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1.
Chinese Medical Journal ; (24): 1199-1208, 2021.
Article in English | WPRIM | ID: wpr-878101

ABSTRACT

BACKGROUND@#For patients with B cell acute lymphocytic leukemia (B-ALL) who underwent allogeneic stem cell transplantation (allo-SCT), many variables have been demonstrated to be associated with leukemia relapse. In this study, we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT.@*METHODS@#A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People's Hospital from December 2010 to December 2015 were enrolled in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT, and establish a risk score to identify patients with different probabilities of relapse. The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables.@*RESULTS@#All patients achieved neutrophil engraftment, and 95.4% of patients achieved platelet engraftment. The 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality were 20.7%, 70.4%, 65.6%, and 13.9%, respectively. Multivariate analysis showed that patients with positive post-transplantation minimal residual disease (MRD), transplanted beyond the first complete remission (≥CR2), and without chronic graft-versus-host disease (cGVHD) had higher CIR (P  < 0.001, P = 0.004, and P  < 0.001, respectively) and worse LFS (P  < 0.001, P = 0.017, and P  < 0.001, respectively), and OS (P  < 0.001, P = 0.009, and P  < 0.001, respectively) than patients without MRD after transplantation, transplanted in CR1, and with cGVHD. A risk score for predicting relapse was formulated with the three above variables. The 5-year relapse rates were 6.3%, 16.6%, 55.9%, and 81.8% for patients with scores of 0, 1, 2, and 3 (P  < 0.001), respectively, while the 5-year LFS and OS values decreased with increasing risk score.@*CONCLUSION@#This new risk score system might stratify patients with different risks of relapse, which could guide treatment.


Subject(s)
B-Lymphocytes , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Recurrence , Retrospective Studies , Risk Factors , Stem Cell Transplantation
2.
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
3.
Article in Chinese | WPRIM | ID: wpr-702537

ABSTRACT

Objective To compare the performance of Prestroke Independence, Sex, Age, National Institutes of Health Stroke Scale (ISAN) score, Age, Atrial fibrillation, Dysphagia, Sex, Stroke Severity (A2DS2) score, acute ischemic stroke-as-sociated pneumonia score (AIS-APS), and Preventive ANtibacterial THERapy in Acute Ischemic Stroke (PAN-THERIS) score in predicting the risk of stroke-associated pneumonia (SAP). Methods The baseline characteristics and laboratory data of 338 patients with ischemic stroke in emergency ward from April, 2014 to December, 2017 were retrospectively analyzed. Patients were allocated into SAP group (n=125) and non-SAP group (n=213). Receiver operating characteristic curve (ROC) was used to evaluate the predictive effect of four different scoring systems for ischemic SAP. Results Totally, 125 (37.0%) patients developed SAP. There were significant differences in age, complications (atrial fi-brillation, coronary heart disease and history of stroke), Glasgow Coma Scale (GCS) score, National Institute of Health Stroke Scale (NIHSS) score, ISAN score, A2DS2 score, AIS-APS score and PANTHERIS score between two groups (P<0.05). The A value of PANTHERIS score was 0.818, which was the lowest among four scoring systems (P<0.05). No significant difference was found in the A value between A2DS2 score and ISAN score (P>0.05). Conclusion ISAN, A2DS2 and AIS-APS scoring systems all present good discrimination and calibration in predicting the risk of ischemic SAP. The AIS-APS score calculation is relatively complex, so it is suggested that ISAN and A2DS2 scoring systems be used in emergency.

