Aplasia

In HSCT, very high doses of chemotherapy with or without total-body radiation (TBI) are given in an attempt to potentiate leukemia cell kill. Hematopoiesis is restored by the infusion of stem cells harvested from an HLA-compatible donor, thereby rescuing the patient from the consequences of total aplasia.13 It is the most effective antileukemic therapy currently available. 

HGFs may be used prior to an HCT to mobilize PBPCs during the period of aplasia after an autologous HCT to hasten recovery and in cases where the patient fails to engraft.19... 

There has been interest in miniaturizing and automating electrophoresis of proteins. Ruchel (1997) reported a miniaturized system where proteins are first separated by isoelectric focusing in millimeter diameter tubes. The tube s contents are transferred to a slab gel that is a few centimeters on a side. This technology was used to separate the proteins from a single giant neuron from Aplasia califomicus. More recently, native fluorescence has been used to resolve 200 proteins from a similar miniaturized electrophoresis system (Sluszny and Yeung, 2004). 

McBride KL, Gilchrist GS, Smithson WA et al. Severe 6-thioguanine-induced marrow aplasia in a child with acute lymphoblastic leukemia and inhibited thiopurine methyltransferase deficiency. J Pediatr Hematol Oncol 2000 22 441-445. Weinshilboum RM, Sladek SL. Mercaptopurine pharmacogenetics monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet 1980 32 651-662. 

Beagle dog inhalation "CeCl, AMAD t.5-2,4 ion a, 1.6-2.1 13-16 mos 70 life span (in progress) death, bone marrow aplasia and pancytopenia, radiation pneumonitis, pulmonary fibrosis, hepatic necrosis 11/48 Yes pulmonary adenoma, bronchtogenic adenocarcinoma 3/48 Yes he man- Yes giocarcinoma osteosarcoma, 6/48 leukemia 3/34 (primary) Benjamin et al. (1972b 1976c) Merickel et al. (1978)... 

Roberts, H.J. 1990. Pentachlorophenol-associated aplastic anemia, red cell aplasia, leukemia and other blood disorders. Jour. Florida Medic. Assoc. 77 86-90. 

Problems associated with these drugs include troublesome and potentially dangerous side effects, including extrapyramidal reactions, hypersensitivity reactions with possible liver dysfunction, marrow aplasia, and excessive sedation. 

In respect to other SERMs, Bishai et al. (1999) have communicated a case of intrauterine exposure to clomiphene (100 mg/d for approximately 4 weeks) and neonatal persistent hyperplastic primary vitreous. These same authors mention another described case in humans with congenital retinal aplasia. Regarding raloxifene, no relation to ocular problems has been reported. 

Kharagjitsingh, A.V. et al., Incidence of recombinant erythropoietin (EPO) hyporesponse, EPO-associated antibodies, and pure red cell aplasia in dialysis patients, Kidney Int., 68, 1215, 2005. 

It has been postulated that wood dust carcinoma results from a multistep process Exposure causes loss of cilia and hyperplasia of the goblet cells and initiation of cuboidal cell metaplasia, followed (after a quiescent period) by squamous cell metaplasia. Decades later, cellular aplasia leads to nasal adenocarcinoma. The time between first occupational exposure to wood dust and the development of nasal cavity adenocarcinoma averages 40 years. Other cancers, including lung cancer, Hodgkin disease, multiple myeloma, stomach cancer, and colorectal cancer and lymphosarcoma, have been mentioned in relation to wood... 

Pure red cell aplasia (PRCA) PRCA has been reported in a limited number of patients exposed to epoetin alfa. This has been reported predominantly in patients with CRF. Evaluate any patient with loss of response to epoetin alfa for the etiology of loss of effect. Discontinue epoetin alfa in any patient with evidence of PRCA and evaluate the patient for the presence of binding and neutralizing antibodies to epoetin alfa, native erythropoietin, and any other recombinant erythropoietin administered to the patient. In patients with PRCA secondary to neutralizing antibodies to erythropoietin, do not administer epoetin alfa, and do not switch such patients to another product as anti-erythropoietin antibodies cross-react with other erythropoietins. 

