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1.
Chinese Medical Journal ; (24): 2808-2816, 2018.
Article in English | WPRIM | ID: wpr-772917

ABSTRACT

Background@#Several studies have shown that detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) is an independent prognostic factor. This study aimed to evaluate the significance of dynamic MRD pretransplantation on outcome of AML patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*Methods@#We retrospectively analyzed 145 consecutive AML patients undergoing allo-HSCT in complete remission status between June 2013 and June 2016. MRD was determined with multiparameter flow cytometry after the first and second courses of chemotherapy and pre-HSCT.@*Results@#In matched sibling donor transplantation (MSDT) settings, patients with positive MRD had higher cumulative incidence of relapse (CIR) than those without MRD after the first (32.3 ± 9.7% vs. 7.7 ± 3.1%, χ = 3.661, P = 0.055) or second course of chemotherapy (57.1 ± 3.6% vs. 12.5 ± 2.7%, χ = 8.759, P = 0.003) or pre-HSCT (50.0 ± 9.7% vs. 23.0 ± 3.2%, χ = 5.547, P = 0.019). In haploidentical SCT (haplo-SCT) settings, the MRD status at those timepoints had no significant impact on clinical outcomes. However, patients with persistent positive MRD from chemotherapy to pre-HSCT had higher CIR than those without persistent positive MRD both in MSDT and haplo-SCT settings. Patients with persistent positive MRD underwent MSDT had the highest relapse incidence, followed by those with persistent positive MRD underwent haplo-SCT, those without persistent MRD underwent haplo-SCT, and those without persistent MRD underwent MSDT (66.7 ± 9.2% vs. 38.5 ± 6.0% vs. 18.8 ± 8.7% vs. 12.0 ± 1.0%, χ = 20.763, P < 0.001). Multivariate analysis showed that persistent positive MRD before transplantation was associated with higher CIR (hazard ratio [HR] = 1.69, 95% confidence interval [CI]: 1.200-2.382, P = 0.003), worse leukemia-free survival (HR = 1.812, 95% CI: 1.168-2.812, P = 0.008), and overall survival (HR = 2.354, 95% CI: 1.528-3.627, P < 0.001).@*Conclusion@#Our results suggest that persistent positive MRD before transplantation, rather than positive MRD at single timepoint, could predict poor outcome both in MSDT and haplo-SCT settings.


Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Flow Cytometry , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute , Pathology , Therapeutics , Male , Middle Aged , Neoplasm, Residual , Diagnosis , Prognosis , Retrospective Studies , Transplantation, Homologous , Young Adult
2.
Article in Chinese | WPRIM | ID: wpr-264938

ABSTRACT

The aim of this study was to develop and investigate the significance of a new multi-factor risk score system to predict the outcome of patients with hematological malignancies received allogeneic hematopoietic stem cell transplantation (allo-HSCT). The impact of pre-, peri-, and post-transplant factors on the outcome including overall survival (OS), disease-free survival (DFS), relapse and transplant-related mortality (TRM) after allo-HSCT were retrospectively analyzed in 122 patients with hematological malignancies at our center. A new risk score system based on the independent risk factors was established and tested. The results showed that absolute monocyte count at day 30 after transplantation (AMC-30, ≥ 536 cells/µl) [hazard ratio (HR) = 0.313, 95% confidential interval (CI):0.156-0.63], WT1( ≥ 1.0%) (HR = 3.268, 95% CI:1.644-6.499), pre-transplant risk grouping (HR = 1.999, 95% CI = 0.993-4.023) were independent prognostic factors of OS and DFS. Patients were divided into 3 groups based on the risk scoring system:group A (no risk factor; score 0), group B (1 risk factor; score 1) and group C (2-3 risk factors; score 2-3). OS at 5 years were 95.1% ± 3.4%, 62.9% ± 6.6% and 36.1% ± 9.6%, respectively (P < 0.0001). DFS at 5 years were 92.6% ± 4.9%, 60.4% ± 6.8% and 15.4% ± 7.1%, respectively (P < 0.0001). The akaike information criterion(AIC) value of the new score system for OS was 331, less than those of AMC-30, WT1, and pre-transplant risk group (346, 343, 346), AIC value for DFS and relapse were 378 and 231, both less than the three single elements(417, 397, 411 and 268, 238, 257). It is concluded that the risk scoring system based on AMC-30, WT1, pre-transplant risk grouping is more highly predictive for clinical outcomes of allo-HSCT than any one of the three single elements.