4.
Journal of Medical Postgraduates ; (12): 595-601, 2018.
Article in Chinese | WPRIM | ID: wpr-700879

ABSTRACT

Objective Little is known about the effect of RNAi on mitochondrial apoptotic pathways. This study aims to explore the effects of the Survivin shRNA-APC double-gene on colon cancer mitochondrial apoptosis pathway-related factors survivin,cytochrome C (Cytc),second mitochondria-derived activator of caspases (Smac),and cysteine aspartic acid specific protease 9 (Caspase-9) as well as on the apoptosis of colon cancer transplanted tumor (CCTT) cells. Methods Thirty nude mice were randomly divided into five groups of equal number,Survivin shRNA-APC double-gene,survivin shRNA,APC,empty vector and blank transfection. The CCTT model was established in the nude mice by subcutaneous injection of the colon cancer cell strains stably transfected with the Survivin shRNA-APC double-gene,survivin shRNA,APC,an empty vector and HT-29,respectively,into the mid-posterior part of the left armpit of the nude mice. The rate of tumor growth inhibition was calculated by measuring the volume and weight of the CCTTs in the nude mice. The mRNA and protein expressions of survivin,Cytc,Smac and Caspase-9 in the tumor tissue were detected by real time PCR and immunohistochemistry,respectively,and the apoptosis rate of the CCTT cells was detected by TUNEL. Results The model of CCTT was successfully established in the nude mice. Com-pared with the empty vector and blank transfection groups,the mice in the double-gene,survivin shRNA and APC groups showed sig-nificantly decreased average volume and weight of the tumor tissue (P<0.05) but increased inhibition rate of its volume and weight (P<0.05). In comparison with the survivin shRNA and APC groups,the double-gene group exhibited remarkably decreased average volume and weight of the tumor tissue (P<0.05) but increased inhibition rate of its volume and weight (P<0.05). The mRNA and pro-tein expressions of survivin were significantly lower while those of Cytc,Smac and Caspase-9 markedly higher in the double-gene,sur-vivin shRNA and APC groups than in the empty vector and blank transfection groups (P<0.05),the former even lower (P<0.05) and the latter even higher in the double-gene than in the survivin shRNA and APC groups (P<0.05). The apoptosis rate of the CCTT cells was significantly increased in the double-gene ([56.78±3.04]%),survivin shRNA ([33.61±2.02]%) and APC groups ([30.16± 1.72]%) as compared with the empty vector ([10.05±0.42]%) and blank transfection groups ([9.87±0.30])% (P<0.05),even higher in the double-gene group than in the survivin shRNA and APC groups (P<0.05). Conclusion The Survivin shRNA-APC double-gene may induce apoptosis of colon cancer transplanted tumor cells by down-regulating the expression of the apoptosis inhibitor survivin,upregulating the expressions of Cytc,Smac and Caspase-9,and suppressing the growth of the colon transplanted tumor,with more significant abilities than a single gene in regulating apoptosis-related factors,inducing cell apoptosis and inhibiting the growth of the transplanted tumor.

5.
Article in English | WPRIM | ID: wpr-310852

ABSTRACT

<p><b>OBJECTIVE</b>To confirm the efficacy and safety of Wufuxinnaoqing Soft Capsule (, WSC) in the treatment of chronic stable angina (blood stasis syndrome).</p><p><b>METHODS</b>A multicenter, randomized, double-blind, placebo-controlled trial with superiority test was designed. A total of 240 patients with chronic stable angina (blood stasis syndrome) from multiple centers were randomly and equally assigned to the treatment group and the control group. Based on standard treatment of Western medicine, the treatment group was given WSC, while the control group was given WSC mimetic, both for 12 weeks. Observed indicators included the efficacy in angina, the efficacy in Chinese medicine syndrome, the withdrawal or reduce rate of nitroglycerin and routine safety indices.</p><p><b>RESULTS</b>After 12-week treatment, the significant effective rate and total effective rate of the treatment group were significantly better than those of the control group (23.5% vs. 9.2%, 64.7% vs. 30.8%), respectively, with statistically significant difference (P<0.01). After 12-week treatment, the decreased points and the decreased rate of angina symptom score in the treatment group were better than in the control group (5.1±4.2 points vs. 2.8±3.5 points, 44.9%±37.2% vs. 25.4%±30.7%) respectively, with significant difference (P<0.01). After 12-week treatment, the significant effective rate and total effective rate of the treatment group were better than the control group (respectively, 30.3% vs. 15.0%, 67.2% vs. 45.0%,P<0.01). After 8- or 12-week treatment, the decreased points and the decreased rate of Chinese medicine syndrome score in the treatment group were better than the control group (P<0.05 orP<0.01). After 12-week treatment, nitroglycerin withdrawal rate and the withdrawal or reduce rate in treatment group were better than the control group (P<0.01). On safety evaluation, the incidence of adverse events (7.563% vs. 7.500%) and the incidence of cardiovascular events (0.840% vs. 0.000%) in the treatment group were similar with the control group, and the difference was not statistically significant (P>0.05).</p><p><b>CONCLUSION</b>In treatment of chronic stable angina (blood stasis syndrome), WSC can reduce angina attacks and consumption of nitroglycerin, decrease angina severity degree, effectively relieve the blood stasis syndromes, such as chest pain, chest tightness, palpitations, dark purple tongue and other symptoms. Besides, adverse events and cardiovascular adverse events in the treatment group and the control group showed no difference. All shows that the drug is safe and effective. [This study was registered in Chinese Clinical Trial Registry (ChiCTR), with registration number: ChiCTR-TRC-14005158.].</p>


Subject(s)
Aged , Angina, Stable , Therapeutics , Double-Blind Method , Drugs, Chinese Herbal , Therapeutic Uses , Female , Humans , Male , Medicine, Chinese Traditional , Middle Aged , Placebos
6.
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
7.
Chinese Medical Journal ; (24): 2489-2494, 2013.
Article in English | WPRIM | ID: wpr-322173

