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1.
Exp Hematol Oncol ; 11(1): 25, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35505384

RESUMO

BACKGROUND: Acute graft-versus-host disease (aGVHD) remains the major cause of early mortality after haploidentical related donor (HID) hematopoietic stem cell transplantation (HSCT). We aimed to establish a comprehensive model which could predict severe aGVHD after HID HSCT. METHODS: Consecutive 470 acute leukemia patients receiving HID HSCT according to the protocol registered at https://clinicaltrials.gov (NCT03756675) were enrolled, 70% of them (n = 335) were randomly selected as training cohort and the remains 30% (n = 135) were used as validation cohort. RESULTS: The equation was as follows: Probability (grade III-IV aGVHD) = [Formula: see text], where Y = -0.0288 × (age) + 0.7965 × (gender) + 0.8371 × (CD3 + /CD14 + cells ratio in graft) + 0.5829 × (donor/recipient relation) - 0.0089 × (CD8 + cell counts in graft) - 2.9046. The threshold of probability was 0.057392 which helped separate patients into high- and low-risk groups. The 100-day cumulative incidence of grade III-IV aGVHD in the low- and high-risk groups was 4.1% (95% CI 1.9-6.3%) versus 12.8% (95% CI 7.4-18.2%) (P = 0.001), 3.2% (95% CI 1.2-5.1%) versus 10.6% (95% CI 4.7-16.5%) (P = 0.006), and 6.1% (95% CI 1.3-10.9%) versus 19.4% (95% CI 6.3-32.5%) (P = 0.017), respectively, in total, training, and validation cohort. The rates of grade III-IV skin and gut aGVHD in high-risk group were both significantly higher than those of low-risk group. This model could also predict grade II-IV and grade I-IV aGVHD. CONCLUSIONS: We established a model which could predict the development of severe aGVHD in HID HSCT recipients.

2.
Front Cell Infect Microbiol ; 12: 862526, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35392613

RESUMO

Objective: We aimed to establish a model that can predict refractory/recurrent cytomegalovirus (CMV) infection after haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT). Methods: Consecutive acute leukemia patients receiving HID HSCT were enrolled (n = 289). We randomly selected 60% of the entire population (n = 170) as the training cohort, and the remaining 40% comprised the validation cohort (n = 119). Patients were treated according to the protocol registered at https://clinicaltrials.gov (NCT03756675). Results: The model was as follows: Y = 0.0322 × (age) - 0.0696 × (gender) + 0.5492 × (underlying disease) + 0.0963 × (the cumulative dose of prednisone during pre-engraftment phase) - 0.0771 × (CD34+ cell counts in graft) - 1.2926. The threshold of probability was 0.5243, which helped to separate patients into high- and low-risk groups. In the low- and high-risk groups, the 100-day cumulative incidence of refractory/recurrent CMV was 42.0% [95% confidence interval (CI), 34.7%-49.4%] vs. 63.7% (95% CI, 54.8%-72.6%) (P < 0.001) for total patients and was 50.5% (95% confidence interval (CI), 40.9%-60.1%) vs. 71.0% (95% CI, 59.5%-82.4%) (P = 0.024) for those with acute graft-versus-host disease. It could also predict posttransplant mortality and survival. Conclusion: We established a comprehensive model that could predict the refractory/recurrent CMV infection after HID HSCT. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT03756675.


Assuntos
Infecções por Citomegalovirus , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Doença Aguda , Infecções por Citomegalovirus/etiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Recém-Nascido , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/terapia , Estudos Retrospectivos
3.
Front Immunol ; 13: 757002, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35154096

