Predictive significance of high neutrophil ratio for thrombosis in myeloproliferative neoplasms: JSH-MPN-R18 subanalysis.

Thrombosis in myeloproliferative neoplasms (MPNs) is an important clinical problem, and risk-stratified management is essential. To identify the clinical characteristics of thrombosis in patients with MPNs, a nationwide multi-institutional retrospective analysis (JSH-MPN-R18) was conducted. The aim of the present study was to perform a sub-analysis of JSH-MPN-R18 findings to clarify the predictive parameters for thrombosis among complete blood count (CBC) results. Among the patients enrolled in JSH-MPN-R18, those with essential thrombocythemia (ET; n = 1152) and polycythemia vera (PV; n = 456) were investigated. We analyzed and compared CBC parameters between patients with and those without any thrombotic events using Welch's T-test. Statistical analyses were performed using the R statistical software. Thrombotic events were observed in 74 patients with ET. In multivariate analysis, only the neutrophil ratio was slightly but significantly higher for ET patients with thrombosis than for those without (p < 0.05). Of note, the absolute neutrophil count (aNeu) was considered a useful predictive tool for thrombosis among patients classified as low-risk according to the revised International Prognostic Score of Thrombosis for Essential Thrombocythemia. Among PV patients, those with thrombosis showed significantly higher hematocrit and aNeu than did those without thrombosis. As a thrombosis-associated factor, the neutrophil ratio was slightly but significantly elevated in patients with ET. This myeloid skew might reflect a higher value of JAK2 V617F allelic frequency in patients with ET with thrombosis; this was not clarified in JSH-MPN-R18. Further accumulation of evidence, including genetic information for JAK2 and other passenger mutations, is warranted.

[Ovarian hyperstimulation syndrome with controlled ovarian stimulation after induction therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia].

A 27-year-old woman with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia received induction therapy with dasatinib and prednisolone. From the time of diagnosis, oocyte storage was planned in accordance with the patient's wishes. After progesterone administration for suppression of menstruation, and blood cell recovery, ovarian stimulation was performed and a sufficient number of eggs was collected. The patient was considered at high risk for ovarian stimulation syndrome (OHSS) and received cabergoline and letrozole. However, ovarian enlargement and ascites were observed on ultrasonography 2 days after egg collection, and a diagnosis of moderate OHSS was made. Circulatory management was performed and low-molecular-weight heparin was administered. Dasatinib was discontinued due to the appearance of pleural effusion. Fluid retention improved after menstruation resumed, and the patient was able to continue consolidation with dasatinib and cord blood transplantation. Although tyrosine kinase inhibitors are expected to simplify planning of oocyte storage, the risk of complicating OHSS should be noted.

Clinical utility of genomic profiling of AML using paraffin-embedded bone marrow clots: HM-SCREEN-Japan 01.

Next-generation sequencing of AML has identified specific genetic mutations in AML patients. Hematologic Malignancies (HM)-SCREEN-Japan 01 is a multicenter study to detect actionable mutations using paraffin-embedded bone marrow (BM) clot specimens rather than BM fluid in AML patients for whom standard treatment has not been established. The purpose of this study is to evaluate the presence of potentially therapeutic target gene mutations in patients with newly diagnosed unfit AML and relapsed/refractory AML (R/R-AML) using BM clot specimens. In this study, 188 patients were enrolled and targeted sequencing was undertaken on DNA from 437 genes and RNA from 265 genes. High-quality DNA and RNA were obtained using BM clot specimens, with genetic alterations successfully detected in 177 patients (97.3%), and fusion transcripts in 41 patients (23.2%). The median turnaround time was 13 days. In the detection of fusion genes, not only common fusion products such as RUNX1-RUX1T1 and KMT2A rearrangements, but also NUP98 rearrangements and rare fusion genes were observed. Among 177 patients (72 with unfit AML, 105 with R/R-AML), mutations in KIT and WT1 were independent factors for overall survival (hazard ratio = 12.6 and 8.88, respectively), and patients with high variant allele frequency (≥40%) of TP53 mutations had a poor prognosis. As for the detection of actionable mutations, 38% (n = 69) of patients had useful genetic mutation (FLT3-ITD/TKD, IDH1/2, and DNMT3AR822 ) for treatment selection. Comprehensive genomic profiling using paraffin-embedded BM clot specimens successfully identified leukemic-associated genes that can be used as therapeutic targets.

