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Objectives: Patients with myeloproliferative neoplasms (MPNs) are at higher risk of developing secondary malignancies. In this study, we focused on patients with MPNs that complicated lymphoid neoplasms. To analyze the real-world status of lymphoid neoplasm treatment in patients with pre-existing MPNs in Japan, we conducted a multicenter retrospective study., Methods: Questionnaires were sent to collect the data on patients who were first diagnosed with either polycythemia vera, essential thrombocythemia or myelofibrosis and who later were complicated with lymphoid neoplasms defined as malignant lymphoma, multiple myeloma, or chronic lymphocytic leukemia/small cell lymphoma., Results: Twenty-four patients with MPNs complicated by lymphoid neoplasms were enrolled (polycythemia vera, n  = 8; essential thrombocythemia, n  = 14; and primary myelofibrosis, n  = 2). Among these, diffuse large B-cell lymphoma (DLBCL) was the most frequently observed ( n  = 13, 54.1%). Twelve (92.3%) of the patients with DLBCL received conventional chemotherapy. Among these 12 patients, regarding cytoreductive therapy for MPNs, 8 patients stopped treatment, one continued treatment, and two received a reduced dose. Consequently, most patients were able to receive conventional chemotherapy for DLBCL with a slightly higher dose of granulocyte colony-stimulating factor support than usual without worse outcomes. All 3 patients with multiple myeloma received a standard dose of chemotherapy., Conclusion: Our data indicate that if aggressive lymphoid neoplasms develop during the course of treatment in patients with MPNs, it is acceptable to prioritize chemotherapy for lymphoma.

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.

Background: Helicobacter pylori ( H. pylori ) eradication treatment for primary gastric mucosa-associated lymphoid tissue (MALT) lymphoma has already been established. However, t (11;18) (q21;q21)/ API2-MALT1 translocation-positive lesions are a type of primary gastric MALT lymphoma in which a response to eradication treatment is difficult to achieve. In addition, trisomy 18 may be associated with diffuse large B-cell lymphoma (DLBCL) transformation of gastric MALT lymphoma., Case Summary: A 66-year-old man was diagnosed with MALT lymphoma in the ascending colon by colonoscopy and biopsy. Two years later, esophagogastroduodenoscopy revealed chronic atrophic gastritis that was positive for H. pylori , and eradication treatment was administered. Two years and nine months later (at the age of 70), a new ulcerative lesion suggestive of MALT lymphoma appeared in the gastric body, and six months later, a similar lesion was also found in the fundus. One year later (4 years and 3 months after H. pylori eradication), at the age of 72, the lesion in the gastric body had become deeper and had propagated. A biopsy revealed a pathological diagnosis of DLBCL. Both MALT lymphoma lesions in the ascending colon and DLBCL lesions in the stomach were positive for the t (11;18) (q21;q21)/ API2-MALT1 translocation, and trisomy 18q21 was also detected. After 6 courses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy, all of the above lesions disappeared [complete remission (CR)], and CR has been maintained for more than 3 years. In addition, both the colonic and gastric lesions were proven to have the same clonality., Conclusion: Because the patient had a MALT1 translocation with trisomy 18q21, it was thought that this gastric MALT lymphoma developed independently of H. pylori infection and progressed., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

It has been suggested that the effect of coronavirus disease 2019 (COVID-19) booster vaccination in patients with B-cell non-Hodgkin's lymphoma (B-NHL) is inferior to that in healthy individuals. However, differences according to histological subtype or treatment status are unclear. In addition, there has been less research on patients who subsequently develop breakthrough infections. We investigated the effects of the first COVID-19 booster vaccination for patients with B-NHL and the clinical features of breakthrough infections in the Omicron variant era. In this study, B-NHL was classified into two histological subtypes: aggressive lymphoma and indolent lymphoma. Next, patients were subdivided according to treatment with anticancer drugs at the start of the first vaccination. We also examined the clinical characteristics and outcomes of patients who had breakthrough infections after a booster vaccination. The booster effect of the COVID-19 mRNA vaccine in patients with B-NHL varied considerably depending on treatment status at the initial vaccination. In the patient group at more than 1 year after the last anticancer drug treatment, regardless of the histological subtype, the booster effect was comparable to that in the healthy control group. In contrast, the booster effect was significantly poorer in the other patient groups. However, of the 213 patients who received the booster vaccine, 22 patients (10.3%) were infected with COVID-19, and 18 patients (81.8%) had mild disease; these cases included the patients who remained seronegative. Thus, we believe that booster vaccinations may help in reducing the severity of Omicron variant COVID-19 infection in patients with B-NHL.

