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1.
Br J Haematol ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31696939

RESUMO

Donor selection for older leukaemia patients undergoing haematopoietic cell transplant (HCT) is not well defined: outcomes might be improved with a younger offspring donor rather than an older human leukocyte antigen (HLA)-matched sibling donor (MSD). We extended our multicentre dataset. A total of 185 acute leukaemia patients (≥ 50 years) transplanted in first complete remission who received HCT from offspring (n = 62) or MSD (n = 123) were included. A 1:1 ratio matched-pair analysis was performed. We were able to match 54 offspring with 54 MSD patients. Outcomes were compared between the two matched-pair groups. The cumulative incidence of grade II/IV acute graft-versus-host disease (GVHD) (26% vs. 35%; P = 0·23) and chronic GVHD (37% vs. 24%; P = 0·19) was comparable between groups (MSD vs. offspring). The lower three-year transplant-related mortality (9% vs. 26%; P = 0·023) and relapse incidence (6% vs. 17%; P = 0·066) resulted in higher overall survival (85% vs. 58%; P = 0·003) and leukaemia-free survival (LFS) (85% vs. 56%; P = 0·001) in offspring HCT compared with that in MSD HCT. These data might favour a young offspring over an older MSD in patients >50 years. The current analyses confirm that non-HLA donor characteristics, such as kinship and donor age, rather than HLA disparity, predominantly influence survival in older acute leukaemia patients.

2.
EBioMedicine ; 49: 213-222, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31668569

RESUMO

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) after allo-HSCT is a devastating complication with limited therapeutic options. We aimed to assess the efficacy and safety of mesenchymal stem cells (MSCs) in BOS after allo-HSCT. METHODS: This multicenter prospective cohort study enrolled 81 allo-HSCT recipients whose BOS were diagnosed within 6 months. The choice of prednisone and azithromycin combined with or without MSCs was based on patient preferences (MSC n = 49, non-MSC n = 32). The primary endpoint was response rate at 3 months, defined as the proportion of patients achieving FEV1 improvement or steroid sparing. The trial was registered at ClinicalTrials.gov (NCT02543073). FINDINGS: Response rate was 35/49 patients (71%, 95% CI 59 to 84%) and 14/32 (44%, 27 to 61%) in MSC and non-MSC group, respectively (p = 0.013). The addition of MSCs was associated with a better difference for change in FEV1 rate of decline, compared to non-MSC group (53 mL/months, 2 to 103; p = 0.040). The 3-year overall survival post-diagnosis was 70.6% (55.9 to 85.3%) and 58.2% (36.1 to 78.5%) in MSC and non-MSC group, respectively (p = 0.21). Clinical improvement was accompanied by a significant increase of interleukin (IL)-10-producing CD5+B cells. There was no statistical difference in the rates of infections and leukemia relapse between the two groups. MSCs were well-tolerated with no serious adverse events. INTERPRETATION: MSCs offer an effective and safe therapeutic option for BOS after allo-HSCT. Our study strengthens evidence for clinical use of MSC therapy in BOS. These data also provide novel insight into potential biological mechanisms of MSC treatment and support further investigation in larger randomized controlled trials. FUNDING: National Key R&D Program of China, National Natural Science Foundation of China, Health Collaborative Innovation Major Projects of Guangzhou City, Science and Technology Planning Project of Guangdong Province.

3.
Am J Transplant ; 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31605563

RESUMO

Although studies have reported that intestinal microbiota is associated with aGVHD, they lacked a satisfactory method for predicting aGVHD. We collected stool and blood samples at day 15 post-transplantation from 150 patients, who underwent myeloablative conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT) from two centers. Stool microbiota was detected by 16S rRNA gene sequencing, inflammatory factors and T lymphocyte were detected by multiplex immunoassays and flow cytometry respectively. A gut microbiota score (GMS) from a LASSO (least absolute shrinkage and selection operator) model was developed and validated to predict aGVHD. In the discovery cohort, the GMS could predict II-IV aGVHD (area under the ROC curve, AUC = 0.904, P < 0.0001). Furthermore, the validation model was consistent with the discovery set (AUC = 0.887, P < 0.0001). Treg/Th17 cells ratio in the low GMS subgroup was higher compared with the high GMS (P = 0.012), and the validation set consisted with the discovery set (P = 0.003). In addition, high cytokine levels were associated with high GMS. In conclusions, the GMS at neutrophil engraftment could predict aGVHD, and it was a potential and novel method. The GMS was associated with the inflammatory factor and Treg/Th17 balance.

