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2.
Pediatr Hematol Oncol ; 39(2): 97-107, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34156313

RESUMO

Abnormally high ecotropic viral integration site 1 (EVI1) expression has been recognized as a poor prognostic factor in acute myeloid leukemia patients. However, its prognostic impact in B cell precursor acute lymphoblastic leukemia (BCP-ALL) remains unknown. A total of 176 pediatric Ph-negative BCP-ALL patients who received at least 1 course of chemotherapy and received chemotherapy only during follow-up were retrospectively tested for EVI1 transcript levels by real-time quantitative PCR at diagnosis, and survival analysis was performed. Clinical and EVI1 expression data of 129 pediatric BCP-ALL patients were downloaded from therapeutically applicable research to generate effective treatments (TARGET) database for validation. In our cohort, the median EVI1 transcript level was 0.33% (range, 0.0068-136.2%), and 0.10% was determined to be the optimal cutoff value for patient grouping by receiver operating characteristic curve analysis. Low EVI1 expression (<0.10%) was significantly related to lower 5-year relapse-free survival (RFS) and overall survival (OS) rates (P = 0.017 and 0.018, respectively). Multivariate analysis showed that EVI1 expression <0.10% was an independent adverse prognostic factor for RFS and OS. TARGET data showed that low EVI1 expression tended to be related to a lower 5-year OS rate (P = 0.066). In conclusion, low EVI1 expression at diagnosis could predict poor outcomes in pediatric Ph-negative BCP-ALL patients receiving chemotherapy.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.1939818 .


Assuntos
Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
3.
PeerJ ; 9: e11402, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34221707

RESUMO

BACKGROUND: The phylogenetic relationships of Odonata (dragonflies and damselflies) and Ephemeroptera (mayflies) remain unresolved. Different researchers have supported one of three hypotheses (Palaeoptera, Chiastomyaria or Metapterygota) based on data from different morphological characters and molecular markers, sometimes even re-assessing the same transcriptomes or mitochondrial genomes. The appropriate choice of outgroups and more taxon sampling is thought to eliminate artificial phylogenetic relationships and obtain an accurate phylogeny. Hence, in the current study, we sequenced 28 mt genomes from Ephemeroptera, Odonata and Plecoptera to further investigate phylogenetic relationships, the probability of each of the three hypotheses, and to examine mt gene arrangements in these species. We selected three different combinations of outgroups to analyze how outgroup choice affected the phylogenetic relationships of Odonata and Ephemeroptera. METHODS: Mitochondrial genomes from 28 species of mayflies, dragonflies, damselflies and stoneflies were sequenced. We used Bayesian inference (BI) and Maximum likelihood (ML) analyses for each dataset to reconstruct an accurate phylogeny of these winged insect orders. The effect of outgroup choice was assessed by separate analyses using three outgroups combinations: (a) four bristletails and three silverfish as outgroups, (b) five bristletails and three silverfish as outgroups, or (c) five diplurans as outgroups. RESULTS: Among these sequenced mitogenomes we found the gene arrangement IMQM in Heptageniidae (Ephemeroptera), and an inverted and translocated tRNA-Ile between the 12S RNA gene and the control region in Ephemerellidae (Ephemeroptera). The IMQM gene arrangement in Heptageniidae (Ephemeroptera) can be explained via the tandem-duplication and random loss model, and the transposition and inversion of tRNA-Ile genes in Ephemerellidae can be explained through the recombination and tandem duplication-random loss (TDRL) model. Our phylogenetic analysis strongly supported the Chiastomyaria hypothesis in three different outgroup combinations in BI analyses. The results also show that suitable outgroups are very important to determining phylogenetic relationships in the rapid evolution of insects especially among Ephemeroptera and Odonata. The mt genome is a suitable marker to investigate the phylogeny of inter-order and inter-family relationships of insects but outgroup choice is very important for deriving these relationships among winged insects. Hence, we must carefully choose the correct outgroup in order to discuss the relationships of Ephemeroptera and Odonata.

