A 54-year-old woman presented with a chief concern of right back pain that had persisted for 3 weeks. Laboratory tests revealed pancytopenia, liver dysfunction, and coagulation abnormalities. She had hepatomegaly and splenomegaly but no lymphadenopathy. No abnormal cells were detected in the bone marrow or on a liver biopsy. Epstein-Barr virus (EBV) DNA levels in the peripheral blood were high at 6.44 log IU/ml, and clonality of EBV-infected cells was confirmed by Southern blot hybridization with a probe targeting the EBV terminal repeat. EBV-infected NK cells were detected using the magnetic bead method. This led to a diagnosis of EBV-associated lymphoproliferative disease (EBV-LPD). As pancytopenia and coagulation abnormalities induced by the development of hemophagocytic syndrome continued to worsen after steroid therapy, we performed intensive chemotherapy followed by umbilical cord blood transplantation. After transplantation, EBV-DNA levels in the peripheral blood were undetectable, with complete donor chimerism. In the present case, the rapid disease progression with an extremely high EBV-DNA level indicated a poor prognosis. Intensive chemotherapy followed by upfront allogeneic hematopoietic cell transplantation may be necessary in patients with rapidly progressing EBV-LPD.

Patient 1 was a 65-year-old woman diagnosed with chronic myeloid leukemia (CML) in 2016. She was treated with dasatinib at a dose of 100 mg. After achievement of deep molecular remission (DMR) in 2018, the dasatinib dose was decreased to 50 mg a day. In April 2021, the patient suddenly developed high fever, skin swelling and redness, muscle swelling, and pain in bilateral lower extremities. Detection of G type hemolytic streptococcus in blood culture led to a diagnosis of streptococcal toxic shock syndrome (STSS). The patient recovered from disseminated intravascular coagulation and multiple organ failure by treatment with several antibiotics, fresh frozen plasma (FFP), and plasma exchange over a period of 2 months. Patient 2 was a 53-year-old man who developed CML in 2011. He was prescribed nilotinib, but efficacy could not be evaluated due to poor treatment adherence. Treatment with dasatinib was started instead within a year. DMR was achieved, but the patient developed STSS in July 2021. Both of these cases of STSS occurred in patients treated with dasatinib, which suggests that STSS may be related to dasatinib treatment in CML patients. We conducted a literature review to determine whether CML treatment selection was appropriate in these patients.

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytic disease with no established therapeutic approach. Here we report a case of ECD treated with molecular targeted therapy. A 61-year-old woman diagnosed with ECD with BRAF^V600E mutation received combination therapy with a BRAF inhibitor (dabrafenib) and MEK inhibitor (trametinib). Grade 1 fever and liver injury were detected early in the course of treatment, leading to temporary interruption. However, treatment was successfully resumed with concomitant administration of prednisolone. The BRAF^V600E allele frequency in plasma cell-free DNA became negative at 8 weeks of treatment, and PET/CT confirmed a partial metabolic response at 24 weeks. Recent studies have demonstrated the benefit of molecular targeted therapy for ECD. However, due to the rarity of ECD, treatment guidelines remain poorly defined, with limited guidance on indicators of treatment efficacy, optimal treatment duration, and criteria for treatment cessation. In the case of our patient as well, it will be necessary to consider the duration of treatment while carefully monitoring the clinical course.

A 31-year-old man presented with abdominal colic, lumbago, shortness of breath on exertion, and nausea that had begun one month earlier. Imaging and endoscopic findings were unremarkable, but the patient was referred to a hematologist due to detection of normocytic anemia. Blood tests showed increased reticulocytes with a pattern of impaired iron utilization. Bone marrow examination revealed erythroid hyperplasia with a predominance of type II-III sideroblasts. However, the dysplasia remained mild, and no chromosomal abnormalities were observed. Further workup was conducted based on the patient’s occupational history as an auto mechanic and the characteristic abdominal symptoms. This revealed a significant increase in blood free protoporphyrin and urinary δ-aminolevulinic acid levels as well as an elevated blood lead concentration (71.8 µg/dl), leading to a diagnosis of lead poisoning. Symptoms improved with chelation therapy. Lead poisoning is caused by oral or respiratory ingestion of lead present in paint, ceramics, batteries, and other products. Anemia, abdominal pain, and neurological symptoms are the three main symptoms, but irreversible encephalopathy and renal dysfunction may develop in severe cases. It is important to consider lead poisoning as a differential diagnosis in cases of unexplained abdominal pain and anemia.

A 71-year-old man was diagnosed with extranodal NK/T-cell lymphoma (ENKTL) in 2008. He underwent chemoradiotherapy and achieved complete remission, with no relapse during follow-up (discontinued in 2013). In 2022, he presented with nasal obstruction and epistaxis, and ENKTL relapse was suspected because the lesion was localized to the original nasal site. However, histopathological examination of a biopsy specimen confirmed a diagnosis of Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma. Although both diseases are EBV-associated neoplasms, they derive from different lymphoid lineages and may arise metachronously at the same site. Careful differential diagnosis is essential because treatment strategies differ.

