Investigation of biomarkers to predict outcomes in allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Various biomarkers have been developed and evaluated to predict the prognosis and complications of allogeneic hematopoietic cell transplantation (HCT). Most previous studies conducted on different biomarkers evaluated single effects such as those associated with inflammation, immunology, iron metabolism, and nutrition, and only a few studies have comprehensively analyzed markers. OBJECTIVE: The study aimed to survey comprehensive multiple markers prior to HCT and extract those that significantly predict the outcomes. STUDY DESIGN: A prospective multicenter observational study was performed. (UMIN000013506) Patients undergoing HCT for hematologic diseases were consecutively enrolled. Besides the usual clinical biomarkers, serum samples for extra-clinical biomarkers were collected and cryopreserved before starting the conditioning regimen. A total of 32 candidate biomarkers were selected, 23 from hematology, biochemistry, immunology, nutrition, and iron metabolism, and 9 from composite markers. Based on the area under the curve (AUC) values for survival, promising biomarkers was extracted. Internal validation for these markers was applied based on bootstrap methods. Setting the cut-off values for them, log-rank test was applied and outcomes including overall survival (OS), relapse, and non-relapse mortality (NRM) were evaluated using multivariate analyses. Furthermore, detailed analysis including transplant-related complications and external validation were conducted focusing on C-reactive protein (CRP) to platelet (Plt) ratio. RESULTS: A total of 152 patients with hematologic malignancies were enrolled from April 2014 to March 2017. CRP, soluble interleukin-2 receptor (IL2R), CRP to albumin (Alb) ratio, CRP to Plt ratio, Plt to IL2R ratio, and IL2R to Alb ratio were identified as promising markers. Internal validation successfully confirmed their reliability of AUC and multivariate analysis demonstrated the statistical significance between the higher and the lower markers. Above all, a higher CRP to Plt ratio was significantly associated with a lower OS (hazard ratio [HR] 2.77; 95% confidence interval [CI] 1.30-5.91; P = 0.008) and higher non-relapse mortality rates (HR 2.79; 95%CI 1.14-6.80; P = 0.024) at 180 days. Furthermore, univariate analysis showed that a higher CRP to Plt ratio was significantly associated with a higher incidence of sinusoidal obstructive syndrome (P < 0.001) and bloodstream infection (P = 0.027). An external validation test confirmed the significance of the CRP to Plt ratio for these outcomes. CONCLUSION: The multicenter prospective observational study successfully identified significant biomarkers in patients with hematologic malignancies who received HCT. In particular, CRP to Plt ratio was identified as a novel and useful biomarker for predicting transplant outcomes. Further investigations are needed to validate the novel markers, analysis of the pathophysiology, and application to treatment settings other than HCT.

Lenalidomide treatment for recurrent adult T-cell leukemia/lymphoma after allogeneic hematopoietic cell transplantation.

Patients with recurrent adult T-cell leukemia/lymphoma (ATL) after allogeneic hematopoietic cell transplantation (allo-HCT) have a dismal prognosis. We retrospectively evaluated the safety and efficacy of lenalidomide (LEN) in 11 consecutive patients with recurrent ATL after allo-HCT. The median time from allo-HCT to ATL recurrence was 111 days (range, 20-1476), and that from allo-HCT to the initiation of LEN was 162 days (range, 43-1560). The median initial daily dose of LEN was 10 mg (range, 5-25), and the median duration of LEN treatment was 37 days (range, 3-1078). Three patients (27%) achieved complete response and two (18%) achieved partial response (PR). The rates of complete or PR according to the involved site were 57% for skin and 50% for nodal or extranodal lesions. With a median follow-up of 1033 days (range, 601-1465) among survivors, the 1-year probability of overall survival (OS) after ATL recurrence was 55%. Grade ≥3 toxicities included cytopenia (n = 4), superficial vein thrombosis (n = 1), and deep vein thrombosis (n = 1). Graft-versus-host disease (GVHD) newly developed in five patients (45%) and worsened in four patients (36%). The median duration from the initiation of LEN to GVHD onset or worsening was 5 days (range, 1-9). GVHD was manageable in all patients. Seven patients received mogamulizumab (MOG) for recurrent ATL before LEN treatment. The overall response rates to LEN were 57% in patients who had previously received MOG and 25% in those who had not. The 1-year probabilities of OS after recurrent ATL were 71% in patients who had previously received MOG and 25% in those who had not. Although cytopenia and GVHD are common among patients with recurrent ATL after allo-HCT, LEN may improve survival. Administering MOG before LEN may augment treatment efficacy in the allo-HCT population.