4.
Clin Lymphoma Myeloma Leuk ; 21(8): e658-e665, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33941506

RESUMO

BACKGROUND: Adolescents (aged 10-17 years) with acute lymphoblastic leukemia (ALL) represent a unique patient population, with a disproportionate survival disadvantage compared with younger patients. We aimed to determine the outcomes and prognostic factors of adolescent patients treated at our institution. PATIENTS AND METHODS: Between 2005 and 2017, 335 adolescents with ALL were enrolled; clinical characteristics and treatment outcomes were analyzed and compared between adolescents and younger children (1-9 years old, n = 704). RESULTS: Adolescents were more likely to have high-risk factors such as hyperleukocytosis, a T-cell immunophenotype, BCR-ABL1, and/or poor early treatment responses. Compared with younger children, adolescents had significantly worse 5-year event-free survival (EFS) (73.0% ± 2.5% vs. 82.6% ± 1.5%; P < .001) and overall survival (OS) (77.1% ± 2.3% vs. 87.7% ± 1.3%; P < .001). Furthermore, younger adolescents (10-14 years) tended to have better outcomes compared with those older than 15 years (5-year OS: 79.3% ± 2.5% vs. 68.4% ± 5.7%; P = .042), mainly because of the lower frequencies of toxicities. On multivariate analysis, white blood count ≥ 50 × 109/L and extramedullary involvement at diagnosis were the most powerful prognostic factors for both OS and EFS. CONCLUSION: The outcomes among adolescent patients were not as good as that of younger children. Further studies are required to define optimal treatment strategies for adolescents, particularly those aged 15 to 17 years.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Criança , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
5.
Int J Lab Hematol ; 43(4): 752-759, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33988302

RESUMO

INTRODUCTION: Residual disease (RD) detected using multiparametric flow cytometry (MFC) is an independent predictive variable of relapse in acute myeloid leukaemia (AML). However, RD thresholds and optimal assessment time points remain to be validated. MATERIAL AND METHODS: We investigated the significance of RD after induction therapy in paediatric AML with normal karyotype between June 2008 and June 2018. Bone marrow samples from 73 patients were collected at the end of the first (BMA-1) and second (BMA-2) induction courses to monitor RD using MFC. RESULTS: Presence of RD after BMA-1 and/or BMA-2 correlated with poor relapse-free (RFS) and overall survival at 0.1% RD cutoff level. Receiver operating characteristic curve showed that RD cutoff levels of 1.3% and 0.5% after BMA-1 and BMA-2, respectively, predicted events with the highest sensitivity and specificity. In multivariable analysis, RD after BMA-2 was the strongest independent risk predictor for poor RFS (hazard ratio 2.934; 95% confidence interval: 1.106-7.782; P = .031). CONCLUSIONS: Our study therefore suggests that an RD level ≥0.5% after BMA-2 has a significant predictive impact on the prognosis of AML patients having normal karyotype and thus guide the stratification of treatment strategies.


Assuntos
Leucemia Mieloide Aguda/diagnóstico , Neoplasia Residual/diagnóstico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Humanos , Quimioterapia de Indução , Lactente , Cariótipo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Masculino , Neoplasia Residual/genética , Prognóstico , Modelos de Riscos Proporcionais
6.
Leukemia ; 35(11): 3092-3100, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33824464

RESUMO

Although chimeric antigen receptor T-cell (CAR-T) therapy produces a high complete remission rate among patients with relapsed/refractory B-cell acute lymphoblastic leukemia, relapse remains an urgent issue. It is uncertain whether consolidative haploidentical-allogeneic hematopoietic stem cell transplantation (haplo-HSCT) is suitable for achieving sustainable remission. Therefore, we aimed to assess the efficacy and safety of bridging CAR-T therapy to haplo-HSCT. Fifty-two patients with relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia who underwent haplo-HSCT after CAR-T therapy were analyzed. The median time from CAR-T therapy to haplo-HSCT was 61 days. After a median follow-up of 24.6 months, the 1-year probabilities of event-free survival, overall survival, and cumulative incidence of relapse were 80.1% (95% confidence interval (CI), 69.0-90.9), 92.3% (95% CI, 85.0-99.5), and 14.1% (95% CI, 10.7-17.4), respectively, while the corresponding 2-year probabilities were 76.0% (95% CI, 64.2-87.7), 84.3% (95% CI, 74.3-94.3), and 19.7% (95% CI, 15.3-24.0), respectively. No increased risk of 2-year cumulative incidence of graft-versus-host disease, treatment-related mortality, or infection was observed. A pre-HSCT measurable residual disease-positive status was an independent factor associated with poor overall survival (hazard radio: 4.201, 95% CI: 1.034-17.063; P = 0.045). Haplo-HSCT may be a safe and effective treatment strategy to improve event-free survival and overall survival after CAR-T therapy.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Imunoterapia Adotiva/efeitos adversos , Recidiva Local de Neoplasia/terapia , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Terapia de Salvação , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Haploidêntico
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 56-61, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554797

