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1.
Rinsho Ketsueki ; 62(3): 193-195, 2021.
Artículo en Japonés | MEDLINE | ID: mdl-33828014

RESUMEN

Acquired hypofibrinogenemia is observed in patients with severe liver disease, disseminated intravascular coagulation, and high-volume perioperative fluid replacement. In lymphoblastic leukemia, hypofibrinogenemia is most frequently caused by the administration of L-asparaginase. Here we report the cases of two patients with acquired hypofibrinogenemia that occurred during steroid-containing chemotherapy treatment against lymphoblastic blast crisis of chronic myeloid leukemia in the first case and acute lymphoblastic leukemia in the second case. Administration of steroids repeatedly and promptly caused hypofibrinogenemia, irrespective of the products (prednisolone, dexamethasone, or methylprednisolone) or routes (oral or intravenous) that were used. Monitoring of the fibrinogen levels, especially during the first course of steroid therapy, would be useful for early diagnosis.


Asunto(s)
Afibrinogenemia , Coagulación Intravascular Diseminada , Leucemia-Linfoma Linfoblástico de Células Precursoras , Afibrinogenemia/inducido químicamente , Asparaginasa , Fibrinógeno , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 311-315, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33812392

RESUMEN

OBJECTIVE: To investigate the clinical features and prognostic factors of acute lymphoblastic leukemia (ALL) children with P2RY8-CRLF2 gene rearrangement. METHODS: A total of 108 children with B-cell ALL (B-ALL) were diagnosed and systematically treated according to Chinese Children's Leukemia Group (CCLG) -ALL 2008 in our hospital from January 2016 to December 2016. The 108 patients were divided into two groups according to the result of mutiplex polymerase chain reaction: group with P2RY8-CRLF2 gene rearrangement and group without P2RY8-CRLF2 gene rearrangement. The ALL children with P2RY8-CRLF2 gene rearrangement were all treated by CCLG-ALL 2008 high-risk group (HR) regimens, and the ALL children in group without P2RY8-CRLF2 gene rearrangement received different intensity chemotherapy according to clinical risk classification. RESULTS: Five (4 male and 1 female) out of 108 patients with B-ALL had P2RY8-CRLF2 gene rearrangement. In the 5 B-ALL patients with P2RY8-CRLF2 gene rearrangement, the median age of the was 4 (2-6) years old and the median WBC count was 26.2 (2.46-525.1)×109/L. These patients presented different immunophenotype, including 3 cases of common B-ALL and 2 cases of pre B-ALL. Four patients carried a normal karyotype and 1 patient carried 46, XY, der (20) [22]/46, XY[2]. For the children with P2RY8-CRLF2 gene rearrangement, 1 patient (20%) could not achieve complete remission (CR), and minimal residual disease (MRD) of 2 patients (40%) was higher than 1% on day 33 of induction chemotherapy; while in group without P2RY8-CRLF2 gene rearrangement, all the patient achieved CR, and MRD in 6 patients (5.8%) was higher than 1% on day 33 of induction chemotherapy. The 3 year event-free survival (EFS) of ALL children in group with P2RY8-CRLF2 gene rearrangement was significantly lower than that in group without P2RY8-CRLF2 gene rearrangement (60.0%±21.9% vs 85.9%±3.9%) (P<0.05). CONCLUSION: The early treatment response and prognosis of ALL children with P2RY8-CRLF2 gene rearrangement are worse, and more effective protocol is needed for this subtype patients.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Reordenamiento Génico , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pronóstico , Receptores de Citocinas/genética , Receptores Purinérgicos P2Y/genética
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 433-438, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33812411