Poor outcome of allogeneic transplantation for therapy-related acute myeloid leukemia induced by prior chemoradiotherapy.

Therapy-related acute myeloid leukemia (t-AML) is a therapeutic challenge as a late complication of chemotherapy (CHT) and/or radiotherapy (RT) for primary malignancy. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) presents itself as a curative approach. To establish the optimal allo-HSCT strategy for t-AML, we evaluated the relationship between characteristics of primary malignancy and allo-HSCT outcomes. Patients with t-AML or de novo acute myeloid leukemia (AML) who underwent first allo-HSCT in Japan from 2011 to 2018 were identified using a nationwide database. The detailed background of t-AML was obtained by additional questionnaires. Multivariate analysis and propensity score matching (PSM) analysis were performed to detect the prognostic factors associated with t-AML and compare outcomes with de novo AML. We analyzed 285 t-AML and 6761 de novo AML patients. In patients with t-AML, receiving both CHT and RT for primary malignancy was an independent poor-risk factor for relapse and overall survival (OS) (hazard ratio (HR) 1.62; p = 0.029 and HR 1.65; p = 0.009, reference: CHT alone group), whereas other primary malignancy-related factors had no effect on the outcome. Compared to the CHT alone group, complex karyotypes were significantly increased in the CHT + RT group (86.1% vs. 57.5%, p = 0.007). In the PSM cohort, t-AML patients with prior CHT and RT had significantly worse 3-year OS than those with de novo AML (25.2% and 42.7%; p = 0.009). Our results suggest that prior CHT and RT for primary malignancy may be associated with increased relapse and worse OS of allo-HSCT in t-AML.

[A Case of Sigmoid Colon Cancer with Liver Metastasis and Gastric Infiltration for Which Ileus Surgery Was the Impetus for Surgery].

The case is a woman in her 60s. Sigmoid colon cancer surgery, liver metastasis surgery, and adjuvant chemotherapy were performed at another hospital 2 years ago. Later, she developed a metastasis in her liver and was recommended surgery, but she refused treatment and was transferred. Her liver metastasis had invaded the stomach and formed a giant gastric ulcer. This time she had an adhesive ileus and underwent laparoscopic surgery at our hospital. At that time, we observed the state of liver metastasis and gastric infiltration by laparoscopy, so we thought that palliative surgery was possible and recommended it. Although she initially refused treatment, the relative ease with which her ileus surgery was performed encouraged her to undergo palliative surgery. Laparoscopic-assisted gastrectomy and partial hepatectomy were performed, and she was discharged on hospital day 13 after surgery. She subsequently developed liver metastases and died 8 months after palliative surgery, although she was able to eat and maintain her ADL until the end of life. By staying close to the patient, we were able to lead the patient from refusal of surgery to palliative surgery, and we felt that we were able to make the patient reach a favorable end.

Do 'cheese factory-specific' mites (Acari: Astigmata) exist in the cheese-ripening cabinet?

