[Preliminary assessment of immune reconstitution after autologous peripheral hematopoietic stem cell transplantation (AHSCT)].
OBJECTIVE
Though high dose chemo-therapy combined with autologous hematopoietic stem cell transplantation (AHSCT) has made great progress on the treatment of chemo-sensitive malignant tumors, the relapse rate remains high. Successful immune reconstitution after AHSCT may reduce recurrence; therefore this study was to explore the characteristics of immune reconstitution after AHSCT and assess its feasibility in clinical use.


METHODS
Twenty four cases after AHSCT were enrolled in our study. There were 19 Non-hodgkin Lymphoma (NHL), 3 Hodgkin Lymphoma (HD) and 2 rhabdomyosarcoma. Nineteen cases had achieved complete remission (CR) while 5 partial remission (PR) before AHSCT. All cases were administered Interleukin (IL)-2 and Interferon (IFN)-alpha after AHSCT. Some patients were given thymus factor and/or CIK infusion. Phenotypes of peripheral blood T, B, NK subsets and immunological profile of TH1/TH2 by intracellular staining of cytokines after PMA/ionomycin stimulation were evaluated.


RESULTS
75% of the cases achieved CR while 4.17% were progression of disease (PD) and 16.67% were relapsed during the median follow-up time of 12 (2-60) months. The changes of immune parameters after AHSCT were as followed: (1) CD4+T cells (normal control 33.5+/-6.9%) started to decrease dramatically one month after AHSCT, which was 2.5-13% (median rate 5.6%)in the 2nd month; and then slowly increased to 10-20% in the 7th month, but did not return back to normal even after one year in all patients. In addition, reversed ratio of CD4/CD8 lasted for a long period of time. B cells also began to decrease 1 month after AHSCT, and recovered to normal in the 4th month. But B cells remained 0% in the 6th month and 1% in 12th month in patients treated by rituximab before receiving AHSCT. The ratio of NK cells was 10-20% (higher than normal controls) in the 2nd month, then returned to normal thereafter. (2) The cytokine secretion by T cell: there were 48.79% patients whose TH1 was lower than normal controls or at the lower limit of normal range. All the patients with normal TH1 were treated by IFN-alpha or CIK cell infusion. TH2 was much higher than normal level among 68.29% cases and this abnormality lasted at least for 1 year in some cases. TH2 at normal range was only observed in cases receiving IFN-alpha treatment. Furthermore, IFN-alpha could significantly decrease TH2 level. (3) Increasing tendency of CD4+CD25+/CD4+, CD4+CD69+/CD4+ ratio was observed in patients received additional thymus factor treatment compared to those did not.


CONCLUSIONS
Administration of CIK cells, thymus factor, IL-2 and IFN-alpha after AHSCT could improve the immunologic function of patients, and TH1/TH2 ratio may virtually reflect the immune status of patients. However more information is required to make prognostic assessments of immune reconstruction and the long-term survival rate.
Huang
Hui-Qiang
HQ
State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, 510060, P. R. China. huang_sysu@163.com
Cai
Qi-Chun
QC
Shi
Yan-Xia
YX
Lin
Xu-Bin
XB
Wei
Jing
J
Guo
Ying
Y
Pan
Zhan-He
ZH
D000293:Adolescent; D000328:Adult; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D055612:Cytokine-Induced Killer Cells / Q000637:transplantation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013949:Thymus Extracts / Q000627:therapeutic use; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D055815:Young Adult
D016207:Cytokines; D016898:Interferon-alpha; D007376:Interleukin-2; C019108:TFX; D013949:Thymus Extracts