Juvenile myelomonocytic leukemia (JMML) is a pediatric hematological malignancy with a poor prognosis. Although several case series have been published describing hematological and molecular ...responses to azacitidine (AZA) treatment in patients with JMML, the efficacy and safety profile of AZA is not well investigated, especially in Asian children and children undergoing hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed 5 patients who received a total of 12 cycles (median 2 cycles) of AZA treatment in Japan. All five patients were boys and their ages at the time of treatment were 21, 23, 24, 26, and 46 months, respectively. All five patients tolerated AZA treatment, including four patients who received AZA after HSCT. Therapeutic toxicity with AZA was mostly limited to hematological toxicity. The only serious non-hematological adverse event was hyperbilirubinemia (grades III–IV) observed in a patient who received AZA after a second HSCT. Two out of five patients treated with AZA achieved a partial response (PR), while three patients treated for post-transplant relapse did not have an objective response. Future prospective studies should be conducted to develop combination therapies with AZA and other molecular targeted drugs for high-risk patients.
In this paper, we consider an output tracking problem of a parallel-flow heat exchange process with distributed and boundary inputs. As the distributed inputs to the system, the output feedback ...control is first applied. Under zero boundary inputs, it is shown that the
C
0
-semigroup describing the closed-loop system satisfies the spectrum determined growth condition. Next, we apply a backstepping method to the design of the boundary inputs for output tracking. Our main result shows that the output of the system reaches a reference signal in finite time under both the output feedback control and the boundary control law derived by the backstepping method.
We study the sample-data control problem of output tracking and disturbance rejection for unstable well-posed linear infinite-dimensional systems with constant reference and disturbance signals. We ...obtain a sufficient condition for the existence of finite-dimensional sampled-data controllers that are solutions of this control problem. To this end, we study the problem of output tracking and disturbance rejection for infinite-dimensional discrete-time systems and propose a design method of finite-dimensional controllers by using a solution of the Nevanlinna–Pick interpolation problem with both interior and boundary conditions. We apply our results to systems with state and output delays.
This paper is concerned with secure communication of RGB images using lumped parameter/distributed parameter chaotic synchronization. As a lumped parameter system generating chaos, we use a ...discrete-time system describing by a generalized Henon map and construct its synchronization system. Since the discrete-time chaotic system has three-dimensional state variables, it is convenient when designing a secure communication system for RGB images. However, the generalized Henon system and its synchronization system have only a few common encryption keys. To increase the common encryption key, we introduce another chaotic system described by a hyperbolic partial differential equation with logistic boundary condition. Several snapshots of the solution of the hyperbolic system are used to generate a long-length common encryption key of the secure communication system proposed in this paper.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the preferred treatment for children with high-risk hematologic malignancies, but post-allo-HSCT relapse has a poor prognosis and ...limited treatment options. We evaluated the feasibility, outcome, and risk factors influencing survival after T-cell-replete haploidentical HSCT with low-dose anti-thymocyte globulin (ATG) in 30 patients with post-allo-HSCT relapse of acute lymphoblastic leukemia and acute myeloid leukemia. Overall, 50% of the patients had complete remission (CR) before the second transplant and the overall survival (OS) rate was 52%. In surviving patients (median follow-up 614 days), Kaplan–Meier analysis revealed estimated 2-year leukemia-free survival and OS rates of 48.1% and 61.1%, respectively. Cumulative incidences of 2-year non-relapse mortality and relapse were 24.7% and 36.3%, respectively. Achieving CR before the second allo-HSCT was a predominant independent prognostic factor identified in the multivariate analysis, with a significantly improved 2-year OS rate of 86.7%. T-cell-replete haplo-HSCT with low-dose ATG for second allo-HSCT may benefit a selected patient population.
We retrospectively analyzed nationwide records of 163 Fanconi anemia (FA) patients aplastic anemia (AA),
n
= 118; myelodysplastic syndrome (MDS),
n
= 30; acute leukemia,
n
= 15 who underwent first ...allogeneic hematopoietic stem cell transplantation (HSCT) between 1987 and 2015 in Japan. An alternative donor was used in 119 (73%) patients, and 160 (98%) patients received a non-T-cell-depleted graft. With an 8.7-year median follow-up, 5-year overall survival (OS) was 81%. The 5-year OS was significantly higher in AA patients than in MDS and acute leukemia patients (89%, 71%, and 44%, respectively). In the MDS/leukemia group, factors associated with poor outcome in univariate analysis were older age at HSCT (≥ 18 years), conditioning regimen without anti-thymocyte or lymphocyte globulin, and grade II–IV acute graft-versus-host disease. After 1 year, of 137 survivors, 15 developed subsequent malignancies, of whom 12 were diagnosed with head and neck (HN)/esophageal cancer. An irradiation regimen and older age were associated with the risk of HN/esophageal cancer. Five of seven deaths were attributed to subsequent malignancies more than 5 years after HSCT. On the basis of the risk factors for HSCT in MDS/leukemia patients and subsequent malignancies, a more effective HSCT approach is required.