RESUMO

For allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, preemptive interferon-α (IFN-α) therapy is considered as a useful method to eliminate the minimal residual disease (MRD). Our purpose is to assess the long-term efficacy of preemptive IFN-α therapy in acute myeloid leukemia (AML) patients following allo-HSCT based on two registry studies (#NCT02185261 and #NCT02027064). We would present the final data and unpublished results of long-term clinical outcomes with extended follow-up. We adopted polymerase chain reaction (PCR) and multiparameter flow cytometry (MFC) to monitor MRD, and a positive result of bone marrow specimen examined by either of them would be identified as the MRD-positive status. Subcutaneous injections of recombinant human IFN-α-2b were performed for 6 cycles, and prolonged IFN-α therapy could be permitted at the request of patients. The median cycles were 3.5 (range, 0.5-30.5) cycles. A total of 9 patients suffered from grade ≥3 toxicities (i.e., infectious: n = 6; hematologic: n = 3). The 6-year cumulative incidences of relapse and non-relapse mortality following IFN-α therapy were 13.0% (95% confidence interval [CI], 5.4-20.6%) and 3.9% (95%CI, 0.0-17.6%), respectively. The probability of disease-free survival at 6 years following IFN-α therapy was 83.1% (95%CI, 75.2-91.9%). The probability of overall survival at 6 years following IFN-α therapy was 88.3% (95%CI, 81.4-95.8%). The cumulative incidences of total chronic graft-versus-host disease (cGVHD) and severe cGVHD at 6 years following IFN-α therapy were 66.2% (95%CI, 55.5-77.0%) and 10.4% (95%CI, 3.6-17.2%), respectively. Multivariable analysis showed that an alternative donor was associated with a lower risk of relapse and the better disease-free survival. Thus, preemptive IFN-α therapy could clear MRD persistently, prevent relapse truly, and improve long-term survival in AML patients following allo-HSCT.


Assuntos
Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Fatores Imunológicos/administração & dosagem , Interferon alfa-2/administração & dosagem , Leucemia Mieloide Aguda/terapia , Sistema de Registros , Prevenção Secundária/métodos , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Criança , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Injeções Subcutâneas , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Estudos Prospectivos , Recidiva , Transplante Homólogo/efeitos adversos , Adulto Jovem
4.
Ther Adv Hematol ; 13: 20406207211072838, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35096361

RESUMO

PURPOSE: Graft-versus-host disease (GVHD) is an important complication after human leukocyte antigen (HLA) haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT), which may lead to poor prognosis. Our study intends to identify the efficacy and safety of mesenchymal stem cells (MSCs) for multidrug-resistant (MDR)-GVHD after HID HSCT. METHODS: MDR-GVHD was referring to GVHD remaining no response to at least two types of therapy, and hUCB-MSCs were given at the dose of (1.0-2.0) × 106/kg once a week. RESULTS: A total of 21 patients were enrolled in this retrospective study (acute GVHD (aGVHD): n = 14, chronic GVHD (cGVHD): n = 7). The median dose of MSCs was 1.2 × 106 cells/kg (range, 0.8-1.8 × 106) cells/kg, and the median numbers of infusion were 2 (range, 1-7) and 3 (range, 2-12) for MDR-aGVHD and MDR-cGVHD patients, respectively. In MDR-aGVHD patients, the overall response rate (ORR) was 57.1%, including 50.0% complete response (CR) and 7.1% partial response (PR), and the median time to response was 49.5 days (range, 16-118) days. The 2-year probability of overall survival after MSCs was 64.3%. Five patients (35.7%) developed infections after MSCs, and no obvious hematologic toxicities were observed. Five MDR-aGVHD patients died after MSCs treatments because of GVHD progression (n = 1), severe infection (bacterial central nervous system infection: n = 1; fungal pneumonia: n = 2), and poor graft function (n = 1). In MDR-cGVHD patients, three patients (42.9%) achieved PR after MSCs and the median time to response was 56 days (22-84) days. The ORRs for moderate and severe cGVHD were 50.0% and 33.3%, respectively. Four MDR-cGVHD patients died after MSCs treatments because of GVHD progression (n = 2), severe fungal pneumonia (n = 1), and relapse (n = 1). CONCLUSION: MSCs treatment may be safe and effective for MDR-GVHD after HID HSCT.

