Search

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with genetic alterations. The FMS-like tyrosine kinase 3 (FLT3) gene is frequently mutated in adult de novo AML, with two types of mutations: internal tandem duplication (ITD) and point mutations in the tyrosine kinase domain. This study aimed to investigate the impact of FLT3 inhibitors and hematopoietic cell transplantation (HCT) on survival outcomes in patients with FLT3-ITD AML in a real-world setting. We retrospectively analyzed 139 patients with FLT3-ITD-positive AML between 2012 and 2021. The median age was 63 years. In the propensity score-matched cohort, FLT3 inhibitors improved overall survival (OS) compared with patients treated without FLT3 inhibitors (3-year OS: 33.7% vs. 25.8%, p = 0.021). Patients who underwent HCT had superior outcomes to those without HCT (3-year OS: 45.3% vs. 2.2%, p < 0.0001). The combination of FLT3 inhibitors and HCT resulted in the highest OS and relapse-free survival (RFS) rates (3-year OS: 62.4%; 3-year RFS: 44.4%). Disease status before transplantation did not predict the prognosis, but use of FLT3 inhibitors increased survival in patients without complete remission before HCT. These results demonstrate the clinical impact of FLT3 inhibitors on survival outcomes in patients with FLT3-ITD-positive AML, particularly when combined with HCT. FLT3 inhibitors can improve the prognosis of AML with FLT3 mutations, especially in patients who undergo HCT., Competing Interests: Declarations. Ethical approval: All procedures involving human participants were in accordance with the ethical standards of institutional research committees, national guidelines, and with the Declaration of Helsinki. This study was approved by the institutional review board of Hokkaido University Hospital (#022–0085). Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Information regarding follow-up duration after treatment for newly diagnosed diffuse large B-cell lymphoma (DLBCL) is important. However, a clear endpoint has yet to be established. We enrolled a total of 2,182 patients newly diagnosed with DLBCL between 2008 and 2018. The median age of the patients was 71 years. All patients were treated with rituximab- and anthracycline-based chemotherapies. Each overall survival (OS) was compared with the age- and sex-matched Japanese general population (GP) data. At a median follow-up of 3.4 years, 985 patients experienced an event and 657 patients died. Patients who achieved an event-free survival (EFS) at 36 months (EFS36) had an OS equivalent to that of the matched GP (standard mortality ratio [SMR], 1.17; P=0.1324), whereas those who achieved an EFS24 did not have an OS comparable to that of the matched GP (SMR, 1.26; P=0.0095). Subgroup analysis revealed that relatively old patients (>60 years), male patients, those with limited-stage disease, those with a good performance status, and those with low levels of soluble interleukin 2 receptor already had a comparable life expectancy to the matched GP at an EFS24. In contrast, relatively young patients had a shorter life expectancy than matched GP, even with an EFS36. In conclusion, an EFS36 was shown to be a more suitable endpoint for newly diagnosed DLBCL patients than an EFS24. Of note, younger patients require a longer EFS period than older patients in order to obtain an equivalent life expectancy to the matched GP.

Yezo virus is a novel virus transmitted by tick bites that causes fever with thrombocytopenia. To date, two reports have been published on patients with Yezo virus infection. However, the clinical characteristics of Yezo virus infection remain unclear. A patient who presented with fever, fatigue, headaches, and muscle pain and was admitted to our hospital. The patient had thrombocytopenia, leukopenia, and elevated liver enzyme and serum ferritin levels. The patient was diagnosed with Yezo virus and Borrelia miyamotoi coinfection based on the detection of Yezo virus in a blood sample by polymerase chain reaction and the detection of elevated serum antibody titers to Yezo virus and Borrelia miyamotoi.

