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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): 1765-1772, 2019.
Article in English | WPRIM | ID: wpr-771162

ABSTRACT

BACKGROUND@#Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect. This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM, and compare the main outcomes with matched-related donors (MRDs).@*METHODS@#Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017. A matched-pair analysis was designed. For each haplo recipient, the recipients were randomly selected from the MRD group and were matched according to the following criteria: year of the hematopoietic SCT (±2 years), disease status at transplantation, and the length of follow-up.@*RESULTS@#Seventy cases received MRD and 27 received haploidentical transplantation. The two groups showed no significant differences regarding age, gender, cytogenetic risk, and diagnostic stage. The cumulative incidences of non-relapse mortality (NRM) at 1 and 3 years based on donor type were 20.5% (95% confidence interval [CI], 10.90-30.10%) and 24.2% (95% CI, 13.81-34.59%) for the MRD group and 16.80% (95% CI, 1.71-31.89%) and 28.70% (95% CI, 8.71-48.69%) for the haplo group, respectively. Cumulative incidence of NRM did not differ significantly between the two groups (χ = 0.031, P = 0.861). The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8% (95% CI, 48.24-71.36%) and 45.4% (95% CI, 33.44-57.36%), and 65.6% (95% CI, 47.18-84.02%) and 26.8% (95% CI, 7.59-46. 01%) for MRD and haploidentical donor, respectively. Cumulative incidence of PFS did not differ significantly between the two groups (χ = 0.182, P = 0.670). In multivariate analyses, no statistically significant differences were observed between haploidentical and MRD for relapse, NRM, PFS, and overall survival. There were no statistically differences on main outcomes after haploidentical and MRD.@*CONCLUSION@#Haploidentical SCT could be performed safely and feasibly for patients with MM in need.

3.
Chinese Medical Journal ; (24): 1765-1772, 2019.
Article in English | WPRIM | ID: wpr-802695

ABSTRACT

Background@#Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect. This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM, and compare the main outcomes with matched-related donors (MRDs).@*Methods@#Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017. A matched-pair analysis was designed. For each haplo recipient, the recipients were randomly selected from the MRD group and were matched according to the following criteria: year of the hematopoietic SCT (±2 years), disease status at transplantation, and the length of follow-up.@*Results@#Seventy cases received MRD and 27 received haploidentical transplantation. The two groups showed no significant differences regarding age, gender, cytogenetic risk, and diagnostic stage. The cumulative incidences of non-relapse mortality (NRM) at 1 and 3 years based on donor type were 20.5% (95% confidence interval [CI], 10.90–30.10%) and 24.2% (95% CI, 13.81–34.59%) for the MRD group and 16.80% (95% CI, 1.71–31.89%) and 28.70% (95% CI, 8.71–48.69%) for the haplo group, respectively. Cumulative incidence of NRM did not differ significantly between the two groups (χ2 = 0.031, P = 0.861). The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8% (95% CI, 48.24–71.36%) and 45.4% (95% CI, 33.44–57.36%), and 65.6% (95% CI, 47.18–84.02%) and 26.8% (95% CI, 7.59–46. 01%) for MRD and haploidentical donor, respectively. Cumulative incidence of PFS did not differ significantly between the two groups (χ2 = 0.182, P = 0.670). In multivariate analyses, no statistically significant differences were observed between haploidentical and MRD for relapse, NRM, PFS, and overall survival. There were no statistically differences on main outcomes after haploidentical and MRD.@*Conclusion@#Haploidentical SCT could be performed safely and feasibly for patients with MM in need.

4.
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
5.
Chinese Medical Journal ; (24): 2185-2192, 2018.
Article in English | WPRIM | ID: wpr-690246

ABSTRACT

<p><b>Background</b>The dose of certain cell types in allografts affects engraftment kinetics and clinical outcomes after allogeneic stem cell transplantation (SCT). Hence, the present study investigated the association of cell compositions in allografts with outcomes after unmanipulated haploidentical SCT (haplo-SCT) for patients with acquired severe aplastic anemia (SAA).</p><p><b>Methods</b>A total of 131 patients with SAA who underwent haplo-SCT were retrospectively enrolled. Cell subsets in allografts were determined using flow cytometry. To analyze the association of cellular compositions and outcomes, Mann-Whitney U nonparametric tests were conducted for patient age, sex, weight, human leukocyte antigen mismatched loci, ABO-matched status, patient ABO blood type, donor-recipient sex match, donor-recipient relationship, and each graft component. Multivariate analysis was performed using logistic regression to determine independent influence factors involving dichotomous variables selected from the univariate analysis.</p><p><b>Results</b>A total of 126 patients (97.7%) achieved neutrophil engraftment, and 121 patients (95.7%) achieved platelet engraftment. At 100 days after transplantation, the cumulative incidence of II-IV acute graft-versus-host disease (GVHD) was 32.6%. After a median follow-up of 842 (range: 124-4110) days for surviving patients, the cumulative incidence of total chronic GVHD at 3 years after transplantation was 33.7%. The probability of overall survival at 3 years was 83.0%. Multivariate analysis showed that higher total doses of CD14 (P = 0.018) and CD34 cells (P < 0.001) were associated with a successful platelet engraftment. A successful platelet was associated with superior survival (P < 0.001). No correlation of other cell components with outcomes was observed.</p><p><b>Conclusions</b>These results provide evidence and explain that higher doses of CD34 and CD14 cells in haploidentical allografts positively affect platelet engraftment, contributing to superior survival for patients with SAA.</p>


