| Objective:(1) To investigate the relationship between the reconstitution of lymphocyte subsets of patients after allo-HSCT and a GVHD, and to screen the risk factors of a GVHD.(2) To determine the efficacy of anti-CD25 m Ab as second-line treatment choice for steroid-refractory a GVHD.(3) To evaluate a novel induction regimen composing with,idarubicin, cytarabine and cladribine(IAC regimen) for AML patients, and to identify prognostic factors affecting treatment outcomes.Methods:(1) The distribution of T lymphocyte subsets in peripheral blood was dynamically monitored in 65 patients who received allo-HSCT in the First Affiliated Hospital of Soochow University from Jan 2012 through Nov 2013. Flow cytometry was applied to detect the proportion of each subsets in the samples acquired at 1 month, 3months, 6 months, 12 months post-transplantation respectively. The risk factors of a GVHD were analyzed by Logistic regression.(2) The clinical data of 64 patients with steroid-refractory a GVHD who received anti-CD 25 m Ab as alternative treatment in our hospital from December 2011 to April 2014 were analyzed retrospectively. Clinical responses were observed and were compared according to the organs involved. The CD25+lymphocytes proportion levels before and after anti-CD25 m Ab therapy were also assessed,and were compared among different response groups(CR/PR/NR) as well. Related complications and long-term prognosis including infections, c GVHD and survival were furtherly analyzed.(3) The clinical data of 27 untreated AML patients received the IAC regimen as primary induction therapy in our hospital from April 2014 to November 2014 were analyzed retrospectively. Treatment outcomes of IAC regimen was compared to two IA regimens(IDA 10mg/m2 and IDA 12mg/m2) in a pair-matched analysis with comparable constitution of age, sex, FAB subtype, karyotype among three groups of patients. 81 patients in total were recruited into three groups by the different induction regimens: IAC(idarubicin, cytarabine and cladribine), IAL(cytarabine with low-dose idarubicin) and IAH(cytarabine with high-dose idarubicin). The clinical efficacy, adverse events and supportive treatment were compared after the induction therapy. Multiviriate analysis with sex, age,WBC at diagnosis, karyotype and induction regimen as co-viariates was performed by Logistic regression.Results:(1) CD3+T subsets of the proportion of the peripheral blood lymphocyte in patients who accepted allo-HSCT have decreased obviously since implantation. The CD3+T subsets on the day one month after transplantation decreased significantly; then gradually rose to normal((63.65±6.64)%) 3 months after transplantation; Among them,CD3+CD4+T subsets was lowest on one month after transplantation and reconstructed slowly to normal until 12 months after transplantation((23.94±3.15)%); CD3+CD8+T subsets decreased and rose to normal((31.06±8.40)%) on one month after transplantation;CD3+CD4+/CD3+CD8+ratio was at a low level after transplantation, and still lower than normal at 12 months after a slow recovery, which was approximately 0.54±0.11;CD3+CD25+was low on one month((2.16±0.93)%) and increased to normal at 3 months;CD3-CD(16+56)+cells increased significantly to(42.31±8.47)%, but gradually fell to normal at 6 months. In the first 3 months after implantation, CD3+T cells from patients with a GVHD(grade III-IV) significantly increased comparing to patients without a GVHD(1 month: P=0.037, 3 months: P=0.045) as well as CD3+CD25+T cells(1 month: P=0.025,3 months: P=0.041), which was opposite to CD3+CD4+/CD3+CD8+(1 month: P=0.040, 3months: P=0.043). On one month after transplantation, CD3+CD4+T cells from patients without a GVHD displayed higher than patients with a GVHD(grade III-IV)(P=0.032) as well as CD3-CD(16+56)+cells(P=0.046), which was opposite to CD3+CD8+cells(P=0.029). Multivariate analysis showed that donor-recipient HLA mismatching(OR=2.511, P=0.024), unrelated donor(OR=2.964, P=0.018) and GVHD prophylaxis without ATG(OR=2.792, P=0.033) were risk factors for a GVHD.(2) At day 28 after initiation of anti-CD25 m Ab therapy, the total response rate was 83%, among which the complete response(CR) rate and partial response(PR) rate were 58% and 25%,respectively. During follow-up with a median time of 14.1 months(range, 0.4-30.5months), 47 patients were alive; 17 patients had died, the mainly causes of death were serious infection(10/17) and GVHD(5/17); 22 patients developed chronic GVHD(c GVHD), and the median time to develop c GVHD was 6.5months(range, 3.6-14.0months). Patients responding to anti-CD25 m Ab(CR+PR) have a less non-relapse mortality and a better overall survival probability but a similar c GVHD incidence compared with those with no response(NR). After anti-CD25 m Ab treatment, the CD25+lymphocyte proportion decreased significantly compared with the pretreatment value.(3)Complete remission rate(CR rate) in the IAC arm was higher compared to the IALarm(77.8% v 37%; P=0.002) as well as a higher effective rate(including complete remission and partial remission)(85.2% v 55.5%; P=0.017). There was no significant difference in outcome between the IAC and IAHarms. According to risk stratification, the IAC arm got significant higher CR rates than the IALarm in both of the intermediate group(90% vs50%, P=0.050) and the unfavorable group(66.7% vs 16.7%, P=0.013). Neither hematologic nor non-hematologic toxicity differed among the experimental(IAC) and control(IALor IAH) arms(P>0.05). In addition, the number of RBCs and platelet transfusions as well as the duration of hospital stay were comparable among three arms,with no significant differences observed for the IAC arm compared with the IALor IAH arms(P>0.05). Multivariate analysis showed that high WBC counts at diagnosis(OR=4.930, P=0.022) and unfavorable karyotype(OR=14.012, P=0.026) were related to a poorer response. What’s more, IAC regimen(OR=6.439, P=0.013) revealed a superiority over IALregimen on efficacy rather than IAHregimen(OR=4.107, P=0.041).Conclusion:(1) Our results support the utility of post-transplant monitoring of a peripheral blood lymphocyte subset for early warning a GVHD of patients undergoing allo-HSCT.Donor-recipient HLA mismatching,unrelated donor and GVHD prophylaxis without ATG were risk factors for a GVHD.(2) Humanized anti-CD25 m Ab is an effective second-line treatment for Chinese patients with steroid-refractory a GVHD.(3) IAC regimen achieves a more significant advantage over IALregimen than IAHregimen without increasing risk of adverse events. Efficacy of induction therapy is associated with WBC at diagnosis,karyotype and induction regimen. |
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