Improved treatment results for childhood acute myeloid leukemia in Taiwan.

To improve treatment results for children with de novo acute myeloid leukemia (AML), we introduced a novel protocol, Taiwan Pediatric Oncology Group-AML-97A, for AML other than acute promyelocytic leukemia (APL), for which modified conventional protocols were used. From January 1, 1997, to December 31, 2002, 141 children younger than 17 years old with de novo AML were enrolled. In total, 117 patients with non-APL AML were treated with induction therapy of idarubicin and cytarabine (Ara-C), postremission therapy with high-dose Ara-C - containing regimens for four monthly courses, and moderate-dose therapy with idarubicin and Ara-C for four monthly courses. The first 19 patients with APL were treated with all-trans retinoic acid, idarubicin and Ara-C, with the remaining five patients receiving all-trans retinoic acid and idarubicin, followed by maintenance therapy for 2 years. Stem cell transplantation was performed in 29 patients in first remission with a similar outcome as chemotherapy alone. The remission rate in the AML-97A study was 90%, the 5-year survival 51 +/- 5.3% (s.e.) and the 5-year event-free survival 50 +/- 4.8%; for APL, these were 100%, 86 +/- 7.0, and 75 +/- 9.8%. For the whole group, the 5-year survival was 57 +/- 4.7% and the 5-year event-free survival 54 +/- 4.4%. The AML-97A regimen was well tolerated.

Diabetic ketoacidosis and hypogonadotropic hypogonadism in association with transfusional hemochromatosis in a man with beta-thalassemia major.

We report a 23-year-old man with beta-thalassemia major and transfusional hemochromatosis, which manifested as diabetic ketoacidosis and hypogonadotropic hypogonadism. This unusual presentation of diabetic ketoacidosis in hemochromatosis has rarely been reported. Magnetic resonance imaging of the abdomen showed decreased signal intensity in the liver, spleen, and pancreas. In addition, the pituitary gland also showed heterogeneous low signal intensity, compatible with hemochromatosis. He was treated with insulin supplements and pulsatile human chorionic gonadotropin administration. Clinical improvement was noted after hormone replacement. Intensive iron chelation therapy was given to prevent cardiac complications, and to restore his gonadal function. During follow-up, the patient experienced improvement in libido and sexual potency.

Abnormal glucose tolerance in transfusion-dependent beta-thalassemic patients.

OBJECTIVE: To study the prevalence of and risk factors for abnormal glucose tolerance in transfusion-dependent beta-thalassemic patients. RESEARCH DESIGN AND METHODS: A total of 89 transfusion-dependent beta-thalassemic patients were interviewed. Diabetes was previously diagnosed in 14 of them. In the remaining 75 patients, 68 participated in an oral glucose tolerance test. Potential risk factors were identified using the independent t test, chi2 test, and Fisher's exact test. Logistic regression analysis was used to select the independent risk factors that best predicted abnormal glucose tolerance A two-tailed P value of <0.05 was considered to be statistically significant. RESULTS: The prevalence of impaired glucose tolerance was 8.5% (7 of 82) and that of diabetes was 19.5% (16 of 82). Presentation with diabetic ketoacidosis was 31.1% (5 of 16). The risk factors for abnormal glucose tolerance found in transfusion-dependent beta-thalassemic patients were serum ferritin concentration and hepatitis C infection. CONCLUSIONS: The interaction of iron overload and hepatitis C infection worsened the prognosis of thalassemic patients. Aggressive iron-chelation therapy as well as prevention and treatment of hepatitis C infection should be mandatory in managing glucose homeostasis in transfusion-dependent beta-thalassemic patients in Taiwan.

Results of therapy for beta-thalassemia major.

During the last 10 years, 92 transfusion-dependent beta-thalassemia patients have been encountered at the National Taiwan University Hospital and Provincial Taoyuan General Hospital. Seventy-seven of them were followed up regularly. Long-term results of conventional therapy in 63 cases and allogeneic bone marrow transplantation (BMT) in 14 cases are reported. The conventional therapy included regular red cell transfusion and desferrioxamine iron chelation therapy. Preliminary results of conventional therapy showed a mortality of 7/63 (11%). Of those who were alive, the morbidity was 56/56 (100%). There was no disease-free-survival (0/56; 0%). BMT was performed after preparatory regimens of busulfan, cyclophosphamide, and/or total body or lymphoid irradiation. Preliminary results of BMT showed a mortality of 5/14 (36%). For those who were alive, the morbidity was 3/9 (33%), and the disease-free-survival rate was 6/9 (67%) during a follow-up period of three to six years. It is concluded that the only way to cure beta-thalassemia major at present is BMT. However, the risks of BMT and donor non-availability make conventional therapy unavoidable. Further study is needed to decrease the risk of BMT and to improve the efficacy of conventional therapy.

Effects of bombesin on thermoregulatory responses and hypothalamic neuronal activities in the rat.

Direct administration of bombesin (1, 10, and 100 ng/microliter) into the preoptic anterior hypothalamic area caused a dose-related fall in rectal temperature at ambient temperatures (Ta) of 8 and 22 degrees C. The hypothermia in response to bombesin was brought about by a decrease in metabolism at Ta 8 degrees C, whereas at Ta 22 degrees C the hypothermia was brought about by both a decrease in metabolism and an increase in cutaneous temperature. However, at Ta 30 degrees C, intrahypothalamic administration of bombesin caused an insignificant change in thermoregulatory responses. On the other hand, 51 single neurons in the preoptic anterior hypothalamic area were examined in 20 rats under urethan anesthesia. Each animal was subjected to scrotal warming or cooling and to the administration of bombesin. Microiontophoretic application of bombesin resulted in inhibition of the majority (62.5%) of cold-responsive neurons as well as excitation of the majority (50%) of warm-responsive neurons recorded in the preoptic anterior hypothalamic area. However, the majority (74%) of thermally unresponsive neurons were not affected by bombesin application. The data indicate that bombesin, when administered intrahypothalamically, excites warm-responsive neurons and inhibits cold-responsive neurons within the preoptic anterior hypothalamic area to induce hypothermia by promoting an increase in heat loss and a decrease in heat production.