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The purpose of this study was to investigate growth changes in human plantar flexor muscle and tendons. In addition, we ascertained whether growth changes in muscle and tendon were more closely related to skeletal age than chronological age. 22 elementary school children (ESC), 19 junior high school students (JHS), and 23 young adults (ADT) men participated in this study. Maximal strain and hysteresis of tendon structures and cross-sectional area of Achilles tendon were measured using ultrasonography. In addition, skeletal age was assessed using Tanner-Whitehouse III method. Maximal strain of ESC was significantly greater than that of other groups, while no significant difference was observed between JHS and ADT. There was no difference in hysteresis among 3 groups. Relative cross-sectional area (to body mass2/3) of ADT was significantly smaller than that of other groups. For ESC and JHS, measured variables of muscle and tendon were significantly correlated to both chronological and skeletal ages. These results suggested that immature musculoskeletal system was protected by more extensible and larger tendon structures in ESC and only by larger tendon structures in JHS, respectively. Furthermore, there were no differences in correlation coefficient values between measured variables of muscle and tendon and chronological or skeletal ages. [ABSTRACT FROM AUTHOR]

Human herpesvirus-6 (HHV-6) encephalitis following allogeneic hematopoietic cell transplantation is a serious and often fatal complication accompanying reactivation of HHV-6B. Incidence varies among studies, but is reportedly 0-11.6% after bone marrow or PBSC transplantation and 4.9-21.4% after umbilical cord blood transplantation, typically around 2-6 weeks post transplant. Symptoms are characterized by memory loss, loss of consciousness and seizures. Magnetic resonance imaging (MRI) typically shows bilateral signal abnormalities in the limbic system. This complication is considered to represent acute encephalitis caused by direct virally induced damage to the central nervous system, but our understanding of the etiologies and pathogenesis is still limited. The mortality rate attributable to this pathology remains high, and survivors are often left with serious sequelae such as impaired memory and epilepsy. Despite the poor prognosis, no validated treatments or preventative measures have been established. Establishment of preventative strategies represents an important challenge. This article reviews the current knowledge of the clinical features, incidence, pathogenesis and treatment of HHV-6 encephalitis, and discusses issues needing clarification in the future to overcome this serious complication. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of the saline flush (SF) technique on the depiction of lesions and the reduction of perivenous artefacts in the head and neck region using dual-energy computed tomography (CT) with virtual monochromatic imaging (VMI).Materials and Methods: Fifty patients with head and neck cancer were divided into two groups: group A, without a SF and group B, with a 30-ml SF. All images were acquired using fast kilovolt-switching CT (Revolution HD, GE Healthcare, Milwaukee, WI, USA). Contrast-to-noise ratios (CNRs) of the lesions were calculated at VMI energy levels ranging from 40 to 80 keV. Subjective analysis of overall image quality, delineation of lesions, and perivenous artefacts was conducted by two reviewers at both VMI energy level 40 keV and the optimal energy level (which showed optimal CNR by objective analysis).Results: Optimal energy level was 63 keV for group A and 61 keV for group B. At VMI energy levels ranging from 40 to 80 keV, the CNR was higher for group B. The highest subjective overall image quality was shown for group B at the optimal energy level (subjective image quality mean value, 3.40). Subjective delineation of lesions was comparable. The perivenous artefact score was significantly higher for group B (2.44 versus 2.74 [p<0.05] at 40 keV, 3.20 versus 3.46 [p<0.05] at the optimal energy level).Conclusion: The SF technique results in an improvement of lesion CNR and a reduction of perivenous artefacts in VMI using duel-energy CT, especially at 40 keV. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the organ specific dose constraints in head and neck carcinoma treated with intensity-modulated radiation therapy (IMRT) using data from a multi-institutional clinical trial (JCOG1015). Dose constraints used in the JCOG1015 were as follows; Spinal cord Dmax <50 Gy, Brain Dmax <70 Gy, Brainstem Dmax <54 Gy, Optic nerve Dmax <50 Gy, Eyeball Dmax <40 Gy, Lens Dmean <6 Gy, Parotid gland Dmean <26 Gy, pharyngeal constrictor muscle (PCM) Dmean <54 Gy, Larynx Dmean <54 Gy, Inner ear Dmean <45 Gy. Brain D1cc, brainstem D1cc, and thyroid Dmean were not stated but recorded. Patient data and dose-volume histograms (DVH) of organs-at-risk (OARs) were collected from 74 patients with nasopharyngeal carcinoma treated with IMRT who enrolled in the JCOG1015 trial. The incidence of late toxicities was evaluated using the cumulative incidence method or prevalence. ROC analysis was used to estimate the optimal DVH cut-off value that predicted toxicities. Estimated DVH cut-off values were brainstem D1cc:55.8 Gy for G1 myelitis, brain D1cc:72.1 Gy for ≥G1 central nerve necrosis, optic nerve Dmax:53.3 Gy for G2 vision impaired, eye-ball Dmax:36.6 Gy for G2 impaired, PCM Dmean:41.2 Gy for ≥G2 dysphagia, ipsilateral inner ear Dmean:44.0 Gy for ≥G2 hearing impaired, ipsilateral inner ear Dmean:51.5 Gy for ≥G2 middle ear inflammation, and thyroid Dmean: 45.6 Gy for G1 hypothyroidism. The 3- and 5-year cumulative incidence of late toxicity by dose metrics were shown in Table 1. The estimated cut-off values were similar to dose constraints criteria used in the JCOG1015 except for PCM. In patients who received higher dose than the dose constraints in brainstem and inner ear, incidence of myelitis and hearing impaired were notably high. The dose constraints criteria of the JCO1015 were appropriate for most OARs, although more strict dose constraints might be necessary for PCM. Dose constraints for inner ear and brainstem should be archived with higher priority. [ABSTRACT FROM AUTHOR]