4.
Oncol Rep ; 42(6): 2333-2344, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638252

RESUMO

Gene mutations play an important role in the development and progression of AML1­ETO­positive acute myeloid leukemia (AE­AML). Nevertheless, the gene mutation profile in this subtype of leukemia remains unclear. In addition, the clinical and prognostic effects of different mutant genes may be underestimated. In the present study, gene sequencing was conducted at diagnosis and relapse with next­generation sequencing (NGS) in 64 patients with newly diagnosed AE­AML, and 44/64 (68.8%) patients were found to present with a median of 2 (1­10) recurrent mutations at diagnosis and 6/11 (54.5%) cases were found to present with genetic alterations at relapse. c­KIT mutation was the most common in this cohort, with an incidence of 27/64 (42.2%) at diagnosis, followed by ASXL1 (n=10, 15.6%), MET (n=8, 12.5%), MLH1 (n=6, 9.4%), TET2 (n=5, 7.8%), and FBXW7, TP53 and DNMT3A (n=5, 7.8%). Survival analysis showed that c­KIT (exon 8, 17) but not exon 10 adversely affected survival. In addition, ASXL1 and TP53 were poor impact factors for recurrence­free survival (RFS) (P<0.05), and ASXL1, MET, FBXW7 and TP53 had a negative impact on overall survival (OS) (P<0.05). Multivariate analysis showed that c­KIT (exon 8, 17) [RFS: hazard ratio (HR) 3.36, 95% confidence interval (CI) 1.54­7.34, P=0.002; OS: HR 2.84, 95% CI 1.20­6.71, P=0.018] and ASXL1 mutations (RFS: HR 3.13, 95% CI 1.34­7.32, P=0.009; OS: HR 3.94, 95% CI 1.62­9.61, P=0.003) were independent adverse factors for survival. Further, co­mutation of these two genes showed even worse effect on disease outcome. Collectively, additional gene mutations play critical role in AE­AML. C­KIT and ASXL1 mutations are the two most common mutations in this subtype of leukemia. C­KIT (exon 8, 17) but not exon 10, and also the ASXL1 mutation poorly affect the disease outcome of this disease.

5.
Cancer Med ; 8(15): 6549-6558, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31502764

RESUMO

To investigate the incidence and risk factors as well as prognosis of autoimmune hemolytic anemia (AIHA) following allogeneic hematopoietic stem cell transplantation (allo-HSCT), a total of 1377 adult hematological malignancies at three institutions were enrolled in this study. The 3-year cumulative incidence of AIHA was 2.2 ± 0.4%. Multivariate analysis showed that haploidentical donors (HRDs) and chronic graft vs host disease (cGVHD) were the independent risk factors for AIHA. Patients with AIHA treated initially with corticosteroids combined with cyclosporine A (CsA) had a higher complete response rate than those with corticosteroids monotherapy (66.7% vs 11.1%; P = .013). The 3-year cumulative incidence of malignant diseases relapse was 4.4 ± 4.3% and 28.0 ± 1.3% (P = .013), treatment-related mortality (TRM) was 8.9 ± 6.3% and 17.4 ± 1.2% (P = .431), disease-free survival (DFS) was 56.1 ± 1.5% and 86.7 ± 7.2% (P = .011), and overall survival (OS) was 86.3 ± 7.4% and 64.1 ± 1.5% (P = .054), respectively, in the patients with AIHA and those without AIHA. Our results indicate that HRDs and cGVHD are risk factors for AIHA and corticosteroids combined with CsA are superior to corticosteroids as initial treatment for AIHA. Autoimmune hemolytic anemia does not contribute to increase TRM and could reduce the malignant diseases relapse and increase DFS.