To determine whether the mites used in the ripening process of traditional cheeses are genetically unique to cheese factories, we investigated mites from three types of traditional cheeses, that use mites in the ripening process: 'Würchwitzer Milbenkäse' from Germany and 'Mimolette' and 'Artisou' from France. In addition, traditional ripened cheeses were purchased from cheese specialty stores in France (Mimolette) and Japan ('Laguiole' from France) as well as stores in temporary markets in France ('Salers' and 'Cantal vieux') and the mites obtained from those cheeses were analyzed in this study. Partial sequences of the 28S rRNA gene (28S) were determined and used to reconstruct a phylogenetic tree. Tyrolichus casei, the dominant cheese mite species from the ripening cabinets of three traditional cheese producers and two cheese specialty stores in France and Japan, had identical partial 28S sequences. All specimens from Cantal vieux from a store in the temporary market in France had an identical sequence with Acarus siro and Acarus immobilis in the determined region of the 28S sequences. Mite individuals from Salers from a store in the temporary markets in France shared the same haplotype as Acotyledon paradoxa. For the T. casei individuals from five different localities (19 individuals in total), the nuclear loci were obtained using MIG-seq. More than several thousand genomic regions are amplified simultaneously by multiplex PCR, and targeting regions surrounded by inter-simple sequence repeats (ISSRs) in the genome were sequenced using the MiSeq system (Illumina). SNPs extracted from this genome-wide analysis showed that no genetic structure existed in the populations from any region. Among the five samples from the three regions, which were more than 500 km apart and from completely different environments, the mites had no geographic bias, but all mite individuals were genetically nearly identical. Thus, we found no evidence to support the existence of 'cheese factory-specific' T. casei mites, at least in terms of genetic analysis.

Outcomes of hematopoietic cell transplantation for transformed follicular lymphoma.

This study characterized the outcomes of patients who underwent hematopoietic cell transplantation (HCT) for transformed follicular lymphoma (tFL), and clarified the association of low-dose anti-thymocyte globulin use with outcomes after allogeneic HCT. The retrospective study cohort included 74 consecutive patients who underwent autologous (n = 23) or allogeneic (n = 51) HCT at our center from 2000 to 2017. Compared with the allogeneic HCT group, the autologous HCT group underwent fewer systemic regimens before HCT (median 2 vs. 5, p < 0.001) and were more likely to have chemosensitive disease at HCT (100% vs. 82%, p = 0.05), while age, sex and HCT-specific comorbidity index were similar between the two groups. With a median follow-up of 5.8 years among survivors, the 5-year probability of progression-free survival was 64% after autologous HCT and 55% after allogeneic HCT (p = 0.21). The 5-year cumulative incidence of non-relapse mortality was 0% after autologous HCT and 9.5% after allogeneic HCT (p = 0.062). The 5-year cumulative incidence of disease progression was similar between autologous and allogeneic HCT (36% vs. 36%, respectively, p = 0.88). In the allogeneic HCT group, the use of low-dose anti-thymocyte globulin was associated with a lower incidence of severe acute GVHD but not with an increased risk of mortality or disease progression. More than half of patients with early phase chemosensitive tFL and approximately half of those with advanced-phase tFL achieved long-term progression-free survival with autologous and allogeneic HCT, respectively. Disease progression was the major cause of treatment failure after both types of HCT. Further strategies are needed to reduce the risk of disease progression.

Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Myelodysplastic/Myeloproliferative Neoplasms-Unclassifiable: A Retrospective Nationwide Study of the Japan Society for Hematopoietic Cell Transplantation.

To date, there are no data focusing on outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U). This study aimed to evaluate outcomes and prognostic factors in patients with MDS/MPN-U after allo-HSCT using Japanese nationwide registry data. The primary endpoint was 3-year overall survival (OS); secondary endpoints included the cumulative incidence of relapse and nonrelapse mortality (NRM). We evaluated the prognostic factors for 3-year OS by univariate analysis using the log-rank test. In our cohort of 86 patients with MDS/MPN-U, we found a 3-year OS of 48.5%, cumulative incidence of relapse of 23.7%, and NRM of 26.3%. The 3-year OS was significantly worse in patients age ≥50 years compared with those age <50 years (38.1% versus 65.0%; P = .049) and in patients with disease progression compared with those without disease progression (28.4% versus 57.2%; P = .042). Our results suggest that allo-HSCT may offer a curative option for patients with MDS/MPN-U, and that age and disease status could be important indicators in helping clinicians determine treatment options for these patients.