Acute myeloid leukemia (AML) is associated with various genetic abnormalities in its development and progression, which also affect treatment response and prognosis. The advent of gene panel testing is expected to clarify the involvement of these genetic mutations, which will provide useful information for treatment decision-making and prediction of prognosis in clinical practice. Some therapies have already been developed for actionable mutations: quizartinib for FLT3-ITD mutations is available for newly diagnosed AML, and ivosidenib for IDH1 mutations is awaiting approval. Knowledge of baseline genetic characteristics also allows for diagnosis according to the ICC 2022 and 5th edition of the WHO Classification, as well as risk stratification by the ELN2022 risk classification for patients receiving intensive chemotherapy and ELN2024 risk classification for patients receiving reduced-intensity chemotherapy. CPX-351, a liposomal formulation of cytarabine and daunorubicin, has also shown efficacy in patients with MDS-related gene mutations. Decisions on allogeneic transplantation and accessibility of investigational drugs are also expected. Detailed diagnosis and prognosis prediction based on the profile of genetic abnormalities should enable precision medicine.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a key curative option in the treatment of acute myeloid leukemia (AML), and its indication should be carefully determined on the basis of prognostic factors and treatment response. Recent advances in genetic profiling and measurable residual disease (MRD) monitoring using RT-qPCR or flow cytometry have significantly influenced decisions on transplant timing and necessity. This review outlines current transplant indications according to the ELN risk classification, strategies for patients not in remission, the clinical utility of MRD assessment, and recent developments in post-transplant maintenance and relapse treatment, while also taking into account current practices and perspectives in Japan. Rather than relying on fixed criteria, transplant strategies should be tailored through an integrated evaluation of disease biology, MRD status, age, comorbidities, and overall patient fitness. This individualized approach helps optimize patient outcomes in the evolving treatment landscape of AML. Ongoing reassessment of transplant eligibility is needed to reflect current evidence and clinical realities.

Acute myeloid leukemia (AML) is common in elderly adults and is a genetically heterogeneous disease. Many factors such as adverse chromosomal and/or genetic abnormalities contribute to disease risk, along with defining features related to antecedent hematologic disorders and a history of exposure to radiation or cytotoxic agents in the case of secondary AML. The “7+3” regimen combining cytarabine and anthracycline, along with its reduced-dose variant, was once the only first-line treatment option for AML in Japan. However, treatment options have expanded in recent years to include azacitidine with or without venetoclax, as well as CPX-351 and quizartinib combination chemotherapy. Nevertheless, there are still many high-risk conditions with a low chance of cure even with these new drugs or allogeneic transplantation, and many other issues remain to be addressed. This article outlines the current best treatment options and future prospects for high-risk disease types.

Treatment strategies for unfit patients with acute myeloid leukemia (AML) are undergoing fundamental changes. Recent advances in molecularly targeted therapies have led to the development of safe and effective regimens, providing new treatment options. Every day, important findings are emerging that are dramatically changing the treatment paradigm for patients with unfit AML. New risk classifications based on clinical data from unfit cases are being developed in response to identification of prognostic factors determining response to the new standard therapy, venetoclax plus azacitidine, as well as to newer regimens. This article reviews validated clinical trial data for unfit AML and discusses the current best treatment options and future challenges.

Relapsed or refractory acute myeloid leukemia (AML) continues to have a poor prognosis, highlighting the urgent need for novel therapeutic approaches. Immunotherapy, with its distinct mechanisms of action from chemotherapy or molecularly targeted therapies, offers a promising option for treatment-resistant cases. To date, numerous chimeric antigen receptor (CAR) T cell products targeting surface antigens such as CD33, CD123, and CLL-1 have been developed and evaluated in clinical trials. T cell receptor (TCR)-T therapies targeting intracellular antigens such as WT1 are also in development, with some clinical studies reporting encouraging results. However, the development of cell therapies for AML presents unique challenges, including the identification of suitable surface target antigens and overcoming the immunosuppressive tumor microenvironment. Consequently, no cellular product has yet achieved regulatory approval. This article provides an overview of the current landscape and key challenges in the development of cell therapies for AML.

While acute myeloid leukemia (AML) treatment has significantly advanced in recent years, many promising novel agents remain unapproved in Japan. This review focuses on menin inhibitors and covers IDH inhibitors, oral azacitidine, antibody-drug conjugates, bispecific antibodies, radioisotope therapies, and CAR-T cell therapies for AML. Menin inhibitors, which are particularly effective against AML with KMT2A rearrangements or NPM1 mutations, have shown promising results in clinical trials. These novel agents may expand treatment options and improve outcomes for AML patients.