6.
J Hematol Oncol ; 12(1): 88, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481121

RESUMO

BACKGROUND: Low-dose post-transplant cyclophosphamide (PTCy) in conjunction with anti-thymocyte globulin (ATG) appears as a potentially effective graft-versus-host disease (GVHD) prevention strategy in haploidentical hematopoietic cell transplant (haplo-HCT). Our study aims to assess the efficacy of this regimen. METHODS: We extended our prospective study in patients treated with low-dose PTCy (14.5 mg/kg on days 3 and 4) in ATG/granulocyte colony-stimulating factor (G-CSF)-based regimen and compared the results to the contemporary cohort of patients without low-dose PTCy (ATG cohort). Both study cohort and control are transplanted from maternal donor or collateral relatives. RESULTS: We identified 239 consecutive patients (ATG-PTCy cohort = 114; ATG cohort = 125). All patients but one in ATG cohort achieved myeloid engraftment by day 30 post-HCT. We found that both the cumulative incidence of 100-day grade III-IV aGvHD and non-relapse-mortality (NRM) in the ATG-PTCy cohort was significantly reduced than that in the ATG group (5% vs 18%; P = 0.003; and 6% vs 15%; P= 0.045); the 2-year cumulative incidences of relapse and overall survival were comparable between the two cohorts (13% vs 14%; P = 0.62; and 83% vs 77%; P = 0.18, respectively). Furthermore, GVHD-free, relapse-free survival (GRFS) was significantly improved in the ATG-PTCy arm (63% vs 48%; P = 0.039). In multivariate analysis, the joint treatment resulted in lower grade II-IV acute GVHD (HR 0.58; P = 0.036), grade III-IV aGvHD (HR 0.28; P = 0.006), chronic GVHD (HR 0.60; P = 0.047), NRM (HR 0.26; P = 0.014), and higher GRFS (HR 0.59; P = 0.021) but slower myeloid and platelet recovery (HR 0.29 and 0.30; both P < 0.001). CONCLUSIONS: These results suggested that ATG/PTCy (low-dose) can reduce both acute and chronic GVHD as compared with standard ATG-based prophylaxis using maternal donor or collateral relatives at particular high GVHD risk.

8.
Sci China Life Sci ; 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31420852

RESUMO

This study compared G-CSF/ATG and PTCy in myeloablative haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for hematologic malignancies between January 2013 and March 2018 reporting to the Chinese Bone Marrow Transplantation Registry Group (CBMTRG). For each PTCy, G-CSF/ATG subjects (1:4) were selected using the nested case-pair method. In total, 220 patients including 176 in G-CSF/ATG group and 44 in PTCy group were analyzed. The incidences of 30-day neutrophil engraftment (88.6% vs. 96.6%, P=0.001), 90-day platelet engraftment (84.1% vs. 94.2%, P=0.04), the median time to neutrophil engraftment (17 days vs. 12 days, P=0.000) and platelet engraftment (22 days vs. 17 days, P=0.001) were significantly inferior in PTCy group. The incidences of grades 2-4 and 3-4 acute graft-versus-host disease (GVHD), chronic GVHD and severe chronic GVHD were comparable. Among G-CSF/ATG and PTCy groups, the 3-year progression-free survival, overall survival, cumulative incidences of nonrelapse mortality and relapse was 74.3% vs. 61% (P=0.045), 78.3% vs. 65.2% (P=0.039), 12% vs. 27.3% (P=0.008), and 14.9% vs. 11.7% (P=0.61), respectively. G-CSF/ATG can achieve better engraftment, PFS and OS, and lower incidence of NRM compared to PTCy in myeloablative haplo-HSCT for hematologic malignancies.