Outcome and Risk Factors for Therapy-Related Myeloid Neoplasms Treated with Allogeneic Stem Cell Transplantation in Japan.

This study aimed to investigate allogeneic hematopoietic cell transplantation (HCT) outcomes and risk factors in adult patients with therapy-related myeloid neoplasm (t-MN) using Japanese registry data. Between 2002 and 2012, a total 12,169 adult patients underwent HCT for acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML). Of these, 565 with t-MN were identified. The median patient age was 54 years (range, 16 to 80 years). Three hundred and ninety-eight patients had AML, 154 had MDS, and 13 had CMML. Lymphoma and breast cancer were the major previous malignancies. Favorable karyotypes were detected in 84 patients, and poor karyotypes were identified in 235. Two-thirds (66%) of the patients were in nonremission at HCT. Overall survival at 3 years in patients with t-MN was 31% (95% confidence interval [CI], 27% to 35%), equivalent to that in those with secondary MN (32%; 95% CI, 30% to 34%), and 44% in the de novo cohort (95% CI, 43% to 45%). The cumulative incidence of relapse and nonrelapse mortality at 3 years was 40% and 33%, respectively. The outcomes of HCT for t-MN in Japan were comparable to those in large-scale studies in Europe and the United States.

Conditioning Intensity for Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Patients with Poor-Prognosis Cytogenetics in First Complete Remission.

The optimal intensity of conditioning regimen may be dependent on not only age and comorbidities but also disease characteristics and risk of relapse after allogeneic hematopoietic cell transplantation (HCT). We, therefore, analyzed the transplant outcomes of 840 adult patients with cytogenetically poor-risk acute myeloid leukemia (AML) in first complete remission (CR1) who received first allogeneic HCT with either myeloablative conditioning (MAC; n = 652) or reduced-intensity conditioning (RIC; n = 188) between 2006 and 2017. The median age at HCT was 50.5 years (range: 16 to 77 years). The multivariate analysis showed that patients receiving MAC had a significantly higher overall survival and lower leukemia-related mortality than those receiving RIC (P = .011 and P = .025, respectively). In the subgroup analysis, these results applied to patients aged 16 to 59 years, with HCT-comorbidity index scores ≥3, and with cytogenetic remission. Among MAC regimens, there was a trend for worse survival and nonrelapse mortality with the busulfan/fludarabine-based regimen compared with the total body irradiation (TBI) ≥8 Gy-based regimen (P = .082 and P = .062, respectively), whereas the busulfan/cyclophosphamide-based regimen and the fludarabine/melphalan-based regimen had similar outcomes with the TBI-based regimen. These data suggest that MAC is preferable to RIC for patients with cytogenetically poor-risk AML undergoing allogeneic HCT in CR1.

[Multiple Cysts Formation in Pulmonary Light Chain Deposition Disease(LCDD)-A Case Report].

AIM: To review the clinical features of the patient with cystic pulmonary light chain deposition disease(LCDD)and record high-resolution CT and histopathological findings. PATIENT: A 60-year-old woman who diagnosed multiple myeloma was admitted. There were diffuse proliferation of plasma cells by the bone marrow puncture that she received. And multiple cystic pulmonary tumors found in CT. We analyzed the method and result of the diagnosis. CT showed multiple cystic pulmonary tumors in the both lung which vessels traversing the cysts with thin wall ranged 5 to 30 millimeters. There were no abnormality in the heart, kidney and liver. Right upper lobe wedge resection was performed via video-assisted thoracic surgery( VATS)to establish a definitive diagnosis. Thoracoscopic findings revealed multiple white oval formed tumors in the visceral pleura. Histological HE staining findings of the surgical specimen revealed amyloid-like acidophilic material, and the immunohistochemical Congo red staining revealed monoclonal IgG with a kappa component. According to the above results these tumors had a diagnosis of pulmonary LCDD. CONCLUSION: VATS was effective to diagnose pulmonary LCDD in multiple cysts formation.

