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1.
Transplant Cell Ther ; 29(5): 331.e1-331.e8, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36775200

RESUMO

Reduced-intensity conditioning (RIC) haploidentical (haplo-) hematopoietic stem cell transplantation (HSCT) requires more hematopoietic progenitor and stem cells (HPSCs) to promote engraftment and immune reconstitution and needs a stronger graft-versus-leukemia effect. Peripheral blood stem cells (PBSCs) offer advantages over bone marrow; however, the use of higher-dose non-T cell-depleted (non-TCD) in vitro PBSCs may increase the occurrence of severe graft-versus-host disease (GVHD). This prospective, single-arm clinical study was performed to investigate using high-dose non-TCD in vitro PBSCs as the graft source, using fludarabine/Ara-C/busulfan (FAB) as the conditioning regimen, using rabbit antithymocyte globulin to remove T cells in vivo, and enhancing GVHD prophylaxis with an IL-2 receptor antagonist in RIC-haplo-HSCT in patients with hematologic malignancies age 50 to 70 years or <50 years with comorbidities (Hematopoietic Cell Transplantation Comorbidity Index score ≥2) classified as intermediate to high risk. The primary endpoint was day 100 acute GVHD (aGVHD). A total of 47 patients were enrolled; the median age was 52 years (range, 30 to 68 years), the median duration of follow-up was 34 months (range, 2 to 99 months), and the medium-infused doses of mononuclear cells, CD34+ cells, and CD3+ cells were 15.93 × 108/kg, 8.68 × 106/kg, and 5.57 × 108/kg, respectively. The cumulative incidence of grade II-IV aGVHD at day 100 was 30.3% (95% confidence interval [CI], 15.9% to 44.8%), and that of grade III-IV aGVHD was 10.2% (95% CI, .6% to 19.8%). The 2-year cumulative incidence of chronic GVHD (cGVHD) was 34.9% (95% CI, 19.0% to 50.8%). The 2-year cumulative incidences of localized and extensive cGVHD were 26.1% (95% CI, 11.80% to 40.40%) and 8.7% (95% CI, 3.26% to 20.65%), respectively. The 2-year cumulative incidence of relapse was 17.3% (95% CI, 5.1% to 29.5%), the 2-year overall survival rate was 71.2% (95% CI, 57.9% to 84.5%), and the 2-year disease-free survival rate was 66.2% (95% CI, 52.1% to 80.3%). The incidence of aGVHD was not high, and the overall efficacy was good. This study demonstrates that this unique RIC-haplo-PBSC transplantation protocol was effective in treating hematologic malignancies. Nonetheless, larger prospective multicenter clinical trials and experimental studies should be performed to further confirm our findings.


Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Humanos , Estudos Prospectivos , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Doença Enxerto-Hospedeiro/prevenção & controle , Estudos Multicêntricos como Assunto
2.
J Clin Oncol ; 38(36): 4249-4259, 2020 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-33108244

RESUMO

PURPOSE: Relapse is a major cause of treatment failure after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) for high-risk acute myeloid leukemia (HR-AML). The aim of this study was to explore the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) combined with minimal-dose decitabine (Dec) on the prevention of HR-AML relapse after allo-HSCT. PATIENTS AND METHODS: We conducted a phase II, open-label, multicenter, randomized controlled trial. Two hundred four patients with HR-AML who had received allo-HSCT 60-100 days before randomization and who were minimal residual disease negative were randomly assigned 1:1 to either rhG-CSF combined with minimal-dose Dec (G-Dec group: 100 µg/m2 of rhG-CSF on days 0-5 and 5 mg/m2 of Dec on days 1-5) or no intervention (non-G-Dec group). The primary outcome was relapse after transplantation, and the secondary outcomes were chronic graft-versus-host disease (cGVHD), safety of the treatment, and survival. RESULTS: The estimated 2-year cumulative incidence of relapse in the G-Dec group was 15.0% (95% CI, 8.0% to 22.1%), compared with 38.3% (95% CI, 28.8% to 47.9%) in the non-G-Dec group (P < .01), with a hazard ratio (HR) of 0.32 (95% CI, 0.18 to 0.57; P < .01). There was no statistically significant difference between the G-Dec and non-G-Dec groups in the 2-year cumulative incidence of cGVHD without relapse (23.0% [95% CI, 14.7% to 31.3%] and 21.7% [95% CI, 13.6% to 29.7%], respectively; P = .82), with an HR of 1.07 (95% CI, 0.60 to 1.92; P = .81). After rhG-CSF combined with minimal-dose Dec maintenance, increasing numbers of natural killer, CD8+ T, and regulatory T cells were observed. CONCLUSION: Our findings suggest that rhG-CSF combined with minimal-dose Dec maintenance after allo-HSCT can reduce the incidence of relapse, accompanied by changes in the number of lymphocyte subtypes.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Decitabina/uso terapêutico , Filgrastim/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Antimetabólitos Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Criança , Pré-Escolar , Decitabina/farmacologia , Feminino , Filgrastim/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Fatores de Risco , Adulto Jovem
3.
Exp Ther Med ; 19(3): 1725-1732, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32104226

