Benefit of high-dose cytarabine (HD-AraC) for acute myeloid leukemia (AML) prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unknown. We retrospectively analyzed data from 79 non-core-binding-factor AML patients who underwent allo-HSCT in their first complete remission (CR1). In univariate analysis, HD-AraC (>= 4 g/m(2)/day) before allo-HSCT improved disease-free survival (DFS) (p = .018), overall survival (OS) (p = .029), and cumulative incidence of relapse (CIR) (p = .033). Four-year DFS, OS, and CIR of patients receiving and not receiving HD-AraC were 79% vs. 49%, 82% vs. 56%, and 18% vs. 42%, respectively. In multivariate analysis, HD-AraC was a positive prognostic factor for DFS (hazard ratio (HR) = 0.36, 95% confidence interval (CI): 0.14-0.88), OS (HR = 0.37, 95% CI: 0.14-0.99), and CIR (HR = 0.38, 95% CI; 0.14-1.0). Our study demonstrates that HD-AraC before allo-HSCT at a dose >= 4 g/m(2)/day is effective for treating AML patients in CR1.

BACKGROUND: Processed blood volume (PBV) required to obtain a predefined number of stem cells can be estimated from peripheral blood CD34+ cell concentration, body weight, and collection efficiency (CE). Because CE is indefinite, this study was designed to formulate and validate a new model of PBV based on stochastic CE distribution. STUDY DESIGN AND METHODS: Data were retrospectively collected on 146 peripheral blood stem cell harvests from 114 patients and donors in a single institution from April 2014 to February 2018. The training set consisted of all procedures performed from April 2014 to June 2016 and the validation set of all procedures performed from July 2016 to February 2018. A new algorithm, based on CE2 distribution of the training set, was affirmed using the validation set. The positive predictive value of the model was estimated from the expected percentage of procedures that reached the target CD34-positive dose, with predicted PBV processed as the gold standard. RESULTS: The 10th and 50th percentiles of CE2 were 33.4% and 52.5%, respectively. When PBV was assorted into three categories, defined as greater than 90%, 50% to 90%, and less than 50% of procedures reaching the targeted CD34-positive dose, the positive predictive values of the new model were 100%, 70%, and 100%, respectively. CONCLUSION: The new model was validated with a high positive predictive value and can reliably estimate the required PBV and the success rate corresponding to the PBV. The model can be utilized easily with a Webbased tool.

Crystallization that proceeds above the glass transition temperature upon heating the glassy or amorphous state is referred to as "cold crystallization", which has often been observed in supercooled phases of molecular materials followed by the transition to the thermodynamically stable crystalline phase. Although this behavior is common for the macromolecules with high structural flexibility among segments preserving the wide temperature range of corresponding glassy phases, cold crystallization of small molecules is relatively rare and there is still less knowledge on the design guideline of such molecules. Here we report a ferrocene-hinged molecule DC12 carrying two units of didodecyl-substituted pentathiophenes at the 1,1'-positions. Due to the rotational freedom of the ferrocene unit, DC12 forms amorphous solid on cooling from its isotropic melt. The amorphous state was realized even by slow cooling such as 0.1 °C min-1. The possible reason for the easy formation of the amorphous phase is the coexistence of various conformations of DC12 originating from the open conformers of the ferrocene. On heating from the amorphous phase, DC12 shows cold crystallization with the estimated activation energy of 61 kJ mol-1. The crystalline phase is composed of the closed form of DC12 molecules packed in a lamellar fashion, and the degree of crystallinity is remarkably high compared with the case of macromolecular materials. The crystallization is triggered by the intermolecular interactions among the dodecyl chains and rotational flexibility of the ferrocene unit. This work provides an unprecedented example that ferrocenes act as heat-controllable rotational hinges in condensed phases. Considering that the cold crystallization phenomenon is related to heat-storage materials, the design strategy presented in this work will be novel to realize both easily formed amorphous phases and highly crystalline phases formed through cold crystallization.

