Differential regulation of CCR5 expression on T lymphocytes in healthy donors after mobilization with rhG-CSF and its correlation with aGVHD / 中国实验血液学杂志

This study was to investigate the differential regulation of CCR5 expression on T cells in healthy donors after mobilization with recombinant human granulocyte colony-stimulating factor (rhG-CSF) and analyze its correlation with acute graft-versus-host disease (aGVHD) so as to understand the possible mechanisms underlying rhG-CSF-induced immune tolerance. Sixty-eight related healthy donor and their corresponding recipient for allogeneic hematopoietic stem cell transplantation (allo-HSCT) were enrolled in this study. The expression of CCR5 on CD4(+) and CD8(+) T cells in the peripheral blood (PB) before and after mobilization were detected by using flow cytometry (FCM) respectively. According to the changes of CCR5 expression on CD4(+) and CD8(+) T cells, the Sixty-two evaluable donors were divided into the downregulated and unchanged/upregulated (non-downregulated) groups, and the incidence of grades II to IV aGVHD in two groups were compared. The results showed that the mean value of CCR5 expression on CD4(+) and CD8(+) T cells in PB was not different significantly after mobilization (P > 0.05). Apparent inconsistency was showed among different individuals. Thirty-four (50%) donors displayed downregulation of CCR5 expression, while 34 (50%) donors manifested unchanged or upregulated CCR5 expression on CD4(+) T cells. CCR5 expression on CD8(+) T cells was downregulated in 42 (61.8%), unchanged or upregulated in 26 (38.3%) donors. The cumulative incidence of grades II to IV aGVHD in the downregulated and non-downregulated groups for CD4(+) T cells were 16.1% and 41.9% (P = 0.032), and recipients with CCR5 downregulation on CD8(+) T cells showed an increased tendency of developing aGVHD (37.8% vs 16.0%, P = 0.065). In conclusion, rhG-CSF mobilization could lead to differential regulation of CCR5 expression on T cells, which might influence the migration of T cells in vivo, decrease T cell trafficking towards GVHD target organs, and thus reduce the incidence of aGVHD after transplantation.

Efficacy analysis of sequential treatment with chemotherapy, ATRA and As(2)O(3) for acute promyelocytic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and treatment outcome of different induction regimens, and different post-remission therapies for adult acute promyelocytic leukemia (APL).</p><p><b>METHODS</b>The outcome of 73 patients with newly diagnosed APL were retrospectively analyzed. According to the induction regimens, the patients were divided into three groups: chemotherapy-only (14 cases group I), all-trans retinoic acid (ATRA) or combined with chemotherapy (33 cases group II), and ATRA combined with arsenic trioxide (As(2)O(3)) (26 cases group III). The complete remission (CR) rate and the time to CR (TTC) were analyzed. After CR, the patients were divided into 2 groups for post-remission therapies: one with sequential treatment of chemotherapy/ATRA/As(2)O(3) and the other with alternative treatment of chemotherapy/ATRA. The overall survival (OS), disease free survival (DFS) and relapse rate were compared between these two groups. Patients induced CR with both ATRA and As(2)O(3), and then sequentially treated with chemotherapy/ATRA/As(2)O(3) (group A), and those induced CR with ATRA or As(2)O(3) alone and then with non-chemotherapy/ATRA/As(2)O(3) sequentially (group B) were also analyzed and compared for CR, OS and DFS.</p><p><b>RESULTS</b>(1) For induction treatment, the CR rate in ATRA and As(2)O(3) combination group was 100%, in ATRA combined with chemotherapy group was 78.8%, and in chemotherapy-only group was 57.1% (P = 0.030). The median TTC in ATRA with As(2)O(3) combination group was 26 (13 - 40) days being the shortest among the three groups. (2) For the post-remission treatment, 3-year OS rates in group I and group II were (95.7 ± 4.3)% and (68.6 ± 11.2)% (P < 0.05), and 3-year DFS rates were (79.0 ± 9.5)%, and (32.9 ± 15.5)%, respectively (P < 0.01). The relapse rate was 14.8% in group I, and 50.0% in group II (P = 0.011). (3) The CR, 3-year OS and DFS rates in group A were all 100%. The CR rate in ATRA or As(2)O(3) alone induced group was 72.9%, and 3-year OS was (72.3 ± 9.1)% (P < 0.05).</p><p><b>CONCLUSIONS</b>For adult APL induction with ATRA and As(2)O(3) combination can obtain a higher CR rate, and shorter TTC. The post-remission treatment with sequential chemotherapy, ATRA and As(2)O(3) results in a lower relapse rate, and significantly improves OS and DFS. The ATRA and As(2)O(3) combination induction with the sequential post-remission therapy is the best strategy for APL treatment.</p>