Vaccination with a coronavirus disease-2019 (COVID-19) vaccine is an effective public health measure for reducing the risk of infection and severe complications from COVID-19. However, serious hematological complications after COVID-19 vaccination have been reported. Here, we report a case of new-onset hypomegakaryocytic thrombocytopenia (HMT) with the potential for progression to aplastic anemia (AA) that developed in a 46-year-old man 4 days after the fourth mRNA COVID-19 vaccination. Platelet count rapidly decreased after vaccination and white blood cell count declined subsequently. Bone marrow examination immediately after disease onset showed severely hypocellular marrow (cellularity of almost 0%) in the absence of fibrosis, findings that were consistent with AA. Since the severity of pancytopenia did not meet the diagnostic criteria for AA, the patient was diagnosed with HMT that could progress to AA. Treatment with eltrombopag and cyclosporine was started immediately after diagnosis and cytopenia improved. Although it is difficult to determine whether the post-vaccination cytopenia was vaccine induced or accidental because the association was chronological, vaccination with an mRNA-based COVID-19 vaccine may be associated with development of HMT/AA. Therefore, physicians should be aware of this rare, but serious adverse event and promptly provide appropriate treatment., (© 2023. The Author(s).)

Background: Unlike the already established effect of Helicobacter pylori ( H. pylori ) eradication on gastric mucosa-associated lymphoid tissue (MALT) lymphoma, its therapeutic effect on primary gastric diffuse large B-cell lymphoma (DLBCL) is still unclear., Aim: To clarify the efficacy of H. pylori eradication treatment for primary gastric DLBCL., Methods: We reported on 3 new cases, and added them to 3 previously reported cases. We analyzed the usefulness of H. pylori eradication treatment for gastric DLBCL for a total of 6 cases at our center., Results: Of the 6 patients (27-90 years old, 3 males and 3 females), all 3 patients with single lesions (one transformed from MALT lymphoma) achieved complete remission (CR) after H. pylori eradication. Regarding the 2 newly reported cases, CR was maintained for more than 6 years with eradication treatment alone. In contrast, none of the 3 patients with 2 lesions achieved CR. In 1 newly reported case, endoscopic CR was achieved in one lesion, while stable disease was obtained in the other lesion. Two patients with progressive disease responded to standard chemotherapy ± radiation and remained in CR for more than 6 years., Conclusion: We believe it is worthwhile to attempt H. pylori eradication for elderly patients with primary gastric DLBCL in a single lesion with a small tumor burden., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: The aim of this study was to investigate the influences of hemodialysis (HD) on activities of daily living (ADL) in patients with hip fracture., Methods: This study included 28 patients (14 HD and 14 non-HD patients) with acute hip fracture. The effects of variables such as age, sex, surgical procedure, length of hospital stay, serum albumin, C-reactive protein (CRP), number of physical therapy units, and functional independence measure (FIM) were assessed. For each factor, a two-group comparison was conducted between the HD and non-HD groups. Multiple regression analysis was used to examine the factors affecting FIM efficacy (E-FIM)., Results: For HD patients, total and motor FIM at discharge, E-FIM, and albumin level were significantly lower than in non-HD patients. Length of hospital stay was significantly longer for HD patients. Multiple regression analysis showed that HD had a negative effect on E-FIM., Conclusions: The results suggest that rehabilitation for HD patients with hip fractures require intervention that not only provides standard rehabilitation but also addresses aspects of renal rehabilitation., Competing Interests: CONFLICTS OF INTEREST: The authors declare no conflict of interest., (2023 The Japanese Association of Rehabilitation Medicine.)

The JSH Practical Guidelines for Hematological Malignancies, 2018 expanded edition, newly adopted brentuximab vedotin, doxorubicin, vinblastine, dacarbazine(A+AVD)protocol as a standard treatment for advanced-stage classical Hodgkin lymphoma(CHL). Therefore, this retrospective analysis compared 15 patients who received A+AVD therapy with 21 patients who received doxorubicin, bleomycin, vinblastine, dacarbazine(ABVD)therapy. All patients were newly diagnosed with CHL and received induction therapy between April 2015 and June 2022 in our hospital. All except 1 patient of the A+AVD group had advanced-stage CHL. The median age was 63(23-85)years. The estimated 2-year overall survival of the A+AVD group was better than that of the ABVD group which included 6 patients with clinical stage Ⅲ or higher CHL (100% vs 66.7%, p=0.047). In contrast, there was no significant difference in the complete response rate(53.8% vs 100%, p=0.109)between the 2 groups. The overall response rate after first-line treatment(69.2% vs 100%, p=0.255), and the estimated 2-year progression-free survival(70.1% vs 66.7%, p=0.321)between the A+AVD and the ABVD groups were similar.