IKZF1 deletion is a recurrent genomic alteration in B-cell acute lymphoblastic leukemia (B-ALL) and is divided into dominant-negative (DN) and loss of function (LOF) deletions. The prognostic impact of each deletion has not been fully elucidated. We retrospectively analyzed 117 patients with adult B-ALL including 60 patients with BCR::ABL1-positive B-ALL and 57 patients with BCR::ABL1-negative B-ALL by the fluorescence in situ hybridization (FISH) method for IKZF1 deletion and multiplex PCR for the 4 most common IKZF1 deletions (∆4-7, ∆2-7, ∆2-8, and ∆4-8). Samples, in which IKZF1 deletion was detected by FISH but a specific type of deletion was not identified by the PCR, were categorized as "other." Patients were classified into a DN group that had at least 1 allele of ∆4-7 (n = 23), LOF and other group (n = 40), and wildtype group (n = 54). DN type IKZF1 deletions were found in 33.3% of BCR::ABL1-positive cases and 5.2% of BCR::ABL1-negative cases. LOF and other type IKZF1 deletions were found in 43.4% of BCR::ABL1-positive cases and 24.6% of BCR::ABL1-negative cases. Patients with the DN group showed significantly higher overall survival (OS) than that of the LOF and other and WT groups (P = 0.011). Multivariate analysis including age, WBC counts, complex karyotype, and DN type IKZF1 deletion showed that the DN type of IKZF1 deletion (HR = 0.22, P = 0.013) had a positive impact and age ≥ 65 (HR = 1.92, P = 0.029) had a negative impact on OS. The prognostic impact of IKZF1 deletion depends on the type of deletion and DN type of IKZF1 deletion showed better prognosis in adult B-ALL patients.Clinical trial registration This study was part of a prospective observational study (Hokkaido Leukemia Net, UMIN000048611). It was conducted in compliance with ethical principles based on the Helsinki Declaration and was approved by the institutional review board of Hokkaido University Hospital (#015-0344)., Competing Interests: Declarations. Patient consent statement: Written informed consent was obtained from all individuals included in the study. Conflict of interest: The authors declare no competing interests., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Human T-cell leukemia virus type I (HTLV-1) is a retrovirus known to cause adult T-cell leukemia/lymphoma (ATL). There are few reports on hematopoietic stem cell transplantation (HSCT) for HTLV-1 carriers with diseases other than ATL., Methods: A total of 25,839 patients (24,399 adults and 1440 children) with pre-transplant HTLV-1 serostatus information recorded in the Japanese National Survey Database who had undergone their first HSCT were analyzed. We investigated the overall survival (OS), transplant-related mortality (TRM), and disease-related mortality (DRM) after HSCT in relation to HTLV-1 serologic status., Findings: Three hundred and forty-eight patients were HTLV-1 antibody carriers. The number of HTLV-1 carriers and noncarriers among adult patients who received allogeneic HSCT (allo-HSCT) or autologous HSCT (auto-HSCT) was 237/15,777 and 95/8920, respectively, and was 16/1424 among pediatric patients who received allo-HSCT. No pediatric HTLV-1 carrier recipients undergoing auto-HSCT were identified. There were no significant differences between HTLV-1 carriers and non-carriers regarding stem cell source, disease risk, or HCT-CI score prior to allo-HSCT. Multivariate analysis of OS (P = 0.020) and TRM (P = 0.017) in adult patients showed that HTLV-1 positive status was a significant prognostic factor. In children, TRM was significantly higher (P = 0.019), but OS was not significantly different. In adult patients who underwent auto-HSCT, HTLV-1 positive status was not a significant prognostic factor. In adult allo-HSCT patients, cytomegalovirus reactivation was significantly more common in HTLV-1 carriers (P = 0.001)., Interpretation: HTLV-1 antibody positivity was shown to have a poor prognosis in OS and TRM after allo-HSCT in adult patients and in TRM after allo-HSCT in pediatric patients., Funding: This work was supported in part by the practical research programs of the Japan Agency for Medical Research and Development (AMED) under grant number 17ck0106342h0001., Competing Interests: R.S. has received research grants from Chugai, Kyowa-Kirin, Takeda, Eisai, Shionogi, Ohtsuka, and Taiho, as well as honoraria from Chugai, Kyowa-Kirin, Takeda, Meiji-Seika, Abbvie, Astra Zeneca, Janssen, Ohtsuka, Eisai, Nihon Sin-yaku, Elli Lilly, Amgen, Novartis, Nihon Kayaku, and Sumitomo. Zeneca, Janssen, Ohtsuka, Eisai, Nihon Sin-yaku, Elli Lilly, Amgen, Novartis, Nihon Kayaku, and Sumitomo. Other authors have no conflicts of interest related to this study., (© 2023 The Author(s).)