WEE1 and PARP-1 play critical roles in myelodysplastic syndrome and acute myeloid leukemia treatment.

BACKGROUND: Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder defined by cytopenia and is associated with an increased risk of transformation to acute myeloid leukemia (AML). The outcome of MDS is poor, so alternative therapeutic approaches are needed to improve survival. The inhibition of the DNA damage response pathway, including poly (ADP-ribose) polymerase-1 (PARP-1), has been approved to treat several cancers. In addition, WEE1, a nuclear kinase, is overexpressed in many cancers. Therefore, a WEE1 inhibitor combined with a PARP-1 inhibitor could inhibit the proliferation of MDS and AML. METHODS: We analyzed whether WEE1 was regulated in the progression of MDS and AML. We also evaluated the efficacy of MK-1775 (WEE1 inhibitor) and talazoparib (PARP-1 inhibitor). RESULTS: PARP-1 expression was higher in the AML cells than in the MDS cells. However, WEE1 expression remained unchanged. MK-1775 or talazoparib alone inhibited MDS and AML cells after 72 h, and cellular cytotoxicity and caspase 3/7 activity were increased. The combined use of MK-1775 and talazoparib produced superior efficacy than either drug alone and SKM-1 colony formation was reduced. Significant cell populations in the sub-G1 phase were found in the cell-cycle analyses. Additionally, γ-H2AX expression and caspase 3 activity were increased. The combined treatment also changed the mitochondrial membrane potential. CONCLUSIONS: The combination of a WEE1 inhibitor and PARP-1 inhibitor had enhanced efficacy and is proposed as a new therapeutic option for patients with MDS or AML. Our findings have clinical implications for a potential novel therapeutic strategy for MDS and AML patients.

Effect of asciminib and vitamin K2 on Abelson tyrosine-kinase-inhibitor-resistant chronic myelogenous leukemia cells.

BACKGROUND: Abelson (ABL) tyrosine kinase inhibitors (TKIs) are effective against chronic myeloid leukemia (CML); however, many patients develop resistance during ABL TKI therapy. Vitamin K2 (VK2) is a crucial fat-soluble vitamin used to activate hepatic coagulation factors and treat osteoporosis. Although VK2 has demonstrated impressive anticancer activity in various cancer cell lines, it is not known whether VK2 enhances the effects of asciminib, which specifically targets the ABL myristoyl pocket (STAMP) inhibitor. METHOD: In this work, we investigated whether VK2 contributed to the development of CML cell lines. We also investigated the efficacy of asciminib and VK2 by using K562, ponatinib-resistant K562 (K562 PR), Ba/F3 BCR-ABL, and T315I point mutant Ba/F3 (Ba/F3 T315I) cells. RESULTS: Based on data from the Gene Expression Omnibus (GEO) database, gamma-glutamyl carboxylase (GGCX) and vitamin K epoxide reductase complex subunit 1 (VKORC1) were elevated in imatinib-resistant patients (GSE130404). UBIA Prenyltransferase Domain Containing 1 (UBIAD1) was decreased, and K562 PR cells were resistant to ponatinib. In contrast, asciminib inhibited CML cells and ponatinib resistance in a dose-dependent manner. CML cells were suppressed by VK2. Caspase 3/7 activity was also elevated, as was cellular cytotoxicity. Asciminib plus VK2 therapy induced a significantly higher level of cytotoxicity than use of each drug alone. Asciminib and VK2 therapy altered the mitochondrial membrane potential. CONCLUSIONS: Asciminib and VK2 are suggested as a novel treatment for ABL-TKI-resistant cells since they increase treatment efficacy. Additionally, this treatment option has intriguing clinical relevance for patients who are resistant to ABL TKIs.