RESUMO

OBJECTIVE: To explore the impact of induction treatment response on the prognosis of pediatric core binding factor-acute myeloid leukemia (CBF-AML). METHODS: The result of induce reaction and survival data of 157 pediatric CBF-AML patients in our hospital from September 2008 to December 2018 were retrospectively analyzed.The survival rate of the patients with different degrees of morphological remission after induction chemotherapy was comparative analyzed. RESULTS: Among the 157 children with CBF-AML, 113 (72.4%) patients achieved morphologic leukemia-free state (MLFS) after the first course of induction chemotherapy, 153 (98.1%) patients achieved MLFS after the second course of induction chemotherapy. The 5-year event-free survival (EFS) rate and 5-year overall survival (OS) rate of patients with non-remission (NR) status after the first course of induction of chemotherapy was significantly lower than the patients achieved MLFS and the patients achieved partial remission (PR). The 5-year EFS rate and 5-year OS rate of the patients with PR status after the second course of induction chemotherapy were lower than the patients achieved MLFS, but the difference was not statistically significant. Multivariable analyze showed that NR after the first course of induction chemotherapy and myeloid sarcoma were the independent risk factors affecting EFS of the patients. There were six patients with NR status after the first course of induction chemotherapy, in which all of them harbored t(8;21), three of them with sex chromosome deletion, two of them with myeloid sarcoma. CONCLUSION: NR status after the first course of induction chemotherapy was the independent risk factor affecting EFS and OS of CBF-AML patients, it can be taken as an indicator for higher risk stratification. PR status after the first course of induction chemotherapy may not be used as a diagnostic criterion for primary drug resistance.


Assuntos
Leucemia Mieloide Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Fatores de Ligação ao Core , Intervalo Livre de Doença , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Prognóstico , Indução de Remissão , Estudos Retrospectivos
8.
Inorg Chem ; 60(6): 3980-3987, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33626279

RESUMO

Four new tris-Anderson polyoxometalates (POMs), (NH4)4[ZnMo6O18(C4H8NO3)(OH)3]·4H2O (1), (NH4)4[CuMo6O18(C4H8NO3)(OH)3]·4H2O (2), (TBA)3(NH4)[ZnMo6O17(C5H9O3)2(OH)]·10H2O (3) (TBA = n-C16H36N), and (NH4)4[CuMo6O18(C5H9O3)2]·16H2O (4), were synthesized by a microwave-assisted method. Single-crystal X-ray diffraction revealed that 1 and 2 contained a tris (trihydroxyl organic compounds) ligand grafted on one side, while two tris ligands were grafted on two sides to form χ/δ and δ/δ isomers in 3 and 4, respectively. 1H and 13C NMR spectra of the χ/δ isomer 3 were obtained for the first time, with six methylenes showing six peaks in the 1H NMR spectrum and only four peaks in the 13C NMR spectrum. Mass spectrometry monitoring revealed that during the microwave-assistant process the tris ligand can graft onto POMs to form 1, while tris directly coordinates with metallic heteroatoms to form isopolymolybdates during the conventional reflux synthesis process. In addition, 1-4 can catalyze CO2 with epoxides into cyclic carbonates with high selectivity and yields at an atmospheric pressure of CO2, which is lower than the pressure of CO2 in other catalysis using POMs as catalysts. Furthermore, 1-4 showed good catalytic stability and cycling properties. Mechanism studies substantiated POMs cocatalyzed with Br- to improve the catalytic yields.