RESUMO

The present study was designed to investigate the effect of adipose-derived stem cells (ADSCs) on acute graft vs. host disease (aGVHD) and hematopoietic recovery after allogeneic hematopoietic stem cell transplantation. ADSCs, bone marrow-derived stem cells (BMSCs) and fibroblasts were cultured. ADSCs were cocultured with hematopoietic stem/progenitor cells. Then, ADSCs were infused into the aGVHD rat model. The survival of the rats was recorded. Livers and small intestines were obtained from sacrificed rats for pathological examinations. Expression of the Sry gene in recipient rats that survived longer than 21 days was examined by real-time PCR to detect the presence of donor Y chromosome. Expression of serum interferon (INF)-γ and interleukin (IL)-4 was detected by ELISA at 0, 7, 14, 21 and 50 days after transplantation. Transplantation of ADSCs improved the survival of aGVHD rats. Survived ADSCs participated in hematopoietic reconstitution in aGVHD rats. ADSCs decreased aGVHD severity by immunomodulation. ADSCs support the proliferation of hematopoietic stem/progenitor cells in vitro. The present study demonstrated that ADSCs may reduce aGVHD by influencing the balance of IL-4 and INF-γ and can promote long-term hematopoiesis.

4.
Am J Transl Res ; 9(8): 3623-3632, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28861153

RESUMO

T helper type 9 (Th9) cells have recently been identified as a new effector T cell subset. This study is to analyze the reconstitution of Th9 cell after matched sibling peripheral blood hematopoietic stem cell transplantation (MS-PBSCT) and the relationship between Th9 cell and acute graft-versus-host disease (aGVHD). Flow cytometry and ELISA were used to analyze the percentages of Th9 cell, levels of IL-9, TGF-ß, IFN-γ, and IL-4. The results showed that for patients without aGVHD, Th9 cells recovery started from day 60 after transplantation and reached normal level on day 90. Serum TGF-ß, IL-4, and IFN-γ reached normal levels on day 60, 60, and 90 post transplantation respectively. The serum IL-9 recovery is slower than that of IFN-γ and IL-4. For patients suffering from aGVHD, they had declined Th9 cell numbers, lower IL-9 and TGF-ß levels, but higher serum IFN-γ level when compared with those without aGVHD after transplantation. Serum IFN-γ/IL-9 ratios increased linearly with grades of aGVHD. In conclusion, Th9 cells recovery is delayed after MS-PBSCT in patients with aGVHD but early in patients without aGVHD, indicating quick immune reconstitution of Th9 cells and IL-9 after MS-PBSCT may promote the immune tolerance.

5.
Int J Clin Exp Pathol ; 8(8): 8892-901, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26464630

RESUMO

Related HLA-haploidentical HSCT has been applied more and more recently, but the reconstitution of T lymphocyte subsets and its clinical significance in patients received related HLA-haploidentical non T-cell depleted in vitro high-dose peripheral blood hematopoietic SCT (RHNT-PSCT) are incompletely defined. In the present study of our RHNT-PSCT, we found that in non-aGVHD group, CD3(+) T lymphocyte recovered to normal levels gradually between 60 and 90 days, and the recovery of CD4(+) T lymphocyte was retarded significantly, CD4(+)/CD8(+) ratio was apparently inverted. Whereas, the ratio of CD4(+) CD25(+) Foxp3(+) Treg cells was significantly lower in aGVHD group than in healthy control group and non-aGVHD group, and also in grade III-IV aGVHD patients than in grade I-II aGVHD patients. Meanwhile, we observed the level of interleukin-10 (IL-10) gradually increased in serum of patients without aGVHD, but decreased in III-IV aGVHD patients significantly. Spearman correlation analysis showed that serum IL-10 level was negatively correlated with the grade of aGVHD. These results suggest that the reconstitution of peripheral blood T lymphocyte subsets is good, and dynamic detection of Treg cells and serum IL-10 level might predict aGVHD in the early stage after our RHNT-PSCT.