Background: We have reported that seroconversion rates after the second dose of mRNA-based COVID-19 vaccines for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) were 100% and 95% respectively, with no significant difference from healthy controls (HCs).However, there are very limited data for the response to a third vaccine dose in those patients., Aims: In this complementary study, we investigated the booster effect of a third mRNA-based COVID-19 vaccine dose in patients with myeloid malignancies., Materials & Methods: A total 58 patients including 20 patients with MDS and 38 patients with AML were enrolled. Anti-SARS-CoV-2S immunoassays were performed at 3, 6, and 9 months after the second vaccine dose., Results: Seventy-five percent of the MDS patients and 37% of the AML patients were receiving active treatment at the time of the third vaccination. Both the initial and third vaccine response in AML patients were comparable to those in HCs. In MDS patients, although the initial vaccine immunogenicity was inferior to that in HCs and AML patients, the third vaccine improved the response to a level not inferior to those in HCs and AML patients. Of note, the third vaccine resulted in a significant increase of antibodies in actively treated MDS patients who had shown a response inferior to that in untreated patients after two doses of vaccination., Discussion: In patients with myeloid malignancies, the third vaccine dose showed a booster effect, and disease- and therapy-related factors associated with the booster response have been identified., Conclusion: The third dose of an mRNA-based COVID-19 vaccine showed a booster effect in patients with myeloid malignancies. Such a good booster response has not been reported in other haematological malignancies., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Neurolymphomatosis (NL) is a rare clinical entity characterized by lymphomatous infiltration of the peripheral nervous system. According to recent retrospective data, consolidative high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) may be beneficial for NL. However, few reports to date have discussed optimal conditioning regimens. Herein, we report two cases of NL in patients with relapsed intravascular large B-cell lymphoma who received consolidative thiotepa-containing HDC-ASCT. Case 1: A 56-year-old woman who relapsed 2 months after the first complete remission (CR) and underwent ASCT. Case 2: A 65-year-old woman who relapsed 8 months after the first CR and underwent ASCT. Both patients engrafted. Time to neutrophil engraftment was 10 and 12 days after HDC-ASCT, and CR was sustained for 26 and 18 months, respectively, as of the last follow-up. Although there is little evidence supporting the utility of thiotepa-based HDC-ASCT in patients with NL, the results of this case report suggest that further studies are warranted to determine its efficacy in this setting., (© 2023. Japanese Society of Hematology.)

Serologic responses of COVID-19 vaccine are impaired in patients with B-cell lymphoma, especially those who had recently been treated with anti-CD20 monoclonal antibodies. However, it is still unclear whether those patients develop an immune response following vaccination. We investigated the efficacy of vaccination against SARS-CoV-2 in 171 patients with B-cell non-Hodgkin lymphoma (B-NHL) who received two doses of an mRNA-based COVID-19 vaccine and we compared the efficacy of vaccination to that in 166 healthy controls. Antibody titers were measured 3 months after administration of the second vaccine dose. Patients with B-NHL showed a significantly lower seroconversion rate and a lower median antibody titer than those in healthy controls. The antibody titers showed correlations with the period from the last anti-CD20 antibody treatment to vaccination, the period from the last bendamustine treatment to vaccination and serum IgM level. The serologic response rates and median antibody titers were significantly different between diffuse large B-cell lymphoma (DLBCL) patients in whom anti-CD20 antibody treatment was completed within 9 months before vaccination and follicular lymphoma (FL) patients in whom anti-CD20 antibody treatment was completed within 15 months before vaccination. Moreover, the serologic response rates and median antibody titers were significantly different among FL patients in whom bendamustine treatment was completed within 33 months before vaccination. We demonstrated that B-NHL patients who were recently treated with anti-CD20 antibodies and bendamustine had a diminished humoral response to COVID-19 vaccination. UMIN 000,045,267., (© 2023. The Author(s).)

