 30% with single-agent clofarabine induction chemotherapy. However, a remission rate of approximately 50% was reported with a combination chemotherapy regimen consisting of clofarabine, etoposide, and cyclophosphamide. We treated two cases with refractory and relapsed ALL with combination chemotherapy including clofarabine; one was an induction failure but the other achieved remission. Both cases developed an infectious complication (NCI-CTCAE grade 3) and body pain with infusion. Prophylactic antibiotic and opioid infusions facilitated avoiding septic shock and pain. Further investigation of such cases is required.

Abiraterone acetate(AA)has been approved in more than 80 countries for the treatment of patients with metastatic castration-resistant prostate cancer(mCRPC). In July 2013, a marketing approval application for AA was submitted to the Japanese Ministry of Health, Labour, and Welfare. AA is a selective inhibitor of CYP17A1, a crucial enzyme for androgen biosynthesis. AA exerts its anti-tumor activity by directly inhibiting androgen production at all three sources, i. e., the testes, adrenal glands, and tumor itself. Data from international phase III studies and phase I and II studies in Japan have indicated that AA improves the overall survival and quality of life(QoL)of patients with mCRPC. Herein, we have summarized the development of AA and the results of important international and local clinical trials in Japan. In addition, the effect of food on AA bioavailability, concomitant steroid use, and liver function test abnormalities have been discussed regarding the appropriate use of AA.