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Acute Leukemias: Pharmacokinetics and Management of Relapsed by A. F. List, C. M. Spier, W. S. Dalton (auth.), Prof. Dr. W.

By A. F. List, C. M. Spier, W. S. Dalton (auth.), Prof. Dr. W. Hiddemann, Prof. Dr. T. Büchner, Priv. Doz. Dr. B. Wörmann, Prof. Dr. W. Plunkett, Prof. Dr. M. Keating, Prof. Dr. M. Andreeff (eds.)

This can be the 3rd quantity during this sequence on equipment of treating acute leukemia. a number of drug resistance is mentioned, besides using human granulocyte-macrophage CSF, the position of stem telephone issue, and simple elements of telephone biology and pharmakokinetics. there's additionally a accomplished part facing relapse treatment and postremission treatment. The publication therefore presents the clinician with directions to be used in daily perform.

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Extra info for Acute Leukemias: Pharmacokinetics and Management of Relapsed and Refractory Disease

Sample text

Comparing the two neoplasms, we found no significant difference in DHFR activity. lmollh per mg protein found both in our previous studies and a recent report by Dedhar and colleagues [4]. Eighteen patients' samples were evaluated for formation of MTX polyglutamates. No significant differences were seen in the total amount of MTX plus polyglutamates between the two neoplasms, suggesting that transport resistance is not a common mechanism of intrinsic MTX resistance in ANLL. However, although the total MTX plus polyglutamates was the same in ANLL and ALL, we found lower levels of long chain polyglutamates formed in ANLL ceIls than in ALL ceIls, although the amounts of long chain polyglutamates formed by ANLL blast cells were quite variable, and some ANLL patient samples formed as much MTX polyglutamates as the pediatric ALL blast cells.

Although there was a significant difference in the amount of total MTX plus MTX polyglutamates found in adult versus pediatric ALL blasts, most adult ALL blast cell samples were able to accumulate significant amounts of MTX plus polyglutamates, suggesting that transport resistance is not a common form of intrinsic MTX resistance in adults with ALL. Of interest is that about half of the adult ALL samples formed as many long chain (glu 3-6) polyglutamates as pediatric ALL blasts, whereas the remainder formed significantly less.

Displacement of PT430 in both the CCRF-CEM parent. and transp~rt resistant cell lines following incubation with an increasing concentration of TMTX. Displacement IS most notable at 3 x 10- 7 MTMTX Resistance Due ta Decreased MTX Palyglutamate Synthesis Data from several laboratories have emphasized the importance of MTX polyglutamylation as a determinant of MTX cytotoxicity (reviewed in [3, 22]). Thus both intrinsic resistance to high pulse doses of MTX [23, 24] as well as acquired resistance may result from defective polyglutamate formation [25-27].

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