Subject(s)
Adolescent , Adult , Allografts , Anemia, Aplastic , Therapeutics , Child , Child, Preschool , Female , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Male , Middle Aged , Retrospective Studies , Transplantation Conditioning , Transplantation, Haploidentical , Transplantation, Homologous , Young Adult
6.
Article in Chinese | WPRIM | ID: wpr-256005

ABSTRACT

Based on different binders, the Leonurus Herba extract powders were fluidized and modified. The physical properties such as hygroscopicity, flowability, filling property and compression property were studied by various micromeritics methods before and after modification. The results showed that the physical properties of Leonurus Herba extract were close to those of microcrystalline cellulose, and its comprehensive flow index was between 61-75. Fluidization process can improve hygroscopicity, so the moisture absorption indexes of the samples were significantly lower than those of the original Leonurus Herba extract samples. With the plastic constant, compression ratio and yield stress, Heckel equation and Kawakita equation as the the investigation indicators, results showed that fluidization process based on binder water was superior to other methods in increasing the compressibility of the extracts. In low and medium pressure, the fluidized and modified extract can form the tablets with a certain strength. Fluidized transformation had a greater influence on the properties of original Leonurus Herba extracts, which was instructive to guide significance for the surface modification of pharmaceutical powders and provide the basis for the development of extract tablet.

7.
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
8.
Chinese Medical Journal ; (24): 4254-4259, 2013.
Article in English | WPRIM | ID: wpr-327593

ABSTRACT

<p><b>BACKGROUND</b>In bone marrow transplant patients, the microenvironment in bone marrow is damaged after chemotherapy or radiotherapy. Subsequent to allogenic hematopoietic stem cell transplantation in patients with clinically successful engraftments, the source of mesenchymal stem cells (MSCs) remains controversial. To further verify the stimulatory effect of the simultaneous transplantation of cells from second donors on engraftment success for hematopoietic stem cell transplantation in support of donor MSCs engraftments, the aim of this study is to monitor the dynamics of the engraftment of bone marrow-derived MSCs in patients after transplantation with mismatched-sex hematopoietic stem and third-party cells.</p><p><b>METHODS</b>In this study, the hematopoietic stem cells from 32 clinical donors of different sexes that resulted in successful engraftments were selected for transplantation and were classified into three groups for research purposes: group A consisted of 14 cases of transplantation with bone marrow and recruited peripheral hematopoietic stem cell transplantation, group B contained 8 cases of simultaneous re-transfusion of MSCs from the second donor, and group C contained 10 cases of simultaneous re-transfusion of umbilical blood from the second donor. The bone marrow from 32 patients with successful engraftments of hematopoietic transplantation were selected and sub-cultured with MSCs. Flow cytometry (FCM) was used to measure the expression of surface antigens on MSCs. Denaturing high-performance liquid chromatography (DHPLC) in combination with polymerase chain reaction amplification of short tandem repeats (STRPCR) was used to measure the engraftment status of fifth-generation MSCs in patients. Fluorescence in situ hybridization (FISH) revealed the sex origin of the fifth-generation MSCs in 32 patients. Dynamic examinations were performed on patients receiving donor transplantations.</p><p><b>RESULTS</b>The progenies of fifth-generation MSCs were successfully cultured in 32 cases. The results of FCM demonstrated that the expression levels of CD14+ and CD45+ cells were lower than 0.04% in the fifth-generation MSCs. The analysis using DHPLC and FISH showed similar results. One patient from group B also received a temporary transplantation of MSCs from the donor. The MSCs in the remaining 31 patients all originated from the patients themselves.</p><p><b>CONCLUSIONS</b>After transplantation, the MSCs present in patients originated from the host. In patients transplanted with MSCs from a second donor, the phenomenon of temporary chimerization of MSCs was observed.</p>