[Japanese patient preferences between ravulizumab and eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria].

Ravulizumab is the first long-acting complement inhibitor approved for paroxysmal nocturnal hemoglobinuria (PNH) treatment. We evaluated patient preference for ravulizumab or eculizumab among Japanese adults with PNH. The ALXN1210-PNH-301 (NCT02946463) and ALXN1210-PNH-302 (NCT03056040) studies included 23 Japanese adults who are enrolled in complement inhibitor treatment-naive and eculizumab (≥6 months) treatment. Patient preference was assessed using the PNH-specific patient preference questionnaire (PNH-PPQ©). Most patients preferred ravulizumab (19/23, 82.6%), none preferred eculizumab, and four (17.4%) reported no preference (χ2 test, p<0.005). The preference for ravulizumab was driven by its lower infusion frequency (every 8 weeks) compared with eculizumab (every 2 weeks). The included Japanese patients with PNH preferred ravulizumab because of its reduced infusion frequency, which increases activity planning ability, treatment convenience, and overall quality of life, as compared with eculizumab. These data provide useful insight into patient perspectives and may aid decision-making for PNH treatment.

[RS3PE syndrome with angioimmunoblastic T-cell lymphoma early after the start of immunosuppressive therapy].

A 75-year-old man visited our Collagen Disease Department because of a fever, edema in the lower legs, and arthralgia. He presented with peripheral arthritis of the extremities and was negative for rheumatoid factor, leading to a diagnosis of RS3PE syndrome. A search for malignancy was performed, but no obvious malignant findings were found. After starting treatment with steroid, methotrexate, and tacrolimus, the patient's joint symptoms improved, but after five months, enlarged lymph nodes throughout the body were observed. A lymph node biopsy revealed a diagnosis of other iatrogenic immunodeficiency-associated lymphoproliferative disorders/angioimmunoblastic T-cell lymphoma (OI-LPD/AITL). After discontinuation of methotrexate and follow-up, no lymph node shrinkage was observed, and the patient had strong general malaise, so chemotherapy was started for AITL. After the start of chemotherapy, the patient's general symptoms improved quickly. RS3PE syndrome is a polyarticular, rheumatoid factor-negative, polyarticular synovitis with symmetric dorsolateral hand-palmar symmetric indentation edema that occurs mainly in elderly patients. It is also noted as a paraneoplastic syndrome, with 10%-40% of patients having malignant tumors. When our patient was diagnosed with RS3PE syndrome, a search for malignancy was performed, but there were no findings suggestive of malignant disease. However, after methotrexate and tacrolimus administration was started, the patient developed rapid lymph node enlargement, and the pathology showed AITL. The possibility of AITL as an underlying disease and RS3PE syndrome as a paraneoplastic syndrome, or conversely, OI-LPD/AITL associated with immunosuppressive therapy for RS3PE syndrome is considered. We herein report this case, as sufficient recognition is required for a proper diagnosis to be made and treatment of RS3PE syndrome to be performed.

von Willebrand factor activity levels are influenced by driver mutation status in polycythemia vera and essential thrombocythemia patients with well-controlled platelet counts.

