DIFFERENTIAL RECOVERY OF POLYMORPHONUCLEAR NEUTROPHILS, B-CELL AND T-CELL SUBPOPULATIONS IN THE THYMUS, BONE-MARROW, SPLEEN AND BLOOD OF MICE FOLLOWING SPLIT-DOSE POLYCHEMOTHERAPY

In these studies, we examined the effect of a maximum-tolerated, split -dose chemotherapy protocol of cyclophosphamide, cisplatin, and 1,3-bi s(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 transpla ntation for breast cancer, suppressed both B and T cell populations an d T cell function at times when the absolute neutrophil count had retu rned 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 an imals on the basis of a differential count. The polymorphonuclear neut rophil (PMN) frequency in the bone marrow was increased on day 14 and statistically identical to that in control mice on all other days anal yzed. In contrast to the bone marrow cells and PBL on day 7, the frequ ency 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 per centage of CD3(+) cells in the thymus, spleen and bone marrow was sign ificantly 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 orga ns studied varied only slightly owing to a similar reconstitution of C D4(+) and CD8(+) cells. In contrast to the phenotypic recovery of the CD3(+), CD4(+) and CD8(+) cells, the ability of the splenic lymphocyte s to respond to concanavalin-A was depressed and remained depressed, d espite the phenotypic reconstitution of the T cell subsets, on the bas is of both percentage and absolute cell number. These results show a s elective T and B cell depression following multi-drug, split-dose chem otherapy in tissue and blood leukocyte populations and a chronic depre ssion in T cell function.