Abstract Objective To elucidate the mechanisms by which orally administered tacrolimus was not absorbed in a patient following allogeneic hematopoietic stem cell transplantation. Clinical Course A 17-year-old girl with acute myeloid leukemia underwent HLA-haploidentical peripheral blood stem cell transplantation following fludarabine, busulfan, and total-body irradiation. Graft-vs-host disease prophylaxis was post-transplant cyclophosphamide, followed by intravenous tacrolimus and mycophenolate mofetil. When tacrolimus was switched to oral administration, its blood level declined rapidly, resulting in development of acute graft-vs-host disease, which was ameliorated by switching back to intravenous administration. Methods/Results To elucidate if impaired tacrolimus absorption could be related to genetic polymorphism of tacrolimus-metabolizing enzymes, we analyzed gene polymorphisms of cytochrome P450 3A4, cytochrome P450 3A5, and multidrug resistance 1 (MDR1). The patient had wild-type cytochrome P450 3A4 (*1/*1) and variant-type cytochrome P450 3A5 (*3/*3), while MDR1 genes (2677A/G, 3435C/C) were wild-type. Conclusion Wild-type MDR1 gene product P-glycoprotein expressed in the intestine reduces drug absorption from the gastrointestinal tract and may have contributed to low blood levels of tacrolimus in this patient when tacrolimus was orally administered. Highlights • The patient's gene polymorphism of tacrolimus-metabolizing enzymes, especially MDR1, may be associated with insufficient absorption and lack of increase in blood level of tacrolimus when orally administered following allogeneic hematopoietic stem cell transplantation. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to compare the clinical and demographic features of 62 patients presenting sporadic odontogenic keratocysts (OKCs) or OKCs associated with nevoid basal cell carcinoma syndrome (NBCCS). In conjunction with this, we also evaluated the immunohistochemical expression of Shh, Ptch1, Ptch2, Smo, Gli1, Gli2 and Gli3 proteins in 86 OKCs. By doing this, we add to the understanding of the biology of this type of lesion, providing tools that will help facilitate the early diagnosis of NBCCS in those patients where the first manifestation is that of OKCs.Methods: This is a retrospective study; patients were classified into two groups: group 1 which consisted of those who were not affected by NBCCS (49 patients and 57 OKCs) and group 2 which consisted of those who were diagnosed with NBCCS (13 patients and 29 OKCs). The clinical and demographic features were studied and the immunohistochemical expression of Sonic Hedgehog proteins (Shh, Ptch1, Ptch2, Smo, Gli1, Gli2, and Gli3) was analyzed in all samples.Results: There was an increase in the expression of three proteins in the syndromic OKC, when compared to that of sporadic cysts. Shh and Gli1 showed higher cytoplasmic expression, while Smo revealed stronger nuclear and cytoplasmic expressions.Conclusion and clinical relevance: Our findings suggest that the expression patterns of important Shh pathway proteins can represent valuable markers for early diagnosis of NBCCS-associated OKCs, as the major criterion for the diagnosis of NBCCS is currently based on the late appearance of basal cellular carcinomas. Thus, standardizing a new diagnostic tool for diagnosis of NBCCS could be of great importance in the identification of therapeutic targets. We therefore suggest, as based on our findings, that OKCs showing high expression of Shh, Smo, and Gli1 are potentially associated with NBCCS. [ABSTRACT FROM AUTHOR]

