mercaptopurine and Diabetes-Insipidus

Treatment of Langerhans cell histiocytosis (LCH) remains problematic. To test the hypothesis that rapid initiation and long-term continuation of chemotherapy can improve survival and reduce recurrence and late consequences of disseminated LCH, we have completed a prospective clinical trial (DAL HX-83). One hundred six newly diagnosed patients were stratified into three risk groups (A: multifocal bone disease [n = 28]; B: soft tissue involvement without organ dysfunction [n = 57]; C: organ dysfunction [n = 21]). All patients received an identical initial 6-week treatment (etoposide [VP-16], prednisone, and vinblastine), and continuation treatment for 1 year, slightly adapted according to stratification at diagnosis. It included oral 6-mercaptopurine and eight pulses of vinblastine and prednisone for all patients, plus VP-16 in group B and VP-16 and methotrexate in group C. Eighty-nine percent and 91% of patients in groups A and B and 67% of the most severely affected group C, achieved complete resolution of disease. The speed of resolution was rapid (median 4 months) and independent of disease severity. The frequency of recurrence after initial resolution was low (12%, 23%, and 42% in groups A, B and C); overall fully 77% of patients have remained free of recurrence. Permanent consequences developed after diagnosis in 20% of the patients. Diabetes insipidus after initiation of treatment occurred in only 10% of patients. Mortality (9%) was limited to patients of groups B (two patients) and C (eight patients). Finally, among the 106 patients treated by DAL HX-83 none have developed a malignancy (median follow-up 6 years, 9 months). The shorter duration of active disease, low rate of recurrence and permanent consequences, and improved survival among patients with poor prognosis support the strategy of rapid initiation of a predefined prolonged treatment upon the diagnosis of disseminated LCH.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Diabetes Insipidus; Etoposide; Female; Histiocytosis, Langerhans-Cell; Humans; Infant; Infant, Newborn; Male; Mercaptopurine; Methotrexate; Prednisone; Prognosis; Prospective Studies; Recurrence; Remission Induction; Severity of Illness Index; Survival Analysis; Treatment Outcome; Vinblastine

We report a case of AML with diabetes insipidus (DI). A 68-year-old female was admitted to our hospital because of fever and leukocytosis. The WBC was 197,000/microliter with 98% blasts positive for myeloperoxidase, CD33, CD34 and HLA-DR. While, on admission, urine volume was more than 6 liters daily. Blood vasopressin level was 0.3 microgram/ml. The patient was diagnosed as having AML with DI. By chemotherapy consisting of BHAC, DNR, 6-MP and PSL and intrathecal administration of AraC, MTX and PSL, and nasal drip of DDAVP, complete remission was attained and the urine volume was reduced to normal. Finally DDAVP became unnecessary. Although the exact cause of DI cannot be ascertained, rapid increase of leukemic blasts and leukostasis in small vessels might be associated with hypothalamus-pituitary system damage. Reportedly, DI is a rare complication of leukemia and administration of DDAVP could be halted in only two patients with leukemia and DI.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisolone; Renal Agents

Topics: Adrenal Glands; Adult; Cicatrix; Diabetes Insipidus; Hemorrhage; Humans; Leukemia, Myeloid, Acute; Leukopenia; Male; Mercaptopurine; Metyrapone; Pituitary Gland, Posterior; Pituitary-Adrenal Function Tests; Sodium Chloride; Specific Gravity; Urine

Topics: Autopsy; Bone Marrow Examination; Busulfan; Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Humans; Leukemia; Leukemia, Myeloid; Mercaptopurine; Polyuria; Prednisone; Vasopressins