Incidence and risk factors of hemorrhagic cystitis after hematopoietic stem cell transplantation / 中国实验血液学杂志

The aim of this study was to analyze the risk factors of hemorrhagic cystitis (HC) after hematopoietic stem cell transplantation (HSCT). The data of 188 transplant patients treated from July 2003 to August 2009 in Peking University First Hospital were studied. The patients were followed up to 180 days after HSCT. Clinical records of the total 188 cases and the 150 cases underwent allogeneic HSCT out of 188 cases were analyzed by using a Cox regression model respectively. The results indicated as follows: (1) 51 of 188 patients developed HC (27.12%). Univariate analysis showed that sex (male RR = 1.673, p = 0.076), allogeneic HSCT (RR = 1.848, p = 0.061) were related to HC, and allogeneic HSCT (RR = 4.508, p = 0.037) was the independent risk factor for HC by multivariate analysis. (2) HC occurred in 32.67% (49/150) patients who underwent allogeneic HSCT, with 42 cases of grade II-IV HC (28.00%). For the incidence of grade II-IV HC, univariate analysis revealed mismatched related donor/matched unrelated donor (RR 2.444, p = 0.018), CMV viruria (RR 2.059, p = 0.021) and CMV positive in serum and urine at the same time (RR 2.497, p = 0.003) were risk factors. The following factors, as conditioning with Fludarabine (Flu) (RR 0.504, p = 0.059) and TBI (RR 0.185, p = 0.095), were associated with a decreased tendency of II-IV HC at age of 26 - 40 (compared with age ≤ 25 or ≥ 41, RR 0.454, p = 0.056). Some others, as conditioning with CTX (RR2.015, p = 0.063), the application of ATG (RR 2.343, p = 0.054) and CMV viremia (RR 2.123, p = 0.088), were associated with an increased tendency of II-IV HC by univariate analysis. Multivariate analysis demonstrated that CMV positive in serum and urine at the same time (RR 2.269, p = 0.008), conditioning without Flu (RR = 2.106, p = 0.040) were the independent risk factor for grade II-IV HC. And the application of ATG (RR = 2.154, p = 0.083) was related to the tendency of higher incidence of grade II-IV HC. It is concluded that the incidence of HC is high in patients underwent allogeneic HSCT. CMV positive in serum and urine at the same time, while conditioning without Flu are the independent risk factors of grade II-IV HC. Application of ATG is related to the increased trend of grade II-IV HC.

Alteration of chemokines after allogeneic hematopoietic stem cell transplantation and its clinical significance / 中国实验血液学杂志

The objective of this study was to analyze the relationship between some chemokines and the pathogenesis of GVHD and to find some biomarkers with diagnostic significance through observing and comparing the changes of some chemokine levels in samples from patients with or without aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT). 26 plasma samples were obtained from 26 patients undergoing allo-HSCT at various time points after transplantation, of which 13 samples from patients with aGVHD were served as investigating group and 13 samples from patients without GVHD after Allo-HSCT were used as control group. The patient characteristics between the two groups were compared, the levels of 40 chemokines in these samples were detected by ELISA, the changes of chemokine levels in samples of 2 groups were analyzed by means of significance analysis microarray (SAM), clustering method and c-test. The results showed that there were significant differences in levels of 6 chemokines including HCC-1, MIF, IP-10, ITAC, TARC and NAP-2 between 2 groups, in which the level of MIF in plasma samples after HSCT was the highest, the difference of TARC level between 2 groups was over 10-fold. It is concluded that the level changes of chemokines mentioned above can be used as a indicator of GVHD presence, but their pathogenetic role in occurrence of aGVHD remains to be determined.