Abstract Background Recent reports have highlighted an adverse impact of TP53 mutations on the prognosis of patients with myeloid malignancies. TP53 mutational analysis is useful in classifying these patients with respect to treatment strategies. High Resolution Melt (HRM) analysis is based on differences in the patterns of melting curves obtained when the targeted double strand DNA (dsDNA) dissociates during heating. HRM analysis is more cost- and time-effective than next-generation sequencing (NGS). In this study, we used HRM analysis to evaluate the impact of TP53 mutations on the clinical features and prognosis of patients at our institute with myeloid malignancies. Methods In this retrospective case study, HRM analysis was performed on 23 patients with MDS and 131 with AML, from October 2011 to January 2018. We targeted ten genes recurrently mutated in myeloid malignancies (TP53, NPM1, FLT3-ITD, IDH1, IDH2, NRAS, KRAS, WT1, DNMT3A, CEBPA) using HRM analysis for screening. For TP53 mutation detection, the entire coding region of TP53 gene from exons 1 to 11 was analyzed using the HRM method. Positive samples were validated using Sanger sequencing. We excluded frequently reported single nucleotide polymorphisms (P47S and R72P), silent mutations, and mutations which were not reported in the Catalogue of Somatic Mutations in Cancer database. NGS of TP53 mutations was done in 18 cases to validate mutations found by HRM analysis. Other non-TP53 gene mutations were similarly analyzed. The primary clinical endpoint of this study was overall survival (OS), measured from the time of diagnosis till time of death due to any cause, or till the last follow-up. The secondary clinical endpoint was relapse-free survival (RFS), measured from time of complete remission to relapse, or the last follow-up. The OS and RFS were compared using the log-rank test. Results We evaluated gene mutations in 131 AML and 23 cases of MDS using HRM analysis. Costs for one HRM analysis were $25 (USD, excluding labor) and required approximately 7 hours processing time per sample. If the screen was positive, add-on cost was an additional $20 with 2 hours of processing time. In total, we identified 28 TP53 somatic mutations in 27 cases from this cohort using HRM analysis (17 newly-diagnosed AML, 4 refractory/relapsed AML, and 6 MDS). Out of the total 154 cases, 18 were also analyzed by NGS; TP53 mutations were detected in 4 cases (median variant allele frequencies = 0.42) and no TP53 mutations were detected in the remaining 14 cases, consistent with the results of HRM analysis. Among the 28 somatic TP53 mutations, 26 were missense, 1 frameshift, and 1 affecting splice sites. Most missense mutations detected (22/26) were localized to the DNA-binding domain of the gene. Cases with TP53 mutations frequently had a complex karyotype (P=0.001), but rarely had NPM1 mutations (P=0.039). In comparison with patients with myeloid malignancies but no TP53 mutations, patients with TP53 mutations had lower counts of white blood cells (3,000 ·μL-1 vs 12,700 ·μL-1 ; P=0.006), lower hemoglobin (7.9 g·dL-1 vs 9.3 g·dL-1 ; P=0.048), and lower platelet counts (2.7×104 ·μL-1 vs 5.7×104 ·μL-1 ; P=0.024). TP53 mutations were associated with shorter OS (median OS, 260 days vs 687 days; P=0.02). In newly-diagnosed AML patients, TP53 mutations were associated with lower counts of both white blood cells (3,200 ·μL-1 vs 26,550 ·μL-1; P=0.006) and lower platelet counts (2.0×104 ·μL-1 vs 6.2×104 ·μL-1; P=0.008) in the peripheral blood. Analysis of bone marrow aspirate revealed that more cases with TP53 mutations had a low myeloid:erythroid ratio than those with TP53 wildtype (53.8% vs 12.7%; P=0.02), suggesting that cases with TP53 mutations have a higher proportion of erythroid precursors, such as in acute erythroid leukemia or erythroid/myeloid leukemia (M6) , as per the FrenchAmerican-British (FAB) classification. Among the patients treated with intensive therapy (either conventional chemotherapy or allogeneic stem cell transplantation), cases with TP53 mutations had shorter overall survival (median OS, 265 days vs not reached; P= 0.04) and shorter relapse-free survival (median RFS, 188 days vs not reached; P=0.02). Conclusion Patients with TP53 mutations have a much poorer prognosis than those without, and exhibit refractoriness to conventional therapies. HRM analysis is a cost- and time-effective method to detect TP53 mutations. Disclosures No relevant conflicts of interest to declare.