Background: We assessed the non-inferiority of accelerated fractionation (AF) (2.4 Gy/fraction) compared with standard fractionation (SF) (2 Gy/fraction) regarding progression-free survival (PFS) in patients with T1-2N0M0 glottic cancer (GC). Patients and methods: In this multi-institutional, randomized, phase III trial, patients were enrolled from 32 Japanese institutions. Key inclusion criteria were GC T1-2N0M0, age 20-80, Eastern Cooperative Oncology Group performance status of 0-1, and adequate organ function. Patients were randomly assigned to receive either SF of 66-70 Gy (33-35 fractions), or AF of 60-64.8 Gy (25-27 fractions). The primary end point was the proportion of 3-year PFS. The planned sample size was 360 with a non-inferiority margin of 5%. Results: Between 2007 and 2013, 370 patients were randomized (184/186 to SF/AF). Three-year PFS was 79.9% (95% confidence interval [CI] 73.4-85.4) for SF and 81.7% (95% CI 75.4-87.0) for AF (difference 1.8%, 91% CI-5.1% to 8.8%; onesided P=0.047>0.045). The cumulative incidences of local failure at 3 years for SF/AF were 15.9%/10.3%. No significant difference was observed in 3-year overall survival (OS) between SF and AF. Grade 3 or 4 acute and late toxicities developed in 22 (12.4%)/21 (11.5%) and 2 (1.1%)/1 (0.5%) in the SF/AF arms. Conclusion: Although the non-inferiority of AF was not confirmed statistically, the similar efficacy and toxicity of AF compared with SF, as well as the practical convenience of its fewer treatment sessions, suggest the potential of AF as a treatment option for early GC. [ABSTRACT FROM AUTHOR]

Background. Pre-emptive therapy with valganciclovir (VGCV) has become the standard therapy for preventing cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (HSCT). The effectiveness of low-dose VGCV (900 mg per day) has been shown to be equal to that of standard-dose VGCV (900 mg twice daily); however, individualized optimal dosing and toxicity of VGCV have not been reported. Methods. We conducted a retrospective study to evaluate the optimal dose of VGCV as pre-emptive therapy for preventing CMV infection by comparing the frequency of adverse events (AEs) and clinical efficacy in a low-dose VGCV group with those in a standard-dose VGCV group. Thirty-eight patients who were administered VGCV because of CMV antigenemia after HSCT were analyzed. Results. Neutropenia (standard-dose group: 33%, low-dose group: 15%, P = 0.26) and thrombocytopenia (standard-dose group: 39%, low-dose group: 15%, P = 0.14) were frequent AEs of VGCV, and a significantly higher frequency of overall AEs was detected in the standard-dose group than in the low-dose group (P < 0.01). In comparison of dosage based on weight, dosage of VGCV >27 mg/kg was closely related to onset of AEs (P = 0.04). Conclusions. Low-dose VGCV was not inferior in clinical efficacy, including clearance rate of CMV antigenemia and incidence of consequent CMV disease, to standard-dose VGCV as was previously reported. Initial low-dose VGCV for pre-emptive CMV therapy markedly reduces hematologic toxicity and has clinical efficacy equivalent to that of standard-dose VGCV. It is therefore reasonable for patients, except for noticeably overweight patients, to be given initial low-dose VGCV. [ABSTRACT FROM AUTHOR]