9.
Int J Hematol ; 113(4): 547-555, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33386596

RESUMO

Acute lymphoblastic leukemia (ALL) is a heterogeneous disease whose prognostic factors include minimal residual disease (MRD) and cytogenetic abnormalities. To explore the significance of MRD in ALL subtypes, we analyzed the outcomes of 1126 children treated with risk-stratified therapy based on sequential MRD monitoring. MRD distributions and treatment outcomes differed between distinct leukemia subtypes. Patients with ETV6-RUNX1 or hyperdiploidy had the best prognosis (5-year OS: 97 ± 1.5% and 89.2 ± 2.7%). However, hyperdiploidy patients with MRD ≥ 10% on day 15 had a higher risk of relapse (36.4%) than those with ETV6-RUNX1. TCF3-PBX1 patients had the fastest disease clearance (negative MRD rate on day 33: 92.1%), but the overall prognosis was intermediate (5-year OS: 82.5%). Patients with high-risk characteristics and ALL-T had inferior outcomes: even with undetectable MRD on day 33, cumulative incidence of relapse was 19.9% and 23.4%, respectively. Moreover, those with poor early-treatment response and detectable week-12 MRD had a worse prognosis. After adjusting for other risk factors, re-emergent MRD was the most significant adverse prognostic indicator overall. Sequential MRD measurement is important for MRD-guided therapy, and integration of MRD values at different timepoints based on leukemia subtype could allow for more refined risk stratification.


Assuntos
Neoplasia Residual/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Biomarcadores Tumorais , Criança , Pré-Escolar , Bases de Dados Factuais , Gerenciamento Clínico , Suscetibilidade a Doenças , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Avaliação de Resultados da Assistência ao Paciente , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Resultado do Tratamento
10.
J Cancer Res Clin Oncol ; 147(4): 1189-1201, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33006673

RESUMO

PURPOSE: Early death (ED) and treatment-related toxicity emerge as two major barriers for curing paediatric acute promyelocytic leukaemia (APL) patients. This study aims to investigate the effect of idarubicin on controlling hyperleukocytosis in induction therapy and the efficacy and safety of a risk-adapted attenuated consolidation chemotherapy. METHODS: We summarised the characteristics and long-term outcomes of 73 paediatric APL patients treated at our institution from February 2002 to October 2018, during which treatment protocols evolved over three periods and were defined as protocol A, B and C chronologically. All of the patients received an all-trans retinoic acid (ATRA)-arsenic trioxide (ATO) combination remission induction therapy, with hydroxyurea (group A) or idarubicin (group B and C) to control hyperleukocytosis. Consolidation chemotherapy was modified with risk-adapted attenuated intensity and minimised cumulative doses of anthracyclines for group C (144 mg/m2 and 288 mg/m2 of daunorubicin equivalents for standard- and high-risk patients, respectively). RESULTS: The median initial WBC, platelet count, and fibrinogen were 2.9 × 109/L (range 0.9-158.3 × 109/L), 32 × 109/L (range 4-226 × 109/L), and 160 mg/dL (range 53-549 mg/dL), respectively. High-risk and standard-risk were seen in 20.5% and 79.5% of patients, respectively. Three patients (4.1%) suffered early haemorrhagic death. At the end of induction therapy, 68 (93.2%) patients achieved haematologic complete remission (HCR). At a median follow-up of 91.97 months, the estimated 5-year overall survival (OS) and event-free survival (EFS) rates for the whole cohort were 95.9 ± 2.3% and 88.7 ± 3.8%, respectively. A comparison of HCR rates and documented instances of toxicity between groups A and B + C showed no significant differences. However, idarubicin significantly reduced the peak WBC count (Z = - 3.292, P = 0.001) and duration of hyperleukocytosis (Z = - 2.827, P = 0.005). Estimated 3-year EFS (91.7 ± 8.0%) and OS (100%) rates for group C were not significantly different from those for group B, whereas the risk of treatment-related infections was significantly reduced (χ2 = 5.515, P = 0.019). CONCLUSIONS: Idarubicin (8-10 mg/m2/day for 2 days) for hyperleukocytosis control in induction therapy is safe and effective for paediatric APL. Risk-adapted attenuated consolidation chemotherapy is advocated.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia de Consolidação/mortalidade , Leucemia Promielocítica Aguda/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Leucemia Promielocítica Aguda/patologia , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
11.
Clin Lymphoma Myeloma Leuk ; 21(2): e126-e136, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33060049