Subject(s)
Adolescent , Adult , Child , Female , Hematologic Neoplasms , Therapeutics , Hematopoietic Stem Cell Transplantation , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Assessment , Risk Factors , Transplantation, Homologous , Treatment Outcome , Young Adult
3.
Chinese Journal of Hematology ; (12): 679-684, 2013.
Article in Chinese | WPRIM | ID: wpr-272138

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the association of the ratio of regulatory and effector T cells with recurrence and chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Thirty patients with hematological malignancies who underwent allo-HSCT were classified as recurrence with cGVHD (n=4), non-recurrence with cGVHD (n=14), recurrence without cGVHD (n=5) and non-recurrence without cGVHD (n=7). The different percentage of CD4⁺CD25⁻CD69⁺ regulatory T cells in bone marrow and CD4⁺CD25⁺FoxP3⁺ regulatory T cells, Th1 cells and Th17 cells in peripheral blood were analyzed by flow cytometry.</p><p><b>RESULTS</b>There were no significant differences in all these T-cell subsets among different groups (P>0.05). While the ratio of CD4⁺CD25⁻CD69⁺ regulatory T cells and Th1 cells (0.211±0.177) in 9 recurrence patients was significant higher than that (0.133±0.160) in 21 non-recurrence patients (P=0.033). The ratio were also significance between recurrence without cGVHD and non-recurrence without cGVHD patients (0.167±0.073 vs 0.073±0.057, P=0.048), and between recurrence with cGVHD and non-recurrence without cGVHD patients (0.218±0.113 vs 0.073±0.057, P=0.024). Furthermore, the ratio of CD4⁺CD25⁺FoxP3⁺ regulatory T cells and Th17 cells was significant lower (1.975±2.045) in 18 cGVHD patients than that of 12 without cGVHD patients (3.198±1.132, P=0.010), and the ratio was also significant lower in non-recurrence patients with cGVHD (1.695±1.178) than that of without cGVHD (3.446±1.376, P=0.028).</p><p><b>CONCLUSION</b>Our results show that the ratio of CD4⁺CD25⁻CD69⁺ regulatory T cells and Th1 cells raise in recurrence patients, and the ratio of CD4⁺CD25⁺FoxP3⁺ regulatory T cells and Th17 decrease in cGVHD patients, which suggest that the ratio of regulatory and effector T cells had association with recurrence and cGVHD in patients with allo-HSCT.</p>


Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Graft vs Host Disease , Allergy and Immunology , Pathology , Hematologic Neoplasms , Allergy and Immunology , Therapeutics , Hematopoietic Stem Cell Transplantation , Humans , Male , Middle Aged , Recurrence , T-Lymphocytes, Regulatory , Cell Biology , Allergy and Immunology , Transplantation, Homologous , Young Adult
4.
Chinese Journal of Hematology ; (12): 745-750, 2013.
Article in Chinese | WPRIM | ID: wpr-272121