Background Intestinal microbial ecology is actively regulated by Paneth cell-derived antimicrobial peptides, α-defensins. Graft-versus-host disease ( GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation ( SCT). We previously demonstrated that Paneth cells are targeted by GVHD, and their expression of antimicrobial peptide α-defensins is impaired, leading to a loss of physiological diversity among the microflora and development of bloodstream infection. Herein, we evaluated whether fecal levels of α-defensins could be surrogate marker of intestinal dysbiosis. Methods We directly measured α-defensin cryptdin-1 (Crp1) in fecal pellets of mice with GVHD by using a novel enzyme-linked immunosorbent assay. Results Fecal levels of Crp1 were significantly decreased in mice with GVHD but unchanged in mice without GVHD after SCT. These were correlated with intestinal flora diversity. Conclusion We demonstrate a link between reduced secretion of Paneth cell α-defensins and dysbiosis of intestinal flora in GVHD. Fecal levels of α-defensins could be surrogate markers for intestinal microbial homeostasis. [ABSTRACT FROM AUTHOR]

PBSC products for auto- and allografting can be cryopreserved in liquid nitrogen with controlled-rate freezing until their use. Alternatively, they can be stored at −80 °C in a mechanical chest freezer, but it remains to be clarified whether PBSCs can be stored for the long term. We evaluated viability and functions of PBSCs cryopreserved for more than 10 years with this simplified method. Although recovery rate and viability of CD34+ cells were significantly decreased, myeloid differentiation potential and in vivo reconstitution and self-renewal potential of CD34+ cells in a xenogeneic engraftment assay were maintained for more than 10 years. These results indicate that PBSCs can be stored at −80 °C for years. Although accumulation of clinical engraftment data is required to confirm our results, this simplified cryopreservation will thus meet the increasing worldwide demand for PBSC transplantation in a region with limited resources. [ABSTRACT FROM AUTHOR]

The impact of the conditioning intensity and TBI on acute GVHD (aGVHD) is still a matter of debate. We analyzed 6848 adult recipients who received allogeneic hematopoietic cell transplants (HCT) between 2006 and 2011 in Japan. The subjects were divided into groups who had received myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC), either with or without TBI. There was a significant difference in the incidence of aGVHD 2-4 among the different conditioning types: 39% in TBI-MAC, 35% in TBI-RIC and 32% in both no-TBI MAC and no-TBI-RIC (P<0.001). In a multivariate analysis, TBI-MAC, but not no-TBI MAC, was significantly associated with an increased risk of aGVHD 2-4 (hazard ratio (HR) 1.33, P<0.01), whereas TBI-RIC was associated with an increased risk of GVHD 3-4 (HR 1.36, P=0.048). TBI-MAC and TBI-RIC were significantly associated with skin and gastrointestinal aGVHD. Subgroup analyses demonstrated that not only TBI-MAC, but also TBI-RIC, was significantly associated with aGVHD 2-4 in older patients. Furthermore, high-dose TBI only had an adverse impact on aGVHD 2-4 in HLA-matched HCT. Impacts of intensity and TBI on aGVHD differ by patient backgrounds, and this difference should be considered to establish a risk-adapted strategy for the prevention of aGVHD. [ABSTRACT FROM AUTHOR]

