Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DMP 406 is an atypical antipsychotic, antischizophrenic drug, biochemically related to clozapine, which exerts its desired pharmacologic effects through selective antagonism of 5-hydroxytryptamine and dopamine-receptor subtypes. Clozapine therapy is clinically associated with severe granulocytopenia in a small subset of patients. In the course of a 3-month toxicity study in dogs, severe neutropenia, thrombocytopenia, marked myeloid and erythroid left-shifted bone marrow hyperplasia with increased erythrophagocytosis, positive Coombs' tests, and hypergammaglobulinemia occurred in individual females dosed with 30 mg/kg/day of DMP 406. Related but less severe changes were also observed in males. Sera or purified immunoglobulins from affected and control dogs were tested in methylcellulose-based, canine hematopoietic colony-forming unit (CFU) assays with or without DMP 406. Neither size nor number of erythroid or myeloid CFUs differed between cultures containing control or affected dog serum components. Sera from individual affected dogs but not controls resulted in moderate numbers of fibroblast-like CFUs, suggesting DMP 406-associated marrow stromal cell-modifying, serum activities to be present. DMP 406 alone resulted in a concentration-dependent reduction of erythroid and myeloid CFUs with an approximate IC50 of 3.0 microg/mL. Taken together, DMP 406-induced granulocytopenia and bone marrow dyscrasia appear likely to result from both immune-mediated and direct drug-induced myelotoxicity.
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PMID:Atypical antipsychotic-induced neutropenia in dogs. 1007 8

Fifty-seven patients with acute myelogenous leukemia (AML) received the following treatment in our hospital between May 1992 and April 2005. Group A: combination of enocitabine, daunorubicin, 6-mercaptopurine riboside and prednisolone (BHAC-DMP) for remission induction, BHAC-DMP or idarubicin (IDR)+cytarabine (Ara-C) for first consolidation, combination of prednisolone, Ara-C, mitoxantrone and etoposide (PAME) for second consolidation, and PAME for late intensification; Group B: IDR+Ara-C for remission induction, PAME for first consolidation, and high-dose Ara-C+mitoxantrone for second consolidation; Group C (acute promyelocytic leukemia, APL) : all-trans retinoic acid (ATRA) for remission induction, BHAC-DMP or IDR+Ara-C for first consolidation, and PAME for second consolidation. The complete remission (CR) rate was 77% in Group A, 76% in Group B, and 71% in Group C. Five-year relapse-free survival rate of the CR patients was 35% in Group A, 49% in Group B, and 70% in Group C. All of the patients had severe neutropenia, but the number of infectious death was small. A short duration treatment with intensive consolidation therapy was effective for patients with AML and improved their quality of life (QOL).
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PMID:[A short duration treatment with intensive consolidation therapy for patients with acute myelogenous leukemia--13 year experience in a single institute]. 1803 12