We conducted a prospective randomized study to assess the optimal postremission therapy for adult acute myeloid leukemia in patients younger than 65 years in the first complete remission. A total of 781 patients in complete remission were randomly assigned to receive consolidation chemotherapy of either 3 courses of high-dose cytarabine (HiDAC, 2 g/m 2 twice daily for 5 days) alone or 4 courses of conventional standard-dose multiagent chemotherapy (CT) established in the previous JALSG AML97 study. Five-year disease-free survival was 43% for the HiDAC group and 39% for the multiagent CT group (P ‫؍‬ .724), and 5-year overall survival was 58% and 56%, respectively (P ‫؍‬ .954). Among the favorable cytogenetic risk group (n ‫؍‬ 218), 5-year diseasefree survival was 57% for HiDAC and 39% for multiagent CT (P ‫؍‬ .050), and 5-year overall survival was 75% and 66%, respectively (P ‫؍‬ .174). In the HiDAC group, the nadir of leukocyte counts was lower, and the duration of leukocyte less than 1.0 ؋ 10 9 /L longer, and the frequency of documented infections higher. The present study demonstrated that the multiagent CT regimen is as effective as our HiDAC regimen for consolidation. Our HiDAC regimen resulted in a beneficial effect on disease-free survival only in the favorable cytogenetic leukemia group. This trial was registered at www.umin.ac.jp/ ctr/ as #C000000157. IntroductionApproximately 70% to 80% of the newly diagnosed younger adult patients with acute myeloid leukemia (AML) achieve complete remission (CR) when treated with an anthracycline, usually daunorubicin (DNR) or idarubicin (IDR), and cytarabine (Ara-C); however, only approximately one-third of these patients remain free of disease for more than 5 years. [1][2][3][4][5] If CR patients are left untreated, almost all of them will relapse and die. 6 Therefore, postremission therapy is indispensable. Postremission therapy is divided into consolidation and maintenance therapy. In the previous studies of Japan Adult Leukemia Study Group (JALSG) for adult AML (AML87, 89, 92, and 95), 1-3,5 we administered 3 courses of consolidation therapy and 6 courses of intensified maintenance therapy. In the AML97 study, 7 we conducted a randomized study to compare the conventional 3-course consolidation and 6-course maintenance therapies with 4 courses of intensive consolidation therapy without maintenance and demonstrated no difference in overall survival (OS) and disease-free survival (DFS). Therefore, the 4 courses of conventional standard-dose multiagent chemotherapy (CT) became the standard regimen in Japan. On the other hand, multiple cycles of high-dose cytarabine (HiDAC) have been commonly used as consolidation therapy in the United States and other countries. However, our national medical insurance system did not allow us to use HiDAC until 2001, and thus we could not use HiDAC in the previous treatment regimens for leukemia. We therefore conducted this prospective, multicenter cooperative An Inside Blood analysis of this article appears at the front of this issu...

Summary:Eighty patients receiving hematological stem cell transplantation (HCT) with a preparative regimen consisting of total body irradiation (12.5 Gy), cyclophosphamide (4000 or 4500 mg/m 2 ), and thiotepa (400 mg/m 2 ) were evaluated for the development of cardiac toxicity. Patients in whom the pretransplant cumulative dose of anthracycline was more than or equal to 300 mg/m 2 showed a lower left ventricular ejection fraction (EF) before HCT compared to patients with less than 300 mg/m 2 (0.61 ؎ 0.09 vs 0.67 ؎ 0.06, P = 0.0010). Patients who had undergone more than or equal to six courses of chemotherapy showed a decreased EF before HCT compared to those after less than six courses (0.67 ؎ 0.05 vs 0.63 ؎ 0.09, P = 0.03). Three of seven patients (43%) whose pretransplant EF had been less than or equal to 0.55 developed severe cardiac toxicity, characterized by congestive heart failure (CHF) compared with none of 83 patients (0%) whose pretransplant EF had been more than 0.55 (P = 0.00026). Of the three patients who developed severe cardiac toxicity, two were given more than 300 mg/m 2 of cumulative anthracycline and underwent 23 courses and six courses of chemotherapy, while the other patient received only two courses of chemotherapy with a total dose of 139 mg/m 2 of anthracycline. These results indicate that an increased cumulative dose of anthracycline and number of chemotherapy treatments are correlated with a decrease of the EF and that the EF before HCT is useful for predicting the risk of cardiac complications for recipients who have received chemotherapy. Bone Marrow Transplantation (2001) 27, 307-310. Keywords: ejection fraction; cardiac toxicity; cyclophospamide; anthracycline; BMT High-dose cyclophosphamide (CY) used in transplant conditioning can induce cardiac toxicity. It occurs most com- monly after doses of 180 mg/kg or more, and signs and symptoms of congestive heart failure (CHF) occur within the initial 2 or 3 weeks after hematological stem cell transplantation (HCT). 1,2 Many patients receive anthracycline antibiotics, which impair cardiac function in a dose-dependent manner. 3 It is unclear whether anthracycline given prior to a transplant increases the risk of CY-induced cardiac toxicity and whether the occurrence of cardiac toxicity is correlated with a reduction in left ventricular ejection fraction (EF) before HCT. One clinical study showed that a reduced EF but cumulative pretransplant anthracycline dose has a tendency to provoke severe cardiac toxicity. 4 Others observed that severe cardiac toxicity is not predicted by EF value before HCT. 5 In these studies, a variety of preparative regimens was used, and some regimens did not contain CY, which was shown to be a significant risk factor for the development of cardiac toxicity. 6 These factors make it impossible to assess whether cardiac toxicity is directly influenced by the preparative regimen.We retrospectively analyzed the development of cardiac complications in patients who had undergone HCT with the same preparative regimen con...

