The JAK2V617F mutation is a driver mutation of myeloproliferative neoplasms (MPNs). V617F allele burden is considered a risk factor for complications associated with MPNs and is a predictor of prognosis. In Japan, V617F allele burden has been measured in laboratory settings using the i-densy^TM IS-5320 genetic analyzer with the quenching probe-Tm (QP-Tm) method. However, since 2020, allele-specific quantitative PCR (AS-qPCR) is being performed in clinical settings for measuring V617F allele burden. To investigate the clinical usefulness of the QP-Tm method in patients with MPNs, we evaluated the V617F allele burden measured by both the methods. A good correlation was observed between the V617F allele burden determined using QP-Tm and that determined using AS-qPCR (P<0.001, rs=0.952). The median mutant allele burden, as determined using the QP-Tm method, was significantly higher in patients with polycythemia vera than in those with essential thrombocythemia. The results of this study suggested that the QP-Tm method will continue to be useful clinical ancillary test for measuring V617F allele burden.

Sarcopenia is associated with poor clinical outcomes in elderly patients with diffuse large B-cell lymphoma (DLBCL). However, the clinical significance and optimal assessment of sarcopenia remain unclear. We retrospectively evaluated the prognostic value of low skeletal muscle mass based on the psoas muscle index (PMI) in patients with DLBCL aged 70 years and older treated with R-CHOP therapy. We included 71 patients, including 27 classified under low PMI. There were no differences in baseline characteristics (body mass index, lactate dehydrogenase, performance status [PS], stage, revised-IPI, relative dose intensity) and overall response rate between the low and high PMI groups. The low PMI group had a significantly worse overall survival (OS, p=0.015), but not progression-free survival (PFS, p=0.252), compared with the high PMI group. On multivariate analysis, low PMI and PS were independent negative prognostic factors for OS. Subgroup analysis revealed that the low PS groups had significantly worse PFS regardless of the PMI status. The low PMI and low PS group had markedly poorer OS than all the other groups. However, the poor prognosis associated with low PS was overcome by a high PMI.

A 60-year-old woman developed a fifth thoracic spine fracture with progressive paraplegia and underwent posterior spine fusion in June 2018. Based on the histopathological analysis of the surgical specimen, she was diagnosed with KIT D816V-positive systemic mastocytosis (SM). In June 2019, peripheral blood examination revealed remarkable eosinophilia. She was given prednisolone, which resulted in the resolution of eosinophilia. In May 2020, she developed acute myeloid leukemia (AML). Induction therapy was initiated and complete remission achieved. Subsequently, she received one course of consolidation therapy and allogeneic hematopoietic stem cell transplantation (allo-SCT). Although the residual mast cell tumor aggravated during chemotherapy for AML, the tumor regressed after allo-SCT, suggesting a graft-versus-mastocytosis effect. Nine months after the transplantation, the patient is alive and healthy without recurrence of AML and SM.

Immunosuppressive therapies, including antithymocyte globulin and cyclosporine (CsA), are used for the treatment of aplastic anemia, but they reportedly cause lymphoproliferative diseases. Here, we report two cases of aplastic anemia in which diffuse large B-cell lymphoma developed during treatment with CsA. In both the cases, CsA was discontinued and combination therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisolone) plus the thrombopoietin receptor agonist eltrombopag was initiated. Furthermore, supportive care, including blood transfusion and granulocyte colony-stimulating factor, was provided. After six or eight courses of R-CHOP therapy, a complete metabolic response was achieved without serious adverse events. These cases illustrate the safety of combining R-CHOP with eltrombopag therapy in patients at a high risk of severe pancytopenia.

At initial diagnosis, central nervous system (CNS) involvement in acute promyelocytic leukemia (APL) is rare. Here, we report a case of newly diagnosed APL with CNS involvement that was successfully treated with all-trans retinoic acid (ATRA)-combined chemotherapy. A 64-year-old woman was referred to our hospital to evaluate a bleeding tendency, and she was diagnosed with APL. Induction chemotherapy with ATRA via a nasogastric tube was initiated under mechanical ventilation because of respiratory failure and disturbance of consciousness. Although her respiratory condition improved a few days after initiating treatment, the disturbance of consciousness remained. Brain magnetic resonance imaging showed mixed signals of tumor infiltration and acute cerebral infarction with a focus on the right cerebellum. The patient was diagnosed with CNS involvement of APL and acute cerebral infarction. Three months after the initiation of induction therapy, her consciousness improved along with the reduction in CNS involvement, and complete molecular remission was achieved. Thus, patients with APL can have CNS involvement at initial diagnosis. Administering ATRA via nasogastric tube can be a good therapeutic option in patients with difficulty swallowing due to disturbance of consciousness.