Risk Stratification and Prognosticators of Acute Myeloid Leukemia with Myelodysplasia-Related Changes in Patients Undergoing Allogeneic Stem Cell Transplantation: A Retrospective Study of the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation.

Although the prognosis of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is worse than that of AML not otherwise specified (AML-NOS), transplantation outcomes and prognosticators of AML-MRC patients undergoing allogeneic stem cell transplantation (allo-SCT) remain unclear. Transplantation outcomes of AML-MRC (n = 4091) were compared with those of AML-NOS (n = 3964) in patients who underwent allo-SCT between 2003 and 2016 using a nationwide registration database. The 3-year overall survival (OS; 35.5% versus 50.6%) was lower and the relapse (42.3% versus 32.1%) and nonrelapse mortality (26.3% versus 22.0%) rates were higher in the AML-MRC group than in the AML-NOS group. Based on the hierarchical AML-MRC classification, myelodysplasia as the sole criterion was associated with better OS compared with AML-NOS, whereas monosomal or complex karyotype and -5/del(5q) were associated with poor OS. A history of myelodysplastic syndrome and -7/del(7q) did not affect OS. Accordingly, AML-MRC with complex karyotype or -5/del(5q) and that with monosomal karyotype were classified as intermediate and high risks, respectively, whereas the remaining cases were classified as low risk. The 3-year OS rates were 50.7%, 36.9%, and 13.8% in the low-, intermediate-, and high-risk groups, respectively (P < .001). Risk classification, older age, and low performance status score were significant risk factors for survival in AML-MRC, independently of the disease status. Grades I to II acute graft-versus-host disease significantly reduced the 3-year relapse (24.7% versus 31.6%), leading to better survival (hazard ratio, .64). Our prognostic risk stratification can potentially aid in elucidating the diverse transplantation outcomes in patients with AML-MRC.

Increased opportunity for prolonged survival after allogeneic hematopoietic stem cell transplantation in patients aged 60-69 years with myelodysplastic syndrome.

We conducted a nationwide retrospective study to evaluate the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 651 patients aged 60-69 years with de novo myelodysplastic syndrome (MDS). We divided patients into two groups: 152 and 499 patients with an early and advanced disease status, respectively. The 3-year overall survival (OS) rate of patients with an early disease status was 45.9% (95% confidence interval [CI], 37.0 to 54.2%). A multivariate analysis revealed five adverse factors for OS: performance status (PS) 2-4 (hazard ratio [HR] 4.48; P < .001), poor cytogenetic risk group (HR 1.83; P = .041), male recipient (HR 2.58; P = .003), use of HLA-mismatched related grafts (HR 4.75; P = .003), and unrelated cord blood (HR 2.47; P = .023). The 3-year OS rate of patients with an advanced disease status was 37.2% (95% CI 32.4 to 41.9%). Five factors correlated with worse OS: PS 2-4 (HR 1.72; P = .003), poor cytogenetic risk group (HR 1.49; P = .003), use of HLA-mismatched related grafts (HR 1.96; P = .015), unrelated cord blood (HR 2.05; P < .001), and the high number of red blood cell transfusions before transplantation (HR 1.85; P = .018). The present results revealed the more frequent utilization of allo-HSCT for MDS patients aged 60-69 years, which increases the curative potential.

Allogeneic hematopoietic cell transplantation for patients with a history of multiple relapses of acute myeloid leukemia.