Atypical lipomatous tumors (ALTs) are locally aggressive adipocytic malignancies that frequently occur in middle-aged adults. We report the rare case of an ALT of the thigh that occurred in a ...4-year-old girl. Since the tumor was initially diagnosed as a lipoblastoma by incisional biopsy, marginal resection was performed. Histopathological findings of the surgical specimen revealed the proliferation of mature and variously sized adipocytes, as well as ectopic ossification; these features differ from the typical findings of lipoblastoma. Immunohistochemical findings showed nuclear positivity for a murine double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) and negativity for pleomorphic adenoma gene 1 (PLAG1). Fluorescence in situ hybridization showed abnormal amplification of the MDM2 gene. The patient was thus finally diagnosed as having an ALT. No signs of local recurrence or metastasis were noted 1 year postoperatively. This case is instructive in the differential diagnosis of primary adipocytic tumors. Lipoblastomas are the most common adipocytic tumors in children, but if a tumor is located in the deep tissue or imaging findings are not typical, the possibility of ALT should be considered and immunohistochemistry for MDM2 and CDK4 should be added.
Chimerism analysis is a surrogate indicator of graft rejection or relapse after allogeneic hematopoietic stem cell transplantation (HSCT). Although short tandem repeat PCR (STR-PCR) is the usual ...method, limited sensitivity and technical variability are matters of concern. Quantitative PCR-based methods to detect single nucleotide polymorphisms (SNP-qPCR) are more sensitive, but their informativity and quantitative accuracy are highly variable. For accurate and sensitive chimerism analysis, a set of KMR kits (GenDx, Utrecht, Netherlands), based on detection of insertions/deletions (indels) by qPCR, have been developed. Here, we investigated informativity and validated the accuracy of KMR kits in Japanese donor/recipient pairs and virtual samples of DNA mixtures representative of Japanese genetic diversity. We found that at least one recipient-specific marker among 39 KMR-kit markers was informative in all of 65 Japanese donor/recipient pairs. Moreover, the percentage of recipient chimerism estimated by KMRtrack correlated well with ratios of mixed DNA in virtual samples and with the percentage of chimerism in HSCT recipients estimated by STR-PCR/in-house SNP-qPCR. Moreover, KMRtrack showed better sensitivity with high specificity when compared to STR-PCR to detect recipient chimerism. Chimerism analysis with KMR kits can be a standardized, sensitive, and highly informative method to evaluate the graft status of HSCT recipients.
In this paper, we treat the problem of constructing secure communication systems using chaotic synchronization of distributed parameter systems. In particular, we concentrate on the chaotic vibration ...of a wave equation with a van der Pol boundary condition. In general, a secure communication system consists of three components, a synchronization system, and modulation and demodulation components. In the present work, a wave equation generating non-isotropic spatiotemporal chaotic vibration is used. The non-isotropic characteristic makes it harder for the mechanism behind the synchronization system to be detected. To simulate the chaotic vibration accurately, a numerical algorithm is also developed. Finally, through security analysis by numerical simulations, it is shown that the introduction of non-isotropy makes one of the system parameters more sensitive.
In this paper, we treat the problem of constructing secure communication systems using chaotic synchronization of distributed parameter systems. In particular, we concentrate on the chaotic vibration ...of a wave equation with a van der Pol boundary condition. In general, a secure communication system consists of three components, a synchronization system, and modulation and demodulation components. In the present work, a wave equation generating non-isotropic spatiotemporal chaotic vibration is used. The non-isotropic characteristic makes it harder for the mechanism behind the synchronization system to be detected. To simulate the chaotic vibration accurately, a numerical algorithm is also developed. Finally, through security analysis by numerical simulations, it is shown that the introduction of non-isotropy makes one of the system parameters more sensitive.
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