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1.
J Hematol Oncol ; 12(1): 87, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477147

RESUMO

BACKGROUND: Haploidentical transplantation has been proposed as an effective treatment for severe aplastic anemia (SAA). The majority of patients have more than one HLA-haploidentical donor. Herein, we compared the outcomes between different donor-recipient relationships for optimal haploidentical donor selection in acquired SAA. METHODS: We conducted a multicenter study based on a registered database of 392 patients with SAA treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) between 2006 and 2018. In total, 223 patients received grafts from father donors, 47 from mother donors, 91 from siblings, 29 from children, and 2 from collateral donors. RESULTS: Of the 381 patients who survived more than 28 days, 379 (99.5%) recipients were engrafted. The 2-year overall survival (OS) was 86.6 ± 2.5%, 87.1 ± 4.9%, 84.3 ± 3.9%, and 92.2 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.706). The 2-year failure-free survival (FFS) was 82.8 ± 2.7%, 86.7 ± 5.1%, 80.8 ± 4.2%, and 92.5 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.508). There was no difference in the incidence of either acute or chronic graft-versus-host disease (GVHD) among the different donor sources in multivariate analyses. There were also no differences in the OS or FFS among the different donor sources in the Cox regression analysis. However, OS was significantly better in the patients with a shorter history of aplastic anemia (< 12 months), better performance status (ECOG scores 0-1), or moderate graft mononuclear cell (MNC) counts (6-10 × 108/kg), and in female recipients with male donors. The FFS was also higher in patients with a shorter history of aplastic anemia (< 12 months) and better performance status (ECOG scores 0-1). CONCLUSIONS: Fathers, mothers, siblings, and children are all suitable haploidentical donors for patients with SAA.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31424628

RESUMO

BACKGROUND: This study aimed to determine the impact of the pre- and post-minimal residual disease (MRD) status as well as the peri-transplant MRD kinetics on clinical outcomes in pediatric ALL patients who received haploidentical allografts. METHODS: A retrospective study (n = 166) was performed. MRD was determined using multiparameter flow cytometry. RESULTS: Pediatric ALL patients with pre-MRDneg had a lower cumulative incidences of relapse (CIR) compared to those with pre-MRDpos (19.7% vs. 41.2%, P = 0.009). Compared to post-MRDneg group, patients with post-MRDpos experienced higher CIR (81.0% vs. 15.9%, P < 0.001), inferior LFS (14.3% vs. 66.9%, P < 0.001) and OS (19.1% vs. 66.9%, P < 0.001). In regard to peri-MRD kinetics, compared with the MRD-decreasing group and MRDneg/MRDneg group, MRD-increasing group had higher CIR, lower probabilities of LFS and OS (P < 0.001). Compared to pre-MRDneg/post-MRDneg group, a higher CIR was found in the pre-MRDpos/post-MRDpos group (66.7% vs. 12.5%, P < 0.001), pre-MRDpos/post-MRDneg group (32.0% vs. 12.5%, P = 0.016), and pre-MRDneg/post-MRDpos group (91.7% vs. 12.5%, P < 0.001). A lower incidence of LFS and OS were found in pre-MRDpos/post-MRDpos group and pre-MRDneg/post-MRDpos group than in pre-MRDneg/post-MRDneg group (P < 0.05). Multivariate analyses confirmed the association of pre-MRD status, post-MRD status, and peri-MRD kinetics with outcomes (P < 0.05). CONCLUSIONS: The results indicate that, in the pediatric ALL subgroup, not only pre-MRD status or post-MRD status but also peri-SCT MRD dynamics, were associated with an increased CIR after haploidentical allografts. Patients are put into different risk group based on MRD kinetics versus single time MRD status. © 2019 International Clinical Cytometry Society.