Interdigitating dendritic cell sarcoma (IDCS) is a rare neoplasm considered to derive from a dendritic cell. Recent studies have shown that B- or T-lymphoblastic leukemia/lymphomas can develop clonally related histiocytic/dendritic cell (H/DC) neoplasms, such as histiocytic sarcoma, Langerhans cell

In acute myeloid leukemia (AML), MLL (KMT2A) rearrangements are among the most frequent chromosomal abnormalities; however, knowledge of the genetic landscape of MLL-rearranged AML is limited. In this study, we performed whole-exome sequencing (n = 9) and targeted sequencing (n = 56) of samples from pediatric MLL-rearranged AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 study. Additionally, we analyzed 105 pediatric t(8;21) AML samples and 30 adult MLL-rearranged AML samples. RNA-sequencing data from 31 patients published in a previous study were also reanalyzed. As a result, we identified 115 mutations in pediatric MLL-rearranged AML patients (2.1 mutations/patient), with mutations in signaling pathway genes being the most frequently detected (60.7%). Mutations in genes associated with epigenetic regulation (21.4%), transcription factors (16.1%), and the cohesin complex (8.9%) were also commonly detected. Novel CCND3 mutations were identified in 5 pediatric MLL-rearranged AML patients (8.9%) and 2 adult MLL-rearranged AML patients (3.3%). Recurrent mutations of CCND1 (n = 3, 2.9%) and CCND2 (n = 8, 7.6%) were found in pediatric t(8;21) AML patients, whereas no CCND3 mutations were found, suggesting that D-type cyclins exhibit a subtype-specific mutation pattern in AML. Treatment of MLL-rearranged AML cell lines with CDK4/6 inhibitors (abemaciclib and palbociclib) blocked G1 to S phase cell-cycle progression and impaired proliferation. Pediatric MLL-MLLT3-rearranged AML patients with coexisting mutations (n = 16) had significantly reduced relapse-free survival and overall survival compared with those without coexisting mutations (n = 9) (P = .048 and .046, respectively). These data provide insights into the genetics of MLL-rearranged AML and suggest therapeutic strategies.

Optimal salvage chemotherapy has not been established for patients with acute myeloid leukemia (AML) who fail to attain complete remission (CR) after one course of induction chemotherapy. This retrospective study aimed to assess the efficacy and safety of an MEC (mitoxantrone, 6 mg/m2, 1-3 days; etoposide, 80 mg/m2, 1-6 days; cytarabine, 1 g/m2, 1-6 days) regimen in patients with AML who failed to attain CR after one course of induction chemotherapy. Twenty-four patients were included in this study (median age, 58 years; range, 28-79 years). After one course of MEC, 11 patients (45.8%) attained CR. Febrile neutropenia was observed in all patients, and acute infection was observed in 7 patients (29.2%). However, no therapy-related death occurred. All patients eligible for transplantation and who attained CR after MEC salvage chemotherapy underwent allogeneic hematopoietic stem cell transplantation. The MEC regimen exhibited a good response rate with tolerable adverse events. Therefore, the MEC regimen can be safely used as a salvage treatment for patients with AML who failed to attain CR after one course of induction chemotherapy.

BACKGROUNDA few cases of primary autoimmune neutropenia (AIN) have been reported in adults, but cyclic primary AIN, which is characterized by the periodic oscillation of neutrophils, is uncommon in adults.STUDY DESIGN AND METHODSHerein, we report a 70‐year‐old man referred to our hospital with severe neutropenia and thrombocytopenia. He had experienced intermittent episodes of low‐extremity purpura for the past 3 months, with cellulitis on the skin of the scalp 1 month previously.RESULTSThe patient presented with severely low neutrophil and platelet (PLT) counts. Myeloid progenitors and megakaryocytes were increased in the marrow, but mature neutrophils were remarkably decreased. Anti‐neutrophil antibodies to specific epitopes were detected at neutropenia. Based on these findings, AIN accompanied by autoimmune thrombocytopenia was diagnosed. The patient experienced synchronous fluctuations of neutrophil and PLT counts three times. Despite no treatment, the neutrophil count fluctuated within the range of 0.06 × 109 to 1.65 × 109/L, and the PLT count fluctuated from 0.7 × 1010 to 20.5 × 1010/L. We identified an inverse relationship between neutrophil count and anti‐neutrophil antibody titers, establishing the conclusive diagnosis of cyclic AIN. After prednisolone treatment, the neutrophil and PLT counts normalized, and the patient has maintained long‐term remission.CONCLUSIONWe report a rare case of cyclic AIN diagnosed from the inverse association between periodic oscillation of anti‐neutrophil antibody titers and neutrophil counts. This clinical course suggests that in AIN patients, laboratory data and recurrent signs of infection should be monitored regularly, including shortly after neutrophil recovery.