ABSTRACT

<p><b>BACKGROUND</b>The occurrence of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare but severe. We examine the role of pre-HSCT chemotherapeutic exposure, pre-HSCT comorbidities, and transplant-related complications in the development of BOS after allo-HSCT.</p><p><b>METHODS</b>A nested case-control study was designed. Cases with BOS and controls matched for the year of allo-HSCT and length of the follow-up were identified from a cohort of 1646 patients who underwent allo-HSCT for treatment of hematologic malignancies between 2006 and 2011. Antithymocyte globulin was used in the partial matched related and unrelated matched donor HSCT, or patients with severe aplastic anemia.</p><p><b>RESULTS</b>Thirty-six patients suffered from BOS; the mean age at the time of presentation was (32.7 ± 12.4) years, and the mean time to presentation was (474 ± 350) days post-HSCT. A pre-HSCT cyclophosphamide dose of ≥ 3.2 g/m(2)(OR = 8.74, P = 0.025), chronic graft-versus-host disease (moderate to severe) (OR = 12.02, P = 0.000), and conditioning regimens without antithymocyte globulin (OR = 2.79, P = 0.031) were independently associated with BOS.</p><p><b>CONCLUSIONS</b>We found that higher pre-HSCT cyclophosphamide exposure, a conditioning regimen without antithymocyte globulin, and moderate to severe chronic graft-versus-host disease are significantly and independently associated with BOS. Based on these results, we can identify patients who are at a higher risk of developing BOS after allo-HSCT, select a more appropriate therapeutic strategy, and improve the outcome of HSCT recipients.</p>


Subject(s)
Adult , Bronchiolitis Obliterans , Case-Control Studies , Female , Follow-Up Studies , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Male , Middle Aged , Risk Factors , Transplantation Conditioning , Transplantation, Homologous
8.
Chinese Medical Journal ; (24): 2499-2503, 2013.
Article in English | WPRIM | ID: wpr-322171

ABSTRACT

<p><b>BACKGROUND</b>Umbilical cord blood (UCB) has grown substantially as an alternative source of hematopoietic stem cells for unrelated donor transplantation in both adult and pediatric patients. Our aim was to assess the leukemia-free survival (LFS) and some primary results, such as hematologic recovery, risk of graft-versus-host disease (GVHD), relapse, and long-term survival, after unrelated cord blood transplantation compared with the outcomes of transplantations from other unrelated graft source.</p><p><b>METHODS</b>The clinical outcomes of 112 consecutive patients with acute leukemia who received umbilical cord blood (UCBT) as a primary unrelated stem cell source (n = 38), bone marrow (UBMT n = 28, transplanted before January 2003), or peripheral blood stem cells (UPBSCT n = 46, transplanted after January 2003) between July 2000 and July 2008 were analyzed.</p><p><b>RESULTS</b>Except that the patients were much younger in the UCBT group (median age, 10.5 years in UCBT, 30 years in UPBSCT, and 20 years in UBMT), other pre-transplant parameters, such as gender, diagnosis, and the phase of disease, were comparable. All patients received myeloablative regimens, primarily including BUCY; however, there was less anti-thymocyte globulin (ATG) used for the UBMT patients (2/38 in UCBT, 0/46 in UPBSCT, and 8/28 in UBMT did not use ATG, P = 0.000). Significant delays in engraftment occurred after UCBT for both neutrophil cells and platelets. The cumulative allo-engraftment rates were also significantly lower (87.8% vs. 97.8% vs. 100% for WBC, P = 0.000; 73.0% vs. 97.5% vs. 89.5% for PLT, P = 0.000) for UCBT. The incidence of Grade 2-4 and 3-4 acute graft versus host disease (aGVHD) was much higher in the UBMT group but did not differ among the other groups (51% and 13.2%, 40.2% and 10.5%, and 77.4% and 41.2%, respectively, for UCBT, UPBSCT, and UBMT, P = 0.000). The occurrence of extensive chronic GVHD (cGVHD) was significantly decreased for recipients of UCBT (4%) compared with that of UPBSCT (39.1%) and UBMT (49.1%, P = 0.000), although the rates of whole cGVHD were not significantly different (30.3%, 63.1%, and 60.1% for UCBT, UPBSCT, and UBMT, respectively). The patients had a similar rate of CMV infection (21/38, 28/46, and 22/28 for UCBT, UPBSCT, and UBMT, respectively), while the HC occurrence was lower after UCBT (7/38, 16/46, and 14/28 for UCBT, UPBSCT, and UBMT, respectively). As of August 2012, there was no apparent difference in 5-year overall survival (OS), LFS, or the relapse rate for each graft source (52.5%, 52.6%, and 20.8% in UCBT; 48.7%, 46.4%, and 27.9% in UPBSCT; and 46.4%, 42.9%, and 16.0% in UBMT).</p><p><b>CONCLUSION</b>These data support the use of UCB donors as an alternative allogeneic donor.</p>