von Willebrand factor ristocetin cofactor (vWF activity) and platelet count (PLT) are negatively correlated in patients with polycythemia vera (PV) and essential thrombocythemia (ET). However, vWF activity does not always normalize upon controlling PLT in those patients. To address this issue, we investigated the correlation between vWF activity and PLT in PV and ET patients. The negative correlation between vWF activity and PLT was stronger in calreticulin mutation-positive (CALR+) ET than in Janus kinase 2 mutation-positive (JAK2+) PV or ET groups. When PLT were maintained at a certain level (<600 × 109 /L), low vWF activity (<50%) was more frequently observed in JAK2+ PV patients than in JAK2+ ET (p = .013) or CALR+ ET (p = .013) groups, and in PV and ET patients with ≥50% JAK2+ allele burden than in those with allele burden <50% (p = .015). High vWF activity (>150%) was more frequent in the JAK2+ ET group than in the CALR+ ET group (p = .005), and often associated with vasomotor symptoms (p = .002). This study suggests that some patients with JAK2+ PV or ET have vWF activity outside the standard range even with well-controlled PLT, and that the measurement of vWF activity is useful for assessing the risk of thrombosis and hemorrhage.

A pilot study examining the efficacy of hochuekkito for improving quality of life in patients with myeloproliferative neoplasms.

BACKGROUND: The prognosis of Philadelphia chromosome-negative myeloproliferative neoplasms is relatively favorable, but the quality of life can be severely affected by myeloproliferative neoplasm-related symptoms such as fatigue, pruritus, night sweats, bone pain, fever and weight loss. In this study, we administered hochuekkito, a traditional herbal medicine, to patients with myeloproliferative neoplasms and investigated whether there was a reduction in myeloproliferative neoplasm-related symptoms. METHODS: We conducted a randomized parallel-group pilot study. Patients were assigned to a hochuekkito administration or non-hochuekkito administration group. Myeloproliferative neoplasm-related symptoms based on Myeloproliferative Neoplasm Symptom Assessment Form total symptom score and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 were examined before hochuekkito administration and 4 and 8 weeks after administration. RESULTS: Among the 42 patients included in the analysis, 21 were assigned to the hochuekkito group and 21 were assigned to the control group. After administering hochuekkito, the median values of Myeloproliferative Neoplasms Symptom Assessment Form total symptom score at 4 and 8 weeks in the hochuekkito group demonstrated a decreasing trend; however, the difference between the two groups was not significant. CONCLUSIONS: In this study, we were unable to demonstrate significant differences between the hochuekkito and control groups in terms of the efficacy of hochuekkito in treating myeloproliferative neoplasm-related symptoms. However, there were cases that presented prominent improvement in symptoms in the hochuekkito group. The only reported adverse event was grade 1 impaired hepatic function. Therefore, hochuekkito might be a therapeutic option for patients with severely affected quality of life due to myeloproliferative neoplasm-related symptoms.

Mutated KIT Tyrosine Kinase as a Novel Molecular Target in Acute Myeloid Leukemia.

KIT is a type-III receptor tyrosine kinase that contributes to cell signaling in various cells. Since KIT is activated by overexpression or mutation and plays an important role in the development of some cancers, such as gastrointestinal stromal tumors and mast cell disease, molecular therapies targeting KIT mutations are being developed. In acute myeloid leukemia (AML), genome profiling via next-generation sequencing has shown that several genes that are mutated in patients with AML impact patients' prognosis. Moreover, it was suggested that precision-medicine-based treatment using genomic data will improve treatment outcomes for AML patients. This paper presents (1) previous studies regarding the role of KIT mutations in AML, (2) the data in AML with KIT mutations from the HM-SCREEN-Japan-01 study, a genome profiling study for patients newly diagnosed with AML who are unsuitable for the standard first-line treatment (unfit) or have relapsed/refractory AML, and (3) new therapies targeting KIT mutations, such as tyrosine kinase inhibitors and heat shock protein 90 inhibitors. In this era when genome profiling via next-generation sequencing is becoming more common, KIT mutations are attractive novel molecular targets in AML.

[Idiopathic esophageal submucosal hematoma during antithrombotic therapy for essential thrombocythemia].