3.
Biol Blood Marrow Transplant ; 25(8): 1629-1636, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31048087

RESUMO

Immune-mediated neuropathies (IMNs) following hematopoietic stem cell transplantation have been described recently, which, excluding Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy, may present with atypical patterns. This retrospective, nested, case-control study reviewed data from 3858 patients who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT) during the past 10 years at a single center, and 40 patients (1.04%) with IMN following haplo-HSCT were identified. Chronic graft-versus-host disease (cGVHD) (P = .043) and cytomegalovirus (CMV) viremia (P = .035) were recognized as independent risk factors for the development of IMN after haplo-HSCT. There were no significant differences in overall survival (P = .619), disease-free survival (P = .609), nonrelapse mortality (P = .87), or the incidence of relapse (P = .583) between patients with and without IMN after haplo-HSCT. However, patients with post-transplant IMN were at higher risk of developing cGVHD (P = .012) than patients who did not develop IMN. Twenty-four of the 40 patients with IMN (60%) attained neurologic improvement after treatments including vitamins B1 and B12 and/or immunomodulatory agents. However, 19 (47.5%) patients still had persistent motor/sensory deficits despite receiving timely treatment. More studies are needed to help develop standardized diagnostic and therapeutic strategies for patients with post-transplant IMN.

4.
Blood Adv ; 3(8): 1303-1317, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015207

RESUMO

Poor graft function (PGF) and prolonged isolated thrombocytopenia (PT) remain life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Endothelial cells (ECs) play a crucial role in regulating hematopoiesis in the bone marrow (BM) microenvironment. However, whether the impaired BM ECs are responsible for defective hematopoiesis in PGF and PT patients requires clarification, and clinical management is challenging. Two prospective clinical trials were included in the current study. In the first trial (N = 68), PGF and PT patients demonstrated defective BM ECs pre-HSCT and impaired BM EC dynamic reconstitution at early time points post-HSCT, which was positively correlated with reactive oxygen species (ROS) levels. Receiver operating characteristic curves showed that BM EC < 0.1% pre-HSCT could identify high-risk patients with PGF and PT. The second trial enrolled patients (N = 35) with EC < 0.1% who accepted oral N-acetyl-l-cysteine (NAC; 400 mg 3 times per day) from -14 days pre-HSCT to +2 months post-HSCT continuously, whereas the remaining EC ≥ 0.1% patients (N = 39) received allo-HSCT only. Prophylactic NAC intervention was safe and effective in preventing the occurrence of PGF and PT in EC < 0.1% patients by promoting the dynamic reconstitution of BM ECs and CD34+ cells, along with reducing their ROS levels, which was further confirmed by in situ BM trephine biopsy analyses. These findings suggest that the impaired BM ECs pre-HSCT are responsible for the defective hematopoiesis in PGF and PT patients. Therefore, improvement of BM ECs through prophylactic NAC intervention may be a promising therapeutic approach to promote hematopoietic reconstitution post-HSCT. This trial was registered at www.clinicaltrials.gov as #NCT03236220 and #NCT02978274.

8.
Bone Marrow Transplant ; 54(10): 1694-1700, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30903023

RESUMO

The aim of this study was to evaluate the frequency of severe cardiac complications and to assess the ability of various factors to predict these complications in severe aplastic anaemia (SAA) patients after haploidentical transplantation. A retrospective study was conducted in 216 consecutive SAA patients who underwent haploidentical transplantation from 2006 to 2017. All patients received a unified regimen including busulfan, cyclophosphamide (CTX) and antithymocyte globulin at a single centre. A total of 12 (5.6%) patients developed grade III or IV cardiac toxicity. Patients with cardiotoxicity had significantly poorer overall survival (OS) than did those without cardiotoxicity (12.5 vs. 89.6%, P < 0.001). A multivariable model identified four independent adverse predictors of severe cardiotoxicity: pre-transplant ECOG score ( ≥ 2), abnormal ST-T wave on 12-lead ECG, hyperlipaemia and recalculated CTX dose ( ≥ 1.8 g/m2/d). The incidences of severe cardiotoxicity were 50.0%, 6.0% and 1.3% in the high- (3-4 factors), intermediate- (2 factors) and low-risk (0-1 factor) groups, respectively (P < 0.001). The corresponding OS rates were 49.0%, 80.4% and 90.3%, respectively (P < 0.001), at final follow-up. Therefore, patients with high-risk scores had the poorest outcomes and should be monitored closely. Reduced intensity conditioning might be recommended for these patients.

