A 24-year-old male patient with T-cell acute lymphoblastic leukemia was diagnosed with severe hypertriglyceridemia after the sixth administration of L-asparaginase during remission-induction therapy of the Japan Adult Leukemia Study Group (JALSG) -ALL 202-U protocol. Lipoprotein analysis revealed type IV hyperlipidemia, which is associated with a relatively low risk for pancreatitis. Hypertriglyceridemia immediately resolved after discontinuing L-asparaginase and beginning a lipid-restricted diet. The patient did not develop any severe complications of hypertriglyceridemia (e.g., pancreatitis and thrombosis) ; therefore, L-asparaginase could be readministered according to the treatment protocol. Four adult patients with L-asparaginase-induced severe hypertriglyceridemia have been reported to date; however, none of the reports indicated that L-asparaginase had been readministered. Thus, this is the first report of a patient receiving such readministeration. In order to evaluate the safety of continuing L-asparaginase, it is considered necessary to accumulate similar readministration cases.

Although all-trans retinoic acids (ATRA) are most commonly used as agents in acute promyelocytic leukemia (APL), there are few reports on the administration of ATRAs to patients with liver insufficiency. We report two cases of APL; a 57-year-old man with APL complicated by liver cirrhosis (Child-Pugh class B) and hepatocellular carcinoma who is receiving transcatheter arterial chemoembolization (TACE) and a 50-year-old man with APL complicated by liver cirrhosis (Child-Pugh class B) who is being prepared for receiving a living-donor liver transplantation. Both patients were successfully treated with a normal dosage of ATRA alone during remission-induction therapy. Because the total bilirubin and hepatic transaminases in the two cases were almost at normal levels; the patients received three courses of ATRAs plus a 42%-70% dose of anthracyclines as a consolidation therapy. At 1 year after receiving intermittent ATRA therapy, the patients are maintaining molecular remission. These cases suggest that the administration of ATRA and modifications of doses of chemotherapeutic agents are applicable to APL patients with liver dysfunction.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease that develops with a skin lesion and is often accompanied by leukemic transformation. The normal counterparts of BPDCN tumor cells are progenitors of plasmacytoid dendritic cells, whereas the origins are thought to be hematopoietic stem cells. Approximately 10%-20% of BPDCN patients develop other hematologic malignancies, including chronic myelomonocytic leukemia (CMML). Mutations in epigenetic regulators are frequently observed in both BPDCN and CMML tumors. Azacitidine, a drug that targets epigenetic dysregulation, is known to be an effective treatment for CMML. However, it has been used in few BPDCN patients. Here, we report a BPDCN patient with skin lesions, bone marrow infiltration, and lymphadenopathy. CMML also developed during the course of BPDCN. Azacitidine had positive effects on CMML; however, BPDCN aggressively relapsed during treatment. Two TET2 mutations were found in both BPDCN and CMML tumors; one of which was commonly identified in both tumors.

A 30-year-old primigravid woman without a history of thrombocytopenia was referred to our hospital because of severe thrombocytopenia (<1,000 thrombocytes/µl) at 16 weeks of gestation and diagnosed with idiopathic thrombocytopenic purpura (ITP). There was no improvement in the platelet count after treatment with 0.5-1.0 mg/kg/day prednisolone, and the 400 mg/day intravenous immunoglobulin (IVIg) administered for 5 days gradually became ineffective; therefore, a laparoscopic splenectomy was performed at 25 weeks of gestation. The increase in the platelet count after the splenectomy was temporary, but the effects of IVIg therapy improved, and the patient received IVIg therapy seven times in total during her pregnancy. Her platelet count ranged between 10,000 and 70,000/µl after the splenectomy, compared with <5,000/µl before the surgery. The patient underwent an elective cesarean section at 34 weeks of gestation without any significant bleeding. The baby was diagnosed with thrombocytopenia at birth (34,000 thrombocytes/µl) and was administered only one dose of IVIg, which increased the baby's platelet count to a normal level after 14 days. The patient's platelet count also increased after delivery. Splenectomy and repeated IVIg therapy can be considered for refractory severe ITP during pregnancy.

A 17-year-old woman was urgently transported to our hospital due to consciousness disturbance. A blood examination revealed intracerebral hemorrhage, WBC 233,800/l, blasts 93%, and disseminated intravascular coagulation. The results of bone-marrow aspiration indicated acute myeloid leukemia (M2 in FAB classification) with t (7;11) (p15;p15) and the resulting chimeric gene NUP98-HOXA9 and with FLT3-ITD. Following hematoma evacuation, induction therapy was initiated and the leukocytes in the cerebrospinal fluid observed in the spinal drainage were monitored. Because they increased on days 5 and 9 after the completion of induction therapy, intrathecal chemotherapy (IT) was performed; this finally contributed to controlling AML in the central nervous system (CNS), together with the restoration of normal hematopoiesis. Subsequently, after complete molecular remission with consolidation therapies containing high-dose cytarabine, a bone-marrow transplantation with a myeloablative regimen was conducted from a 1-allele mismatched sibling donor. Finally, the patient was discharged without major sequela on day 228 after the first visit. The management of CNS disease in AML with intracerebral hemorrhage remains unclear. Our case suggests that IT at the appropriate time based on the monitored number of cerebrospinal fluid leukocytes could be useful in controlling AML in the CNS after intracerebral hemorrhage.