ABSTRACT

<p><b>OBJECTIVE</b>To compare the differences of the T helper cell reconstitution kinetics between HLA matched or HLA mismatched allo-HSCT through exploring the reconstitution kinetics of CD4+ CD25+Foxp3+ cells (CD4+ Treg), CD8+CD25+Foxp3+ cells (CD8+Treg), CD4+CD25-CD127+ conventional T cells (Tcon) and the secretion of IL-17a and IFN-γ in CD4+ T cells (Th17 and Th1 cells) or CD8+ T cells (Tc17 and Tc17 cells) post allogeneic hematopoietic stem cells transplantation (allo-HSCT).</p><p><b>METHODS</b>From December 2011 to October 2012, the peripheral blood (PB) of 20 patients undergoing HLA matched (10 patients) or mismatched (10 patients) allo- HSCT without acute graft-versus-host disease (aGVHD) and of 10 related healthy donors were collected to analyze the expression of CD25+Foxp3+, IL-17a, IFN-γ and CD127 expression through 8-colour Flow cytometer.</p><p><b>RESULTS</b>(1) The reconstitution kinetics of CD3+ T cells, CD4+ T cells, CD8+ T cells absolute numbers were comparable within 2 month post HLA matched and mismatched transplantation. (2)The absolute numbers of CD4+ Treg cells[+30 d, 8.46 (0.36-27.41) cells/μl 1.10 (0.04-8.03) cells/μl, P<0.05; +60 d, 8.50 (1.16-36.20) cells/μl vs 2.73 (0.34-6.84) cells/μl, P<0.05], Tcon cells[+30 d, 72.69 (3.85-211.73) cells/μl vs 13.41 (0.48-96.17) cells/μl, P<0.05; +60 d, 100.85 (16.28-267.20) cells/μl vs 47.75 (6.34-143.04) cells/μl, P<0.05], as well as Th17 cells[+30 d, 2.34 (0.02-6.87) cells/μl vs 0.20 (0.02-1.34) cells/μl, P<0.05; + 60 d, 1.90 (0.36- 7.82) cells/μl vs 0.46 (0.03-1.39) cells/μl, P<0.05]and Tc17 cells[+ 30 d, 1.08 (0.07-15.03) cells/μl vs 0.25 (0.01- 0.81) cells/μl, P<0.05;+60 d, 1.85 (0.63-26.57) cells/μl vs 0.46 (0.01-3.66) cells/μl, P<0.05]within 2 month post HLA matched HSCT were significantly higher than those post HLA- mismatched HSCT. However, the absolute numbers of Th1 cells or Tc1 cells within 2 month post HLA-matched or HLA-mismatched HSCT were comparable. (3) The ratio of Th1 and Th17 cells, or the ratio of Tc1 and Tc17 cells were significantly higher within 2 month post HLA-mismatched allo-HSCT compared to those post HLA-matched HSCT.</p><p><b>CONCLUSION</b>The reconstitution kinetics of T helper cells subset were different at early stage post HLA-matched or HLA-mismatched allo-HSCT, which might be help to explain the different rate or the different involved organ of the acute graft-versus-host diseases (aGVHD) post HLA-matched or -mismatched allo-HSCT.</p>


Subject(s)
Adult , Female , HLA Antigens , Hematopoietic Stem Cell Transplantation , Humans , Male , Middle Aged , T-Lymphocytes, Helper-Inducer , T-Lymphocytes, Regulatory , Th1 Cells , Th17 Cells , Transplantation, Homologous , Young Adult
5.
Chinese Journal of Hematology ; (12): 545-550, 2010.
Article in Chinese | WPRIM | ID: wpr-353593

ABSTRACT

<p><b>OBJECTIVE</b>To observe the relationship between variation of IL-2, IL-4, IL-18 and IP10 mRNA expressions in peripheral blood and the occurrence of acute graft-versus-host disease (aGVHD), and investigate whether some cytokines combined expression profiles could improve the diagnostic accuracy of aGVHD.</p><p><b>METHODS</b>A total of 58 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) were enrolled for the study. Peripheral blood samples were collected at different time points after transplantation. The mRNA expression levels of 4 kinds of cytokines (IL-2, IL-4, IL-18, IP10) were measured by real-time quantitative PCR (RQ-PCR). The relationship between mRNA expression level and the occurrence of aGVHD was analyzed with clinical features.</p><p><b>RESULTS</b>The expression levels of IL-2 and IL-18 at the onset of aGVHD were much higher than those after engraftment, being 2.69-fold and 3.12-fold increase, respectively (P = 0.000 & P = 0.000). The expressions of IL-2 and IL-18 mRNAs were slightly increased in patients with infection, but not statistically significant (P = 0.208 & P = 0.123). There was a slight but not statistically significant decrease of IL-4 and IP10 mRNA expressions at the onset of aGVHD (P = 0.230 & P = 0.325). Either IL-2 or IL-18 expression level could diagnose aGVHD as an independent factor (P = 0.000 & P = 0.000). The multivariate logistic regression analysis showed that the main factors related to aGVHD were IL-2, IL-18 and IL-4 (β = 1.13, P = 0.068 & β = 1.339, P = 0.047 & β = -0.600, P = 0.008 respectively). A composite panel of these three cytokines produced a better model for the diagnosis of aGVHD (AUC: 0.862, 95%CI: 0.768 - 0.957, P = 0.000), and the sensitivity and specificity were 75.0% & 83.3% respectively.</p><p><b>CONCLUSION</b>The diagnosis of aGVHD can be optimized with a composite cytokines panel.</p>