The prognosis of patients with acute myeloid leukemia (AML) is dismal after experiencing multiple relapses. This study retrospectively analyzed outcomes of allogeneic hematopoietic cell transplantation (HCT) for 192 adults with AML in third or subsequent complete remission (CR3+), 300 in second relapse (REL2), and 50 in third or subsequent relapse (REL3+) who were enrolled in a Japanese nationwide transplantation registry. The study population included patients undergoing umbilical cord blood transplantation, but not those undergoing haploidentical HCT. Patients transplanted in CR3+ had better survival than those transplanted in REL2 and REL3+ (48%, 21%, and 12% at 4 years; P < 0.001), and this was due to a reduction in post-transplant relapse (23%, 57%, and 52%; P < 0.001). The corresponding cumulative incidence of non-relapse mortality was 33%, 26%, and 36% (P = 0.022). Multivariate analysis revealed significantly lower relapse and overall mortality for those in CR3+ and significantly lower non-relapse mortality for those in REL2. Hazard ratios (95% confidence intervals) for overall mortality were 2.02 (1.56-2.64) for REL2+ versus CR3+ (P < 0.001) and 2.12 (1.40-3.19) for REL3+ versus CR3+ (P < 0.001). Our analysis demonstrates the curative potential of allogeneic HCT for patients with a history of multiple AML relapses and suggests the potential benefits and risks of reinduction attempt before transplantation, highlighting the need for an individualized approach in determining whether to give reinduction therapy in this setting.

Development of specific chemiluminescent immunoassays for three subtypes of vitellogenin in grey mullet (Mugil cephalus).

Chemiluminescent immunoassays (CLIAs) were developed for each of three subtypes of vitellogenin (VtgAa, VtgAb and VtgC) in grey mullet, primarily for use in monitoring estrogenic pollution of the environment. The working range of VtgAa-CLIA and VtgAb-CLIA was from 0.975 to 1,000 ng/ml, while that of VtgC-CLIA was from 0.487 to 1,000 ng/ml. Each CLIA appeared to be specific to the targeted Vtg subtype. Intra- and inter-assay coefficients of variation in the developed CLIAs were lower than 10%. In male serum, VtgAa, VtgAb and VtgC were detected in ranges from 0.01 to 0.38, 0.02 to 1.01, and 0.01 to 3.12 µg/ml, respectively, during various sampling periods. In vitellogenic females (October), serum VtgAb levels (1,192.05 ±â€¯237.81 µg/ml) were significantly higher than levels of the other two Vtg subtypes (120.82 ±â€¯30.42 and 119.23 ±â€¯16.95 µg/ml for VtgAa and VtgC, respectively). When immature mullet were fed diets containing 17α-ethinylestradiol (EE2) at three different doses (0.4, 40 and 4,000 ng/g body weight), all Vtg subtypes were induced by 40 ng/g and 4,000 ng/g EE2. The VtgC (610.30 ±â€¯150.18 µg/ml) was most highly expressed among the three Vtgs in fish fed 40 ng/g EE2, while VtgAb (33.25 ±â€¯13.58 mg/ml) was highest in expression in fish fed 4,000 ng/g EE2. The present study provided practical subtype-specific Vtg assays for the first time in grey mullet, providing the necessary means to evaluate estrogenic activities in aquatic environments.

[A Case of Systemic Chemotherapy Combined with Molecular Drug Treatment Following Biliary Stent Implantation for Obstructive Jaundice Due to Metastases of Liver Gland Lymph Node after Colorectal Cancer Surgery].