Objective: Tube feeders are prone to membranous substance formation on the palate, and those with membranous substances have a risk of fever, with the probable involvement of their oral bacteria. However, the palatal microbiota of those with membranous substances has not been elucidated. Therefore, we evaluated the differences in palatal microbiota between tube-fed individuals with and without membranous substances to clarify the microbiota., Materials and Methods: This study included 19 participants aged 65 years who required tube feeding. The participants' characteristics were collected from nursing records and oral examinations. If membranous materials were found on the palate, a specimen was collected. Membranous substances were defined as keratotic degeneration observed under a microscope. Additionally, we performed a comprehensive microbiome analysis by extracting DNA from the samples and performing 16 S rRNA gene sequencing. Finally, we compared the participant demographics and oral microbiota between patients with and without membranous substances., Results: A total of 11 participants had membranous substances associated with "mouth dryness" (p < 0.001) and "constant mouth opening" (p = 0.020). Palatal microbiota differed between those with and without membranous substances. Among the bacteria with a relative abundance greater than 1.0%, the abundance of Streptococcus (p = 0.007), Fusobacterium (p = 0.041), Streptococcus agalactiae (p = 0.009), and Fusobacterium nucleatum subsp. vincentii (p = 0.026) was significantly higher in the membranous substance group than in the non-membranous substance group., Conclusions: The palatal microbiota of individuals undergoing tube feeding differed depending on the presence or absence of membranous substances. Membrane substance formation associated with dry mouth purportedly alters the palatal microbiota. Streptococcus , Fusobacterium , S . agalactiae , and F . nucleatum subsp. vincentii were more abundant in the oral microbiota of patients with membranous substances. Thus, preventing this formation may help in controlling the growth of these microbes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Mutation status of FLT3, NPM1, and CEBPA is used to classify the prognosis of acute myeloid leukemia, but its significance in patients with cytogenetically normal (CN) AML is unclear. We prospectively analyzed these genes in 295 patients with CN-AML and identified 76 (25.8%) FLT3-ITD, 113 (38.3%) NPM1 mutations, and 30 (10.2%) CEBPA biallelic mutations. We found that patients with FLT3-ITD had a poor prognosis at any age, while patients with CEBPA biallelic mutation were younger and had a better prognosis. FLT3-ITD and NPM1 mutations were correlated, and the favorable prognostic impact of being FLT3-ITD negative and NPM1 mutation positive was evident only in patients aged 65 years or more. For CEBPA, 86.7% of the patients with biallelic mutation and 9.1% of patients with the single allele mutation had in-frame mutations in the bZIP domain, which were strongly associated with a favorable prognosis. Multivariate analysis showed that age < 65 years, FLT3-ITD and CEBPA bZIP in-frame mutation were independent prognostic factors. The results suggest that analyzing these gene mutations at diagnosis can inform selection of the optimal intensity of therapy for patients with CN-AML., (© 2023. Japanese Society of Hematology.)