Assuntos
Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Subpopulações de Linfócitos T/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Antígenos HLA/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
6.
J Clin Oncol ; 33(34): 3999-4006, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26392095

RESUMO

PURPOSE: For recipients of allogeneic hematopoietic stem-cell transplantation (alloHSCT), we hypothesized that prophylactic therapy during neutropenia with granulocyte-macrophage colony-stimulating factor (GM-CSF) decreases invasive fungal disease (IFD). PATIENTS AND METHODS: We randomly assigned 206 patients undergoing alloHSCT to receive once-daily subcutaneous GM-CSF (5 to 7 µg/kg per day), granulocyte colony-stimulating factor (G-CSF; 5 to 7 µg/kg per day), or a combination of G-CSF and GM-CSF (2 to 3 µg/kg per day each). Treatment was started on day 5 after transplantation and was continued until the absolute neutrophil count was ≥ 1.5 × 10(9)/L for 2 consecutive days. The primary outcomes were 100-day incidence of proven and probable IFD and response rate of antifungal treatment. RESULTS: For the intent-to-treat population, there was no significant difference in 100-day incidences of proven and probable IFD among the three groups. The antifungal treatment response was better in the GM-CSF group and G-CSF+GM-CSF group than in G-CSF group from day 22 to day 100 (P = .009). The 100-day cumulative mortality after transplantation was lower in the GM-CSF group than in the G-CSF group (10.3% v 24.6%, respectively; P = .037). The GM-CSF and G-CSF+GM-CSF groups had lower 100-day transplantation-related mortality than the G-CSF group (8.8%, 8.7%, and 21.7%, respectively; P = .034). After a median follow-up of 600 days, IFD-related mortality was lower in the groups that received GM-CSF or G-CSF+GM-CSF compared with G-CSF (1.47%, 1.45%, and 11.59%, respectively; P = .016). There were no significant differences in relapse, graft-versus-host disease, or hemorrhage-related mortality among the three groups of patients. CONCLUSION: For recipients of alloHSCT, compared with G-CSF, prophylactic GM-CSF was associated with lower 100-day transplantation-related mortality, lower 100-day cumulative mortality, and lower 600-day IFD-related mortality.


Assuntos
Antifúngicos/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Micoses/tratamento farmacológico , Adolescente , Adulto , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Doenças Hematológicas/mortalidade , Doenças Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/etiologia , Micoses/mortalidade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Transplante Homólogo , Adulto Jovem
7.
Zhonghua Xue Ye Xue Za Zhi ; 35(12): 1100-6, 2014 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-25543706

RESUMO

OBJECTIVE: To study the clinical features of acute graft-versus-host disease (aGVHD) and its risk factors for the related HLA-haploidentical non T cell-depleted in vitro peripheral hematopoietic stem cell transplantation (RHNT-PBSCT). METHODS: From July 2002 to December 2012, 104 patients who underwent the RHNT-PBSCT were enrolled to analyze the incidences, location and its risk factors of aGVHD, compared with those of the 103 patients who received the HLA-matched sibling non T cell-depleted in vitro PBSCT (MSNT-PBSCT) in the same period. RESULTS: (1)The cumulative incidence of aGVHD in the RHNT-PBSCT group was significantly higher than the MSNT-PBSCT group [(56.2±4.7)% vs (34±3.6)%, P<0.05], but the cumulative incidences of II-IV and III-IVgrade aGVHD had no significant difference between the two groups[(39.5±2.9)% vs (21.2±5.4)%, P>0.05; (12.6±4.1)% vs (10.8±2.4)%, P>0.05]. (2)The cumulative incidence of cutaneous aGVHD was significantly higher in RHNT-PBSCT group than that in MSNT-PBSCT group [(42.3±3.2)% vs (17.5±2.3)%, P<0.05]. The cumulative incidences of liver and gastrointestinal aGVHD between the two groups had no significant difference [(7.7±2.1)% vs (12.6±3.4)%, P>0.05; (16.3±4.5)% vs (10.3±2.5)%, P>0.05]. (3)The 3-year disease free survival (DFS) and overall survival(OS) of RHNT-PBSCT group and MSNT-PBSCT group were (63±5.5)%, (65.2±4.7)% and (74.2±5.4)%, (77.4±5)% respectively, without significance (P=0.078, P=0.052). (4)aGVHD occurrence with HLA haplotype (P=0.003) and matched loci (P=0.002) were significantly correlated by univariate analysis. Multivariate analysis showed that only the HLA typing is a risk factor for aGVHD (HR=1.891, P=0.03). CONCLUSION: Although the incidence of total aGVHD in RHNT-PBSCT protocol is higher than that in MSNT-PBSCT, but there was no significance in severe aGVHD and cutaneous aGVHD was the common type, which indicates that RHNT-PBSCT protocol is feasible.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Intervalo Livre de Doença , Haplótipos , Teste de Histocompatibilidade , Humanos , Técnicas In Vitro , Incidência , Transplante de Células-Tronco de Sangue Periférico , Fatores de Risco , Irmãos , Linfócitos T
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 22(4): 976-81, 2014 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-25130813