We report a case of systemic chemotherapy after biliary stent placement for obstructive jaundice due to hepatic portal lymph node metastasis after colorectal cancer surgery. The patient was a 40s woman. Laparoscopic anterior resection for rectosigmoidRS cancer was performed. The pathological diagnosis was T3N0M0PUL0R0, pStage Ⅱ according to the 8th edition of colorectal cancer handling regulations. Because multiple liver metastases were observed 8 months after the surgery, partial resection of the posterior region of the liver was performed. Multiple lung metastases were observed 1 year after hepatectomy, but she wantedto undergo follow-up observation. Jaundice was observed 1 year after the diagnosis of lung metastasis, and obstructive jaundice due to hepatic portal lymph node metastasis was diagnosed. Endoscopic retrograde biliary drainage(ERBD)was performed, and a bile duct stent was placed. After improving jaundice, 12 courses of mFOLFOX6 plus cetuximab therapy were performed. Currently, because of the exacerbation of lung metastasis, FOLFIRI plus bevacizumab therapy is being administered. Systemic chemotherapy containing a molecular-targeted drug is being administered in our case, but complications relatedto the biliary stent have not been observed. There are few reports on similar cases, andfollow - up observation with careful attention to long-term safety is necessary.

Prognostic Impact of Donor Source on Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in Adults with Chronic Myelomonocytic Leukemia: A Nationwide Retrospective Analysis in Japan.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapeutic option for patients with chronic myelomonocytic leukemia (CMML). We retrospectively compared the post-transplantation outcomes of 159 patients with CMML who underwent allo-HSCT using 4 types of donor sources: HLA-matched related donor graft, unrelated bone marrow (U-BM), unrelated cord blood (U-CB), and HLA-mismatched related donor graft. The median patient age at allo-HSCT was 54 years (range, 16 to 75 years). In multivariate analyses, the use of HLA-matched related donor grafts correlated with better overall survival than U-BM (hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.21 to 3.48; P = .008), U-CB (HR, 3.80; 95% CI, 2.07 to 6.95; P < .001), or HLA-mismatched related donor grafts (HR, 6.18; 95% CI, 2.70 to 14.15; P < .001). Mortality after the relapse or progression of CMML did not significantly differ among the 4 types of donor source. Transplantation-related mortality was highest in recipients of U-CB (HR, 3.32; 95% CI, 1.33 to 8.26; P = .010). In patients with CMML, allo-HSCT using an alternative donor may contribute to durable remission; however, further improvements in transplantation-related mortality are required for this type of transplantation.

Magnetic Resonance Imaging Diagnosis of Medial Meniscal Ramp Lesions in Patients With Anterior Cruciate Ligament Injuries.

PURPOSE: To prospectively evaluate the sensitivity and specificity of magnetic resonance imaging (MRI) for diagnosing ramp lesions, to compare them between 1.5- and 3-T MRI, and to evaluate whether bone contusion of the posterior lip of the medial tibial plateau was associated with ramp lesions. METHODS: For 155 knees that underwent primary ACL reconstruction, we prospectively examined for ramp lesions and medial meniscal body tears on MRI. MRI diagnosis of ramp lesions required high signal irregularity of the capsular margin or separation in the meniscocapsular junction of the medial meniscus posterior horn on sagittal images. Bone contusion of the posterior lip of the medial tibial plateau was verified in 105 knees with MRI performed within 6 weeks after injury. All ramp lesions were identified by transcondylar observation during surgery. The sensitivity and specificity of MRI for ramp lesions and body tears were measured. Furthermore, we evaluated whether bone contusion of the medial tibial plateau was associated with ramp lesions. The χ-square test was used for statistical analysis. RESULTS: During surgery, ramp lesions were observed in 46 knees and medial meniscal body tears were seen in 35 knees. The sensitivity of MRI for ramp lesions was 71.7% and specificity was 90.5%. The sensitivity for ramp lesions was significantly lower than that for meniscal body tears (94.3%) (P = .01). The sensitivity of 3-T MRI (83.3%) was superior to that of 1.5-T MRI (67.6%), but not significantly different. The incidence of bone contusions was not significantly different among ramp lesions (38.5%), body tears (40.0%), or no tears (30.5%). CONCLUSIONS: The sensitivity of MRI for diagnosing ramp lesions was significantly lower than that for medial meniscal body tears. Bone contusion of the posterior lip of the medial tibial plateau on MRI was not associated with ramp lesions. LEVEL OF EVIDENCE: Level III, comparative trial.