Objectives: 10 years of placenta accreta patients in our hospital were retrospectively analysed to summarise the risk factors, the relationship between ultrasonic manifestations and clinical outcome. Methods: The medical records and ultrasound examination information were retrospectively analysed in patients of placenta accreta and its variants (including increta and percreta) who hospitalised in our hospital from 2007 to 2016 and the diagnosis confirmed by Caesarean delivery (CD). Results: There were 24 patients aged 26-44 years with 1-6 pregnancy (average 3.6). Parity was 0 in 6 cases, parity 1 in 14 cases (CD in 13), parity 2 in 4 cases (all CD). The time between the last CD and the current pregnancy was 2-12 years. The interval between 2 CDs was 3-8 years. 23 patients had previous uterine surgery. The volume of blood loss during delivery was 300-8500ml (average 2714). There were 20 patients with placenta previa. The antenatal ultrasound diagnosis of placenta accrete and its variants was confirmed by Caesarean hysterotomy and histopathological examination in 15 patients. 9 cases were missed by ultrasound examination including 6 patients with parity 0 and 2 placenta previa patients with posterior accrete as well as 1 normal position placenta with posterior accreta. 15 patients out of 17 with previous CD underwent hysterectomy (13 Panhysterectomy with 2 bladder injury and repair, 2 subtotal hysterectomy). 3 patients out of 4 with 2 previous CDs performed hysterectomy before 30 weeks’ gestation (2 after uterine artery embolisation). 20 patients delivered liveborn neonates between 32 and 40 weeks. Conclusions: Placenta previa and previous uterine surgery are the major risk factors for placenta accrete. Prediction of placental accreta is possible using prenatal ultrasound. Prenatal diagnosis improves perinatal outcome.

Few studies have examined the prognostic impact of blood markers [other than the five factors in the enhanced International Prognostic Index (NCCN-IPI)] in elderly patients with diffuse large B cell lymphoma (DLBCL). We retrospectively analyzed 391 DLBCL patients receiving rituximab plus anthracycline-containing chemotherapy to examine the prognostic impact of simple blood markers. The NCCN-IPI was more accurate for discriminating prognoses than the original IPI. Multivariate analysis identified platelet count (<100,000/μl) and albumin (<3.5 g/dl) levels as significantly associated with lower overall survival (OS), independently of the NCCN-IPI. These parameters stratified patients into three risk groups: platelet–albumin (PA) score low (platelet count ≥100,000/μl, albumin ≥3.5 g/dl, n = 243); intermediate (platelet count <100,000/μl, albumin ≥3.5 g/dl or platelet count ≥100,000/μl, albumin <3.5 g/dl, n = 125); and high (platelet count <100,000/μl, albumin <3.5 g/dl, n = 23). The 5-year OS rates were 81.5, 48.6, and 20.2 %, respectively (p < 0.001). Notably, most patients with a low platelet count (n = 30) were stratified into the high-risk subgroup, suggesting that platelet count was prognostic for high-risk patients with a dismal outcome. In elderly patients (n = 291), the prognostic value of the NCCN-IPI might be diminished because the low-risk category was excluded; however, the PA score was predictive of survival: the 5-year OS rates for PA score low (n = 171), intermediate (n = 101), and high (n = 19) groups were 77.6, 47.9, and 19.0 %, respectively (p < 0.001). Platelet count and albumin levels are useful prognostic factors, and their combined use can predict survival, even in elderly patients.

