Immune reconstitution after autologous hematopoietic stem cell transplantation in relation to underlying disease, type of high-dose therapy and infectious complications.
OBJECTIVE
Autologous peripheral stem cell transplantation (APSCT) is increasingly used for various hematologic malignancies and solid tumors. The objective of this study was to analyze the immune reconstitution after APSCT and see if there was any correlation with diagnosis, age, type of high-dose therapy, CD34(+) selection of the autograft and double vs single APSCT.


METHODS
Lymphocyte subset recovery was studied in 46 consecutive patients with hematologic malignancies and breast cancer, who underwent APSCT. Eleven patients with multiple myeloma received tandem autografts. Thirty-one patients were given total body irradiation (TBI) as part of the high-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(-)) and T-cell subpopulations (CD4(+), CD8(+), CD4(+)CD45RA(+), CD4(+ )CD45RO(+), CD4(+)DR(+), CD8(+ )CD45RO(+), CD8(+)DR(+)), were monitored with flow cytometry during the first year after APSCT.


RESULTS
The total B-cell (CD19(+)) and T-cell (CD3(+)) counts were reconstituted 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 CD4(+) cells and elevated numbers of CD8(+) cells. The low number of CD4(+) cells was due to a persistently low level of naive CD4(+)CD45RA(+) cells. A high proportion of the CD8+ cells displayed a phenotype compatible with activated T-cells (CD8(+)DR(+)) up to 10 months after autografting. The number of NK cells (CD56(+)3(-) or CD16(+)3(-)) reached normal values within one month post-transplant. No single variable, such as diagnoses, age, TBI as part of the high-dose treatment, tandem autografting or CD34(+) selection of the graft, influenced the immune or hematopoietic reconstitution and no correlation with documented infectious complications was found.


CONCLUSIONS
Despite heterogeneity of diseases, age, initial treatment and high-dose regimens, lymphocyte subset analysis did not reveal any differences in hematopoietic or immune reconstitution. All patients had a low CD4(+)/CD8(+) ratio during at least the first year post-transplant, caused by a persistent increase of CD8(+) lymphocytes and a constant reduction of CD4(+) lymphocytes, making the patients susceptible to infections for a prolonged period of time post-transplant.
Steingrimsdottir
H
H
Department of Medicine, Division of Hematology, Karolinska Hospital, SE-171 76 Stockholm, Sweden. hlif@hotmail.com
Gruber
A
A
Björkholm
M
M
Svensson
A
A
Hansson
M
M
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000628:therapy; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy / Q000628:therapy; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D019070:Cell Lineage; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004198:Disease Susceptibility; D005260:Female; D006085:Graft Survival; D019337:Hematologic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000706:statistics & numerical data; D006801:Humans; D007239:Infections / Q000209:etiology / Q000276:immunology*; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000187:drug effects; D008231:Lymphopenia / Q000097:blood / Q000209:etiology*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D011034:Podophyllotoxin / Q000008:administration & dosage / Q000009:adverse effects; D013548:Sweden / Q000453:epidemiology; D019172:Transplantation Conditioning / Q000009:adverse effects; D014182:Transplantation, Autologous
D003561:Cytarabine; D011034:Podophyllotoxin; D008558:Melphalan; D002330:Carmustine