9.
Bone Marrow Transplant ; 54(9): 1462-1470, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30710101

RESUMO

Acute myelogenous leukemia (AML) patients with fetal liver tyrosine kinase 3 (FLT3) internal tandem duplications (ITDs) have poor prognoses if treated with chemotherapy only, primarily as they experience increased relapse rates. To determine whether this alteration also affects outcomes after haploidentical donor (HID) allogeneic hematopoietic stem cell transplantation (allo-HSCT), we compared 334 consecutive FLT3-ITD-positive vs -negative patients with AML (other than acute promyelocytic leukemia) who underwent HID-HSCT. FLT3-ITD was detected in 39 of 334 patients (11.7%). The 2-year relapse rates for FLT3-ITD-positive and -negative patients were 16% and 17%, respectively (P = 0.774). The 3-year disease-free survival (DFS) rates for FLT3-ITD-positive and -negative patients were 74% (95% confidence interval [CI]: 64-81) and 73% (95% CI: 70-81), respectively; P = 0.872); while the 3-year overall survival (OS) rates were 72% (95% CI: 67-81) and 77% (95% CI: 72-84), respectively (P = 0.862). FLT3-ITD mutation had no influence on non-relapse mortality (NRM 15% vs 14%, P = 0.463). Multivariate analyses showed that disease status at HSCT and white blood cell count at diagnosis were independent risk factors associated with relapse, DFS, and OS. In conclusion, FLT3 mutation status has no impact on outcomes after HID-HSCT in patients with AML. HID-HSCT is therefore a valid option for AML patients with FLT3-ITD mutation.

10.
Am J Hematol ; 94(5): 512-521, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30680765

RESUMO

This study evaluated the effects of pretransplantation minimal residual disease (pre-MRD) on outcomes of patients with acute lymphoblastic leukemia (ALL) who underwent unmanipulated haploidentical stem cell transplantation (haplo-SCT). A retrospective study including 543 patients with ALL was performed. MRD was determined using multiparametric flow cytometry. Both in the entire cohort of patients and in subgroup cases with T-ALL or B-ALL, patients with positive pre-MRD had a higher incidence of relapse (CIR) than those with negative pre-MRD in MSDT settings (P < 0.01 for all). Landmark analysis at 6 months showed that MRD positivity was significantly and independently associated with inferior rates of relapse (HR, 1.908; P = 0.007), leukemia-free survival (LFS) (HR, 1.559; P = 0.038), and OS (HR, 1.545; P = 0.049). The levels of pre-MRD according to a logarithmic scale were also associated with leukemia relapse, LFS, and OS, except that cases with MRD <0.01% experienced comparable CIR and LFS to those with negative pre-MRD. A risk score for CIR was developed using the variables pre-MRD, disease status, and immunophenotype of ALL. The CIR was 14%, 26%, and 59% for subjects with scores of 0, 1, and 2-3, respectively (P < 0.001). Three-year LFS was 75%, 64%, and 42%, respectively (P < 0.001). Multivariate analysis confirmed the association of the risk score with CIR and LFS. The results indicate that positive pre-MRD, except for low level one (MRD < 0.01%), is associated with poor outcomes in patients with ALL who underwent unmanipulated haplo-SCT.