Subject(s)
Adolescent , Adult , Bone Marrow Transplantation , Child , Child, Preschool , Cord Blood Stem Cell Transplantation , Female , Graft vs Host Disease , Hematologic Neoplasms , Mortality , General Surgery , Histocompatibility Testing , Humans , Male , Middle Aged , Peripheral Blood Stem Cell Transplantation , Treatment Outcome
9.
Chinese Journal of Hematology ; (12): 113-116, 2013.
Article in Chinese | WPRIM | ID: wpr-323432

ABSTRACT

<p><b>OBJECTIVE</b>To retrospectively review the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelomonocytic leukemia (CMML).</p><p><b>METHODS</b>The engraftment, graft versus host disease (GVHD), infection, relapse and survival of 12 CMML patients received allo-HSCT were observed. The clinical outcome of allo-HSCT for CMML was analyzed.</p><p><b>RESULTS</b>Twelve (7 males and 5 females) CMML patients with a median age of 39 years old received allo-HSCT including 7 from HLA-matched sibling and 5 from haploidentical related donors. All 12 patients achieved engraftment. The median time of neutrophil engraftment and platelet engraftment were 15 (11 - 20) days and 13 (11 - 18) days, respectively. 4 patients occurred acute GVHD, and 3 occurred chronic GVHD. After the median follow-up of 17.5 months (12 - 32 months), the overall survival, disease free survival and relapse rate were 66.7%, 66.7%, and 16.7%, respectively.</p><p><b>CONCLUSION</b>Allo-HSCT can improve the survival of patients with CMML, and is a effective therapy for CMML.</p>


Subject(s)
Adolescent , Adult , Child , Female , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Therapeutics , Male , Middle Aged , Retrospective Studies , Survival Rate , Transplantation, Homologous , Young Adult
10.
Chinese Journal of Hematology ; (12): 651-654, 2013.
Article in Chinese | WPRIM | ID: wpr-272144

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the prevalence of Epstein Barr Virus (EBV) in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>We retrospectively analyzed the clinical characteristics of 720 patients received allo-HSCT from January 2010 through December 2011 in the Stem Cell Transplant Center of People's Hospital.</p><p><b>RESULTS</b>Of 720 patients (469 male presented and 251 females), with a median age of 30 years (range, 2 to 67 years) old, 66 patients were presented with EBV reactivation. The cumulative incidence of EBV reactivation was (9.3±1.1)%, with a median days of 54.5 (range, 18 to 253 days). During one- year post-transplantation, the cumulative incidences of EBV reactivation in sibling allo-HSCT, haploidentical HSCT and unrelated donor HSCT were (1.3±0.7)%, (13.7±1.7)%, and (9.1±4.4)%, respectively. In patients with haplo-identical HSCT, the cumulative incidences of EBV viremia, probable EBV disease, and post-transplant lymphoproliferative disease (PTLD) were (5.8±1.1)%, (5.7±1.1)%, and (2.3±0.7)%. The mortality was (33.9±5.9)% in all patients with EBV infection: (63.6±15.8)% in PTLD, (42.3±9.9)% in probable EBV disease, (13.8±6.5)% in EBV viremia. By univariate and multivariate analysis, the use of ATG was an independent risk factor for EBV infection.</p><p><b>CONCLUSION</b>EBV reactivation is a common complication in patients with allo- HSCT, especially high mortality in PTLD and probable EBV disease. The use of ATG was an independent risk factor for EBV infection.</p>


Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Epstein-Barr Virus Infections , Pathology , Female , Hematopoietic Stem Cell Transplantation , Herpesvirus 4, Human , Humans , Lymphoproliferative Disorders , Virology , Male , Middle Aged , Retrospective Studies , Risk Factors , Transplantation, Homologous , Virus Activation , Young Adult
11.
Chinese Medical Journal ; (24): 1096-1102, 2013.
Article in English | WPRIM | ID: wpr-342232

