Immune reconstitution after autologous hematopoietic stem cell transplantation in relation to underlying disease, type of high-dose therapy and infectious complications

Background and Objectives. Autologous peripheral stem cell transplantation (APSCT) is increasingly used for various hematologic malignancies and sol; id tumors. The objective of this study was to analyze the immune reconstitu tion after APSCT and see ii there was any correlation with diagnosis, age, type of high-dose therapy, CD34(+) selection of the autograft and double vs single APSCT. Design and Methods. Lymphocyte subset recovery was studied in 46 consecutiv e patients with hematologic malignancies and breast cancer, who underwent A PSCT. Eleven patients with multiple myeloma received tandem autografts. Thi rty-one patients were given total body irradiation (TBI) as part of the hig h-dose treatment. Eighteen patients received a CD34(+) selected graft. The percentage and absolute numbers of lymphocyte populations, T-cells (CD2(+), CD3(+)), B-cells (CD19(+)), NK cells (CD56(+) CD3(-) and CD16(+)CD3(-)) an d T-cell subpopulations [CD4(+), CD8(+), CD4(+)CD45RA(+), CD4(+) CD45RO(+), CD4(+)DR(+), CD8(+) CD45RO(+), CD8(+)DR(+)), were monitored with Row cytom etry during the first year after APSCT. Results. The total B-cell (CD19(+)) and T-cell (CD3(+)) counts were reconst ituted to normal levels 2-4 months after APSCT. All patients had a low CD4/ CD8 ratio during the observation period, related to both a low number of CD 4(+) cells and elevated numbers of CD8(+) cells. The low number of CD4(+) c ells was due to a persistently low level of naive CD4(+)CD45RA(+) cells. A high proportion of the CD8(+) cells displayed a phenotype compatible with a ctivated T-cells (CD8(+)DR(+)) up to 10 months after autografting. The numb er of NK cells (CD56(+)3(-) or CD16(+)3(-)) reached normal values within on e month post-transplant. No single variable, such as diagnoses, age, TBI as part of the high-idose treatment, tandem autografting or CD34(+) selection of the graft, influenced the immune or hematopoietic reconstitution and no correlation with documented infectious complications was found. Interpretation and Conclusions. Despite heterogeneity of diseases, age, ini tial treatment and high-dose regimens, lymphocyte subset analysis did not r eveal any differences in hematopoietic or immune reconstitution. AII patien ts had a low CD4(+)/CD8(+) ratio during at least the first year post-transp lant, caused by a persistent increase of CD8(+) lymphocytes and a constant reduction of CD4(+) lymphocytes, making the patients susceptible to infecti ons for a prolonged period of time post-transplant. (C)2000, Ferrata Storti Foundation.