Document 0101
 DOCN  M9490101
 TI    Differential recovery of polymorphonuclear neutrophils, B and T cell
       subpopulations in the thymus, bone marrow, spleen and blood of mice
       following split-dose polychemotherapy.
 DT    9411
 AU    Talmadge JE; Jackson JD; Borgeson CD; Perry GA; University of Nebraska
       Medical Center, Department of Pathology; and Microbiology, Omaha
       68198-5660.
 SO    Cancer Immunol Immunother. 1994 Jul;39(1):59-67. Unique Identifier :
       AIDSLINE MED/94320119
 AB    In these studies, we examined the effect of a maximum-tolerated,
       split-dose chemotherapy protocol of cyclophosphamide, cisplatin, and
       1,3-bis(2-chloroethyl)-1-nitrosourea carmustine on neutrophil and
       lymphocyte, subpopulations in the peripheral blood (PBL), thymus, bone
       marrow and spleen. It was found that this protocol of polychemotherapy,
       modeled after the induction protocol used with autologous bone marrow
       transplantation for breast cancer, suppressed both B and T cell
       populations and T cell function at times when the absolute neutrophil
       count had returned to normal or supernormal numbers. In the peripheral
       blood, 7 days following initiation of chemotherapy, there was a twofold
       increase in the percentage of granulocytes as compared to the level in
       control animals on the basis of a differential count. The
       polymorphonuclear neutrophil (PMN) frequency in the bone marrow was
       increased on day 14 and statistically identical to that in control mice
       on all other days analyzed. In contrast to the bone marrow cells and PBL
       on day 7, the frequency of PMN in the spleen and thymus was depressed. B
       cells (B220+) were depressed in the pBL, spleen and bone marrow and took
       18-32 days to return to their normal frequency, while the frequency of B
       cells in the thymus was increased owing to a loss of immature T cells.
       The percentage of CD3+ cells in the thymus, spleen and bone marrow was
       significantly increased and required 10-18 days to return to normal
       levels, while the absolute number of CD3+ cells in the blood varied
       around the normal value. The ratio of CD4+ to CD8+ cells in all the
       organs studied varied only slightly owing to a similar reconstitution of
       CD4+ and CD8+ cells. In contrast to the phenotypic recovery of the CD3+,
       CD4+, and CD8+ cells, the ability of the splenic lymphocytes to respond
       to concanavalin-A was depressed and remained depressed, despite the
       phenotypic reconstitution of the T cell subsets, on the basis of both
       percentage and absolute cell number. These results show a selective T
       and B cell depression following multi-drug, split-dose chemotherapy in
       tissue and blood leukocyte populations and a chronic depression in T
       cell function.
 DE    Animal  Antineoplastic Agents, Combined/*TOXICITY  B-Lymphocyte
       Subsets/*DRUG EFFECTS  B-Lymphocytes/DRUG EFFECTS/PHYSIOLOGY  Bone
       Marrow/*CYTOLOGY/*DRUG EFFECTS  Carmustine/ADMINISTRATION & DOSAGE  Cell
       Separation  Cisplatin/ADMINISTRATION & DOSAGE  Comparative Study
       Concanavalin A/PHARMACOLOGY  Cyclophosphamide/ADMINISTRATION & DOSAGE
       CD4-CD8 Ratio/DRUG EFFECTS  Female  Flow Cytometry  Mice  Mice, Inbred
       BALB C  Neutrophils/*DRUG EFFECTS/PHYSIOLOGY  Spleen/*CYTOLOGY/*DRUG
       EFFECTS  Stimulation, Chemical  Support, Non-U.S. Gov't  T-Lymphocyte
       Subsets/*DRUG EFFECTS  T-Lymphocytes/DRUG EFFECTS/PHYSIOLOGY  Thymus
       Gland/*CYTOLOGY/*DRUG EFFECTS  JOURNAL ARTICLE

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