Subject(s)
Cytokines , Blood , Graft vs Host Disease , Diagnosis , Hematopoietic Stem Cell Transplantation , Humans , Interleukin-18 , Blood , RNA, Messenger
6.
Chinese Journal of Hematology ; (12): 77-81, 2009.
Article in Chinese | WPRIM | ID: wpr-314532

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the role of real time quantitative polymerase chain reaction (RQ-PCR) in the diagnosis and treatment of recipients cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>318 patients received allo-HSCT were studied. 160 patients received transplants from HLA matched sibling donors; 127 from HLA mismatched related donors; 31 from unrelated donors. Before transplant recipients and donors received CMV serological test by ELISA. After transplant RQ-PCR was used to test and monitor CMV-DNA in plasma of patients. A positive CMV-PCR was defined as > 6 x 10(2) copies/ml. Ganciclovir was used for CMV prophylaxis in all patients at -9 d to -2 d of conditioning regimen period. Ganciclovir, foscarnet, or combination of the two drugs were used as the preemptive therapy.</p><p><b>RESULTS</b>The total 100-day cumulative incidence of CMV infection was 40.6%. The incidence was 17.5%, 66.1% and 45.2% for the HLA matched sibling, HLA mismatched related (MMR) and unrelated donor (MUR) HSCT respectively. Multivariate analysis showed MMR HSCT, MUR HSCT, ATG containing preparative regimen and moderate to severe aGVHD were the risk factors for CMV infection after HSCT. The 100 day cumulative incidence of CMV disease was 8.8% and 5.6%, 9.4%, 22.6% respectively for total and three kinds of HSCT after early preemptive therapy. Two-year survival of CMV infection was similar in the three kinds of SCT.</p><p><b>CONCLUSION</b>Detection of CMV DNA in plasma by real time PCR appears to be effective for the diagnosis and surveillance of CMV infection after HSCT. It may help to initiate antiviral therapy and reduce the incidence of CMV disease in the patients with high risk of CMV infection.</p>


Subject(s)
Adolescent , Adult , Child , Child, Preschool , Cytomegalovirus , Genetics , Cytomegalovirus Infections , Diagnosis , Drug Therapy , DNA, Viral , Blood , Female , Hematopoietic Stem Cell Transplantation , Humans , Male , Middle Aged , Polymerase Chain Reaction , Methods , Postoperative Complications , Diagnosis , Drug Therapy , Retrospective Studies , Young Adult
7.
Article in Chinese | WPRIM | ID: wpr-355672

ABSTRACT

The aim of the study was to determine the expression of cytidine deaminase (CDD) gene in bone marrow cells from patients with acute leukemia (AL) and evaluate the relationship between CDD expression and clinical feature. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was used for detection of expression level of CDD mRNA in bone marrow cells from 83 patients with acute leukemia and from 15 healthy peoples as control. CDD/beta-actin ratio >or= 0.5 was considered to be positive. The results showed that expression levels of CDD of 31 previously untreated patients were higher than those of 23 cases of AL in complete remission and of normal controls. Expression levels of CDD of 29 relapse/refractory patients were also higher than those of 23 AL patients in complete remission and of normal subjects. The expression levels of CDD in relapse/refractory ALL were higher than those in AML while expression levels of CDD were not correlated with the outcome of therapy. It is concluded that the level of CDD mRNA expression varies at the different stage of acute leukemia. The expression level of CDD seems not to be a prognostic factor.


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Bone Marrow Cells , Cytidine Deaminase , Genetics , Female , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Humans , Leukemia, Myeloid, Acute , Drug Therapy , Genetics , Male , Middle Aged , Neoplasm Recurrence, Local , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Drug Therapy , Genetics , RNA, Messenger , Genetics , Metabolism , Remission Induction , Reverse Transcriptase Polymerase Chain Reaction
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