11.
Bone Marrow Transplant ; 54(8): 1287-1294, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30655602

RESUMO

Donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) were associated with graft failure (GF) following haploidentical stem cell transplantation (Haplo-HSCT). The prevalence and risk factors of DSAs in pediatric candidates remain to be determined. In a prospective trial (ChiCTR-OPC-15006672), 486 children with hematological diseases were enrolled to screen for the presence of anti-HLA class I and II antibodies of immunoglobulin G type. Fifty two patients (10.7%) demonstrated positive panel-reactive antibody (PRA) for class I; 24 (4.9%), for class II; and 13 (2.7%), for both. Multivariate analysis showed diagnosis was the independent risk factor for antibodies, as acute lymphoblastic leukemia (ALL) patients (HR0.141, 95% CI: 0.037-0.538, p = 0.004) had a lower incidence of class II PRAs and DSAs against HLA-B, DQ, and DR, whereas myelodysplastic syndrome (MDS) patients had a higher incidence of PRAs for both class I and class II (HR4.790, 95% CI: 1.010-22.716, p = 0.049), and DSAs against HLA-A, B, C, DP, and DQ. Older age (>12 vs. ≤12) was associated with DSAs against HLA-DP (HR0.194, 95% CI: 0.041-0.918, p = 0.039). Our findings provided novel evidence for prevalence and risk factors for PRAs and DSAs in pediatric candidates receiving haplo-HSCT, possibly benefiting anti-HLA antibody monitoring and donor selection.

12.
Chin Med J (Engl) ; 131(23): 2808-2816, 2018 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-30511683

RESUMO

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%, χ2 = 3.661, P = 0.055) or second course of chemotherapy (57.1 ± 3.6% vs. 12.5 ± 2.7%, χ2 = 8.759, P = 0.003) or pre-HSCT (50.0 ± 9.7% vs. 23.0 ± 3.2%, χ2 = 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%, χ2 = 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.

13.
Artigo em Inglês | MEDLINE | ID: mdl-30518981

RESUMO

This study investigated the prognostic factors in patients (n = 89) who experienced relapse and received chemotherapy plus donor leukocyte infusion (Chemo-DLI) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Patients with early relapse (< 6 vs. > 6 months after haplo-HSCT), higher bone marrow blast count before chemo-DLI (> 20% vs. 5-19%), and without chronic graft-versus-host disease (cGVHD) after chemo-DLI had a higher rate of progressive disease (PD) and worse progression-free survival (PFS) and overall survival (OS). In multivariate analysis, non-cGVHD after Chemo-DLI and high blast count predicted a higher risk of PD and poorer PFS, and non-cGVHD after Chemo-DLI and early relapse predicted poorer OS. The patients were stratified into three groups according to these three risk factors. Patients with all three risk factors (n = 14) had the highest PD rate and poorest survival compared with those with one or two risk factors (n = 63) or no risk factors (n = 12). Thus, early relapse, high leukemia burden before Chemo-DLI, and non-cGVHD after Chemo-DLI can predict outcomes in patients who have experienced relapse and received Chemo-DLI after haplo-HSCT. New therapeutic strategies should be identified for these patients.

14.
Br J Haematol ; 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30426480

RESUMO

Hepatitis E virus (HEV) is increasingly found to cause hepatitis in allogeneic haematopoietic stem cell transplantation (HSCT) patients. However, little is known about HEV infection in patients receiving haploidentical HSCT (haplo-HSCT). Here, we retrospectively evaluate the incidence and clinical course of HEV infection in haplo-HSCT patients. From January 2014 to July 2017, 177 patients with unexplained elevated transaminases after receiving haplo-HSCT at Peking University Institute of Haematology were screened for HEV using HEV serology. HEV RNA was assessed in blood samples when HEV-IgG and/or IgM antibodies were positive. Acute HEV infection was identified in 7 patients (3·9%), 1 of whom had developed a chronic HEV infection. The median time from haplo-HSCT to HEV infection was 17·5 (range, 6-55) months. HEV infection was confirmed by the presentation of anti-HEV IgM + anti-HEV IgG (rising) (n = 5) or HEV-RNA + anti-HEV IgM + anti-HEV IgG (n = 2). None of the patients died of HEV infection directly: 2 patients with HEV infection died showing signs of ongoing hepatitis, and 5 patients cleared HEV with a median duration of HEV infection of 1·5 (range, 1·0-5·7) months. In conclusion, HEV infection is a rare but serious complication after haplo-HSCT. We recommend screening of HEV in haplo-HSCT.