9.
BMC Med ; 17(1): 156, 2019 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-31401973

RESUMO

BACKGROUND: The optimal dose of rabbit antithymocyte globulin (ATG, ImtixSangstat) minimizing infections without increasing graft-versus-host disease (GVHD) is unknown in T cell-replete, G-CSF-primed haploidentical hematopoietic stem cell transplantation (haplo-HSCT). METHODS: Four hundred and eight patients were enrolled in this multicenter study to evaluate the effect of 7.5 mg/kg and 10.0 mg/kg rabbit ATG on viral infections and GVHD prophylaxis after haplo-HSCT. The primary endpoint was EBV DNAemia within 1 year posttransplantation. RESULTS: The 1-year incidence of EBV DNAemia was 20.7% (95% confidence interval, 15.4-26.5) and 40.0% (33.3-46.6) in the 7.5 mg/kg and 10.0 mg/kg groups, respectively (P < 0.001). The 100-day cumulative incidence of grade II to IV aGVHD was 27.1% (21.1-33.4) and 25.4% (19.6-31.5) in the 7.5 mg/kg and 10.0 mg/kg ATG groups, respectively (P = 0.548). The 2-year incidence of chronic GVHD was 34.6% (27.8-41.4) and 36.2% (29.1-43.2) in the 7.5 mg and 10.0 mg groups (P = 0.814). The 1-year incidence of CMV DNAemia was 73.4% (67.2-79.4) and 83.4% (77.5-87.9) in the 7.5 mg/kg and 10.0 mg/kg groups (P = 0.038). The 3-year overall survival posttransplantation was 69.5% (63.2-75.8) and 63.5% (56.2-70.8), and the disease-free survival was 62.2% (55.3-69.1) and 60.3% (53.0-67.6) in the 7.5 mg/kg and 10.0 mg/kg groups, respectively (OS: P = 0.308; DFS: P = 0.660). The counts of EBV- and CMV-specific cytotoxic T cells (CTLs) were higher in the 7.5 mg/kg group than in the 10.0 mg/kg group early posttransplantation. CONCLUSIONS: Compared with 10.0 mg/kg, 7.5 mg/kg ATG for GVHD prophylaxis was associated with reduced EBV and CMV infections without increased incidence of GVHD in haplo-HSCT, probably by affecting EBV- and CMV-specific CTLs. TRIAL REGISTRATION: clinicaltrials.gov, NCT01883180 . Registered 14 June 2013.

10.
Haematologica ; 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31289206

RESUMO

Chronic myeloid leukemia is induced by the BCR/ABL1 oncogene, which encodes a protein tyrosine kinase. We examined the effect of direct overexpression of the human p210 BCR/ABL1 oncoprotein in zebrafish. Humanized p210 BCR/ABL1 protein was detectable in Tg(hsp70:p210BCR/ABL1) transgenic zebrafish embryos and adult kidney marrow. Transgenic zebrafish developed chronic myeloid leukemia, which could be induced via cells into recipients. The expression of human BCR/ABL1 promoted myeloid lineages in Tg(hsp70:p210BCR/ABL1) transgenic embryos. A total of 77 of 101 (76.24%) Tg(hsp70:p210BCR/ABL1) adult transgenic zebrafish (age 6 months to 1 year) developed chronic myeloid leukemia. Chronic myeloid leukemia in zebrafish showed a triphasic phenotype, similar to that in humans, involving a chronic phase predominantly characterized by neutrophils in various degrees of maturation, an accelerated phase with an increase in blasts and immature myeloid elements, and a blast phase with > 90% blasts in both the peripheral blood and kidney marrow. Tyrosine kinase inhibitors, as the standard drug treatment for human chronic myeloid leukemia, effectively reduced the expanded myeloid population in Tg(hsp70:p210BCR/ABL1) transgenic embryos. Moreover, we screened a library of 171 compounds and identified 10 new drugs against BCR/ABL1 kinase-dependent or -independent pathways that could also reduce lcp1 + myeloid cell numbers in Tg(hsp70:p210BCR/ABL1) transgenic embryos. In summary, we generated the first humanized zebrafish chronic myeloid leukemia model that recapitulates many characteristics of human chronic myeloid leukemia. This novel in vivo model will help to elucidate the mechanisms of chronic myeloid leukemia disease progression and allow high-throughput drug screening of possible treatments for chronic myeloid leukemia.