RESUMEN

OBJECTIVE: To investigate the significance of low-density lipoprotein receptor-related protein 5 and 6 (LRP5/6) in the Wnt/ß-catenin signaling pathway in the pathogenesis and prognosis of childhood acute lymphoblastic leukemia (ALL). METHODS: A total of 43 children who were newly diagnosed and achieved complete remission after remission induction therapy were enrolled. The children before treatment were included in incipient group, and after treatment when achieved complete remission included in remission group. A total of 39 children with immune thrombocytopenia were enrolled in control group. Three milliliter bone marrow samples were collected from above-mentioned each group. QRT-PCR was used to determine the mRNA expression of LRP5 and LRP6 in blood mononuclear cells of bone marrow. Western blot was used to detect the protein expression of LRP5 and LRP6. According to the protein expression levels of LRP5 and LRP6, the children were divided into low-expression group and high-expression group, and the clinical biological characteristics were compared between these two groups. Survival analysis was performed by Kaplan-Meier method. RESULTS: Both mRNA and protein expression levels of LRP5 and 6 were upregulated in the incipient group compared with the control and remission group (P<0.05). The mRNA and protein expressions of LRP5 and LRP6 in the high-risk group were higher than those in the medium-risk group (P<0.05), it is the same as in the medium-risk group than the low-risk group (P<0.05). The mRNA and protein expressions of LRP5 and 6 positively correlated with risk degree in the incipient group (rLRP5 mRNA=0.84, P<0.05; rLRP6 mRNA=0.66, P<0.05; rLRP5 protein=0.82, P<0.05; rLRP6 protein=0.76, P<0.05). The white blood cell count and lactate dehydrogenase in LRP5 and LRP6 high expression group were significantly higher than those in low expression group (P<0.05), while there was no significant difference in other biological characteristics. Kaplan-meier survival analysis showed that in the 43 children 3-year overall survival rate and event-free survival rate was (91.7±4.7)% and (87.6±5.2)%, respectively. CONCLUSION: The high expression of LRP5/6 may be one of the pathogenesis of childhood ALL, and the degree of LRP5/6 increase may be related to the risk level.


Asunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras , Vía de Señalización Wnt , Niño , Humanos , Lipoproteínas LDL , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad , Receptores de LDL , beta Catenina/metabolismo
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 648-652, 2021 Apr.
Artículo en Chino | MEDLINE | ID: mdl-33812446

RESUMEN

B-cell acute lymphoblastic leukemia (B-ALL) is a common malignant tumor in hematopoietic system. Although the remission rate of the patients with adult B-ALL is similar to those with childhood B-ALL, the rate of long-term disease-free survival (DFS) rate is significantly lower, once recurrence, the remission rate of routine chemotherapy is low and the prognosis is so poor. Based on the expression of tumor cell surface antigens(such as CD19, CD20 and CD22), the specific monoclonal antibodies, bispecific antibodies and chimeric antigen receptor T cells (CAR-T), and other targeted immunotherapy can greatly improve the efficacy of B-ALL patients, especially for patients with relapse and refractory. In this review, the progress of immunotherapy against B-ALL cell surface antigen is summarized briefly.


Asunto(s)
Linfoma de Burkitt , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Antígenos CD19 , Antígenos de Superficie , Linfocitos B , Niño , Humanos , Inmunoterapia Adoptiva , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos de Linfocitos T
5.
Zhonghua Bing Li Xue Za Zhi ; 50(3): 207-212, 2021 Mar 08.
Artículo en Chino | MEDLINE | ID: mdl-33677883

RESUMEN

Objective: To evaluate the expression of LEF1 protein in lymphoblastic lymphoma/acute lymphoblastic leukemia (LBL/ALL) and small B-cell lymphomas, and its value in pathologic diagnosis and differential diagnosis of LBL/ALL. Methods: 53 cases of LBL/ALL were collected at shanghai Tongji Hospital from January 2012 to December 2019. The protein expression of LEF1 and TdT was detected by immunohistochemistry in 53 paraffin-embedded tissue samples of LBL/ALL. The specificity and sensitivity of LEF1 and TdT in the diagnosis of LBL/ALL were compared. The expression of LEF1 protein in 77 cases of small B-cell lymphomas including chronic lymphocytic leukemia/small lymphoid lymphoma (CLL/SLL), follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma and Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma was studied. The correlation between LEF1 expression and overall survival (OS) and progression-free survival (PFS) was performed by univariate analysis. Results: The expression of LEF1 in LBL/ALL was 100% (53/53), the median value was 90%; the expression of TdT was 84.9% (T-LBL/ALL 78.1%, B-LBL/ALL 95.2%), the median value was 80%; the expression rate and median value of LEF1 and TdT were significantly different (P=0.008 and 0.001 respectively). The expression of LEF1 in CLL/SLL was 14/18, the median value was 45%; LEF1 was not expressed in follicular lymphoma (0/16), mantle cell lymphoma (0/16), marginal zone lymphoma (0/19), and Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma (0/8). LEF1 expression was significantly different between B-LBL/ALL and small B-cell lymphomas. The median follow-up time of LBL/ALL cases in this group was 16 months. There was no statistical difference between LEF1 expression and the OS and PFS in LBL/ALL patients. Conclusions: Immunohistochemical staining of LEF1 has high sensitivity and good specificity in the diagnosis of LBL/ALL, and its combination with TdT can improve the diagnostic rate of LBL/ALL.