15.
Clin Infect Dis ; 67(suppl_2): S162-S173, 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30423054

RESUMO

Background: Bloodstream infection (BSI) is a common and serious complication after hematopoietic stem cell transplantation (HSCT). An investigation of the characteristics of pre-engraftment BSI after haploidentical HSCT compared with human leukocyte antigen (HLA)-identical sibling HSCT has not been conducted. Methods: A single-center cohort representing 1847 consecutive patients undergoing haploidentical or HLA-identical sibling HSCT from 2013 to 2016 was selected. We investigated the characteristics of pre-engraftment BSI after haploidentical HSCT and its impact on patient outcome, and we compared it with HLA-identical sibling HSCT. Results: After haploidentical HSCT, the cumulative incidence of pre-engraftment BSI was higher (30-day: 9.2% [7.6, 10.8] vs 1.7% [0.5, 2.9], P < .0001) and median onset of BSI was earlier (day +3 vs day +9, P = .001) than HLA-identical sibling HSCT. Escherichia coli, Klebsiella pneumoniae, and coagulase-negative staphylococci were the most common isolates after haploidentical HSCT. However, Enterococcus faecium was the most common isolate after HLA-identical sibling HSCT. A multivariate analysis suggested that variables associated with BSI after haploidentical HSCT included a diagnosis of myelodysplastic syndrome (MDS), an interval from diagnosis to HSCT ≥190 days, carbapenem therapy, and grade 3-4 intestinal mucositis. The same variables, except MDS, were also associated with BSI after HLA-identical sibling HSCT. The multivariate analysis also suggested that BSI was a risk factor for increased all-cause mortality at 3 months after haploidentical HSCT (hazard ratio = 2.281; 95% confidence interval: 1.334, 3.900; P = .003). Conclusions: Pre-engraftment BSI was more common after haploidentical HSCT than HLA-identical sibling HSCT. It was an independent factor associated with increased all-cause mortality at 3 months after haploidentical HSCT.

16.
Clin Cancer Res ; 2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30478089

RESUMO

PURPOSE: Although myeloablative human leukocyte antigen (HLA) haploidentical hematopoietic stem cell transplantation (haplo-HSCT) following pretransplant ATG and granulocyte colony-stimulating factor (G-CSF) stimulated grafts (ATG+G-CSF) has been confirmed as an alternative to HSCT from HLA-matched sibling donors(MSDs), the effect of haplo-HSCT on postremission treatment of patients with AML with intermediate risk (int-risk AML) who achieved first complete remission (CR1) has not been defined. EXPERIMENTAL DESIGN: In this prospective trial, among 443 consecutive patients aged 16-60 years with newly diagnosed de novo AML with int-risk cytogenetics, 147 patients with molecular int-risk AML who achieved CR1 within two courses of induction and remained in CR1 at 4 months postremission either received chemotherapy (n=69) or underwent haplo-HSCT (n=78). RESULTS: The 3-year leukemia-free survival (LFS) and overall survival (OS) were significantly higher in the haplo-HSCT group than in the chemotherapy group (74.3% vs 47.3%, P=0.0004 and 80.8% vs 53.5%, P=0.0001, respectively). In the multivariate analysis with propensity score adjustment, postremission treatment (haplo-HSCT vs chemotherapy) was an independent risk factor affecting the LFS (HR 0.360, 95% CI 0.163-0.793, P=0.011), OS (HR 0.361, 95% CI 0.156-0.832, P=0.017) and cumulative incidence of relapse (CIR; HR 0.161, 95% CI 0.057-0.459, P=0.001) either in entire cohort or stratified by minimal residual disease after the second consolidation. CONCLUSIONS: Myeloablative haplo-HSCT with ATG+G-CSF is superior to chemotherapy as a postremission treatment in patients with int-risk AML during CR1. Haplo-HSCT might be a first-line postremission therapy for int-risk AML in the absence of MSDs.