ABSTRACT

<p><b>BACKGROUND</b>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for many hematological diseases, but there are many complications following allo-HSCT, among which neurological complications (NC) are one of the most commonly described ones. However, little is known about idiopathic inflammatory demyelinating diseases (IIDDs) of the central nervous system (CNS) in patients following allo-HSCT.</p><p><b>METHODS</b>A nested case-control study was conducted in a large cohort of 1365 patients, who underwent allo-HSCT at the Institute of Hematology and Peking University People's Hospital, between January 2004 and December 2009, 36 patients of whom developed CNS IIDDs. Kaplan-Meier method, univariate and multivariate Cox regression were applied in our statistical analysis using SPSS 16.0.</p><p><b>RESULTS</b>The cumulative incidence of all cases of IIDDs at 6 years posttransplantation was 3.6%. Thirty-five patients (97.2%) suffered IIDDs after transplantation, 16 patients (44.4%) between day 0 to day 100 post-transplantation, 10 patients (27.8%) between day 100 to 1 year post-transplantation, and 9 patients (25.0%) 1 year post-transplantation. Multivariate regression analysis identified donor type (P = 0.031), infection (P = 0.009), and acute lymphatic leukemia (P = 0.017) as independent risk factors for posttransplantation IIDDs. The median survival time of patients with IIDDs was 514 days after transplantation (95%CI: 223 - 805). Survival at 6 years was significantly lower in patients who developed the diseases compared to those who did not (26.6% vs. 73.5%, P < 0.001). Of the 36 patients experiencing IIDDs, 58.3% (n = 21) died. The causes of death were graft-versus-host disease (GVHD) (n = 4), underlying disease relapse (n = 3), infections (n = 12), and other causes (n = 2).</p><p><b>CONCLUSIONS</b>IIDDs is an uncommon but serious complication of allo-HSCT, especially in patients with a primary diagnosis of acute lymphatic leukemia, mismatched transplants, and infections. Our study results indicate that patients with IIDDs tend toward a poor prognosis following allo-HSCT.</p>


Subject(s)
Adolescent , Adult , Case-Control Studies , Central Nervous System , Child , Child, Preschool , Demyelinating Autoimmune Diseases, CNS , Female , Hematopoietic Stem Cell Transplantation , Humans , Infant , Male , Middle Aged , Retrospective Studies , Risk Factors , Young Adult
12.
Chinese Medical Journal ; (24): 3048-3052, 2013.
Article in English | WPRIM | ID: wpr-263527

ABSTRACT

<p><b>BACKGROUND</b>Chronic graft-versus-host disease (GVHD), the commonest long-term complication after allogeneic hematopoietic stem cell transplantation (HSCT), has a negative impact on patients' health related quality of life (HRQoL). This study was designed to investigate the HRQoL in patients with chronic GVHD in China.</p><p><b>METHODS</b>Two hundred and sixty-four patients with chronic GVHD who were ≥ 24 months post-HSCT and had been in continuous complete remission since HSCT were enrolled in this retrospective study. HRQoL was evaluated using an SF-36 questionnaire. Multivariate analysis was used to identify the factors that affect HRQoL in patients with chronic GVHD.</p><p><b>RESULTS</b>HRQoL in patients categorized as having mild and moderate chronic GVHD was significantly better than in those in the severe category. In the moderate chronic GVHD category, markedly poorer HRQoL was observed in patients with both multiple organ involvement and more severe organ impairment than in those without these factors. According to multivariate analysis, chronic GVHD severity had the greatest significant negative impact on patients' HRQoL; whereas being female was associated with a negative impact on psychological health.</p><p><b>CONCLUSION</b>Chronic GVHD severity strongly correlates with negative impacts on patients' HRQoL.</p>


Subject(s)
Adult , Chronic Disease , Female , Graft vs Host Disease , Psychology , Humans , Male , Middle Aged , Quality of Life , Retrospective Studies , Severity of Illness Index
13.
Chinese Journal of Hematology ; (12): 917-921, 2012.
Article in Chinese | WPRIM | ID: wpr-278300

ABSTRACT

<p><b>OBJECTIVE</b>To explore the outcome of human leukocyte antigen (HLA)-mismatched/haploidentical hematopoietic stem cell transplantation (HSCT) for refractory/relapsed acute leukemia (AL) patients and its related risk factors.</p><p><b>METHODS</b>96 refractory/relapsed AL patients who received HLA-mismatched/haploidentical HSCT following conditioning regimen comprised of modified busulfan/cyclophosphamide (BU/CY) plus thymoglobulin (ATG) from Jan 2003 to Jun 2011 were analyzed retrospectively.</p><p><b>RESULTS</b>Of the 96 patients, 61 suffered from acute myeloid leukemia (AML), and 35 acute lymphoid leukemia (ALL), all of them in non-remission (NR) or relapse before transplantation. With a median follow-up of 373 (34 - 3157) d, 33 cases (34%) survived, 31 survived without leukemia, and 35 relapsed. The estimated 3-year overall survival (OS) and disease-free survival (DFS) rate was 30.2% and 29.0%, respectively. The 3-year OS rate was significantly higher for AML patients (39.2%) than for ALL patients (15.4%) (P = 0.005). The estimated 3-year OS probabilities for patients with and without prophylactic donor lymphocyte infusion (DLI) were 38.0% and 11.8%, respectively (P = 0.001). Sex, age, conditioning regimen (BU/CY or not, dosage of ATG), the number of HLA mismatches between the donor and recipient, and the number of infused mononuclear cells were not independent factors affecting OS, DFS and relapse. Multivariate analysis showed that DFS rate was significantly higher in patients receiving prophylactic DLI (P = 0.003), in patients with AML (vs with ALL) (P = 0.037) and with chronic GVHD (P = 0.006).</p><p><b>CONCLUSIONS</b>Haploidentical HSCT may prolong DFS in part refractory/relapsed AL patients and even cure them. Prophylactic DLI may reduce relapse and increase survival; for patients with refractory/relapsed ALL, other therapy for prevention and treatment of post-transplant relapse should be explored.</p>