Recent advances in next-generation sequencing (NGS) have enabled the detection of subclinical minute FLT3-ITD. We selected 74 newly diagnosed, cytogenetically normal acute myeloid leukaemia (AML) samples in which FLT3-ITD was not detected by gel electrophoresis. We sequenced them using NGS and found minute FLT3-ITDs in 19 cases. We compared cases with clinically relevant FLT3-ITD (n = 37), cases with minute FLT3-ITD (n = 19) and cases without detectable FLT3-ITD (n = 55). Molecular characteristics (location and length) of minute FLT3-ITD were similar to those of clinically relevant FLT3-ITD. Survival of cases with minute FLT3-ITD was similar to that of cases without detectable FLT3-ITD, whereas the relapse rate within 1 year after onset was significantly higher in cases with minute FLT3-ITD. We followed 18 relapsed samples of cases with clinically FLT3-ITD-negative at diagnosis. Two of 3 cases with minute FLT3-ITD relapsed with progression to clinically relevant FLT3-ITD. Two of 15 cases in which FLT3-ITD was not detected by NGS relapsed with the emergence of minute FLT3-ITD, and one of them showed progression to clinically relevant FLT3-ITD at the second relapse. We revealed the clonal dynamics of subclinical minute FLT3-ITD in clinically FLT3-ITD-negative AML. Minute FLT3-ITD at the initial AML can expand to become a dominant clone at relapse., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Complex karyotype acute myeloid leukemia (CK-AML) has been classified as an adverse-risk subtype. Although a few reports have further classified CK-AML as typical (including monosomy of chromosomes 5, 7 and 17 or deletion of 5q, 7q and/or 17p) or atypical, the clinical features of these subtypes in Japanese patients remain unclear. We retrospectively analyzed a total of 115 patients with CK-AML, including 77 with typical CK-AML and 38 with atypical CK-AML. Median overall survival (OS) was significantly shorter in patients with typical CK-AML than atypical CK-AML (143 days vs. 369 days, P = 0.009). Among patients with typical CK-AML, those with monosomy 17 or deletion of 17p had significantly shorter OS than patients without such abnormalities (105 days vs. 165 days, P = 0.033). TP53 mutations were more predominant in patients with typical CK-AML than in patients with atypical CK-AML (69.7% vs. 32.4%, P < 0.001). Patients with typical CK-AML had a poor prognosis regardless of TP53 mutation status. Among patients with atypical CK-AML, however, prognosis was worse for those with the TP53 mutation than those without the mutation. In conclusion, prognosis is extremely poor for both typical CK-AML and atypical CK-AML with TP53 mutation., (© 2022. Japanese Society of Hematology.)

A 44-year-old woman was admitted to our hospital with a fever, dizziness, and gait disturbance after undergoing allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia followed by graft-versus-host disease. She presented with cerebellar ataxia, nystagmus, and numbness of the lower extremities. Brain magnetic resonance imaging and perfusion scintigraphy showed progressive cerebellar involvement. Cerebrospinal fluid tests showed mildly elevated protein and IgG levels without pleocytosis. Anti-ganglioside antibodies were detected, but their levels did not follow the patient's clinical course. The patient did not respond sufficiently to steroids or other immunotherapies. We herein report the clinical characteristics of this case and a literature review.

Double minute chromosomes (dmin) are small, acentric, and extrachromosomal fragments that frequently mediate oncogene amplification and induce rapid disease progression with poor prognosis, although they are infrequent in myeloid neoplasms. An 81-year-old woman with anemia and thrombocytopenia was admitted to our hospital. Bone marrow examination showed 54.0% of the blasts. She was diagnosed with acute myeloid leukemia (French-American-British classification, M2; World Health Organization classification, acute myeloid leukemia [AML], not otherwise specified, AML with maturation). Chromosomal analysis revealed the presence of 3-45 dmin in the background of 46 and XX in 14 out of 20 metaphases examined. Spectral karyotyping examination demonstrated that the dmins were derived from chromosome 8. Fluorescence in situ hybridization (FISH) targeting the MYC gene demonstrated that dmins contained full-length MYC genes with multiple signals. Finally, she was diagnosed with AML with dmin via MYC amplification and was administered with venetoclax plus azacitidine chemotherapy. After two cycles of the regimen, FISH found no MYC amplification signals, indicating her state being in cytogenetic remission. At present, she has finished four cycles of the regimen and remained in complete remission. Venetoclax plus azacitidine could be an effective regimen for the poor prognosis of AML with dmin through MYC amplification.