RESUMO

BACKGROUND: The role of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for children with intermediate-risk acute myeloid leukemia (IR-AML) in first complete remission has been controversial. The present study compared the effect of chemotherapy with unmanipulated haplo-HSCT as treatment of patients with IR-AML in first complete remission (CR1). PATIENTS AND METHODS: We retrospectively analyzed the outcomes of 80 children with IR-AML and compared the effects of chemotherapy (n = 47) with those of haplo-HSCT (n = 33) as treatment in CR1. RESULTS: The 3-year overall survival, event-free survival (EFS), and cumulative incidence of relapse (CIR) was 85.4% ± 4.1%, 73.2% ± 5.0%, and 25.4% ± 4.5%, respectively. Compared with the chemotherapy group, the patients in the haplo-HSCT group had a lower CIR (P = .059) and better EFS (P = .108), but roughly equivalent overall survival (P = .841). Multivariate analysis revealed chemotherapy and minimal residual disease (MRD) of ≥ 10-3 after induction therapy as independent risk factors affecting CIR and EFS. EFS (P = .045) and CIR (P = .045) differed significantly between the 2 treatment groups in patients with MRD of ≥ 10-3 after induction therapy. CONCLUSION: Haplo-HSCT might be a feasible option for children with IR-AML in CR1, especially for patients with MRD of ≥ 10-3 after induction therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Recidiva Local de Neoplasia/epidemiologia , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Humanos , Incidência , Leucemia Mieloide Aguda/mortalidade , Masculino , Recidiva Local de Neoplasia/prevenção & controle , Neoplasia Residual , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Transplante Haploidêntico
12.
Clin Lymphoma Myeloma Leuk ; 21(2): e137-e144, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33221150

RESUMO

BACKGROUND: Acute lymphoblastic leukemia (ALL) with t(1;19)/TCF3-PBX1 is a common genotype, and its prognosis has significantly improved owing to risk stratification and intensive treatment. This study aimed to determine the outcomes and prognostic factors of patients with TCF3-PBX1 treated with the modified Berlin-Frankfurt-Münster protocol. PATIENTS AND METHODS: Between 2005 and 2017, a total of 1051 pediatric patients with ALL were enrolled. TCF3-PBX1 was detected by reverse-transcriptase PCR and/or cytogenetic analysis. Clinical characteristics and treatment outcomes were analyzed and compared in patients with TCF3-PBX1 and with other B-precursor ALL (B-ALL). RESULTS: TCF3-PBX1 was detected in 64 patients with ALL (6.1%), and all were of B-cell lineage. These patients were more likely to express the pre-B-ALL immunophenotype (P < .001), be in the National Cancer Institute high-risk group (P = .030), and exhibit more rapid disease clearance during induction therapy (P < .001) compared to patients with other B-ALL. However, the outcomes of this genotype were not better than those of other patients with intermediate risk. At a median (range) follow-up of 60.6 (0.8-184.5) months, the estimated 5-year overall survival was 85.2 ± 4.6% versus 88.2 ± 1.8% (P = .500) and 5-year event-free survival was 76.8 ± 5.5% versus 83.0 ± 2.0% (P = .210) for patients with TCF3-PBX1 and those with other B-ALL. After adjusting for other risk factors, reemergent minimal residual disease (MRD) was the most significant poor prognostic indicator for patients with TCF3-PBX1. CONCLUSION: The overall outcome of patients with TCF3-PBX1 was intermediate at our institution. Sequential MRD measurement is important for this genotype. Thus, more efforts should be made to eradicate reemergent MRD to improve prognosis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/epidemiologia , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Quimioterapia de Consolidação/métodos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lactente , Quimioterapia de Manutenção/métodos , Masculino , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/prevenção & controle , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Indução de Remissão/métodos , Medição de Risco , Fatores de Risco
14.
Front Immunol ; 12: 731435, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35069522