Introduction: Dabigatran is an oral intake thrombin inhibitor for preventive administration against stroke accompanied by atrial fibrillation. Although dabigatran causes prolonged activated partial thromboplastin time (APTT), the effect of dabigatran on each coagulation factor and coagulation factor inhibitor remains to be investigated. Our aim was to analyze the influence of dabigatran on coagulation factors and coagulation factor inhibitors. Methods: We administered dabigatran to 40 patients. In 26 of these 40, we analyzed the activity of several coagulation factors and their inhibitors. We used Fisher's exact test to determine statistical significance. Results: The activities of many coagulation factors changed during the dabigatran therapy. Factor II levels decreased in all patients showing prolongation of partial thromboplastin (PT) and APTT. The antifactor VIII inhibitor was positive in the majority of patients with prolonged PT and APTT, while activities of protein C, protein S, and antifactor IX inhibitor were not associated with PT and APTT prolongation. Conclusion: Dabigatran affects the activities of many coagulation factors, including factors II, V, VIII, and IX, as well as the antifactor VIII inhibitor. [ABSTRACT FROM AUTHOR]

Background Reactivation of hepatitis B virus ( HBV) infection, reverse seroconversion ( RS), is a serious complication after allogeneic stem cell transplantation (allo HSCT). We previously conducted a post-transplant hepatitis B vaccine intervention trial and demonstrated the vaccine efficacy in preventing HBV- RS. This report is an update of the hepatitis B vaccine study. Methods In this trial, 21 patients were enrolled and received a standard 3-dose regimen of hepatitis B vaccine after discontinuation of immunosuppressants, whereas 25 transplant recipients with previous HBV infection did not receive the vaccine and served as controls. Results None of the 21 patients in the vaccine group developed HBV- RS and 12 controls developed HBV- RS in median follow-up periods of 60 months (range 13-245). HBV vaccine resulted in a positive value of hepatitis B surface antibody ( HBsAb) titer in 9 patients, while HBsAb remained negative in 12 patients. Presence of a high titer of HBsAb before vaccination was associated with conversion into HBsAb positivity after vaccination. Conclusion These results demonstrated the long-term effects of HBV vaccine for preventing HBV- RS after allo HSCT. Of note, no HBV- RS occurred, even in patients who did not achieve conversion into HBsAb positivity after vaccination. [ABSTRACT FROM AUTHOR]

The Graft Processing subcommittee of the Worldwide Network for Blood and Marrow Transplantation wrote this guideline to assist physicians and laboratory technologists with the setting up of a cell processing laboratory (CPL) to support a hematopoietic stem cell transplant program, thereby facilitating the start-up of a transplant program in a new location and improving patient access to transplantation worldwide. This guideline describes the minimal essential features of designing such a laboratory and provides a list of equipment and supply needs and staffing recommendations. It describes the typical scope of services that a CPL is expected to perform, including product testing services, and discusses the basic principles behind the most frequent procedures. Quality management (QM) principles specific to a CPL are also discussed. References to additional guidance documents that are available worldwide to assist with QM and regulatory compliance are also provided. [ABSTRACT FROM AUTHOR]

Poster: Clinical track: Gynaecological (endometrium, cervix, vagina, vulva) PO-1129: Impact of individualized ITV margins for IMRT of cervical cancer on target coverage K. Wada, E. Nakanishi, M. Toratani, T. Ikawa, N. Kanayama, M. Morimoto, K. Konishi, T. Teshima. [Extracted from the article]

Late graft failure is a rare but significant complication after allogeneic stem cell transplantation, which is often complicated by severe infections. We report a case of late graft failure, which was successfully treated with a T-cell replete hematopoietic stem cell boost without conditioning that induced rapid engraftment and relieved the patient of infection. Discontinuation of immunosuppressants and nilotinib administration suppressed the host cells. Achieving full donor chimerism allowed us to administer a peripheral blood stem cell boost without conditioning. [ABSTRACT FROM AUTHOR]