A 73-year-old woman was hospitalized with sudden chest pain and hematemesis. Chest computed tomography and upper gastrointestinal endoscopy revealed an idiopathic submucosal hematoma from the cervical esophagus to the esophagogastric mucosal junction. Idiopathic esophageal submucosal hematoma is often prone to a bleeding tendency of an underlying disorder. The patient had a history of essential thrombocythemia (ET) and was taking aspirin. She successfully recovered after aspirin discontinuation and conservative treatment; however, died of cardiopulmonary arrest in the ward on day 9 of hospitalization. The autopsy revealed that the cause of death was pulmonary thromboembolism. This is the first report of ET with submucosal hematoma of the esophagus. The possibility of an esophageal submucosal hematoma should be considered when patients with ET complain of chest pain since ET and treatment with aspirin are considered risk factors for bleeding. Additionally, close attention should be focused on the risk of developing thrombosis if a patient with myeloproliferative neoplasm is required to discontinue antithrombotic therapy due to a bleeding event.

[Desquamative esophagitis associated with unrelated allogeneic peripheral blood stem cell transplantation using the FBM conditioning regimen].

Desquamative esophagitis (DE) is a rare benign condition characterized by sheet-like shedding of esophageal squamous epithelial tissue. Although cases of drug-induced DE, such as those induced by direct oral anticoagulants, have been reported, cases of DE complicated with hematopoietic stem cell transplantation (HSCT) are rare. We herein report the case of a 52-year-old woman with FLT3-ITD mutation-positive acute myeloid leukemia who presented with DE immediately after HSCT. Allogeneic peripheral blood HSCT with FBM (fludarabine 180 mg/m2, busulfan 12.8 mg/m2, and melphalan 80 mg/m2) was performed during the first remission. Tacrolimus plus short-term methotrexate was planned for graft-versus-host disease prevention. Common Terminology Criteria for Adverse Events grade 3 equivalent vomiting was observed during treatment with the conditioning regimen. On day 5 after HSCT, a white band of 10 cm in length and 1 cm in width was discharged from the oral cavity during vomiting. Upper gastrointestinal endoscopy revealed mucosal detachment in the entire esophagus and the diagnosis of DE was made. DE improved on providing conservative treatment. We concluded that the mechanical pressure that developed on the esophagus due to frequent vomiting contributed to the mucosal detachment owing to regimen-related toxicity. Even in the FBM regimen, which is widely used as a conditioning regimen, caution is required to prevent DE.

[Examination of the effect of immunosuppressive therapy on acquired hemophilia A in elderly patients with bloodstream infections].

AIM: Acquired hemophilia A (AHA) is an acquired autoantibody (inhibitor) against blood coagulation factor VIII (FVIII) that significantly reduces FVIII activity and causes a bleeding tendency. Immune acquired coagulation factor deficiency. The peak age of onset is in the 70s. In Japan, which has an aging society, the number of reports has recently been increasing, and it should be noted that AHA is a bleeding disease that can occur in the elderly. Examined 5 cases of AHA that were experienced in our hospital. The FVIII inhibitor level, APTT, underlying disease, treatment history, and outcome were retrospectively examined using medical records. RESULTS: The age of onset was 76-93 years. At the time of diagnosis, the Hb (mg/dL) value was 6.1-10.3, the APTT was 75.6-203.2 seconds, the FVIII inhibitor value (BU/mL) was 18-686, and the platelet count was within the normal range in all cases. Bleeding control was possible using a bypass hemostatic agent in 4 patients. All patients underwent immunosuppressive therapy. Two patients were discharged alive and 3 patients died. The cause of death was infectious disease in all cases. The total prednisolone-equivalent dose of the deceased patients was 1,240-3,206 mg; one patient was treated with cyclophosphamide and was treated with dexamethasone. CONCLUSION: Long-term immunosuppressive therapy is expected to increase the risk of infection in elderly patients. The risk assessment of AHA treatment-related bloodstream infections is insufficient, and it will be necessary to accumulate data and consider appropriate assessments and countermeasures.

Successful cord blood transplantation for myelodysplastic syndrome complicated by Mycobacterium kansasii pneumonia.