17.
Artigo em Inglês | MEDLINE | ID: mdl-30481596

RESUMO

This long-term follow-up study evaluated the effects of corticosteroid prophylaxis on GVHD-free, relapse-free survival (GRFS) based on a controlled open-label randomized trial in which 228 allotransplant recipients were categorized as low-risk (N = 83, group A) or high-risk; patients at high-risk were randomly assigned to receive (N = 72, group B) or not receive (N = 73, group C) low-dose methylprednisolone prophylaxis. The cumulative incidences of chronic GVHD, relapse, NRM, LFS, OS, and GRFS were 60%, 19%, 16%, 68%, 73%, and 46%, respectively, in the total cases. Compared with the patients in group C, the cases in group B experienced a lower cumulative incidence of moderate to severe chronic GVHD (42% vs. 20%; P=0.010), herpes zoster infection (28% vs. 12%; P=0.010), pulmonary infections (42% vs. 21%; P=0.040), and osteonecrosis of the femoral head (ONFH, 16% vs. 6%; P=0.045) as well as better GRFS (59% vs. 33%; P=0.017). Factors associated with GRFS included total dose of corticosteroid used in the first 100 days after transplantation (HR, 1.547; P = 0.015) and platelet recovery (HR, 1.456; P = 0.037). Our results suggest that low-dose glucocorticoid prophylaxis reduces GVHD and thus reduces the total dose of steroids, which might contribute to lower incidence of infections and ONFH, as well as a superior GRFS, indicating that higher steroid doses are harmful- reducing the total dose is of course beneficial. (ClinicalTrials.gov number, NCT01607580).

18.
Front Immunol ; 9: 2528, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30443256

RESUMO

γδ T cells perform antitumor and antiviral effector functions and are involved in both innate and adaptive immunity. Vδ2+ T cells represent the predominant γδ T subset in the peripheral blood of healthy subjects. Vδ2+ T cells can be selectively activated and expanded by phosphoantigens (pAgs). Dendritic cells (DCs), as potent antigen-presenting cells, are capable of mediating pAgs-triggered Vδ2+ T cells expansion. However, the association between DCs and Vδ2+ T cell recovery in the context of hematopoietic stem cell transplantation (HSCT) remains unclear. We previously demonstrated that the recovery of Vδ2+ T cells was hampered and inversely correlated with Epstein-Barr virus (EBV) reactivation in patients undergoing haploidentical HSCT (haploHSCT). Whether Vδ2+ T cells from haploHSCT recipients can be expanded by stimulation with aminobisphosphonates or pAg-presenting DCs is of particular interest. Herein, we showed that Vδ2+ T cells recovered after haploHSCT failed to expand after ex-vivo stimulation with pamidronate. In addition, we found that the recovery of DC subsets was significantly decreased, and the concentration of myeloid DCs (mDCs) correlated significantly with Vδ2+ T cell recovery in the setting of allogeneic HSCT. Furthermore, coculture of peripheral lymphocytes from recipients with monocyte-derived and pamidronate-pretreated autologous or allogeneic DCs induced the successful expansion of Vδ2+ T cells. Of note, allogeneic DCs from third-party donors stimulated a significantly higher efficiency of Vδ2+ T cell expansion than autologous DCs. More importantly, the memory features were well-retained and the cytotoxic cytokines-production capacity was significantly enhanced in the expanded Vδ2+ T cells. Taken together, these results suggest that the frequency and function of DCs are critical for the recovery of Vδ2+ T cells after allogeneic HSCT. The fact that vigorous expansions of Vδ2+ T cells were induced by phosphoantigen-pretreated DCs, especially by allogeneic third-party DCs, provides additional options for the development of individualized immunotherapy strategies that utilize the anti-viral and anti-leukemic effects of γδ T cells in the context of hematopoietic transplantation.