Subject(s)
Adolescent , Adult , Cells, Cultured , Chromatography, High Pressure Liquid , Female , Flow Cytometry , Hematopoietic Stem Cell Transplantation , Humans , Leukocyte Common Antigens , Metabolism , Lipopolysaccharide Receptors , Metabolism , Male , Mesenchymal Stem Cells , Cell Biology , Metabolism , Middle Aged , Young Adult
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 Journal of Hematology ; (12): 664-668, 2013.
Article in Chinese | WPRIM | ID: wpr-272141

ABSTRACT

<p><b>OBJECTIVE</b>To explore the kinetics of platelet reconstitution and its prognostic significance in patients received unmanipulated haploidentical stem cell transplantation (Haplo-HSCT) without in vitro T cell depletion.</p><p><b>METHODS</b>A total of 291 patients received Haplo-HSCT without in vitro T cell depletion between January 2007 to December 2008 were retrospectively reviewed. They were categorized into 3 groups according to the platelet count on day 30, day 60 and day 90: (1) persistent thrombocytopenia (Group A) was defined as the platelet count never reached 50×10⁹/L on the three time points; (2) unstable thrombocytopenia (Group B): the platelet count recovered to a level of 50×10⁹/L by day 30 or 60 or 90, yet did not reach a level of more than 100×10⁹/L; (3) non-thrombocytopenia (Group C): the platelet count was higher than 100×10⁹/L on day 90. The kinetics of platelet reconstitution, overall survival (OS) and treatment related mortality (TRM) were compared between 3 groups.</p><p><b>RESULTS</b>Of the 291 consecutive patients, 288 cases engrafted successfully and 262 cases were platelet transfusion independent. The median intervals of neutrophil and platelet engraftment were 13 (9-29) days and 17 (7-180) days, respectively. The cumulative incidence of grade III-IV acute graft versus host disease (GVHD) on day 100 and chronic GVHD at 3 years were 14.7% and 56.4% respectively. OS and TRM at 3 years were 64.6% and 22.3% respectively. At the end of the follow-up, 266 cases were platelet transfusion independent: including 71 (24.4%) cases in Group A, 147 (50.5%) in Group B and 73 (25.1%) in Group C. OS in group A, B and C was 38.0%, 69.4% and 80.8% (P<0.05) respectively. TRM in Group A, B and C was 53.5%, 17.7% and 1.4% (P<0.05) respectively. Persistent thrombocytopenia was related with lower OS and higher TRM in multivariate analysis.</p><p><b>CONCLUSION</b>Persistent thrombocytopenia was common after Haplo-HSCT without in vitro T cell depletion, and patients with persistent thrombocytopenia have poor OS and higher TRM.</p>


Subject(s)
Adolescent , Adult , Blood Platelets , Child , Child, Preschool , Female , Hematopoietic Stem Cell Transplantation , Methods , Humans , Lymphocyte Depletion , Male , Middle Aged , Platelet Count , Prognosis , Retrospective Studies , Thrombocytopenia , Treatment Outcome , 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 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
14.
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
15.
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
16.
Chinese Journal of Hematology ; (12): 473-477, 2013.
Article in Chinese | WPRIM | ID: wpr-235423

ABSTRACT

<p><b>OBJECTIVE</b>To describe the constituent ratio of different kinds of antifungal agents as first choice in empirical or preemptive antifungal therapy for patients with hematological malignancies received chemotherapy or hematopoietic stem cell transplantation (HSCT).</p><p><b>METHODS</b>Between 2008 January and 2009 December, 367 patients received chemotherapy or HSCT from 15 medical centers in China were collected. The strategies of antifungal therapy and the first-choice antifungal agents were analyzed.</p><p><b>RESULTS</b>Of them, 282(76.8%) patients received empirical antifungal therapy, 85(23.2%) preemptive therapy. The number of first choice antifungal agents were 55(15.0%) of fluconazole, 174(47.4%) of itraconazole, 39(10.6%) of voriconazole, 57(15.5%) of traditional/lipid formulation amphotericin B, 26(7.1%) of caspofungin, 7(1.9%) of micafungin, and 9(2.5%) of combination antifungal therapy respectively. Moreover, voriconazole and combination antifungal agents were more often selected for preemptive antifungal therapy, while the probabilities of itraconazole were the highest in both empirical and preemptive strategies. More patients undergoing HSCT were first given itraconazole or caspofungin for antifungal therapy, while amphotericin B, fluconazole and voriconazole were more administered in patients received chemotherapy. Caspofungin and combined antifungal agents were more often used for patients with secondary antifungal prophylaxis, while itraconazole was usually used for patients with no prophylaxis or primary antifungal prophylaxis.</p><p><b>CONCLUSION</b>Empirical antifungal therapy was more administered in hematological malignancies patients received chemotherapy or HSCT. Itraconazole was the most commonly used agent for antifungal therapy followed by amphotericin, fluconazole, voriconazole and echinocandin agents.</p>