Patients with lymphoid malignancies have impaired humoral immunity caused by the disease itself and its treatment, placing them at risk for severe coronavirus disease-19 (COVID-19) and reduced response to vaccination. However, data for COVID-19 vaccine responses in patients with mature T cell and NK-cell neoplasms are very limited. In this study of 19 patients with mature T/NK-cell neoplasms, anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike antibodies were measured at 3 months, 6 months, and 9 months after the second mRNA-based vaccination. At the time of the second and third vaccinations, 31.6% and 15.4% of the patients were receiving active treatment. All patients received the primary vaccine dose and the third vaccination rate was 68.4%. In patients with mature T/NK-cell neoplasms, both seroconversion rate (p < 0.01) and antibody titers (p < 0.01) after the second vaccination were significantly lower than those in healthy controls (HC). In individuals who received the booster dose, patients had significantly lower antibody titers than those in HC (p < 0.01); however, the seroconversion rate in patients was 100%, which was the same as that in HC. The booster vaccine resulted in a significant increase of antibodies in elderly patients who had shown a response that was inferior to that in younger patients after two doses of vaccination. Since higher antibody titers and higher seroconversion rate reduced the incidence of infection and mortality, vaccination more than three times may have the advantage for patients with mature T/NK-cell neoplasms, especially in elderly patients. Clinical trial registration number: UMIN 000,045,267 (August 26th, 2021), 000,048,764 (August 26th, 2022)., (© 2023. The Author(s).)

Data for COVID-19 vaccine response in patients with immune thrombocytopenia (ITP) are very limited. In a study of 28 patients with ITP, anti-severe acute respiratory syndrome coronavirus 2 spike antibody titres were measured after vaccination. The seroconversion rate for ITP patients was 91.3%, comparable to that in healthy controls (HCs). However, the antibody titre in ITP patients was significantly lower than that in HCs and declined with ageing. Furthermore, the antibody titre in ITP patients who received a minimum prednisolone dose of at least 5 mg/day at any time-point at or after initial vaccination was lower than that in other patients., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Acute hand edema often results in loss of fine hand motor activities, especially without appropriate care. There is still no reliable and easy to use method to measure hand edema. In this study, we tested a handheld three-dimensional (3D) scanner on plastic male and female hand models using a whole hand measuring method (WM) and a modified method (MM) which excluded fingers. We evaluated the intra-rater reliability and inter-rater reliability and compared the measured volumes to computed tomography (CT) findings. Statistical analysis showed that the 3D scan method was valid and reliable for both WM and MM methods. In WM, intra-rater and inter-rater reliability were 0.97 and 0.84, with 95% confidence interval (CI) of 0.87-1.00 and 0.61-0.94, respectively. In MM, intra-rater and inter-rater reliability were 0.96 and 0.83, with 95% CI of 0.84-1.00 and 0.61-0.94, respectively. In comparison to the CT, the differences between 3D scan and CT in the male model volumes were 30.35 ± 2.70 cm 3 (mean ± standard deviation) for WM and 11.60 ± 2.07 cm 3 for MM. In the female model, the differences were 18.92 ± 2.66 cm 3 and 11.18 ± 2.35 cm 3 , respectively. In both models, MM was significantly more accurate than WM ( p  < 0.001). When used in a clinical case, the scanner recorded changes in actual volume through the course of treatment. This cost-effective handheld 3D camera can be a reliable tool for evaluating hand edema even in cases of acute injury.

Objective Endoscopic reports are conventionally written at the end of each procedure, and the endoscopist must complete the report from memory. To make endoscopic reporting more efficient, we developed a new speech recognition (SR) system that generates highly accurate endoscopic reports based on structured data entry. We conducted a pilot study to examine the performance of this SR system in an actual endoscopy setting with various types of background noise. Methods In this prospective observational pilot study, participants who underwent upper endoscopy with our SR system were included. The primary outcome was the correct recognition rate of the system. We compared the findings generated by the SR system with the findings in the handwritten report prepared by the endoscopist. The initial correct recognition rate, number of revisions, finding registration time, and endoscopy time were also analyzed. Results Upper endoscopy was performed in 34 patients, generating 128 findings of 22 disease names. The correct recognition rate was 100%, and the median number of revisions was 0. The median finding registration time was 2.57 [interquartile range (IQR), 2.33-2.92] seconds, and the median endoscopy time was 234 (IQR, 194-227) seconds. Conclusion The SR system demonstrated high recognition accuracy in the clinical setting. The finding registration time was extremely short.

