[Haploidentical stem cell transplantation for acute myeloid leukemia associated with adult-onset Shwachman-Diamond syndrome].

A 21-year-old man presented with bone marrow failure, short stature, fatty degeneration of the pancreas on CT images, and Shwachman-Bodian-Diamond syndrome (SBDS) gene abnormalities (exon 2: c.258+2T>C and deletion of exon 3). Thus, the patient was diagnosed with Shwachman-Diamond syndrome (SDS). In the clinical course, the patient developed acute myeloid leukemia (AML). Hematopoietic stem cell transplantation from the human-leukocytic-antigen-haploidentical father of the patient was performed. The patient was conditioned with 150 mg/m2 fludarabine, 6.4 mg/kg busulfan, and 4 Gy total body irradiation. Graft-versus-host disease prophylaxis included tacrolimus, micophenolate mofetil, and posttransplant cyclophosphamide. Although the patient achieved a complete remission on day 21, AML relapsed on day 434 after the transplantation. He died of sepsis. The prognosis of patients with SDS and AML is poor. Adult-onset cases must be recognized, and transplantation should be performed during bone marrow failure.

Granulocyte colony-stimulating factor protects cardiac mitochondria in the early phase of cardiac injury.

Although granulocyte colony-stimulating factor (G-CSF) reportedly plays a cardioprotective role in several models of cardiac injury, clinical use of this drug in cardiac patients has been controversial. Here, we tested, in vivo and in vitro, the effect of G-CSF on cardiac mitochondria, which play a key role in determining cardiac cellular fate and function. Mild stimulation of C57/BL6 mice with doxorubicin (Dox) did not induce cardiac apoptosis or fibrosis but did induce damage to mitochondrial organization of the myocardium as observed through an electron microscope. Cardiac catheterization and echocardiography revealed that Dox did not alter cardiac systolic function or left ventricular size but did reduce diastolic function, an early sign of cardiac damage. Treatment with G-CSF attenuated significantly the damage to mitochondrial organization and rescued diastolic function. In an in vitro model for rat neonatal cardiomyocytes, a subapoptotic dose of Dox induced severe mitochondrial damage, including marked swelling of the cardiac mitochondria and/or decreased mitochondrial membrane potential. These mitochondrial changes were completely blocked by pretreatment with G-CSF. In addition, G-CSF dramatically improved ATP generation, which rescued Dox-impaired mitochondrial electron transport and oxygen consumption mainly through complex IV. These findings clearly indicate that G-CSF protects cardiac mitochondria, which are key organelles in the determination of cardiac cellular fate, in the early phase of cardiac injury.

Endoscopic injection sclerotherapy for esophageal varices in cirrhotic patients without hepatocellular carcinoma: a comparison of longterm survival between prophylactic therapy and emergency therapy.

BACKGROUND: This study aimed to determine whether prophylactic endoscopic injection sclerotherapy prolonged survival in patients with esophageal varices complicated by liver cirrhosis in the absence of hepatocellular carcinoma, compared with emergency sclerotherapy. METHODS: The subjects included 160 patients suffering from esophageal varices complicated by liver cirrhosis without hepatocellular carcinoma. Sixty-eight patients underwent emergency therapy for bleeding varices and the remaining 92 patients underwent prophylactic sclerotherapy. All subjects continued to receive therapy until the varices disappeared. RESULTS: Five-year survival was significantly better in the prophylactic group compared with the emergency group. During the 5-year observation period, 20 of the 68 patients in the emergency group experienced rebleeding and 5 patients died as a result of rebleeding. These rates were significantly higher than those in the prophylactic group (1 of 9 patients with bleeding died among the 92 prophylactic sclerotherapy patients). Multivariate analysis showed that prophylactic therapy and Child's C hepatic function were significant factors for 5-year survival. CONCLUSIONS: Prophylactic sclerotherapy for esophageal varices might be more effective in prolonging longterm survival of patients complicated by liver cirrhosis in the absence of hepatocellular carcinoma, compared with emergency sclerotherapy.