11.
Biol Blood Marrow Transplant ; 25(10): 1944-1955, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31299215

RESUMO

The intestinal microbiome plays an important role in the development of acute graft-versus-host disease (aGVHD). However, whether intestinal microbiota can predict the development of aGVHD has been reported only rarely. Here we conducted a prospective study of microbiota in 141 patients after allogeneic hematopoietic stem cell transplantation. We found lower microbiota diversity in the aGVHD group compared with the non-aGVHD group at day 0 and day 15 ± 1 (P = .018 and .009, respectively). Diversity was negatively associated with conditioning intensity (P = .017, day 0; P = .045, day 15) and ß-lactam antibiotic administration (P = .004, day 15). Intensified conditioning and ß-lactam antibiotics were associated with a lower regulatory T (Treg)/T helper 17 (Th17) cell ratio at day 15 (P = .030 and .047, respectively). At day 15, the levels of the inflammatory factors (tumor necrosis factor α, interleukin [IL]-6, IL-17A, IL-1ß, and lipopolysaccharide) were higher in the intensified conditioning group compared with the standard group (P < .05). The accumulated intestinal microbiota (AIM) score was defined as microbiota diversity and gradient of the 4 bacterials (Lachnospiraceae, Peptostreptococcaceae, Erysipelotrichaceae, and Enterobacteriaceae) at day 15 post-transplantation. The AIM score was positively correlated with aGVHD grade (r = .481, P < .001), and the AIM score could be predictive of the development of aGVHD (grade II-IV aGVHD: area under the curve [AUC], .75, P < .001; grade III-IV aGVHD: AUC, .84, P < .001). These findings suggest that intestinal microbiota and conditioning might induce aGVHD by inflammatory factors and the Treg/Th17 balance. The constitution of the intestinal microbiota at neutrophil engraftment may predict the development of aGVHD.

12.
Aging (Albany NY) ; 11(10): 3333-3347, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31164492

RESUMO

Recently, competing endogenous RNAs (ceRNAs) hypothesis has gained a great interest in the study of molecular biological mechanisms of cancer occurrence and progression. However, studies on leukemia are limited, and there is still a lack of comprehensive analysis of lncRNA-miRNA-mRNA ceRNA regulatory network of AML based on high-throughput sequencing and large-scale sample size. We obtained RNA-Seq data and compared the expression profiles between 407 normal whole blood (GTEx) and 151 bone marrows of AML (TCGA). The similarity between two sets of genes with trait in the network was analyzed by weighted correlation network analysis (WGCNA). MiRcode, starBase, miRTarBase, miRDB and TargetScan was used to predict interactions between lncRNAs, miRNAs and target mRNAs. At last, we identified 108 lncRNAs, 10 miRNAs and 8 mRNAs to construct a lncRNA-miRNA-mRNA ceRNA network, which might act as prognostic biomarkers of AML. Among the network, a survival model with 8 target mRNAs (HOXA9+INSR+KRIT1+MYB+SPRY2+UBE2V1+WEE1+ZNF711) was set up by univariate and multivariate cox proportional hazard regression analysis, of which the AUC was 0.831, indicating its sensitivity and specificity in AML prognostic prediction. CeRNA networks could provide further insight into the study on gene regulation and AML prognosis.

13.
Semin Hematol ; 56(3): 209-214, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31202432

RESUMO

In recent years, the human leukocyte antigen-haploidentical stem cell transplantation (haplo-SCT) approach is an attractive option for patients who require transplantation, but relapse is still the main reason that affects the curative effect of transplantation. Some studies have shown that haplo-SCT is superior to sibling or unrelated matching donor transplantation in preventing leukemia relapse after transplantation. In this review, we discussed the known and unknown aspects of relapse post haplo-SCT. Encouragingly, haplo-SCT experienced lower or similar incidence of relapse. But there is currently a lack of multicenter prospective studies evaluating the outcomes of different haplo-SCT strategies. The combination of common prophylactic strategies and pre-emptive interventions might help prevent relapse after transplantation. Novel methods such as target drugs therapy and chimeric antigen receptor T cell therapy may be useful in treatment of relapse.