Adult T-cell leukemia/lymphoma (ATLL) is one of the aggressive peripheral T-cell neoplasms with a poor prognosis. Accumulating evidence demonstrates that escape from adaptive immunity is a hallmark of ATLL pathogenesis. However, the mechanisms by which ATLL cells evade natural killer (NK)-cell-mediated immunity have been poorly understood. Here we show that CD48 expression in ATLL cells determines the sensitivity for NK-cell-mediated cytotoxicity against ATLL cells. We performed unbiased genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screening using 2 ATLL-derived cell lines and discovered CD48 as one of the best-enriched genes whose knockout conferred resistance to YT1-NK cell line-mediated cytotoxicity. The ability of CD48-knockout ATLL cells to evade NK-cell effector function was confirmed using human primary NK cells with reduced interferon-γ (IFNγ) induction and degranulation. We found that primary ATLL cells had reduced CD48 expression along with disease progression. Furthermore, other subgroups among aggressive peripheral T-cell lymphomas (PTCLs) also expressed lower concentrations of CD48 than normal T cells, suggesting that CD48 is a key molecule in malignant T-cell evasion of NK-cell surveillance. Thus, this study demonstrates that CD48 expression is likely critical for malignant T-cell lymphoma cell regulation of NK-cell-mediated immunity and provides a rationale for future evaluation of CD48 as a molecular biomarker in NK-cell-associated immunotherapies., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Duodenal-type follicular lymphoma (D-FL) has been recognized as a rare entity that accounts for approximately 4% of primary gastrointestinal lymphomas. D-FL follows an indolent clinical course compared with common nodal FL and is generally considered to have a better prognosis. Therefore, the "watch and wait" approach is frequently adopted as the treatment method. Alternatively, there is an option to actively intervene in D-FL. However, the long-term outcomes of such cases are poorly understood., Aim: To clarify the clinical outcomes after long-term follow-up in cases of D-FL with treatment intervention., Methods: We retrospectively analyzed patients who met the following criteria: the lesion was confirmed by endoscopy, the diagnosis of D-FL was confirmed histopathologically, and the patient was followed-up for more than 10 years after the intervention at our center., Results: We identified 5 cases of D-FL. Two patients showed a small amount of bone marrow involvement (Stage IV). Rituximab was used as a treatment for remission in all 5 patients. It was also used in combination with chemotherapy in 2 Stage IV patients as well as for maintenance treatment. Radiation therapy was performed in 2 cases, which was followed by complete remission (CR). Eventually, all 5 patients achieved CR and survived for more than 10 years. However, 3 patients experienced recurrence. One patient achieved a second CR by retreatment, and in another case, the lesion showed spontaneous disappearance. The remaining patient had systemic widespread recurrence 13 years after the first CR. Biopsy results suggested that the FL lesions were transformed into diffuse large B-cell lymphoma. The patient died 4 years later despite receiving various chemotherapies., Conclusion: In this study, the treatment for patients of D-FL in Stage IV was successful. In the future, criteria for how to treat "advanced" D-FL should be established based on additional cases. This study of patients with D-FL indicates that whole-body follow-up examinations should continue for a long time due to a fatal recurrence 13 years after reaching CR., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest with respect to the research, authorship, and/or publication of this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Colorectal follicular lymphoma (FL) is rare. In addition, it is even rarer that colon cancer develops synchronously with colorectal lymphoma. The present study reports a case of sigmoid colon cancer that developed 6 months after endoscopic resection of rectal FL. A 71-year-old man with a history of developing mucosa-associated lymphoid tissue lymphoma in his stomach at age 48, right neck region at age 59 (the latter later modified as FL) and lung adenocarcinoma at age 60 now suffers from rectal FL. Endoscopic submucosal dissection (ESD) was performed at our hospital (Aiiku Hospital), and 6 months after the treatment, sigmoid colon cancer was confirmed by colonoscopy for the follow-up study. The patient was successfully curatively resected by ESD plus local resection and has survived without a recurrence for >3 years with no treatment. It was speculated that in the present case, cancer-related genes were changed as a carcinogenic mechanism due to decreased immune function associated with the onset of lymphoma., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Saito et al.)

Data on the response to the COVID-19 vaccine in patients with myeloid malignancy, who are at severe risk in case of infection, have not emerged. In a study of 69 patients with myeloid malignancies, including 46 patients with acute myeloid leukaemia (AML) and 23 patients with myelodysplastic syndrome (MDS), anti-spike SARS-CoV-2 antibody titres were measured 3 months after the second mRNA-based vaccination. Seroconversion rates for AML and MDS were 94.7% and 100% respectively, with no significant difference from healthy controls (HCs). Patients with MDS showed a significantly lower antibody titre than that in HCs or AML patients. In AML patients, the antibody titres were comparable to those in HCs when treatment was completed, but lower in patients under maintenance therapy. The response to COVID-19 vaccine appears to be related to disease and treatment status. Patients with myeloid malignancies may be more responsive to vaccines than patients with lymphoid malignancies., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

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.)