RESUMO

Background: The presence of minimal residual disease (MRD) is an independent risk factor for poor prognosis in patients with acute lymphoblastic leukemia (ALL). Moreover, the role of chimeric antigen receptor T-cell (CAR-T) therapy in patients with MRD is currently unclear. Methods: We conducted a prospective study to investigate the role of CAR-T therapy in patients with persistent/recurrent MRD-positive ALL in first remission. Results: A total of 77 patients who had persistent/recurrent MRD were included. Of these patients, 43 were enrolled in the CAR-T group, 20 received chemotherapy as a bridge to allogeneic hematopoietic cell transplantation (allo-HSCT), and 14 patients received intensified chemotherapy. MRD negativity was achieved in 90.7% of the patients after CAR-T infusion. Patients who received CAR-T therapy had a higher 3-year leukemia-free survival (LFS) than patients who did not (77.8% vs. 51.1%, P = 0.033). Furthermore, patients in the CAR-T group had a higher 3-year LFS than those in the chemotherapy bridge-to-allo-HSCT group [77.8% (95% CI, 64.8-90.7%) vs. 68.7% (95% CI, 47.7-89.6%), P = 0.575] and had a significantly higher 3-year LFS than those in the intensified chemotherapy group [77.8% (95% CI, 64.8-90.7%) vs. 28.6% (95% CI, 4.9-52.3%), P = 0.001]. Among the patients who received CAR-T therapy, eight were not bridged to allo-HSCT, and six (75%) remained in remission with a median follow-up of 23.0 months after CAR-T infusion. Conclusions: Our findings show that CAR-T therapy can effectively eliminate MRD and improve survival in patients with a suboptimal MRD response.


Assuntos
Transferência Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudos Prospectivos , Indução de Remissão , Taxa de Sobrevida
15.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(12): 1286-1294, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33327999

RESUMO

OBJECTIVE: To explore the clinical-biological characteristics and prognosis of pediatric pro-B cell acute lymphoblastic leukemia (pro-B-ALL). METHODS: A total of 64 patients aged less than 18 years old with pro-BALL were enrolled. Clinical characteristics, therapeutic effect and prognostic factors were retrospectively analyzed. RESULTS: Pro-B-ALL occurred in 6.23% (64/1 028) of pediatric ALL. Among the 64 patients, 35 were male and 29 were female. The median age was 7.0 years (range 0.4-16.0 years) at diagnosis, of which 39% and 6% were ≥ 10 years old and < 1 year old respectively. The median WBC count was 25.5×109/L[range (0.4-831.9)×109/L], of which 35.9% were ≥ 50×109/L. MLL-r positivity was the most frequent genetic alteration in pro-B ALL, occurring in 34% of patients, with lower frequency of CD22 and CD13 expression and higher frequency of CD7 expression, while lower frequency of CD33 expression was found in patients with MLL-AF4 positivity. At a median follow-up of 60.0 months (range 4.9-165.3 months), the estimated 5-year overall survival (OS) and event-free survival (EFS) in the 64 patients were (85±5)% and (78±5)% respectively. Cox proportional hazards regression analysis identified MRD ≥ 0.1% at 3 months after chemotherapy as an independent adverse prognostic factor for both 5-year OS and EFS. CONCLUSIONS: Pediatric pro-B ALL is a heterogeneous disease with clinical and biological diversity. Biological characteristics, such as immunological markers, genetic alterations, and MRD at 3 months after chemotherapy may be important factors for the long-term prognosis.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras B , Adolescente , Antígenos CD/genética , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Histona-Lisina N-Metiltransferase/genética , Humanos , Lactente , Masculino , Proteína de Leucina Linfoide-Mieloide/genética , Neoplasia Residual/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Prognóstico , Estudos Retrospectivos
16.
Cancer Lett ; 493: 128-132, 2020 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-32829005

RESUMO

The presence of minimal residual disease (MRD) is a risk factor for relapse among children with acute myeloid leukemia (AML), and eliminating MRD can usually improve survival rates. To investigate the effect of expanded activated autologous lymphocytes (EAALs) combined with chemotherapy on eliminating MRD and improving survival rates of children with AML, we retrospectively analyzed the results of 115 children with low- or intermediate-risk AML with MRD treated at the Pediatric Hematological Center, Peking University People's Hospital, between January 2010 and January 2016. The patients were assigned to the chemotherapy plus EAAL (combined therapy) group (n = 61) and chemotherapy group (n = 54). The MRD-negativity rates were 95.1% (58/61) in the combined therapy group and 63.0% (34/54) in the chemotherapy group (P < 0.0001) during consolidation treatment. The 5-year event-free survival rate was higher in the combined therapy group than in the chemotherapy group (86.3 ± 4.6% vs. 72.1 ± 6.1%, P = 0.025). No severe adverse event was observed after EAAL infusion. The present study showed that EAAL combined with chemotherapy could improve the MRD-negativity rate and event-free survival rate among children with AML with low level MRD-positive status.