14.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(3): 364-368, 2019 Mar 30.
Artigo em Chinês | MEDLINE | ID: mdl-31068313

RESUMO

OBJECTIVE: To analyze the clinical features of chronic myeloid leukemia (CML) with T315 I mutation (CML-T315I) and compare the effectiveness of different treatments. METHODS: We retrospectively analyzed the clinical data and outcomes of 19 patients with CML-T315I receiving different treatments. The T315 I mutations in these patients were detected by examination of BCR-ABL kinase domain (KD) mutation by RTQ-PCR and Sanger sequencing. The relapse following the treatments, defined as hematological, cytogenetic and molecular biological recurrences, were analyzed in these patients. RESULTS: Of the 19 patients with CML-T315I, 14 (73.7%) were in CML-CP stage at the initial diagnosis, and 13 (81.2%) were high-risk patients based on the Sokal scores. All the 19 patients were treated with TKI after the initial diagnosis, and during the treatment, 15 (78.9%) patients were found to have additional chromosomal aberrations, and 10 (52.6%) had multiple mutations; 13 (68.4%) of the patients experienced disease progression (accelerated phase/blast crisis) before the detection of T315I mutation, with a median time of 40 months (5-120 months) from the initial diagnosis to the mutation detection. After detection of the mutation, 12 patients were treated with ponatinib and 7 were managed with the conventional chemotherapy regimen, and their overall survival rates at 3 years were 83.3% and 14.2%, respectively (P < 0.001). CONCLUSIONS: CML patients resistant to TKI are more likely to have T315I mutations, whose detection rate is significantly higher in the progressive phase than in the chronic phase. These patients often have additional chromosomal aberrations and multiple gene mutations with poor prognoses and a high recurrence rate even after hematopoietic stem cell transplantation. Long-term maintenance therapy with ponatinib may improve the prognosis and prolong the survival time of the patients.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Resistencia a Medicamentos Antineoplásicos , Proteínas de Fusão bcr-abl , Humanos , Imidazóis , Mutação , Piridazinas , Estudos Retrospectivos
16.
Sci Rep ; 9(1): 6486, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31019217

RESUMO

This article studies whether heart sound signals can be used for emotion recognition. First, we built a small emotion heart sound database, and simultaneously recorded the participants' ECG for comparative analysis. Second, according to the characteristics of the heart sound signals, two emotion evaluation indicators were proposed: HRV of heart sounds (difference between successive heartbeats) and DSV of heart sounds (the ratio of diastolic to systolic duration variability). Then, we extracted linear and nonlinear features from two emotion evaluation indicators to recognize four kinds of emotions. Moreover, we used valence dimension, arousal dimension and valence-arousal synthesis as evaluation standards. The experimental results demonstrated that heart sound signals can be used for emotion recognition. It was more effective to achieve recognition results by combining the features of HRV and DSV of heart sounds. Finally, the average accuracy of four emotion recognitions on valence dimension, arousal dimension and valence-arousal synthesis was up to 96.875%, 88.5417% and 81.25%, respectively.

17.
Biol Blood Marrow Transplant ; 25(8): 1674-1681, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31009704

RESUMO

The optimal therapy for patients with acute myeloid leukemia (AML) with FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) who relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. In this study we retrospectively evaluated the efficacy of sorafenib combined with other therapeutic strategies as salvage therapy for these patients. Eighty-three AML patients with FLT3-ITD relapsing after allo-HSCT were enrolled in this study. Fifty-three patients received salvage therapy containing sorafenib and 30 patients did not. Salvage therapy containing sorafenib was superior to that without sorafenib with respect to complete remission rates, overall survival (OS), and progression-free survival (PFS) (66.0% versus 30.0%, 46.8% versus 20.0%, and 44.9% versus 16.7%, respectively; P = .002, P = .003, and P = .001). Further subgroup analysis revealed that the OS and PFS of patients who received sorafenib combined with chemotherapy followed by donor lymphocyte infusion (DLI) were superior to those receiving other therapeutic regimens, including sorafenib combined with chemotherapy, chemotherapy followed by DLI, and monochemotherapy (P = .003, P < .001). Multivariate analysis revealed that salvage therapy including sorafenib was the only protective factor for longer OS (P = .035; hazard ratio [HR], .526); salvage therapy including sorafenib and DLI were the protective factors for longer PFS (P = .011, HR, .423; P = .019, HR, .508). Our data suggest that sorafenib therapy is associated with improved outcomes for FLT3-ITD AML relapsing after allo-HSCT, and whether sorafenib combined with chemotherapy followed by DLI reveals an optimal efficacy merits further study.