5.
Front Immunol ; 12: 749266, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621279

RESUMO

Acute graft-versus-host disease (aGVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (HSCT). Corticosteroid is the first-line treatment for aGVHD, but its response rate is only approximately 50%. At present, no uniformly accepted treatment for steroid-refractory aGVHD (SR-aGVHD) is available. Blocking interleukin-2 receptors (IL-2Rs) on donor T cells using pharmaceutical antagonists alleviates SR-aGVHD. This meta-analysis aimed to compare the efficacy and safety of four commercially available IL-2R antagonists (IL-2RAs) in SR-aGVHD treatment. A total of 31 studies met the following inclusion criteria (1): patients of any race, any sex, and all ages (2); those diagnosed with SR-aGVHD after HSCT; and (3) those using IL-2RA-based therapy as the treatment for SR-aGVHD. The overall response rate (ORR) at any time after treatment with basiliximab and daclizumab was 0.81 [95% confidence interval (CI): 0.74-0.87)] and 0.71 (95% CI: 0.56-0.82), respectively, which was better than that of inolimomab 0.54 (95% CI: 0.39-0.68) and denileukin diftitox 0.56 (95% CI: 0.35-0.76). The complete response rate (CRR) at any time after treatment with basiliximab and daclizumab was 0.55 (95% CI: 0.42-0.68) and 0.42 (95%CI: 0.29-0.56), respectively, which was better than that of inolimomab 0.30 (95% CI: 0.16-0.51) and denileukin diftitox 0.37 (95% CI: 0.24-0.52). The ORR and CRR were better after 1-month treatment with basiliximab and daclizumab than after treatment with inolimomab and denileukin diftitox. The incidence of the infection was higher after inolimomab treatment than after treatment with the other IL-2RAs. In conclusion, the efficacy and safety of different IL-2RAs varied. The response rate of basiliximab was the highest, followed by that of daclizumab. Prospective, randomized controlled trials are needed to compare the efficacy and safety of different IL-2RAs.


Assuntos
Doença Enxerto-Hospedeiro/tratamento farmacológico , Imunossupressores/uso terapêutico , Receptores de Interleucina-2/antagonistas & inibidores , Anticorpos Monoclonais/uso terapêutico , Basiliximab/uso terapêutico , Daclizumabe/uso terapêutico , Toxina Diftérica/uso terapêutico , Resistência a Medicamentos , Humanos , Interleucina-2/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Esteroides/uso terapêutico
6.
Front Oncol ; 11: 773394, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35070977

RESUMO

In patients with t(8;21) acute myeloid leukemia (AML), recurrent minimal residual disease (MRD) measured by RUNX1-RUNX1T1 transcript levels can predict relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to compare the efficacy of preemptive interferon (IFN)-α therapy and donor lymphocyte infusion (DLI) in patients with t(8;21) AML following allo-HSCT. We also evaluated the appropriate method for patients with different levels of RUNX1-RUNX1T1 transcripts. In this retrospective study, consecutive patients who had high-risk t(8;21) AML and received allo-HSCT were enrolled. The inclusion criteria were as follows: (1) age ≤65 years; (2) regained MRD positive following allo-HSCT. MRD positive was defined as the loss of a ≥4.5-log reduction and/or <4.5-log reduction in the RUNX1-RUNX1T1 transcripts, and high-level, intermediate-level, and low-level MRDs were, respectively, defined as <2.5-log, 2.5-3.5-log, and 3.5-4.5-log reductions in the transcripts compared with the pretreatment baseline level. Patients with positive RUNX1-RUNX1T1 could receive preemptive IFN-α therapy or DLI, which was primarily based on donor availability and the intentions of physicians and patients. The patients received recombinant human IFN-α-2b therapy by subcutaneous injection twice a week every 4 weeks. IFN-α therapy was scheduled for six cycles or until the RUNX1-RUNX1T1 transcripts were negative for at least two consecutive tests. The rates of MRD turning negative for patients with low-level, intermediate-level, and high-level RUNX1-RUNX1T1 receiving IFN-α were 87.5%, 58.1%, and 22.2%, respectively; meanwhile, for patients with intermediate-level and high-level RUNX1-RUNX1T1 receiving DLI, the rates were 50.0% and 14.3%, respectively. For patients with low-level and intermediate-level RUNX1-RUNX1T1, the probability of overall survival at 2 years was higher in the IFN-α group than in the DLI group (87.6% vs. 55.6%; p = 0.003). For patients with high levels of RUNX1-RUNX1T1, the probability of overall survival was comparable between the IFN-α and DLI groups (53.3% vs. 83.3%; p = 0.780). Therefore, patients with low-level and intermediate-level RUNX1-RUNX1T1 could benefit more from preemptive IFN-α therapy compared with DLI. Clinical outcomes were comparable between preemptive IFN-α therapy and DLI in patients with high-level RUNX1-RUNX1T1; however, they should be further improved.

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