Subject(s)
Acute Disease , Adolescent , Adult , Aged , Child , Female , Hematopoietic Stem Cell Transplantation , Humans , Leukemia , Therapeutics , Leukemia, Myeloid, Acute , Therapeutics , Male , Middle Aged , Recurrence , Retrospective Studies , Transplantation Conditioning , Transplantation, Homologous , Young Adult
14.
Chinese Medical Journal ; (24): 1952-1959, 2012.
Article in English | WPRIM | ID: wpr-283687

ABSTRACT

<p><b>BACKGROUND</b>Chimerism analysis is an important tool for the surveillance of post-transplant engraftment. It offers the possibility of identifying impending graft rejection and recurrence of underlying malignant or non-malignant disease. Here we investigated the quantitative chimerism kinetics of 21 relapsed leukemia patients after allogeneic hematopoietic stem cell transplantation (HSCT).</p><p><b>METHODS</b>A panel of 29 selected sequence polymorphism (SP) markers was screened by real-time polymerase chain reaction (RT-PCR) to obtain the informative marker for every leukemia patient. Quantitative chimerism analysis of bone marrow (BM) samples of 21 relapsed patients and 20 patients in stable remission was performed longitudinally. The chimerisms of BM and peripheral blood (PB) samples of 14 patients at relapse were compared.</p><p><b>RESULTS</b>Twenty-one patients experienced leukemia relapse at a median of 135 days (range, 30 - 720 days) after transplantation. High recipient chimerism in BM was found in all patients at relapse, and increased recipient chimerism in BM samples was observed in 90% (19/21) of patients before relapse. With 0.5% recipient DNA as the cut-off, median time between the detection of increased recipient chimerism and relapse was 45 days (range, 0 - 120 days), with 76% of patients showing increased recipient chimerism at least 1 month prior to relapse. Median percentage of recipient DNA in 20 stable remission patients was 0.28%, 0.04%, 0.05%, 0.05%, 0.08%, and 0.05% at 1, 2, 3, 6, 9, and 12 months, respectively, after transplantation. This was concordant with other specific fusion transcripts and fluorescent in situ hybridization examination. The recipient chimerisms in BM were significantly higher than those in PB at relapse (P = 0.001).</p><p><b>CONCLUSIONS</b>This SP-based RT-PCR assay is a reliable method for chimerism analysis. Chimerism kinetics in BM can be used as a marker of impending leukemia relapse, especially when no other specific marker is available. Based on our findings, we recommend examining not only PB samples but also BM samples in HSCT patients.</p>


Subject(s)
Adolescent , Adult , Child , Female , Hematopoietic Stem Cell Transplantation , Humans , Leukemia , Genetics , Therapeutics , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , Transplantation Chimera , Genetics , Transplantation, Homologous , Young Adult
15.
Chinese Medical Journal ; (24): 947-950, 2012.
Article in English | WPRIM | ID: wpr-269320

ABSTRACT

Both human hereditary spherocytosis (HS) and chronic myelogenous leukemia (CML) are life threatening. Herein we have reported the case of a woman with a combined disorder of HS and CML who underwent the matched sibling allogeneic stem cell transplantation. The complete donor erythroid cells were obtained. The red blood cell counts significantly improved throughout life comparing with pre-hematopoietic stem cell transplantation (HSCT). Reticulocyte counts normalized, and BCR-ABL was cleared away. The total bilirubin level was also corrected in this recipient. Our case is a rare example with a combined disorder of HS and CML following allogeneic stem cell transplantation. HS was not a contraindication for patient in the matched sibling transplant setting.