Objectives: Treatment strategies of fetal heart beat (FHB)-positive Caesarean scar pregnancy (CSP) depend on the medical environment, social environment and gross domestic product. This study aimed to identify the most appropriate strategies by reviewing strategies that were addressed in previous studies in our country. Methods: We searched articles in these 5 years using the key word ”Caesarean scar pregnancy” from our national medical journal article retrieval system. We searched 38 articles. In these articles, we omitted articles in which the subject of the article was not FHB-positive CSP. We finally included 20 articles and reviewed them. We reviewed the treatment techniques and their order and combination as treatment strategies. Results: FHB-positive CSP cases were treated with 10 different treatment techniques. These treatments were (1) feticide (10 articles), (2) general administration of methotrexate (MTX) (10 articles), (3) local administration of MTX (5 articles), (4) misoprostol (1 article), (5) Transarterial embolisation (TAE) (5 articles), (6) laparoscopic blood vessel clipping (1 article), (7) vaginal CSP resection (7 articles), (8) laparoscopic CSP resection (2 articles), (9) hysteroscopic CSP resection (1 article), and (10) hysterectomy (2 articles). Feticide was performed in 50% (10/20) of articles. General MTX, local MTX, and misoprostol were drug therapies. TAE and laparoscopic blood vessel clipping decreased blood supply. Operative (vaginal, laparoscopic, hysteroscopic, and abdominal resection) CSP resection was performed in 12 of 20 (60%) articles. Treatment of CSP was achieved by a combination of some techniques, such as feticide, drug therapy, blood supply-decreasing techniques, and operative CSP resection, in this order. Conclusions: Feticide was considered necessary in 50% of articles. CSP resection was performed in 60% of articles. Treatment of CSP was achieved by a combination of some techniques, such as feticide, drug therapy, decreasing blood supply, and operative CSP resection. OP12: SCREENING

Anti-MDA5 antibody-positive patients with clinically amyopathic dermatomyositis (CADM) are at high risk of developing rapidly progressive interstitial lung disease (ILD), which is associated with a high mortality rate. Approximately half of the patients with ILD recover; however, the long-term clinical course of these patients has not been fully reported and is not completely understood. This report describes the atypical clinical course of an anti-MDA5 antibody-positive CADM patient who experienced three deteriorations of ILD in 9 years. These findings indicate that the ILD in anti-MDA5 antibody-positive patients may not only be rapidly progressive, but may also be chronic and recurrent.

Hemophagocytic lymphohistiocytosis (HLH) associated with herpes simplex virus (HSV)-1 infection (HSV-1-HLH) is uncommon and is potentially fatal without appropriate treatment. We herein report the case of an adult patient with HSV-1-HLH who was successfully treated with acyclovir. A 69-year-old man developed fever, pancytopenia and liver enzyme elevation after the resolution of pneumonia. These findings and the presence of hemophagocytosis in the patient's bone marrow were consistent with a diagnosis of HLH. The patient was diagnosed with HSV-1-HLH based on the results of a polymerase chain reaction (PCR) for HSV-1. The early administration of acyclovir improved his clinical symptoms and laboratory results within two weeks. In the present case, the rapid and precise diagnosis facilitated the successful treatment of HSV-1-HLH.

Whether the lymphocyte-to-monocyte ratio (LMR) at relapse can predict clinical outcomes for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in the rituximab era was investigated. We analyzed 74 patients with relapsed/refractory DLBCL initially treated with a rituximab-containing regimen. A low LMR (< 2.6) was significantly associated with shortened overall survival and progression-free survival. The LMR might facilitate better stratification among patients in the low-and intermediate-risk second-line international prognostic index groups. Background: Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have a poor prognosis, even in the rituximab era. Several studies have reported the clinical importance of the peripheral blood lymphocyte-to-monocyte ratio (LMR) in various malignancies, including lymphoma. However, the prognostic value of the LMR in relapsed/refractory DLBCL has not been well evaluated. The purpose of the present study was to investigate whether the LMR at relapse can predict clinical outcomes for relapsed/refractory DLBCL patients treated with rituximab. Patients and Methods: We analyzed data on 74 patients with relapsed/refractory DLBCL, who were initially treated with R-CHOP (rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone) or an R-CHOP-like regimen. Results: There was a significant association between a low LMR (< 2.6) and shorter overall survival (OS; P< .001) and progress ion-free survival (PFS; P <.001) compared with the high LMR group (v 2.6). Multivariate analysis showed that LMR was an independent prognostic factor for OS (P< .001) and PFS (P< .001), as was the international prognostic index (IPI) at relapse for OS. In addition, the LMR had an incremental value for OS and PFS compared with the IPI at relapse. Conclusion: The LMR predicts OS and PFS outcomes in relapsed/refractory DLBCL patients treated with rituximab, and might facilitate better stratification among patients in low-and intermediate-risk IPI groups.