Human herpesvirus-6 (HHV-6) encephalitis is recognized as a relatively rare, but sometimes lethal, complication of allogeneic hematopoietic stem cell transplantation (HSCT). Although the development of new diagnostic techniques and antiviral therapy has improved, the prognosis of encephalitis is still unclear. We surveyed 197 patients who underwent allogeneic HSCT between January 2004 and March 2008 at our institution, and 8 (4.0%) were diagnosed as having HHV-6 encephalitis. Five were male and 3 were female, with a median age of 40.5 years. The median onset of HHV-6 encephalitis was 18 days after HSCT, and the median duration of antiviral therapy was 41 days. The median survival time from the onset of encephalitis was 23.1 months (range: 2.7-66.7), and 3 patients died of unrelated causes (sepsis in 2 and gastrointestinal tract bleeding in 1). Cord blood transplantation was identified as the only independent risk factor (relative risk [RR] = 4.98; P = .049) by multivariate analysis. There was no statistical significance of survival after HSCT between the patients with HHV-6 encephalitis and those without HHV-6 encephalitis (the 2-year survival rate was 60% and 52.6%, respectively; P = .617). Four of the 5 surviving patients were unable to return to society because of neuropsychological disorders, including anterograde amnesia and seizures with prominent hippocampal atrophy. Although HHV-6 encephalitis occurring after HSCT is now becoming a curable complication, its sequelae, such as neuropsychological disorders, have a marked influence on the quality of life of long-term survivors. Accordingly, it is necessary to identify risk factors for HHV-6 encephalitis and establish methods for prevention of this complication.

The linking of integrin to cytoskeleton is a critical event for an effective cell migration. Previously, we have reported that a novel integrin-linked kinase (ILK)–binding protein, affixin, is closely involved in the linkage between integrin and cytoskeleton in combination with ILK. In the present work, we demonstrated that the second calponin homology domain of affixin directly interacts with α-actinin in an ILK kinase activity–dependent manner, suggesting that integrin–ILK signaling evoked by substrate adhesion induces affixin–α-actinin interaction. The overexpression of a peptide corresponding to the α-actinin–binding site of affixin as well as the knockdown of endogenous affixin by small interference RNA resulted in the blockade of cell spreading. Time-lapse observation revealed that in both experiments cells were round with small peripheral blebs and failed to develop lamellipodia, suggesting that the ILK–affixin complex serves as an integrin-anchoring site for α-actinin and thereby mediates integrin signaling to α-actinin, which has been shown to play a critical role in actin polymerization at focal adhesions.

BackgroundThymoma-associated pure red cell aplasia (PRCA) accounts for a significant proportion of cases of secondary PRCA and immunosuppressive therapy has been reported to be useful in this condition. However, because of its rarity, the long-term response and relapse rates after immunosuppressive therapy are largely unknown, and optimal management of this disorder remains unclear. The aim of this study was to collect more information on the outcome of patients with thymoma-associated PRCA.