Assuntos
Tratamento Farmacológico/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Neoplasia Residual/terapia , Adolescente , Criança , Pré-Escolar , China , Terapia Combinada , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento
17.
Clin Lymphoma Myeloma Leuk ; 20(11): e813-e820, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32680776

RESUMO

BACKGROUND: The impact of extramedullary infiltration (EMI) on the clinical outcomes of pediatric patients with acute myeloid leukemia (AML) are controversial. PATIENTS AND METHODS: A total of 214 pediatric patients with low-risk AML were classified as having EMI (central nervous leukemia [CNSL] and/or myeloid sarcoma [MS]) and not having EMI. Patients with isolated MS before AML diagnosis by bone marrow examination were confirmed with histopathologic examination. For patients diagnosed with AML by bone marrow examination, a thorough physical examination and radiologic imaging were used to confirm MS. RESULTS: Male gender, a high white blood cell count, the FAB-M5 subtype, t(8;21) and t(1;11) abnormalities, and c-KIT mutations were associated with EMI. The presence of MS was associated with a low complete remission rate (63.6% vs. 79.4%; P = .000) and poor 3-year relapse-free survival (RFS) (62.6% ± 7.5% vs. 87.0% ± 2.8%; P = .000) and 3-year overall survival (73.5% ± 7% vs. 88.8% ± 2.6%; P = .011). Multivariate analysis revealed that MS was a poor prognostic factor for RFS and overall survival. Bone infiltration was an independent risk factor for inferior RFS with MS. Patients with CNSL had a low complete remission rate (58.3% vs. 77.2%; P = .045); however, CNSL did not significantly affect the survival of low-risk patients with AML. CONCLUSION: MS should be considered an independent risk factor to guide stratified treatment.


Assuntos
Leucemia Mieloide Aguda/complicações , Infiltração Leucêmica/fisiopatologia , Criança , Feminino , Humanos , Leucemia Mieloide Aguda/fisiopatologia , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
18.
Leuk Res ; 95: 106405, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32590107

RESUMO

PURPOSE: To investigate the effect of tyrosine kinase inhibitors (TKIs) on the statural growth in children with acute lymphoblastic leukemia (ALL). METHODS: We retrospectively collected data from 344 children with ALL younger than 17 years old at diagnosis identified in pediatric department of Peking University People's Hospital. The children were divided into three groups: conventional chemotherapy group, imatinib group and dasatinib group. Height was expressed as standard deviation score(HtSDS). In the three groups, we compared the HtSDS and △HtSDS at the start of treatment and during follow-up period and also compared the adult height and median parental height(MPH). We further compared the HtSDS classified by age and gender in imatinib group. At last, univariate analysis was used to analyze the influencing factors on the deceleration of height growth by imatinib. RESULTS: There were 298 children in conventional chemotherapy group, 39 in imatinib group and 7 in dasatinib group. In imatinib group, the mean HtSDS of children at follow-up time was significantly lower than that at the start of treatment (P < 0.05), regardless of age and gender. In imatinib group, the decrease of HtSDS in girls was more obvious than in boys(P = 0.031). The HtSDS gradually decreased in the first and the second year in imatinib group. After discontinuation of imatinib, the HtSDS had no obvious change. Multivariate analysis showed that the HtSDS at the start of imatinib was negatively correlated with severe growth impairment on imatinib therapy. The HtSDS in dasatinib group and conventional chemotherapy group maintained a high degree of consistency. CONCLUSION: Imatinib can affect growth velocity in children with ALL, regardless of age and gender. With the discontinuation of imatinib, the inhibitory effect will not continue. The lower HtSDS at the start of imatinib therapy, the more obvious effect of imatinib on growth impairment will be, and the effect will be more obvious in girls than boys.