Subject(s)
Adult , Female , Hematopoietic Stem Cell Transplantation , Humans , Spherocytosis, Hereditary , Therapeutics , Transplantation, Homologous
16.
Chinese Medical Journal ; (24): 1517-1523, 2011.
Article in English | WPRIM | ID: wpr-353952

ABSTRACT

<p><b>BACKGROUND</b>The cause of late-onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains obscure. In clinical practice, some LOHC patients respond to immunosuppression. The aim of this study was to determine the immune pathogenesis of LOHC post allo-HSCT.</p><p><b>METHODS</b>With the diagnosis of LOHC, patients were given initial treatment consisting of fluid hydration, alkalization and forced diuresis, and empirical anti-viral therapy for 10 - 14 days or until a week after the virus became negative. The nonresponders were applied corticosteroid. Seven to ten days later, patients' response was evaluated. Along with treatment, CD19(+) B lymphocyte subsets were measured at various study points.</p><p><b>RESULTS</b>From October 2009 to March 2010, we found 28 cases of LOHC occurred in 25 patients who underwent allo-HSCT in our hospital. Except that three cases were not treated according to the protocol, the other 25 cases were divided into three groups: anti-virus responders (Group A, n = 6), corticosteroid responders (Group B1, n = 16), corticosteroid and anti-virus nonresponders (Group C, n = 3) according to their clinical response. Percentages of CD19(+)CD5(+) B lymphocytes were not significantly different among three groups at onset of LOCH. However, in Group B1 after the first anti-virus phase, percentages of CD19(+)CD5(+) lymphocytes significantly increased comparing with those at onset (P = 0.022), and then significantly decreased at PR (P = 0.003) and CR (P = 0.002) with corticosteroid treatment. But significant change was not observed in Groups A and C.</p><p><b>CONCLUSION</b>The immune etiology seems to be involved in the development of LOHC and the proportion of CD19(+)CD5(+) lymphocytes may serve as a cellular biomarker to predict the response to corticosteroid in LOHC.</p>


Subject(s)
Adolescent , Adrenal Cortex Hormones , Therapeutic Uses , Adult , Antigens, CD19 , Metabolism , B-Lymphocytes , Metabolism , CD5 Antigens , Metabolism , Child , Child, Preschool , Cystitis , Drug Therapy , Allergy and Immunology , Therapeutics , Female , Flow Cytometry , Hematopoietic Stem Cell Transplantation , Humans , Male , Middle Aged , Young Adult
17.
Chinese Medical Journal ; (24): 2301-2308, 2011.
Article in English | WPRIM | ID: wpr-292845

ABSTRACT

<p><b>BACKGROUND</b>Analysis of changes in recipient and donor hematopoietic cell origin is extremely useful to monitor the effect of hematopoietic stem cell transplantation (HSCT) and sequential adoptive immunotherapy by donor lymphocyte infusions. We developed a sensitive, reliable and rapid real-time PCR method based on sequence polymorphism systems to quantitatively assess the hematopoietic chimerism after HSCT.</p><p><b>METHODS</b>A panel of 29 selected sequence polymorphism (SP) markers was screened by real-time PCR in 101 HSCT patients with leukemia and other hematological diseases. The chimerism kinetics of bone marrow samples of 8 HSCT patients in remission and relapse situations were followed longitudinally.</p><p><b>RESULTS</b>Recipient genotype discrimination was possible in 97.0% (98 of 101) with a mean number of 2.5 (1-7) informative markers per recipient/donor pair. Using serial dilutions of plasmids containing specific SP markers, the linear correlation (r) of 0.99, the slope between -3.2 and -3.7 and the sensitivity of 0.1% were proved reproducible. By this method, it was possible to very accurately detect autologous signals in the range from 0.1% to 30%. The accuracy of the method in the very important range of autologous signals below 5% was extraordinarily high (standard deviation <1.85%), which might significantly improve detection accuracy of changes in autologous signals early in the post-transplantation course of follow-up. The main advantage of the real-time PCR method over short tandem repeat PCR chimerism assays is the absence of PCR competition and plateau biases, with demonstrated greater sensitivity and linearity. Finally, we prospectively analyzed bone marrow samples of 8 patients who received allografts and presented the chimerism kinetics of remission and relapse situations that illustrated the sensitivity level and the promising clinical application of this method.</p><p><b>CONCLUSION</b>This SP-based real-time PCR assay provides a rapid, sensitive, and accurate quantitative assessment of mixed chimerism that can be useful in predicting graft rejection and early relapse.</p>


Subject(s)
Adolescent , Adult , Child , Female , Genotype , Hematopoietic Stem Cell Transplantation , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Genetics , Real-Time Polymerase Chain Reaction , Methods , Reproducibility of Results , Transplantation Chimera , Genetics , Young Adult
18.
Chinese Journal of Hematology ; (12): 323-327, 2010.
Article in Chinese | WPRIM | ID: wpr-353616

