[Sustained molecular remission with a tyrosine kinase inhibitor alone for seven months in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia].

Herein, we report the case of a 28-year-old man with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL). The patient received induction chemotherapy, including imatinib (IM) therapy, which required early cessation because of a severe infection. After the resolution of the infection, general flaccid paralysis was observed, which was diagnosed as critical illness myopathy (CIM). Ph(+)ALL showed molecular remission (MR) on day 42. We intended to maintain MR with only IM therapy for several months until the improvement of CIM; however, owing to the patient's intolerance to IM, therapy was changed to dasatinib. Because the symptoms of myopathy gradually improved and disappeared completely, the patient was able to undergo one course of intensive chemotherapy and allogeneic stem cell transplantation from an HLA-matched sibling donor, 8 months after admission (7 months after the re-administration of IM). Thus, this case report suggests that a tyrosine kinase inhibitor is an alternative therapy for maintaining the response of Ph(+)ALL patients who refrain from conventional chemotherapy.

[Acute leukemia of ambiguous lineage with monosomy 7 and Philadelphia chromosome].

A 67-year-old female was admitted with a diagnosis of acute leukemia. Immature blasts did not show cytoplasmic granules and were POX(-), ES(-), and PAS(+). Flow cytometry of leukemic cells demonstrated positivity for CD7, CD10, CD19, CD13, CD34, HLA-DR, and coexpression of CD7 and CD34, CD10 and HLA-DR, and CD19 and CD13. Cytogenetic analysis demonstrated -7 and t(9;22)(q34;q11.2), and genomic studies demonstrated minor BCR/ABL chimeric mRNA and rearrangements of IgH and TCR. These findings indicated the clonal proliferation of leukemic blasts that expressed a mixed phenotype. Acute leukemia of ambiguous lineage was diagnosed, although the significance of the specificity of lineage markers remains unclear. The differential diagnosis included CML and B-ALL. The patient was treated according to Ph+ALL. However, the hematological response was poor, with persistent residual blasts and severe pancytopenia. The subsequent administration of imatinib mesylate led to a complication of heart failure, and the patient died on the 19th hospital day.

[Neurological disturbance of the lower extremities by an extramedullary hematopoietic mass complicated with primary myelofibrosis].

A 59-year-old man with primary myelofibrosis developed motor and sensory neurological disturbance of the legs. Magnetic resonance imaging (MRI) demonstrated a mass lesion of the thoracic vertebra at Th4-6, and in the thoracic vertebral canal at Th4-9, which compressed the spinal cord. Needle biopsy of the mass lesion demonstrated extramedullary hematopoiesis. Initial treatment with bolus methylprednisolone was ineffective and, after subsequent radiation therapy, the mass lesion disappeared and the neurological symptoms ameliorated; however, regrowth of the extramedullary lesion was observed one month later. Surgical resection of the extramedullary lesion, laminectomy, and subsequent radiation were performed. The clinical course after the final treatment was good with no neurological symptoms, although the follow-up period is still short.

Massive ascites associated with all-trans retinoic acid treatment in therapy-related acute promyelocytic leukemia.

A 77-year-old man who developed pancytopenia was administered granulocyte colony-stimulating factor (G-CSF) by another doctor, and referred to us for the evaluation of pancytopenia. He had hepatocellular carcinoma and was treated with transcatheter arterial chemoembolization (TACE) containg epirubicin (total dose: 300 mg over the last two years). Bone marrow aspiration smear demonstrated hypercellular marrow with promyelocytes. Cytogenetic analysis demonstrated del(7), t(15;17)(q22;q12), and a fluorescence in-situ hybridization (FISH) study demonstrated chimeric fusion genes of PML-RAR-alpha. He was diagnosed with therapy-related acute promyelocytic leukemia (APL), and treated with all trans-retinoic acid (ATRA). He showed the progressive accumulation of ascites with liver damage, without pulmonary symptoms of ATRA differentiation syndrome. After 60 days of ATRA treatment, complete hematological and cytogenetic responses were achieved. However, the patient died of septic circulatory failure.

Transient severe pancytopenia due to elevated tumor necrosis factor-alpha in overwhelming infection.

A 66-year-old woman complained of fever, sore throat, and neck pain due to pharyngitis and painful lymph node swelling. CBC revealed severe pancytopenia and markedly hypocellular marrow. The administration of antibiotics and granulocyte-colony stimulating factor (G-CSF) successfully ameliorated the inflammatory lesions, and hematopoiesis recovered. Causes for pancytopnenia was unlikely to be virus infection or drugs, and aplastic anemia was also unlikely since only the plasma levels of tumor necrosis factor-alpha (TNF-alpha) was markedly elevated, erythropoietin (EPO) was slightly elevated, interferon-gamma (IFN-gamma) was normal, and flow cytometric analysis for paroxysmal nocturnal hemoglobinuria (PNH)-type cells was negative. These results suggested that the cause of impaired hematopoiesis in the present patient might have been due to elevated TNF-alpha in overwhelming infection, although the pathogen was not identified.

Systemic AL amyloidosis with disseminated intravascular coagulation associated with hyperfibrinolysis.

Many coagulation abnormalities are known to coexist in patients with AL amyloidosis; however, disseminated intravascular coagulation (DIC) is rarely observed. We describe the case of a 61-year-old woman who presented with systemic purpura, macroscopic hematuria, and hepatosplenomegaly as the initial manifestations of systemic AL amyloidosis. A coagulation study revealed severe DIC associated with fibrinolysis. The patient was treated for DIC with gabexate mesilate (GM); however, her bleeding symptoms and thrombocytopenia continued to worsen. The treatment was changed from GM to nafamostat mesilate (NM); DIC improved gradually, and the platelet count normalized in 1 week. After the tapering and cessation of NM therapy, deterioration of DIC did not occur. She underwent autologous peripheral blood stem cell transplantation twice following high-dose melphalan therapy, and received maintenance therapy with thalidomide. Hepatosplenomegaly progression appears to have been halted, and DIC has not recurred. This is the first reported case of AL amyloidosis showing severe DIC with excessive fibrinolysis. The clinical observation that NM was considerably more effective than GM in our patient suggests that NM may be more suitable for the treatment of DIC with a hyperfibrinolytic condition in AL amyloidosis patients.

[Congenital factor XIII deficiency required high-dose factor XIII concentrate in late pregnancy].

Congenital factor XIII (FXIII) deficiency is a rare congenital hemorrhagic disorder. Since FXIII is an essential factor in pregnancy, pregnant patients with congenital FXIII deficiency should receive adequate replacement of FXIII concentrate. We report here on a 19-year-old pregnant woman with congenital FXIII deficiency. Despite regular replacement of FXIII concentrate, FXIII activity decreased rapidly after 32 weeks of gestation and she had to receive a high-dose of FXIII concentrate until delivery. Careful monitoring of FXIII activity is needed in patients with congenital FXIII deficiency, because FXIII activity may decrease rapidly in late pregnancy.