Ultrasound (US) and magnetic resonance imaging (MRI) are widely performed in developed countries to diagnose Caesarean scar pregnancies (CSPs). This study aimed to identify FHB-positive CSP image characteristics in these 5 years by reviewing pictures that were published in our country. We searched articles over these 5 years using the key word “Caesarean scar pregnancy” from our national medical journal article retrieval system. We finally identified 19 images of FHB-positive CSP and reviewed them. There were 19 FHB-positive CSP cases that had ultrasound or MRI images. We used the most representative image of CSP in each case. Eleven transvaginal ultrasound (TVUS) images and eight MRI images were reviewed. The earliest case was at 5 weeks' gestation, the latest was at 9 weeks, and the average was 7 weeks. The CSP niche ratio (depth of the niche/total anterior uterine wall thickness) was calculated in each image. The minimum niche ratio was 0.38, the maximum was 1.00, and the average was 0.76. Uterine muscle wall rupture was observed in the image of one case. We also examined the centre of CSP contents located in the uterine anterior wall or in the uterine cavity. The centre was located in the outer half of the anterior wall in one case, in the inner half in 12, in the uterine cavity in six, and outside of the uterus in none. Vaginal CSP resection was used in five, hysteroscopic resection in one, laparoscopic resection in one, and hysterectomy in five. The patient who was treated with laparoscopic resection had a niche ratio of 1 and had uterine rupture on the CSP scar pouch. FHB-positive CSP is present in the narrow range of 5 to 9 gestational weeks. The centre of CSP contents are usually located in the uterine cavity or in the inner half of the anterior wall. Laparoscopic resection might be possible in the case of uterine muscular rupture was observed in the image.

Donor cell-derived transient abnormal myelopoiesis as a specific complication of umbilical cord blood transplantation

The utility of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from sources other than matched related donors (alternative donors) in the management of elderly acute myeloid leukemia (AML) patients in first complete remission (CR1) has not been clarified. To investigate the benefit of allo-HCST in the management of elderly AML patients in CR1, we retrospectively collected data from consecutive AML patients aged 60-66 years, who had been diagnosed between 2000 and 2014 and achieved CR. A total of 43 patients were included in this study, and 12 patients received allo-HSCT in CR1 only from alternative donors. Compared to chemotherapy alone, allo-HSCT improved overall survival (OS) (P=0.050) and cumulative incidence of relapse (CIR) (P=0.0059) in univariate analysis. OS and CIR at 3 years from CR1 were 82.5% vs 34.2%, and 17.5% vs 74.6%, respectively. In multivariate analysis, allo-HSCT also improved OS (hazard ratio (HR), 0.18; 95% confidence interval (CI), 0.039-0.80) and CIR (HR, 0.090; 95% CI, 0.029-0.28). Allo-HSCT from an alternative donor is a credible option in the treatment of elderly AML patients in CR1.

Background: Normal pressure hydrocephalus (NPH) is characterized by three symptoms, disturbance of gait, dementia and urinary incontinence. Especially, disturbance of gait is known as a relatively early symptom. Differential diagnosis of NPH is not easy since many symptoms overlap with other neurological diseases. The cerebrospinal fluid shunting is expected to ameliorate symptoms of NPH. The late detection of disease may limit the treatment effect. Therefore, the early detection of NPH is important. Previous studies have reported that clinical features of the gait abnormality in NPH. These measurements need relatively large instruments, such as motion capture systems.