While acute myeloid leukemia (AML) could cause an invasion of the central nervous system (CNS), the invasion of the CNS in myelodysplastic syndrome (MDS) is rare. Here, we report a case of juvenile MDS with cerebral infarction concerning the invasion of the CNS by leukemia cells. A 25-year-old male was admitted to our institution because of difficulty in extending the left arm. Magnetic resonance imaging revealed acute-stage cerebral infarction in the right parietal lobe and a diffuse edematous lesion in the surrounding site. In addition, leukemia cells were detected in the spinal fluid. Based on the bone marrow examination finding, he was diagnosed with MDS with excess blast 1. However, no clear disseminated intravascular coagulation and thrombotic diathesis were found in the blood test. If cerebral artery thrombosis occurs in MDS, the invasion of the CNS should be considered as a complication.

Chronic graft versus host disease (cGVHD) of the central nervous system is a rare condition that could occur after allogeneic hematopoietic stem cell transplantation (SCT) but has been poorly documented. Here, we report a patient diagnosed with recurrent acute disseminated encephalomyelitis (ADEM) with longitudinal extensive transverse myelitis (LETM) as cGVHD after HLA haploidentical peripheral blood SCT using posttransplantation cyclophosphamide for mixed-phenotype acute leukemia. We observed clinical and radiological improvement after the rituximab treatment of the condition that had been refractory to steroids. To the best of our knowledge, no report of cGVHD presented recurrent ADEM with LETM after allogeneic SCT and successfully treated with rituximab. Hence, ADEM should be included in the differential diagnosis of neurological symptoms in posttransplant patients with cGVHD.

An 80-year-old female with fever, edema in the lower extremities, and marked eosinophilia was referred to our hospital. Based on the presence of the Philadelphia chromosome, she was diagnosed with chronic myeloid leukemia (CML). Although imatinib induced a complete cytogenetic response (CCyR), CML relapsed after 28 months of starting it. A CCyR was achieved again by nilotinib but was lost after about 14 months. Only transient response occurred to dasatinib, and the patient died. At relapse, neutrophilia was more predominant than eosinophilia. We reviewed 6 patients with CML whose eosinophil rate in the peripheral blood was >50%. Most patients were males with palpable splenomegaly and had cardiac disorders, peripheral vascular disease, or pleural effusion. Typically, CML causes neutrophil-predominant leukocytosis. However, a subgroup of CML with marked eosinophilia resembles chronic eosinophilic leukemia or idiopathic hypereosinophilic syndrome.

A 60-year-old man with chronic hepatitis C was referred to our hospital with significantly elevated total protein and serum IgM (9,500 mg/dl) levels identified via a routine checkup. Blood examination revealed increased serum IgM-monoclonal protein and serum-soluble IL-2 receptor (sIL2R) levels. Computed tomography and fluorodeoxyglucose positron emission tomography revealed pulmonary masses, abnormal soft tissue masses surrounding the bilateral kidneys, and thickened mucous membrane of the bladder with high fluorodeoxyglucose uptake. Pathological examination of the pulmonary mass revealed infiltration of medium-sized lymphocytes and plasma cells. Immunohistochemical analysis revealed tumor cells positive for CD138 and IgM, with a low positive rate of Ki-67 expression. Notably, the tumor cell-surrounding lymphocytes were positive for CD20. Although the patient was initially regarded as having Waldenström's macroglobulinemia owing to the significantly increased serum IgM levels, based on positive IgH-MALT1 translocation and negative MYD88 L265P mutation findings, he was further diagnosed with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Complete remission was achieved following six cycles of rituximab + CHOP therapy. This study data suggest that analysis of the MYD88 L265P mutation in tumor cells is suitable for accurately diagnosing hematopoietic malignancies with increased IgM monoclonal protein.

A 76-year-old woman taking anagrelide (ANA) for essential thrombocythemia (ET) was rushed to the hospital by ambulance because of severe chest pain. Echocardiography revealed apical akinesis with basal and mid-hyperkinesis, and a coronary angiography revealed no significant stenosis in the dominant coronary artery. The patient was diagnosed with takotsubo cardiomyopathy (Tako). Tako is typically believed to be caused by stress; however, no stress was detected except that related to ANA therapy. ANA is useful in treating ET and is known to have severe cardiovascular effects. We must pay careful attention to Tako during ANA therapy.