Non-tuberculous mycobacterial (NTM) disease is a rare cause of neutropenic fever in patients with hematological malignancies. There are few studies on the optimal management for such patients with NTM. We report a case of myelodysplastic syndrome (MDS) treated by umbilical cord blood transplantation (CBT) after Mycobacterium kansasii (M kansasii) pneumonia. A 38-year-old man diagnosed with MDS developed severe pneumonia during induction chemotherapy. Repeated sputum culture uncovered mycobacterium infection. Then, by the polymerase chain reaction of the bronchial lavage fluid, M kansasii infection was proven. After 140 days of anti-NTM therapy, CBT was successfully carried out and the patient recovered without recurrence of NTM infection. This case provides valuable evidence that hematopoietic stem cell transplantation is feasible after a reliable diagnosis and continuous anti-NTM therapy.

Elevation of HHV-6 viral load mimicking HHV-6 reactivation after second umbilical cord blood transplantation in chromosomally integrated human herpesvirus-6.

Human herpesvirus-6 (HHV-6) reactivation is an important complication in patients receiving umbilical cord blood transplantation (CBT). Chromosomally integrated human herpesvirus-6 (ciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the host germline genome and is transmitted in a Mendelian manner. The influence of ciHHV-6 in recipients or donors in cases of CBT is unknown. We report the first case with ciHHV-6 that received CBT twice for acute lymphoblastic T-cell leukemia. HHV-6 DNA in peripheral blood leukocytes (PBLs) was examined over time through two CBTs. After the first CBT, the HHV-6 viral load was significantly reduced by conversion to PBLs derived from the first donor. During the second CBT, an increase in HHV-6 DNA in PBLs and plasma were observed. However, HHV-6 mRNA was not detected in either the sample before 2nd CBT or at the time of HHV-6 DNA elevation. It is considered that the HHV-6 DNA detected in PBLs and plasma samples might be the HHV-6 genome released due to tissue damage. This case suggests that physicians should be aware of HHV-6 DNA variability during allogeneic hematopoietic stem cell transplantation in ciHHV-6 patients.

Epstein-Barr virus-associated post-transplant lymphoproliferative disease during dasatinib treatment occurred 10 years after umbilical cord blood transplantation.

Post-transplant lymphoproliferative disease (PTLD) is defined as a lymphoma that occurs after solid-organ or hematopoietic stem-cell transplantation (HSCT), caused by immunosuppression and Epstein-Barr virus (EBV) reactivation. It is an important post-transplant complication that can be fatal. After HSCT, most PTLD occurs within 2 years. Recent evidence suggests that tyrosine kinase inhibitors (TKIs) are expected to be effective maintenance therapy after HSCT for Philadelphia chromosome-positive leukemia. However, it is unclear whether the use of TKIs might pose a risk of developing PTLD after HSCT. We present the first case of late-onset PTLD during dasatinib treatment, which occurred 10 years after umbilical cord blood transplantation (CBT). A 59-year-old man who received CBT for chronic myeloid leukemia blast phase needed long-term dasatinib therapy for molecular relapse. Ten years after CBT, he developed diffuse-large B-cell lymphoma (DLBCL). We observed chimerism of the DLBCL sample, which indicated complete donor type and EBV-DNA, and the patient was diagnosed with PTLD. Because of treatment resistance, he died 6 months after PTLD onset. Although he received no long-term administration of immunosuppressive agents, he received long-term dasatinib treatment, which suggests that prolonged dasatinib use after CBT caused EBV reactivation and led to PTLD. Our case suggests that the potential contribution of molecular-targeted agents after HSCT to the development of PTLD should be carefully considered.

[Diffuse large B-cell lymphoma with mediastinal bulky mass associated with complication of repeated sinus arrest].