Assuntos
Antineoplásicos/efeitos adversos , Estatura/efeitos dos fármacos , Mesilato de Imatinib/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Adolescente , Criança , Pré-Escolar , Dasatinibe/efeitos adversos , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Caracteres Sexuais
19.
BMC Cancer ; 20(1): 553, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32539815

RESUMO

BACKGROUND: Pediatric acute myeloid leukemia (AML) with t(8;21) (q22;q22) is classified as a low-risk group. However, relapse is still the main factor affecting survival. We aimed to investigate the effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on reducing recurrence and improving the survival of high-risk pediatric t(8;21) AML based on minimal residual disease (MRD)-guided treatment, and to further explore the prognostic factors to guide risk stratification treatment and identify who will benefit from allo-HSCT. METHODS: Overall, 129 newly diagnosed pediatric t(8;21) AML patients were included in this study. Patients were divided into high-risk and low-risk group according to RUNX1-RUNX1T1 transcript levels after 2 cycles of consolidation chemotherapy. High-risk patients were divided into HSCT group and chemotherapy group according to their treatment choices. The characteristics and outcomes of 125 patients were analyzed. RESULTS: For high-risk patients, allo-HSCT could improve 5-year relapse-free survival (RFS) rate compared to chemotherapy (87.4% vs. 61.9%; P = 0.026). Five-year overall survival (OS) rate in high-risk HSCT group had a trend for better than that in high-risk chemotherapy group (82.8% vs. 71.4%; P = 0.260). The 5-year RFS rate of patients with a c-KIT mutation in high-risk HSCT group had a trend for better than that of patients with a c-KIT mutation in high-risk chemotherapy group (82.9% vs. 75%; P = 0.400). Extramedullary infiltration (EI) at diagnosis was associated with a high cumulative incidence of relapse for high-risk patients (50% vs. 18.4%; P = 0.004); allo-HSCT can improve the RFS (P = 0.009). CONCLUSIONS: allo-HSCT can improve the prognosis of high-risk pediatric t(8;21) AML based on MRD-guided treatment. Patients with a c-KIT mutation may benefit from allo-HSCT. EI is an independent prognostic factor for high-risk patients and allo-HSCT can improve the prognosis.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Recidiva Local de Neoplasia/epidemiologia , Proteínas de Fusão Oncogênica/genética , Proteína 1 Parceira de Translocação de RUNX1/genética , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Criança , Quimioterapia de Consolidação/métodos , Análise Mutacional de DNA , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Quimioterapia de Indução/métodos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Masculino , Mutação , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/prevenção & controle , Neoplasia Residual , Proteínas Proto-Oncogênicas c-kit/genética , Transplante Homólogo/métodos
20.
Pharmazie ; 75(4): 142-146, 2020 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-32295690

RESUMO

Methotrexate (MTX) is widely used in the treatment of childhood acute lymphoblastic leukemia (ALL). Gamma-glutamyl hydrolase (GGH) plays an important role in the disposition of MTX. The aim of this study was to investigate the frequency distribution of five SNPs in the human GGH gene and their effects on serum MTX concentrations and clinical outcomes in Chinese children with ALL. Genotyping of 149 pediatric patients for GGH rs11545078 C>T, rs11545077 G>A, rs1800909 T>C, rs11545076 T>G, and rs3758149 C>T was performed using the Sequenom MassARRAY system. Serum MTX concentrations were determined using a fluorescence polarization immunoassay. The five SNPs studied were in strong linkage. The minor allele frequencies for rs11545078, rs11545077, rs1800909, rs11545076, and rs3758149 were 5.3, 15.0, 14.3, 15.0, and 15.0%, respectively. Four haplotypes (CGTTC, CACGT, TACGT, and TATGT) were observed at frequencies of 84.9, 9.8, 4.5, and 0.8%, respectively. The median C/D ratios of serum MTX at 24 h and 42 h in children with variant haplotypes (12.30 and 0.08 µmol/L per g/m², respectively) were higher than those in wild haplotype carriers (11.85 and 0.07 µmol/L per g/m², respectively). The event-free survival of patients with variant haplotypes (89.2%) was significantly better than that of patients with wild haplotypes (71.9%, P < 0.05). The relapse rate in children with variant haplotypes (8.1%) was lower than that in children with wild haplotypes (15.6%). These findings have implications for the efficacious use of MTX in childhood ALL patients.


Assuntos
Frequência do Gene , Polimorfismo de Nucleotídeo Único/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , gama-Glutamil Hidrolase/genética , Doença Aguda , Adolescente , Alelos , Antimetabólitos Antineoplásicos/farmacocinética , Antimetabólitos Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , China/epidemiologia , Feminino , Genótipo , Haplótipos , Heterozigoto , Humanos , Lactente , Masculino , Metotrexato/farmacocinética , Metotrexato/uso terapêutico , Intervalo Livre de Progressão , Recidiva
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