The patient was a 68-year-old woman, diagnosed with acute myelomonocytic leukemia with normal karyotype and FLT3-ITD-negative status in May 2019. She had achieved complete remission (CR) after "7+3" intensive induction chemotherapy and maintained CR by consolidation chemotherapy. However, she relapsed with swelling of the lips and gums in January 2020. She did not achieve CR by salvage chemotherapy with cytarabine-aclarubicin-G-CSF regimen. Comprehensive genomic analysis of leukemic cells revealed the presence of FLT3-N676K mutation, which was undetectable by companion diagnostics at the time. Complete remission with incomplete count recovery was obtained on day 28 after initiation of gilteritinib monotherapy, and the lip and gum swelling improved rapidly. However, she relapsed on day 106 after gilteritinib administration, and gilteritinib was discontinued. Genomic analysis at recurrence revealed NRAS mutation for the first time. Finally, the patient died of the uncontrolled primary disease. This is a case in which comprehensive gene mutation analysis was useful in determining a treatment strategy.

The standard treatment for colorectal mucosa-associated lymphoid tissue (MALT) lymphoma has not yet been established due to the rarity of the disease. Here, we report a case of long-term response to chemotherapy for colorectal MALT lymphoma (stage I). A 77-year-old frail female patient with diabetes mellitus and dementia developed melena of unknown etiology, and a colonoscopy was performed at a nearby hospital. A biopsy suggested malignant lymphoma, and she was referred to our department. As a result of re-examination of colonoscopy, a total of 3 submucosal tumor-like lesions were confirmed. Of these, a biopsy of the lesions in the ascending colon and rectum was performed, and MALT lymphoma was diagnosed on the basis of the histopathological findings. Following close examination, no other lymphoma lesions were found, and the patient was diagnosed with primary colorectal MALT lymphoma, stage I. After 1 course of R-THP-COP chemotherapy (rituximab + cyclophosphamide, pirarubicin, vincristine, and prednisone), the rectal lesion was confirmed to have almost disappeared endoscopically, and lymphoma cells were not found histopathologically. The patient was determined to be in complete remission (CR). However, due to hematological toxicity and a slight worsening of glucose control, the second chemotherapy course was changed to the BR regimen (rituximab + bendamustine), and 4 courses were performed (5 total courses of chemotherapy). Currently, >3 years have passed since reaching CR, and the patient is alive without recurrence., Competing Interests: The authors declare no potential conflicts of interest in this work., (Copyright © 2021 by The Author(s). Published by S. Karger AG, Basel.)

Fms-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in acute myelogenous leukemia (AML) and the mutation is associated with poor prognosis of patients. Two distinct types of activating mutations have been identified in AML samples. One is internal tandem duplications in the juxtamembrane domain ( FLT3 -ITD) and the other is point mutations in the tyrosine kinase domain ( FLT3 -TKD). Gilteritinib is a FLT3 inhibitor that inhibits both FLT3-ITD and FLT3-TKD. It was reported that differentiation of leukemic blasts accompanied by differentiation syndrome occurs in some patients treated with gilteritinib. However, information about the precise clinical course is limited, and appropriate management of differentiation syndrome has not been established. We report a case of relapsed AML with FLT3 -ITD that was treated with gilteritinib. Analysis of the FLT3- ITD variant allele frequency (VAF) revealed that FLT3 -ITD VAF was not decreased despite achievement of complete remission with incomplete hematologic recovery. Remarkable increases of monocytes and granulocytes accompanied by differentiation syndrome were observed at 6 months after the initiation of gilteritinib treatment. Intermittent chemotherapy with low-dose cytarabine and mitoxantrone was effective for reducing myelomonocytosis and resolving differentiation syndrome.

The treatment of immune thrombocytopenia (ITP) has recently changed; however, each treatment has not only advantages, but also disadvantages, and may have unexpected complications. We describe an instructive case of ITP that was complicated by severe portal vein thrombosis during treatment with eltrombopag, an oral thrombopoietin-receptor agonist (TPO-RA) drug, plus prednisolone (PSL) concomitant splenectomy. A male ITP patient who had been receiving eltrombopag treatment for more than four years at our department underwent a splenectomy at the age of 51. Soon after splenectomy, splenic vein and portal vein thrombosis developed, while splenectomy was ineffective. The patient resumed eltrombopag treatment after thrombosis disappeared. Although fluctuations in PLT were observed, eltrombopag and PSL were used together for a while. Subsequently, lower-limb deep vein thrombosis recurred, and edoxaban tosylate was administered for a total of 8.4 months. More than three years after splenectomy, at the age of 54, abdominal computed tomography (CT) revealed a continuous thrombus extending from the intrahepatic portal vein to the superior mesenteric vein. In patients with ITP in whom splenectomy fails and treatment with a TPO-RA ± PSL needs to be continued, clinicians should be aware of the possibility of abdominal thrombotic adverse events, such as severe portal vein thrombosis, by following-up on CT imaging, not only in the short term but also in the medium-long term., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Saito et al.)