A 71-year-old woman presented to a clinic with the chief complaint of facial edema and dyspnea; chest radiography showed mediastinal mass shadow and right pleural effusion. Computed tomography guided biopsy of the mediastinal mass had been performed by her previous doctor, and she was diagnosed with diffuse large B-cell lymphoma. She was referred to our hospital for chemotherapy. Electrocardiography performed before initiating chemotherapy showed sinus arrest for about 4 s, and Holter electrocardiography showed sinus arrest for up to about 7.4 s, which was repeatedly observed 6 times, indicating sick sinus syndrome (SSS). The mediastinal mass completely excluded the superior vena cava, and considering the risk of infection, an extracorporeal pacemaker was not inserted. We believed that the tumor effect was the cause of sinus arrest; hence, chemotherapy initiation was prioritized. R-CHOP therapy preceding vincristine and prednisolone was started, and sinus arrest was not observed after initial treatment. SSS may have been caused by carotid hypersensitivity syndrome that involved the exclusion of carotid artery pressure receptors by the tumor or the direct stimulation of the vagus nerve by microtumor infiltration.

[Human herpesvirus 8-unrelated primary effusion lymphoma-like lymphoma that developed during myelodysplastic syndrome].

Primary effusion lymphoma (PEL) is a large B-cell lymphoma that only proliferates proliferating effusion in the body cavity. It is associated with human herpesvirus 8 (HHV8).HHV8 negative effusion lymphoma, which is different from PEL in many ways, has also been reported and is referred to as HHV8-unrelated PEL-like lymphoma. This lymphoma is very rare and its clinical characteristics have not been fully clarified.A 79-year-old male developed HHV8-negative primary effusion lymphoma during treatment for myelodysplastic syndrome.Abdominal computed tomography revealed abdominal effusion, but did not show any evidence of a tumor mass or lymph node enlargement. A cytological analysis of his pleural effusion revealed atypical lymphoid cells that were negative for CD10, and positive for CD19 and CD20. Corticosteroids were administered to treat the abdominal effusion; however, the patient died of an exacerbation of lymphoma on the 20th day after the initiation of corticosteroid therapy. We herein report the case of an HIV seronegative elderly patient with HHV8-unrelated PEL-like lymphoma.

[A reference guide for paroxysmal nocturnal hemoglobinuria: recent updates and points of medical treatment].

Paroxysmal nocturnal hemoglobinuria (PNH) causes clonal expansion of hematopoietic stem cells with abnormal GPI-anchor biosynthesis. The major pathological condition of PNH is that the erythrocytes lacking the complement regulatory factors CD55 and CD59, which are GPI-anchored proteins, lead to intravascular hemolysis through complement activation. Clonal expansion has been assumed to be involved in an immunological attack on hematopoietic stem cells, and the bone marrow failure associated therewith modifies the pathology to varying degrees. The introduction of eculizumab made complement control possible; however, the problems associated with it became apparent as the treatment progressed. Additionally, the PNH Reference Guide was significantly revised in 2016, partly because PNH was designated as a Japanese medical subsidy. With the revised edition of 2020, minor revisions have been added to reflect further advances in treatment and understanding of the disease, while mainly dealing with the clinical introduction of eculizumab derivative, ravulizumab, which uses recycling antibody technology. This review outlines the points of the 2020 revision, including the important points of the previous revision.

[Persistent malnutrition caused by Nihonkaiense diphyllobothriasis diagnosed during treatment of malignant lymphoma].

A 72-year-old man with ileocecal lymphadenopathy was found to have Epstein-Barr virus-positive diffuse large B-cell lymphoma using open biopsy, and an ileostoma was created. R-CHOP-like chemotherapy was initiated, but his malnutrition did not improve. After 3 cycles of chemotherapy, a 2-m-long Cestoda was removed from the stoma and was identified as Diphyllobothrium nihonkaiense using mitochondria cytochrome c oxidase subunit 1 targeted polymerase chain reaction analysis. Although D. nihonkaiense infections are asymptomatic, the ileostomy was thought to have exacerbated the malabsorption in this patient. Parasitic infections are rare; however, they should be added to the differential diagnosis of malnutrition of unknown cause during chemotherapy for hematological malignancies.