Blood dyscrasias An irreversible type of marrow depression leading to aplastic anemia with a high rate of mortality is characterized by appearance of bone marrow aplasia or hypoplasia weeks or months after therapy. Peripherally, pancytopenia is most often observed, but only 1 or 2 of the 3 major cell types may be depressed. 

Hematoiogic effects Severe leukopenia or thrombocytopenia, macrocytic anemia, severe bone marrow depression, and selective erythrocyte aplasia may occur in patients on azathioprine. Hematologic toxicities are dose-related, may occur late in the... 

The bone marrow is a rapid turn over tissue and can be damaged by drugs causing total aplasia, and single cell line damage such as agranulocytosis and thrombocytopaenia. This latter can also be caused by the rapid removal of platelets from the circulation in an immune reaction. 

The effectiveness of chemotherapy is enhanced by adequate immune function however, some antibiotics suppress immune function. For example, tetracychnes can decrease leukocyte chemotaxis and complement activation. Rifampin decreases the number of T lymphocytes and depresses cutaneous hypersensitivity. Antibiotics such as the sulfonamides may induce granulocytopenia or bone marrow aplasia. These effects are not well understood but may be due to enteric bacterial metabohc byproducts of these antibiotics. 

Contraindications Bone marrow aplasia, historyofgold-induced pathologies (including blood dyscrasias, exfoliative dermatitis, necrotizing enterocolitis, and pulmonary fibrosis), severe blood dyscrasias... 

No adverse effects at 500 mg B/kg diet for 60 days. At 1000 and 2000 mg B/kg, adverse effects measured on male reproductive capacity, including germinal aplasia and infertility effects persisted for at least 8 months following B exposure at highest dose (23)... 

Lee, I.R, R.J. Sherins, and R.L. Dixon. 1978. Evidence for induction of germinal aplasia in male rats by environmental exposure to boron. Toxicol. Appl. Pharmacol. 45 577-590. 

An inverse log-linear relationship has been found between hematocrit and plasma erythropoietin in anemic patients with normal renal function. Patients with chronic renal failure have inappropriately low erythropoietin levels for their degree of anemia [10]. The severity of anemia correlates with the extent of renal dysfunction. Intravenous or subcutaneous recombinant human erythropoietin given three times a week is the treatment of choice. Some patients seem to do well on only one injection per week. One version of erythropoietin, Epocrit, marketed outside the United States, has been associated with pure red cell aplasia. 

Marrow aplasia due to decreased nucleic acid synthesis, e.g. sulphonamides, ganciclovir... 

Flucytosine is converted into the anti metabolite 5-fluorouracil that inhibits thymidilate synthetase, thereby disrupting DNA synthesis. It also interferes with protein synthesis by incorporation of fluorouracil into RNA in place of uracil. Although active against most Candida species, its spectrum of antifungal activity, overall, is narrow. Since resistance can develop rapidly it is usually coadministered with another agent and its main value is that it facilitates a reduction in the dose (and, presumably, the toxic effect) of amphotericin when co-prescribed in this way. The main adverse effects are marrow aplasia and hepatotoxicity. 

Allergic reactions to ESAs have been infrequent. There have been a small number of cases of pure red cell aplasia (PRCA) accompanied by neutralizing antibodies to erythropoietin. PRCA was most commonly seen in dialysis patients treated subcutaneously for a long period with a particular form of epoetin alfa (Eprex with a polysorbate 80 stabilizer rather than human serum albumin) that is not available in the USA. After regulatory agencies required that Eprex be administered intravenously rather than subcutaneously, the rate of ESA-associated PRCA diminished. However, rare cases have still been seen with all ESAs administered subcutaneously for long periods to patients with chronic kidney disease. 

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