Multiband Imaging CMOS Image Sensor with Multi-Storied Photodiode Structure †.

We developed a multiband imaging CMOS image sensor (CIS) with a multi-storied photodiode structure, which comprises two photodiode (PD) arrays that capture two different images, visible red, green, and blue (RGB) and near infrared (NIR) images at the same time. The sensor enables us to capture a wide variety of multiband images which is not limited to conventional visible RGB images taken with a Bayer filter or to invisible NIR images. Its wiring layers between two PD arrays can have an optically optimized effect by modifying its material and thickness on the bottom PD array. The incident light angle on the bottom PD depends on the thickness and structure of the wiring and bonding layer, and the structure can act as an optical filter. Its wide-range sensitivity and optimized optical filtering structure enable us to create the images of specific bands of light waves in addition to visible RGB images without designated pixels for IR among same pixel arrays without additional optical components. Our sensor will push the envelope of capturing a wide variety of multiband images.

Comparison of Conditioning with Fludarabine/Busulfan and Fludarabine/Melphalan in Allogeneic Transplantation Recipients 50 Years or Older.

The optimal conditioning regimen for elderly patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) remains unclear. We retrospectively analyzed 1607 patients aged 50 years or older with acute myeloid leukemia (AML), acute lymphoblastic leukemia, or myelodysplastic syndrome (MDS) who underwent allo-HCT using fludarabine/busulfan (FB) or fludarabine/melphalan (FM) between 2007 and 2014. We compared the clinical outcomes among FB2 (busulfan at 6.4 mg/kg iv, n = 463), FB4 (busulfan at 12.8 mg/kg iv, n = 721), and FM140 (melphalan at 140 mg/m2, n = 423). The nonrelapse mortality (NRM) rates in the FB4 and FM140 groups were higher than that in the FB2 group (hazard ratio [HR], 1.63 [P < .001]; and HR, 1.71 [P < .001], respectively). Conversely, the relapse rates in the FB4 and FM140 groups were lower than that in the FB2 group (HR, .73 [P = .011]; and HR, .56 [P < .001], respectively). There were no significant differences in overall survival (OS) among the FB2, FB4, and FM140 groups. The 3-year OS in patients with high-risk AML and MDS in the FM140 group (37.0% and 60.2%) were superior to those in the FB2 group (24.4% and 45.5%) and the FB4 group (24.6% and 40.6%) (P = .016 and P = .023), whereas there were no differences in OS in the other patients among the 3 groups. In conclusion, the lower rates of relapse in the FB4 and FM140 groups were largely offset by a worse NRM. However, FM140 might be associated with better OS in patients with high-risk AML and MDS.

Role of reduced-intensity conditioning allogeneic hematopoietic cell transplantation in older patients with de novo acute myeloid leukemia.

Reduced-intensity conditioning (RIC) regimens extend the therapeutic use of allogeneic hematopoietic cell transplantation (HCT) to older patients. The survival trend in 2325 patients aged >50 years presenting with de novo acute myeloid leukemia (AML) who underwent first reduced-intensity HCT (RIC-HCT) was assessed by retrospectively analyzing outcomes between 2000 and 2013. The annual number of RIC-HCTs in Japan was higher in the 2008-2013 period (n = 205/year [1229/6 years]) than in the 2000-2007 period (n = 137/year [1096/8 years]). Overall and disease-free survival were higher in the 2008-2013 period (P < 0.001) because of the improvement in transplant-related mortality (TRM). Survival regarding RIC-HCT for AML has improved over time, with an increased number of RIC-HCTs in patients with a Karnofsky performance status (KPS) ≥80. However, TRM remains high and the relapse rate has not improved over time. Multivariate analyses showed that a KPS ≥80 and complete remission at HCT were associated with less TRM and relapse, and better survival regardless of age ≥65 years. Accurate timing and prospective identification of patients at risk of TRM may aid the development of risk-adapted strategies for RIC-HCT in AML patients regardless of age.