Subject(s)
Adult , Antibiotic Prophylaxis , Antifungal Agents , Therapeutic Uses , Antineoplastic Agents , Therapeutic Uses , China , Epidemiology , Female , Hematologic Neoplasms , Drug Therapy , Microbiology , Humans , Male , Middle Aged , Mycoses , Young Adult
17.
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
18.
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
19.
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
20.
Chinese Medical Journal ; (24): 246-252, 2011.
Article in English | WPRIM | ID: wpr-321460

ABSTRACT

<p><b>BACKGROUND</b>Relapse happens frequently after allogeneic hematopoietic cell transplantation (allo-HCT) in the patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL). Detection of the minimal residual disease (MRD) before and after allo-HCT is associated with higher relapse rate. Early administration of imatinib after allo-HCT may prevent recurrent Ph(+) ALL. The aim of this study was to evaluate the safety and efficacy of imatinib in preventing hematological relapse when imatinib was administrated in the first 90 days after allo-HCT.</p><p><b>METHODS</b>Patients with Ph(+) ALL that underwent allo-HCT were enrolled in a prospective study. A TaqMan-based real-time quantitative polymerase chain reaction (RQ-PCR) technique was used to detect the MRD (bcr-abl transcript levels). Imatinib therapy was initiated prior to 90 days after allo-HCT if the patient's absolute neutrophil count (ANC) was above 1.0 × 10(9)/L (without granulocyte colony-stimulating factor (G-CSF) administration) and the platelet count was greater than 50.0 × 10(9)/L, or if the bcr-abl transcript levels were elevated in two consecutive tests, or if the bcr-abl transcript levels were ≥ 10(-2) after the initial engraftment. The initial daily dose of imatinib was 400 mg/d for adults and 260 mg/m(2) for children (younger than 17 years). Imatinib was administered for at least 1 month and the bcr-abl TaqMan results were negative for 3 consecutive tests, or complete molecular remission (CR(mol)) was sustained for at least 3 months.</p><p><b>RESULTS</b>From May 2005 to October 2008, 29 patients were enrolled in this study, of whom, 19 patients were male and 10 were female. The median age of the enrolled patients was 33 years (range 6 - 50 years). Imatinib therapy was started at a median time of 60 days (range 20 - 122 days) post HCT (only one patient started Imatinib therapy at 122nd day after HCT). Twenty-five adult patients could tolerate a dose of 300 - 400 mg/d of imatinib, and three children tolerated a dose of 260 mg×m(-2)×d(-1). Sixty-eight percent of the patients experienced various adverse events during imatinib therapy, hematological toxicity being the most common adverse event. The median duration of imatinib treatment was 3 months (range 7 days-18 months). During the median follow-up of 24 months (range 16.0 - 54.5 months), 3 out of 27 patients that could be evaluated for efficacy died from relapse. The 3-year probability of relapse for the evaluated patients was (11.3 ± 0.61)%. The relapse rates among the subgroup of positive and negative bcr-abl patients before allo-HCT were 13.6% and 0, respectively (P > 0.05). The relapse rates among the subgroups of bcr-abl positive and negative patients after allo-HCT were 20.0% and 5.9%, respectively (P > 0.05). The relapse rates among the patients in first complete remission (CR(1)) and second complete remission/non-remission (CR(2)/NR) before transplantation were 0 and 31.4%, respectively (P < 0.05). The 3-year probability of overall survival (OS) and disease-free survival (DFS) for the all enrolled patients were (75.3 ± 8.1)%. The 3-year probabilities for OS and DFS among the subgroup of patients in CR(1) and CR(2)/NR before transplantation were (87.7 ± 8.2)% and (54.6 ± 15.0)%, respectively (P < 0.05).</p><p><b>CONCLUSIONS</b>Administration of imatinib at a dose of 300 - 400 mg/d in the first 90 days after allo-HCT is feasible in Ph(+) ALL patients. With this treatment, bcr-abl positive patients before or after transplantation do not have a higher relapse rate after allo-HCT compared with the bcr-abl negative patients. Because of lower relapse rate and better OS and DFS, we recommend that Ph(+) ALL patients receive allo-HCT in CR₁.</p>


Subject(s)
Adolescent , Adult , Antineoplastic Agents , Therapeutic Uses , Benzamides , Child , Drug Administration Schedule , Female , Hematopoietic Stem Cell Transplantation , Methods , Humans , Imatinib Mesylate , Male , Middle Aged , Piperazines , Therapeutic Uses , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Drug Therapy , Therapeutics , Prospective Studies , Pyrimidines , Therapeutic Uses , Transplantation, Homologous , Methods , Young Adult
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