Background: From late March through April 2021, we experienced a cluster of patients with COVID-19, named "Cluster K", with rapid severe illness compared with those who were infected before., Methods: Patients with COVID-19 who were enrolled in this study were divided into two groups: 66 patients from November 2020 to March 2021 (group A) and 37 patients whose infection links were traced from Cluster K (group B). The primary outcome was mortality rate, and the secondary outcome was maximal oxygen flow rate as the severity of the disease. Viral genome sequences were compared between the two groups., Results: Mortality rates were 6.1% in group A and 16.2% in group B (odds ratio: 2.97, 95% confidence interval: 0.65-15.38). The patients in group B required high oxygen flow rate (O 2 ≥10 l/min) in the earlier clinical course (P = 0.029). Viral genome sequences revealed five amino acid mutations; of these, four were found on three nonstructural proteins (NSPs): one in nsp3 and nsp15, two in nsp6 (one of them is near the potential sites under positive selective pressure). Another one was on the S protein., Conclusion: This study suggests that mutations in NSPs, especially nsp6, are associated with adverse clinical outcome in patients with COVID-19., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Clinical characteristics, including laboratory parameters, of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant have been limited., Methods: This retrospective case-control study was conducted in a single hospital. Patients with coronavirus disease 2019 (COVID-19) who visited the Asahikawa City Hospital outpatient department as new patients and underwent blood tests were included in this study. We analyzed the data from January 2022 to April 2022 during the Omicron phase and from April 2021 to October 2021 during the Delta phase. Patients who were treated at other hospitals after visiting our hospital were excluded. All blood tests were performed before treatment for COVID-19 was initiated. Demographic information, laboratory data, and clinical courses were extracted from electronic medical records. We matched the two groups by age and comorbidities and compared their characteristics. We also analyzed factors associated with pneumonia in the Omicron phase., Results: A total of 151 Omicron patients and 167 delta patients were analyzed in this study. The mean age, rate of comorbidities, and vaccination were significantly higher in the Omicron group. The number of patients with pneumonia or those requiring oxygen, admissions, or both was significantly lower in the Omicron group. Lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin, aspartate aminotransferase (AST), and neutrophil-to-lymphocyte ratio (NLR) levels were significantly lower in the Omicron group. Compared with the mild symptom and pneumonia groups in the Omicron group, older age, higher body mass index (BMI), higher non-vaccination, higher LDH, and higher CRP levels were associated with the pneumonia group., Conclusion: The Omicron variant is associated with a reduction in hospitalization and the risk of pneumonia compared to the delta variant in a real-life clinical setting. In the Omicron variant, the risk of pneumonia is related to high-risk factors, laboratory data such as LDH and CRP levels, and no vaccination., Competing Interests: The authors declare there are no competing interests., (©2022 Suzuki et al.)

Purpose: To clarify the effect of mouth-closed tooth brushing on the suppression of droplet generation in comparison with ordinary (mouth-open) tooth brushing and to investigate the difference in plaque removal efficacy between mouth-open and mouth-closed tooth brushing., Methods: Fourteen adults participated in the study. The labial/buccal, lingual, and occlusal surfaces of each sextant were brushed with the mouth open and closed, and a high-sensitivity camera and a high-power light source were used to measure the number of generated droplets. The plaque removal efficacy of each type of tooth brushing was evaluated according to the O'Leary Plaque Control Record., Results: Significantly more droplets were generated by mouth-open brushing than by mouth-closed brushing. The number of droplets was highest when the lingual surfaces of the upper anterior sextants were brushed with the mouth open. In mouth-closed brushing, almost no droplets were observed from any region. The plaque removal rate with each type of brushing did not differ significantly among any regions except the lingual surfaces of the upper left sextant., Conclusion: Mouth-closed tooth brushing almost completely suppressed droplet generation and did not reduce the plaque removal efficacy. Therefore, mouth-closed tooth brushing is beneficial as an oral hygiene method during coronavirus disease 2019 outbreaks.

Acute myeloid leukemia (AML) patients older than 65 years have a poor prognosis. Recently, CAR (C-reactive-protein/albumin ratio) has been actively reported as a prognostic index reflecting the nutritional and inflammatory status of elderly patients with solid tumors, but the usefulness of this index as a prognostic indicator in transplant-ineligible elderly AML patients has not been investigated. We studied genetic alterations and CARs in 188 newly diagnosed AML patients aged 65 years or older who were treated in a multicenter setting and had treated without HSCT. Both NCCN 2017 risk group, reflecting the genetic component of the tumor, and CAR, reflecting the inflammatory and nutritional status of the patient, successfully stratified the overall survival (OS) of the patients (2-year OS; CAR low vs high, 42.3% vs 17.8%, P < 0.001). Furthermore, in multivariate analysis, NCCN 2017 poor group and high CAR were extracted as independent poor prognostic factors predicting 2-year OS in the current study. We found, for the first time, that CAR at diagnosis predicted the prognosis of elderly patients with newly diagnosed AML treated without HSCT., (© 2022. The Author(s).)