Monoclonal gammopathy of undermined significance (MGUS) is usually asymptomatic, and untreated follow-up is the standard treatment. However, MGUS progresses to multiple myeloma or related malignancy at a frequency of 1.5% per year. It is sometimes difficult to diagnose the progression of the disease via usual examinations. We herein report a case wherein rapid renal dysfunction led to a diagnosis of disease progression to multiple myeloma in a patient with MGUS that was asymptomatic for a long time. A 66-year-old woman developed rapid renal dysfunction requiring continuous hemodiafiltration 8 years after the diagnosis of IgA-κ type MGUS. A complete examination led to the diagnosis of IgA-κ type multiple myeloma. Chemotherapy was not effective, and she died due to sepsis on the 19th day of admission. A pathological autopsy revealed systemic amyloidosis and multiple abscesses positive for Staphylococcus aureus. An abnormal free light chain κ/λ ratio and M protein other than IgG are reportedly risk factors of disease progression of MGUS. In cases with these risk factors, it is important to always keep in mind the possibility of disease progression and to monitor the patient carefully for an early diagnosis.

Graft-versus-host disease (GVHD) is a life-threating complication of allogeneic hematopoietic cell transplantation (allo-HCT). Prior studies have shown that gastrointestinal (GI) GVHD is associated with a reduction in intestinal microbiota diversity and a change in microbial metabolites. We conducted fecal metabolome analyses using a murine bone marrow transplantation. From this analysis, 290 metabolites were identified; of these, 18 metabolites were significantly or specifically higher and 12 were significantly or specifically lower in the allogeneic group than in the syngeneic one. Particularly, several metabolites in the choline metabolism and tryptophan metabolism were altered in the allogeneic group. Hierarchical clustering analysis demonstrated that the changed metabolites in the allogeneic group had similar profiles. Conclusively, we suggest that alloimmune responses are related to microbial metabolites in recipients receiving allo-HCT. The relationship between metabolites involved in GI GVHD and the intestinal microbiota and its physiological significance warrant further investigations.

Post-transplant cyclophosphamide (PTCy) has improved the efficacy of HLA-mismatched hematopoietic cell transplantation (HCT) by decreasing the risk of graft-versus-host disease (GVHD) and nonrelapse mortality. If an HLA-matched donor is not available, GVHD prophylaxis with PTCy can also be used for HLA-mismatched HCT in patients with pediatric aplastic anemia (AA). We report two cases of pediatric AA that were treated with HLA-mismatched HCT with reduced-intensity conditioning and PTCy. We administered 50 mg/kg/day Cy for GVHD prophylaxis on days 3 and 4, and tacrolimus and mycophenolate mofetil (or methotrexate) were initiated from day 5. In both the cases, the time to engraftment was favorable and GVHD and infection were controllable. PTCy probably allows us to expand donor candidates in pediatric AA when an HLA-matched donor is not available; however, further studies regarding optimal conditioning regimens and late complications are required.

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.

Neuropsychiatric symptoms comprise one of the five classic symptoms of autoimmune thrombotic thrombocytopenic purpura (aTTP). Although aTTP is typically transient, it is sometimes complicated by cerebral infarction with residual disability. This report presents the case of an 87-year-old man previously admitted to a different hospital with fever and transient consciousness loss. After receiving platelet transfusion with diagnosis of Evans syndrome, he was transferred to our hospital with worsening consciousness disturbance. He was subsequently diagnosed with aTTP with a PLASMIC score of 6 points, ADAMTS13 activity of less than 0.5%, and its inhibitor of 7.4 BU/ml. Platelet count and consciousness were rapidly improved with plasmapheresis and steroids, but motor aphasia emerged. MRI showed multiple cerebral infarctions, including a large infarction in the left frontal lobe. Thus, unfractionated heparin was administered. When his platelet count dropped once again on the 20th day, rituximab was added. The treatment eventually proved to be successful, and his aTTP remained in remission one year after the onset. Treatment for cerebral infarctions was switched to DOAC, and rehabilitation was continued. However, his ADL has not yet recovered. Advances in aTTP treatment have cured many similar cases. Thus, rituximab is now considered a treatment option for refractory cases. However, ischemic organ damage in acute phase and sequelae are observed. Therefore, early diagnosis and novel therapy are required.

We report a case of invasive fungal infection (IFI) that ensued during ibrutinib treatment. A 79-year-old female was diagnosed with chronic lymphocytic leukemia seven years prior. She had undergone chemotherapy at the ages of 72 and 75. Subsequently, she was placed on ibrutinib treatment at the age of 79. On the 119th day after the ibrutinib treatment initiation, she was admitted to our hospital with the complaints of frequent urination and hematuria, and three days later, she died of disseminated cryptococcosis.

IFIs should be considered in the event of infections that develop early after the ibrutinib treatment initiation.