Background: Phlegmonous gastritis (PG) is a rare bacterial infectious disease characterized by neutrophil-based purulent inflammation of the gastric wall. The most representative causative bacterium is Streptococcus pyogenes , followed by Staphylococcus , Pneumococcus and Enterococcus . Hepatic portal venous gas (HPVG) is considered a potentially fatal condition and is rarely associated with PG., Case Summary: The white blood cell count of a 70-year-old woman with acute lymphocytic leukemia in complete remission dropped to 100/μL after consolidation chemotherapy. Her vital signs were consistent with septic shock. Venous blood culture revealed the presence of Bacillus cereus . Abdominal computed tomography (CT) and esophagogastroduodenoscopy (EGD) showed marked thickening of the gastric wall. As with the other findings, CT was suggestive of HPVG, and EGD showed pseudomembrane-like tissue covering the superficial mucosa. Histopathological examination of gastric biopsy specimens showed mostly necrotic tissue with lymphocytes rather than neutrophils. Culture of gastric specimens revealed the presence of Bacillus cereus . We finally diagnosed this case as PG with Bacillus cereus -induced sepsis and HPVG. This patient recovered successfully with conservative treatment, chiefly by using carbapenem antibiotics., Conclusion: The histopathological finding of this gastric biopsy specimen should be called "neutropenic necrotizing gastritis"., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest in this work., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

The patient developed Stage Ⅳ transverse colon cancer at the age of 72 years and was treated with an 8-course XELOX regimen(capecitabine and oxaliplatin)every 3 weeks after resection. Six years and 9 months after the end of treatment, at the age of 79 years, WBC levels were found to have markedly increased to 10×104/µL in the patient, and acute leukemia was suspected; subsequently, the patient was hospitalized. Bone marrow was aspirated and analyzed, and the results showed that 95% of leukemic cells were positive for esterase staining. Chromosomal examination revealed t(6 ; 11)(q27 ; q23), ie, the diagnosis of therapy-related acute myeloid leukemia(t-AML)with 11q23 abnormality. CR was achieved by chemotherapy, but the disease soon recurred; the patient died 7 months after the onset of t-AML, with the cause being t- AML with 11q23 abnormality that developed 6 years and 9 months after treatment for colorectal cancer with oxaliplatin and capecitabine without undergoing MDS. Since there is a possibility of leukemia induction following oxaliplatin treatment, more such cases need to be monitored in the future.

The pathogenesis of autoimmune gastritis (AIG) remains unclear. In addition, it is difficult to follow the process of AIG onset endoscopically. Leukemic non-nodal mantle cell lymphoma (MCL) was newly added as a subtype of MCL in the fourth revised edition of the World Health Organization (WHO) classification (2017). Here, we report a case of AIG associated with the progression of leukemic non-nodal MCL. A 74-year-old woman who had been followed up in a nearby hospital for chronic B-cell lymphoproliferative disorder with no treatment for six years presented with fever and fatigue in the previous one month. The patient was admitted to our department and was diagnosed with leukemic non-nodal MCL. Positron emission tomography-computed tomography examination, which indicated no abnormalities in the six preceding years, revealed uptake in the bone marrow and spleen. Since MCL was progressing, esophagogastroduodenoscopy (EGD), which showed almost no abnormal findings in the gastric mucosa 13 preceding months, was conducted again to search for lesions involving gastrointestinal MCL. Lymphoma lesions were not found, but wide atrophic mucosal changes in the stomach were revealed mainly in the corpus, and patchy redness was also observed in the pylorus, consistent with AIG. The patient tested positive for an anti-gastric parietal cell antibody (×80), her gastrin level was significantly elevated (5,280 pg/mL), and her pepsinogen (PG) I/PG II was considerably less than 1.0 (>3.1). Although no pathological confirmation was obtained by biopsy, the patient was clinically diagnosed with AIG. In our patient, AIG was revealed to be associated with the progression of leukemic non-nodal MCL in this short period., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Saito et al.)