Background: Recent data from clinical trials suggest that antibody cocktail therapy, which combined casirivimab and imdevimab, is linked to the reduction of the risk of hospitalization or death among high-risk patients with COVID-19. However, it remains unclear how effective the therapy is in a real-life clinical practice., Methods: We retrospectively analyzed patients with COVID-19 with high-risk factors who underwent the antibody cocktail therapy, compared with those who were not given the cocktail therapy while being isolated in nonmedical facilities during the same period., Results: Data from 55 patients who received the antibody cocktail therapy and 53 patients with initial isolation in nonmedical facilities were analyzed. A total of 22 (41.5 %) of 53 patients staying in isolation facilities were eventually hospitalized and received medical interventions. By contrast, 13 (23.6 %) of 55 patients who received the antibody cocktail therapy subsequently underwent further medical interventions. In multivariate analysis, the antibody cocktail therapy significantly reduced the need for further medical interventions by 70 % compared with isolation (odds ratio=0.30, 95%CI [0.10-0.87], p=0.027). Patients with percutaneous oxygen saturation 96% or higher were significantly favoured for the therapy and had an advantage., Conclusion: The results of this study indicate that the antibody cocktail therapy is associated with reducing burden on hospitals during the COVID-19 pandemic., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In this real-world clinical study, in which we determined eligibility for allogenic hematopoietic stem cell transplantation by prognostic factors and minimal residual disease status, we retrospectively evaluated cytogenetic, genetic, and clinical features in 96 patients with core-binding factor acute myeloid leukemia (CBF-AML) including 62 patients with RUNX1/RUNX1T1 and 34 patients with CBFβ/MYH11. Multivariate analyses for 5-year overall survival (OS) in CBF-AML patients revealed that age of 50 years or older (HR: 3.46, 95% CI 1.47-8.11, P = 0.004) and receiving 2 or more induction cycles (HR: 3.55, 95% CI 1.57-8.05, P = 0.002) were independently associated with worse OS and that loss of sex chromosome (LOS) was independently associated with better OS (HR: 0.09, 95% CI 0.01-0.71, P = 0.022). At the time of complete remission, all 21 karyotyped patients with LOS had a normal karyotype. Furthermore, in all 9 patients with LOS who had a mosaic of metaphase cells with and without t(8;21) or inv(16), the metaphase cells without t(8;21)/inv(16) showed a normal karyotype. These results proved that LOS was not age-related and physiological, but rather a neoplastic chromosomal abnormality., (© 2021. Japanese Society of Hematology.)

Several investigators have reported that oral membranous and pharyngeal viscous deposits developed in bedridden elderly persons requiring nursing care without oral intake. Therefore, this study aimed to clarify the origin of viscous deposits on the pharyngeal mucosa based on characteristics of salivary and tracheal secretory mucin. The participants were 35 elderly people who required nursing care. All 46 collected specimens, including 30 intraoral and 16 pharyngeal specimens, were stained against specific mucins secreted from the respiratory tract and saliva gland using antibodies anti-MUC2 and anti-MUC7, respectively. Out of 35 participants, the intraoral membranous deposits and deposits on the pharyngeal mucosa developed in 17 (48.6%) and 10 persons (28.6%), respectively. The pharyngeal deposits developed in 58.8% of participants who developed intraoral deposits. All pathological specimens shared microscopic findings of various combinations of eosinophilic lamellar structure and a pale-basophilic amorphous substance. Immunohistochemically, both the 30 oral and the 16 pharyngeal specimens obtained from 17 participants were consistently positive for MUC7 but negative for MUC2. In conclusion, we clarified that the mucoid component of both oral and pharyngeal deposits comprised MUC7 salivary mucin, which revealed that both deposits originated from the oral cavity. This result strongly suggests that oral care is intimately related to oral and pharyngeal conditions., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Bendamustine and rituximab (BR) are widely used in patients with follicular lymphoma (FL) previously treated with conventional immunochemotherapy, but the role of consolidation radioimmunotherapy in these patients is unknown. This study evaluated the efficacy and safety of consolidation with 90 Yttrium-ibritumomab tiuxetan ( 90 Y-IT) after re-induction therapy with BR in patients with previously treated FL. This study included adult patients with relapsed FL who had undergone one or two prior therapies. Re-induction therapy with BR was administered every 4 weeks up to 4-6 cycles. If patients achieved at least partial response, 90 Y-IT was administered as consolidation therapy. The primary endpoint was 2-year progression-free survival (PFS) after consolidation. A total of 24 FL patients (median age 60 years) who had undergone one (n = 17) or two (n = 7) prior treatments received BR. After BR therapy, 22 patients proceeded to consolidation with 90 Y-IT, resulting in an overall 88% response rate to the protocol treatment. Within a median observation period of 46.8 months, the estimated 2-year PFS rate after the consolidation among the 22 patients receiving 90 Y-IT was 59% (95% confidence interval [CI], 38%-77%). Patients whose remission after previous treatment had lasted ≥2 years had a significantly higher 2-year PFS rate than patients whose remission after previous treatment had been <2 years (68% vs. 33%, Wilcoxon p = 0.0211). Major adverse events during the protocol treatment and within 2 years after the consolidation were hematological toxicities, but they were generally acceptable. Consequently, the estimated 2-year overall survival after the consolidation was 95% (95% CI, 74%-99%). In conclusion, in a subset of patients with previously treated FL, 90 Y-IT consolidation after BR re-induction conferred a durable remission, indicating that consolidation therapy using 90 Y-IT may be a novel therapeutic option for patients with relapsed FL (UMIN000008793)., (© 2020 John Wiley & Sons Ltd.)

