       Document 0642
 DOCN  M9460642
 TI    Difficulties in precise quantitation of CD4+ T lymphocytes for clinical
       trials: a review.
 DT    9404
 AU    Fei DT; Paxton H; Chen AB; Department of Medicinal and Analytical
       Chemistry, Genentech,; Inc., South San Francisco, CA 94080.
 SO    Biologicals. 1993 Sep;21(3):221-31. Unique Identifier : AIDSLINE
       MED/94161948
 AB    Maintenance of CD4+ T helper lymphocyte counts has been used as a
       surrogate marker of efficacy for drugs in the treatment of AIDS. In a
       multicenter clinical trial, subtle improvement of CD4+ T cell counts may
       be masked and misinterpreted if care is not paid to likely sources that
       can contribute to the variability of measurement of CD4+ T lymphocytes.
       This review addresses major areas that can contribute to the variability
       of measurement of CD4+ T lymphocytes, with emphasis on applications to
       multicenter clinical trials, and proposes areas of improvement that may
       not be well recognized by the medical community. Whereas there are
       excellent guidelines for immunophenotyping, equal attention is needed in
       hematologic enumeration of WBC and absolute lymphocytes. In particular,
       allowing the margin of error acceptable to blood cell standards for
       HIV-infected specimens is unsatisfactory. Special attention should also
       be given to the stability of lymphocytes in the anticoagulant during
       storage, the lysing method, the quality assurance programs as well as
       intrasubject fluctuations which may be derived from exercise,
       medications and diurnal variations. Awareness of these contributing
       factors by physicians and technical analysts will expedite the discovery
       of potential therapy in the treatment of AIDS. For a multicenter
       clinical trial, it is advisable to select a centralized laboratory
       adopting a uniform protocol with regard to sample preparation and
       handling, using more stringent quality controls for hematologic
       analysers, calibration of instruments and immunophenotyping. Pending a
       true reference standard that can monitor the variation of the entire
       analytical procedure, we anticipate that future interlaboratory quality
       assurance programs will include absolute T lymphocyte count, an
       important parameter for assessing the accuracy and consistency of CD4+ T
       helper cell counts generated from a laboratory.
 DE    Acquired Immunodeficiency Syndrome/DRUG THERAPY/PATHOLOGY  Human
       *Leukocyte Count  Multicenter Studies/STANDARDS  Quality Control
       Reproducibility of Results  T4 Lymphocytes/*CYTOLOGY  JOURNAL ARTICLE
       REVIEW  REVIEW, TUTORIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