RESUMO

This study was purposed to compare the therapeutic efficacy and prognosis of acute myeloid leukemia M2a (AML-M2a) patients treated by idarubicin (IDA) combined with cytarabine (Ara-C) (IA) and daunorubicin (DNR) combined cytarabine (Ara-C) (DA) regimens. The clinical data of 65 patients with AML-M2a in our hospital were collected from May 2009 to May 2013 and analyzed. The results indicated the complete remission in IA group was slightly higher than that in DA group, there was no statistically significant difference(P > 0.05); leukocyte minimum value in IA group [(0.58 ± 0.40)×10(9)/L] was obviously lower than that in DA group [(0.99 ± 0.67)×10(9)/L] (P < 0.05); neutrophil minimum value in IA group [(0.19 ± 0.09)×10(9)/L] was significantly lower than that in DA group [(0.21 ± 0.16)×10(9)/L] (P < 0.05); the neutropenia duration in IA group (12.59 ± 5.31)d was much longer than that in DA group (9.17 ± 7.04)d (P < 0.05). The median survival time of patients in IA group was 36.67 months, which was obviously longer than that of patients in DA group (21.45 months) (P < 0.05). The lactate dehydrogenase (LDH) value and chemotherapy regimens were the independently risk factor affecting the prognosis of AML-M2a patients. It is concluded that as compared with DA regimen, the IA regimen can prolong the median survival time and has better long-term therapeutic efficacy, thus it can be used as the first chemotherapy regimen for treatment of AML-M2a.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Adulto , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
9.
Zhonghua Yi Xue Za Zhi ; 91(32): 2254-7, 2011 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-22094090

RESUMO

OBJECTIVE: To explore an efficacious protocol for the patients with acute promyelocytic leukemia (APL) after a complete remission (CR) by all-trans retinoic acid (ATRA). METHODS: A total of 32 APL patients with an induction of CR by ATRA at our hospital from January 2000 to October 2007 received conventional standard chemotherapy as a consolidation regimen. Stratified according to age, those under 50 years old received an intermediate dose of cytarabine(IDAra-C)and over 50 years old non-IDAra-C regimen. Maintenance regimen: all patients received ATRA, arsenic trioxide (As2O3) and 6-mercaptopurine (6-MP) + methotrexate (MTX) alternately and sequentially for 3 years. The efficacy and side effects of these chemotherapies were observed. RESULTS: The median follow-up was 72 (40 - 124) months. The 5-year disease-free survival (DFS) rates of under 50 years old and over 50 years old were 94.7% and 92.3% respectively. The difference was statistically insignificant (P > 0.05). One patient relapsed after a consolidation therapy and so did another on a maintenance regimen. Thirty patients achieved a constant CR. And 16 of 30 patients completed chemotherapy beyond 5 years and survived disease-free. The 5-year DFS rate of 32 patients was 93.8%. CONCLUSION: After the achievement of CR with ATRA, all APL patients have a higher rate of DFS after stratification. The side effects are generally mild. Thus a stratification therapy is both feasible and efficacious.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/uso terapêutico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Seguimentos , Humanos , Leucemia Promielocítica Aguda/terapia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
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