Diffuse large B cell lymphoma (DLBCL) is the most common type of aggressive non-Hodgkin lymphoma. Emerging evidence indicates that poor nutritional status determined with nutritional indices such as geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), and controlling nutritional status score (CONUT) was associated with poor prognosis of DLBCL. We conducted this multicenter retrospective study to validate and compare prognostic values of the three indices in 615 newly diagnosed DLBCL patients. The overall survival (OS) in patients with poor nutritional status determined with each of these nutritional indices were significantly inferior compared with that in those without nutritional risks (5-year OS in patients with GNRI < 95.7 and GNRI ≥ 95.7 were 56.4% and 83.5%, P < 0.001; PNI < 42.4 and PNI ≥ 42.4 were 56.1% and 81.0%, P < 0.001; CONUT > 4 and CONUT ≤ 4 were 53.1% and 77.1%, P < 0.001). GNRI and CONUT were independent prognostic predictors for OS (GNRI < 95.7, hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.22-2.74, P = 0.0032; CONUT > 4, HR 1.53, 95% CI 1.05-2.23, P = 0.028) after multivariate analyses. Nutritional status determined with GNRI affected OS more strongly in the patients with nongerminal center B cell-like (nonGCB) DLBCL compared with that in those with GCB-type DLBCL. In conclusion, baseline poor nutritional status determined based on GNRI or CONUT was an independent risk factor of newly diagnosed DLBCL, and GNRI was also useful as an independent prognostic factor for patients with nonGCB-type DLBCL.

In Helicobacter pylori -positive, localized primary gastric diffuse large B-cell lymphoma (DLBCL), an increasing number of reports have recently been published on the effectiveness of H. pylori eradication (HPE). However, HPE treatment strategies for gastric DLBCL, including its indications, have yet to be examined. No detailed report has been published on a case of gastric DLBCL unsuccessfully treated by HPE. A 64-year-old female and a 70-year-old male were pathologically diagnosed with chronic active gastritis and mucosa-associated lymphoid tissue lymphoma, respectively. Both patients were positive for H. pylori , so HPE was employed. The disease progressed within 1 year, and both patients were pathologically diagnosed with DLBCL by endoscopic biopsy. On reviewing the first pathology slide, both patients were diagnosed with DLBCL. That is, the 2 patients had primary gastric DLBCL; however, they exhibited progressive disease after HPE. This failure of HPE treatment may be due to the initial lymphomas being multiplex ulcerative lesions. In both cases, complete remission was achieved by chemotherapy (plus radiation therapy) without recurrence for more than 3 years., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2020 by S. Karger AG, Basel.)

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.)

Eculizumab has been developed as a breakthrough treatment for paroxysmal nocturnal hemoglobinuria (PNH). Not only for breakthroughs, eculizumab therapy is also known to increase the risk of invasive meningococcal infection. It has also been recently reported that, although rarely, administration of eculizumab may result in disseminated gonococcal infection (DGI). We report here a case in which a young patient who had used eculizumab for PNH developed DGI. A 22-year-old Japanese male with PNH who had been treated with eculizumab complained of high fever, mild nausea, headache and right knee joint pain. The patient was admitted and suspected to have sepsis due to meningococcal infection and began to receive ceftriaxone (CTRX). Gonococci were detected in a venous blood culture a few days later, and this case was diagnosed as DGI. CTRX was effective, and the patient was discharged. However, four weeks later, he complained of the same subjective symptoms as at the beginning and was hospitalized again. The presence of gonococcus was proven by venous blood culture, CTRX was re-administered and the patient responded. After discharge, he was counseled on safer sexual activity, including accurate and consistent use of condoms, by urologists. He has not relapsed with DGI for more than one year. When serious signs of infection occur in patients receiving eculizumab, it is recommended to consider DGI as well as invasive meningococcal infection, and CTRX should be given., Competing Interests: Takeshi Kondo reports personal fees from Novartis Pharma, Bristol Squibb Meyers, Astellas Parma, and Otsuka Pharmaceuticals, outside the submitted work. The authors declare no other possible conflicts of interest in this work., (© 2020 Saito et al.)

Metabolic heterogeneity (MH) can be measured using 18F-fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT), and it indicates an inhomogeneous tumor microenvironment. High MH has been shown to predict a worse prognosis for primary mediastinal B-cell lymphoma, whereas its prognostic value in diffuse large B-cell lymphoma (DLBCL) remains to be determined. In the current study, we investigated the prognostic values of MH evaluated in newly diagnosed DLBCL. In the training cohort, 86 patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone-like chemotherapies were divided into low-MH and high-MH groups using receiver operating characteristic analysis. MH was not correlated with metabolic tumor volume of the corresponding lesion, indicating that MH was independent of tumor burden. At 5 years, overall survivals were 89.5% vs 61.2% (P = .0122) and event-free survivals were 73.1% vs 51.1% (P = .0327) in the low- and high-MH groups, respectively. A multivariate Cox-regression analysis showed that MH was an independent predictive factor for overall survival. The adverse prognostic impacts of high MH were confirmed in an independent validation cohort with 64 patients. In conclusion, MH on baseline 18FDG-PET/CT scan predicts treatment outcomes for patients with newly diagnosed DLBCL., (© 2020 by The American Society of Hematology.)