Bone marrow hypoplasia

Cytarabine is used in the chemotherapy of acute myelogenous leukemia, usually in combination with anthracyclines, thioguanine, or both. It is less useful in acute lymphoblastic leukemia and lymphomas and has marginal activity against other tumors. Myelosuppres-sion is a major toxicity, as is severe bone marrow hypoplasia nausea and mucositis may also occur. 

Sublethal effects in birds are similar to those in other species and include growth retardation, anemia, renal effects, and testicular damage (Hammons et al. 1978 Di Giulio et al. 1984 Blus et al. 1993). However, harmful damage effects were observed at higher concentrations when compared to aquatic biota. For example, Japanese quail (Coturnix japonica) fed 75 mg Cd/kg diet developed bone marrow hypoplasia, anemia, and hypertrophy of both heart ventricles at 6 weeks (Richardson et al. 1974). In zinc-deficient diets, effects were especially pronounced and included all of the signs mentioned plus testicular hypoplasia. A similar pattern was evident in cadmium-stressed quail on an iron-deficient diet. In all tests, 1% ascorbic acid in the diet prevented cadmium-induced effects in Japanese quail (Richardson et al. 1974). In studies with Japanese quail at environmentally relevant concentrations of 10 pg Cd/kg B W daily (for 4 days, administered per os), absorbed cadmium was transported in blood in a form that enhanced deposition in the kidney less than 0.7% of the total administered dose was recovered from liver plus kidneys plus duodenum (Scheuhammer 1988). 

Patients with psoriasis or RA who have any of the following alcoholism, alcoholic liver disease, or other chronic liver disease overt or laboratory evidence of immunodeficiency syndromes preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia). 

Summers DE, Chung EB. 1986. Thorotrast associated anemia and bone marrow hypoplasia. J Natl Med Assoc 78 1161-1165. 

Myelosuppression is a major toxicity, as is severe bone marrow hypoplasia. Nausea and mucositis also may occur. Intrathecal administration occasionally produces arachnoiditis or more severe neurological toxicity. 

Mouse (AKR, C57BI) lifetime 5 d/wk 6 hr/d 100 M (lymphocytopenia, bone marrow hypoplasia) Snyder et al. 1978a, 1980... 

For many years it had been said that there were no cases of aplastic anemia after parenteral administration of chloramphenicol however, a few cases of aplastic anemia have been reported (35). There have also been reports of bone marrow hypoplasia after the use of chloramphenicol eye-drops (36,37). 

Rosenthal RL, Blackman A. Bone-marrow hypoplasia following the use of chloramphenicol eye drops. JAMA 1965 191 136-7. 

Hoffmann A, Kirn E, Krueger GR, Fischer R. Bone marrow hypoplasia and fibrosis following interferon treatment. In Vivo 1994 8(4) 605-12. 

Talpaz M, Kantarjian H, Kurzrock R, Gutterman JU. Bone marrow hypoplasia and aplasia complicating interferon therapy for chronic myelogenous leukemia. Cancer 1992 69(2) 410-12. 

Of 44 patients who took thalidomide for refractory multiple myeloma, 10 developed grade 3 or 4 neutropenia, usually in the first or second week of treatment (70). There was concomitant progression of thrombocytopenia in five cases and bone marrow hypoplasia without a significant increase in myeloma cell numbers in five. Neutropenia was more common in patients with low neutrophil and platelet counts, anemia, or a high percentage of plasma cells in the bone marrow before thalidomide treatment. 

In dogs, high doses of BCNU resulted in severe bone marrow hypoplasia with delayed, reversible thrombocytopenia. The other major toxicides observed were cardiopulmonary (pulmonary edema, myocardial infarction, and pericardial hemorrhage), intestinal mucosal damage with hemorrhage, renal toxicity, and delayed hepatotoxicity. Similar toxicity was seen in monkeys except that cardiopulmonary toxicity did not occur. In rats, initially well-tolerated doses may cause death later. There is sufficient evidence for the carcinogenicity of BCNU in rats. BCNU is embryo-and fetolethal in rats and rabbits at doses nontoxic to the mother and can induce a variety of teratogenic effects in rats. 

Dog (Beagle) 2-22 min once 47 [LTRB] (6/24 died from bone marrow hypoplasia) Gillett et al. 1987a SrClj... 

HUMAN HEALTH RISKS Oral human LDL 50 mg/kg eye human 300 ppm inhalation human TCLo 200 ppm Acute Risks irritation of eyes, skin and upper respiratory tract burning sensation headache shortness of breath nausea chest pain edema death Chronic Risks dermatitis anemia decreased blood cell count bone marrow hypoplasia CNS effects. 

Intrastrand cross-linking also occurs, preferentially at 5 -GA-3 but also at 5 -GG-3 sequences (30). Alkylation of Cys sulfhydryl groups is yet another mechanism of cytotoxicity. Busulfan is used in the treatment of chronic myelogenous leukemia and can be administered either orally or by IV infusion. Serious bone marrow hypoplasia and myelosuppression are possible with this agent, and recovery from busulfan-induced pancytopenia can take up to 2 years. 

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