Elderly patients aged 65 or older with acute myeloid leukemia (AML) have poor prognosis. The risk stratification based on genetic alteration has been proposed in national comprehensive cancer network (NCCN) guideline but its efficacy was not well verified especially in real world elderly patients. The nutritional status assessment using controlling nutritional status (CONUT) score is a prognostic biomarker in elderly patients with solid tumors but was not examined in elderly AML patients. We performed prospective analysis of genetic alterations of 174 patients aged 65 or older with newly diagnosed AML treated without hematopoietic stem cell transplantation (HSCT) and developed simplified CONUT (sCONUT) score by eliminating total lymphocyte count from the items to adapt AML patients. In this cohort, both the NCCN 2017 risk group and sCONUT score successfully stratified the overall survival (OS) of the elderly patients. A multivariable analysis demonstrated that adverse group in NCCN 2017 and high sCONUT score were independently associated with poor 2-year OS. Both risk stratification based on NCCN 2017 and sCONUT score predict prognosis in the elderly patients with newly diagnosed AML.

Introduction: Bendamustine has been reported to be effective against low-grade B-cell lymphoma. We examined the effect of bendamustine on the lymphocyte-monocyte ratio (LMR) in low-grade B-cell lymphoma patients., Methods: We retrospectively reviewed 127 cases of first line or relapse/refractory low-grade B-cell lymphoma in three individual institutions (Asahikawa Municipal Hospital, Aiiku Hospital, and Hakodate Municipal Hospital). Only patients who had received at least three courses of bendamustine therapy were selected; the LMR was evaluated at starting the initial course of bendamustine therapy. Time to next treatment (TTNT) was used to ascertain the efficacy of bendamustine therapy., Results: Follicular lymphoma (FL), at 68.5% (87/127), is the most common histological subtype of low-grade B-cell lymphoma. The receiver operating characteristic (ROC) curve for the LMR showed a cutoff value of 2.0, and 33 cases (26.0%) had an LMR ≤2.0. Cases with LMR ≤2.0 had a significantly earlier progression than those with LMR > 2.0, based on the TTNT (P = .0007). Additionally, LMR ≤2.0 indicates earlier progression in TTNT when comparing only FL and low-grade B-cell lymphoma cases without FL (P = .007, 0.002). For multivariate analysis, the factors associated with an LMR ≤2.0 (HR, 2.741; 95% CI, 1.4330-5.245; P = .002) were considered as early progression factors with regard to the TTNT., Conclusion: Lymphocyte-monocyte ratio effectively predicts the efficacy of bendamustine therapy for low-grade B-cell lymphoma, particularly FL; its application may improve treatment strategies for this disease., (© 2020 John Wiley & Sons Ltd.)