ABSTRACT

<p><b>OBJECTIVE</b>To explore the dissociation of graft-versus-leukemia (GVL) effects from graft-versus-host disease (GVHD) in the patients who experienced GVHD during leukemia relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>The primary disease, disease status, GVHD, response to donor lymphocyte infusion (DLI) and prognosis were analysed in 11 leukemia patients who relapsed with GVHD after allo-HSCT.</p><p><b>RESULTS</b>Of the 11 relapsed, 5 were acute lymphoblastic leukemia and 6 acute myeloid leukemia. Five received DLI before relapse and all developed post-DLI GVHD, including 2 grade II acute GVHD (aGVHD), 1 limited chronic GVHD (cGVHD) plus grade II aGVHD, and 2 extensive cGVHD. After relapse of the 5 patients, 2 received Chemo-DLI, one achieved CR with extensive cGVHD and then relapsed again, the other didn't achieved CR. The other 6 patients didn't received DLI before relapse and also developed post-HSCT GVHD while relapsing, including 3 extensive cGVHD, 1 grade I aGVHD and 2 grade II-IV aGVHD. After relapse, these 6 patients received Chemo-DLI, 2 achieved CR and then relapsed again, 4 didn't achieved CR.</p><p><b>CONCLUSION</b>The elicited GVHD after allo-HSCT may not accompany effective GVL effects inhibiting leukemic relapse.</p>


Subject(s)
Graft vs Host Disease , Graft vs Leukemia Effect , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute , Precursor Cell Lymphoblastic Leukemia-Lymphoma
19.
Chinese Journal of Hematology ; (12): 816-820, 2009.
Article in Chinese | WPRIM | ID: wpr-283900

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the correlation between the change of liver enzymes and the severity of acute graft-versus-host disease (aGVHD).</p><p><b>METHODS</b>The liver enzyme and severity of aGVHD in 82 patients were analyzed retrospectively.</p><p><b>RESULTS</b>Among the 82 aGVHD patients, 7 developed grade I (18.3%), 47 grade II (57.3%), 13 grade III (15.9%) and 7 grade IV (8.5%) aGVHD. The elevation of ALT, AST and ALP was found in 49 (59.8%), 36(43.9%) and 8(9.8%)patients respectively. Among these patients, 34 (69.4%) were ALT > 40 U/L, 18 (50%) AST > 40 U/L and 4 (50%) ALP > 132 U/L before the onset of aGVHD. The elevation of ALT and AST was more common and the peak value was significantly higher in patients with grade III-IV aGVHD than with grade I-II aGVHD, but those of ALP showed no difference between the two groups. Compared with the patients without ALT elevation, the proportion of severe aGVHD was higher in patients with ALT elevation.</p><p><b>CONCLUSIONS</b>The alteration of liver enzymology is common in aGVHD and its level is correlated with the severity of aGVHD. Liver enzymes, especially the ALT, may be used as a predictor of aGVHD.</p>


Subject(s)
Graft vs Host Disease , Humans , Liver , Retrospective Studies
20.
Chinese Journal of Cardiology ; (12): 646-650, 2008.
Article in Chinese | WPRIM | ID: wpr-355921

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the relationship between PPAR coactivator 1 (PGC-1), nuclear respiratory factor (NRF), mitochondrial transcription factor A (mtTFA) expressions of vascular smooth muscle cells (VSMC) and development of atherosclerosis in a rabbit model.</p><p><b>METHODS</b>Atherosclerotic model was established by feeding the rabbits with high-fat diet for 4, 8 and 12 weeks (n = 10 each). Another 8 rabbits fed with normal diet served as normal controls. Intima-media ratio, mRNA and protein expressions of PGC-1, NRF, mtTFA and SMemb, a marker for synthetic VSMC, were detected on aorta specimens.</p><p><b>RESULTS</b>With the blood lipid increased, the intima-media ratio rose from (0.031 +/- 0.010) microm up to (0.814 +/- 0.258) microm during 12 weeks. Increasing SMemb means that synthetic VSMC grew more and more. The expressions of PGC-1 became significant after 4 weeks (P < 0.01), while that of NRF-1 and mtTFA rose significantly after 8 weeks (P < 0.01).</p><p><b>CONCLUSIONS</b>The PGC-NRF-mtTFA pathway might play a critical role in VSMC proliferation and development of atherosclerosis.</p>


Subject(s)
Animals , Atherosclerosis , Blood , Metabolism , Pathology , DNA-Binding Proteins , Metabolism , Disease Models, Animal , Female , Lipids , Blood , Male , Mitochondrial Proteins , Metabolism , Muscle, Smooth, Vascular , Metabolism , Nuclear Respiratory Factor 1 , Metabolism , Rabbits , Trans-Activators , Metabolism , Transcription Factors , Metabolism
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