18.
J Autoimmun ; 100: 95-104, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30878167

RESUMO

Chronic graft-versus-host disease (cGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have shown that T follicular helper cells (Tfh) contribute to immune pathology in cGVHD, but the function of extrafollicular helper T cells during cGVHD pathogenesis remains largely unknown. In the current study, we identified circulating extrafollicular helper T-like cells (CD44hiCD62LloPSGL-1loCD4+, c-extrafollicular Th-like) in human peripheral blood. We performed phenotypic and functional analyses of c-extrafollicular Th-like cells from 80 patients after allo-HSCT to explore the role of these cells in the development of human cGVHD. Patients with active cGVHD had significantly higher frequencies and counts of c-extrafollicular Th-like cells than those of patients without cGVHD. The expansion of c-extrafollicular Th-like cells was more significant in patients with moderate/severe cGVHD than that of patients with mild cGVHD. C-extrafollicular Th-like cells from patients with active cGVHD exhibited increased functional abilities to induce plasmablast differentiation and IgG1 secretion compared to those of patients without cGVHD. Moreover, c-extrafollicular Th-like cell levels were highly correlated with the generation of autoreactive B cells, plasmablasts and IgG1 antibodies. Our studies provide new insights into human cGVHD pathogenesis and identify c-extrafollicular Th-like cells as a key element in the development of human cGVHD.

19.
Infection ; 47(2): 275-284, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30734248

RESUMO

BACKGROUND: Invasive fungal disease (IFD) and graft-versus-host disease (GVHD) are major causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the impacts of IFD on chronic GVHD remain unknown. METHODS: We conducted a retrospective study of 510 patients with hematologic malignancy undergoing allo-HSCT to explore the effects of IFD on chronic GVHD. RESULTS: The 2-year cumulative incidences of overall (limited and extensive) and extensive chronic GVHD post-transplantation were higher in patients with IFD compared with those without IFD (69.5% ± 4.2% versus 32.9% ± 2.4%, P < .001; 43.0% ± 5.2% versus 6.6% ± 1.4%, P < .001, respectively). Moreover, the patients with IFD had higher 5-year transplant-related mortality, lower 5-year overall survival and lower 5-year disease-free survival (29.8% ± 4.3% versus 9.8% ± 1.6%, P < .001; 50.5% ± 4.9% versus 71.3% ± 2.4%, P < .001 and 48.8% ± 4.7% versus 71.8% ± 2.3%, P < .001, respectively). Multivariable analyses demonstrated that IFD increased the risk of chronic GVHD. CONCLUSION: Our results suggest that IFD significantly contributes to the development of chronic GVHD after allo-HSCT.


Assuntos
Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções Fúngicas Invasivas/mortalidade , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , China/epidemiologia , Doença Crônica/epidemiologia , Estudos de Coortes , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/fisiopatologia , Humanos , Incidência , Infecções Fúngicas Invasivas/imunologia , Infecções Fúngicas Invasivas/microbiologia , Infecções Fúngicas Invasivas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/microbiologia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/fisiopatologia , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos , Adulto Jovem
20.
Int J Hematol Oncol ; 7(2): IJH06, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30405901

RESUMO

Aim: Chinese adults with relapsed/refractory Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (Ph- ALL) have poor outcomes. Patients & methods: We conducted a nationwide, retrospective, observational study to assess outcomes in this patient population. Results: Of the 270 enrolled patients, 31% of patients at last salvage achieved complete remission (CR) or CR with partial hematologic recovery (CRh), with median time to CR/CRh of 30 days and median CR/CRh duration of 2.7 months. The CR/CRh rate was more favorable with earlier versus later lines of salvage (41, 24 and 17% at first, second and third or later salvages, respectively). Conclusion: This dataset serves as an important reference of real-world outcomes using currently available chemotherapy regimens for high-risk Chinese adults with relapsed/refractory Ph- ALL.

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