19.
Artigo em Inglês | MEDLINE | ID: mdl-30485788

RESUMO

The aim of this study was to investigate the occurrence and severity of chemotherapy plus donor lymphocyte infusion (Chemo-DLI) associated chronic graft-versus-host disease (cGVHD) in a consecutive cohort of patients with acute leukemia who experienced relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT; n = 104). The 5-year cumulative incidence of complete remission (CR) after Chemo-DLI was 81.0% (95% CI, 73.3-88.7%) and 84.6% (95% CI, 74.5-94.7%) in the moderate and severe cGVHD groups, respectively, which was significantly higher than that of the mild cGVHD 40.9% (95% CI, 29.3-52.5%) and non-cGVHD groups 29.2% (95% CI 23.1-35.3%). The cumulative incidence of non-relapse mortality was comparable between patients with and without cGVHD. The 5-year probabilities of progression-free survival after Chemo-DLI were 42.9% (95% CI, 26.2-70.2%) and 34.6% (95% CI, 15.3-78.2%) in moderate and severe cGVHD groups, respectively, which were both significantly higher than those of mild cGVHD 9.1% (95% CI, 2.4-34.1%) and non-cGVHD groups 8.3% (95% CI 3.3-21.3%). The 5-year probabilities of overall survival after Chemo-DLI were 56.7% (95% CI, 38.9-82.7%) and 43.1% (95% CI, 22.1-84.0%), in moderate and severe cGVHD groups, respectively, which were both significantly higher than those of the mild cGVHD 9.1% (95% CI 1.8-47.1%) and non-cGVHD groups 14.9% (95% CI, 7.3-30.2%). Our observations highlight the close relation between cGVHD and immune-mediated graft-versus-leukemia (GVL) effect in patients with relapse receiving Chemo-DLI; however, mild cGVHD may not be associated with a sufficiently strong GVL effect to induce remission and improve survival.

20.
Artigo em Inglês | MEDLINE | ID: mdl-30127465

RESUMO

A retrospective study (n = 460) was performed to assess the relationship between minimal residual disease (MRD) and transplant outcomes in a haplo-stem cell transplantation (SCT) setting. Patients from the pre-MRDneg group and the pre-MRDpos group had comparable outcomes. Compared to post-MRDneg patients, post-MRDpos patients had a higher incidence of relapse (100.0% vs. 8.3%, p < 0.001), lower incidences of overall survival (OS) (16.9% vs. 78.2%, p < 0.001) and leukemia-free survival (LFS) (0% vs. 76.5%, p < 0.001), and comparable probability of NRM (13.4% vs. 16.9%, p = 0.560). In a second set of analyses, all adult AML patients undergoing haplo-SCT were classified into the MRDneg/MRDneg group, the MRD decreasing group, and the MRD increasing group according to MRD dynamics by flow cytometry peri-SCT. Compared to the other two groups, patients from the MRD increasing group had higher cumulative incidences of relapse (MRD increasing, 100.0%; MRDneg/MRDneg, 9.6%; MRD decreasing, 19.2%; p < 0.001) and worse probabilities of OS (MRD increasing, 28.5%; MRDneg/MRDneg, 76.3%; MRD decreasing, 76.0%; p < 0.001) and LFS (MRD increasing, 0.0%; MRDneg/MRDneg, 73.9%; MRD decreasing, 74.0%; p < 0.001). The results indicated that haploidentical allografts might have a beneficial anti-leukemia effect in eradicating pretransplantation MRD, and MRD assessment peri-SCT is useful for risk stratification from a practical perspective.

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