Asunto(s)
Biomarcadores de Tumor , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , China , Diagnóstico Diferencial , Humanos , Inmunohistoquímica , Factor de Unión 1 al Potenciador Linfoide , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico
7.
JAMA ; 325(9): 833-842, 2021 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-33651090

RESUMEN

Importance: Standard chemotherapy for first relapse of B-cell acute lymphoblastic leukemia (B-ALL) in children, adolescents, and young adults is associated with high rates of severe toxicities, subsequent relapse, and death, especially for patients with early relapse (high risk) or late relapse with residual disease after reinduction chemotherapy (intermediate risk). Blinatumomab, a bispecific CD3 to CD19 T cell-engaging antibody construct, is efficacious in relapsed/refractory B-ALL and has a favorable toxicity profile. Objective: To determine whether substituting blinatumomab for intensive chemotherapy in consolidation therapy would improve survival in children, adolescents, and young adults with high- and intermediate-risk first relapse of B-ALL. Design, Setting, and Participants: This trial was a randomized phase 3 clinical trial conducted by the Children's Oncology Group at 155 hospitals in the US, Canada, Australia, and New Zealand with enrollment from December 2014 to September 2019 and follow-up until September 30, 2020. Eligible patients included those aged 1 to 30 years with B-ALL first relapse, excluding those with Down syndrome, Philadelphia chromosome-positive ALL, prior hematopoietic stem cell transplant, or prior blinatumomab treatment (n = 669). Interventions: All patients received a 4-week reinduction chemotherapy course, followed by randomized assignment to receive 2 cycles of blinatumomab (n = 105) or 2 cycles of multiagent chemotherapy (n = 103), each followed by transplant. Main Outcome and Measures: The primary end point was disease-free survival and the secondary end point was overall survival, both from the time of randomization. The threshold for statistical significance was set at a 1-sided P <.025. Results: Among 208 randomized patients (median age, 9 years; 97 [47%] females), 118 (57%) completed the randomized therapy. Randomization was terminated at the recommendation of the data and safety monitoring committee without meeting stopping rules for efficacy or futility; at that point, 80 of 131 planned events occurred. With 2.9 years of median follow-up, 2-year disease-free survival was 54.4% for the blinatumomab group vs 39.0% for the chemotherapy group (hazard ratio for disease progression or mortality, 0.70 [95% CI, 0.47-1.03]); 1-sided P = .03). Two-year overall survival was 71.3% for the blinatumomab group vs 58.4% for the chemotherapy group (hazard ratio for mortality, 0.62 [95% CI, 0.39-0.98]; 1-sided P = .02). Rates of notable serious adverse events included infection (15%), febrile neutropenia (5%), sepsis (2%), and mucositis (1%) for the blinatumomab group and infection (65%), febrile neutropenia (58%), sepsis (27%), and mucositis (28%) for the chemotherapy group. Conclusions and Relevance: Among children, adolescents, and young adults with high- and intermediate-risk first relapse of B-ALL, postreinduction treatment with blinatumomab compared with chemotherapy, followed by transplant, did not result in a statistically significant difference in disease-free survival. However, study interpretation is limited by early termination with possible underpowering for the primary end point. Trial Registration: ClinicalTrials.gov Identifier: NCT02101853.


Asunto(s)
Anticuerpos Biespecíficos/uso terapéutico , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Inmunoterapia , Leucemia de Células B/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Adulto , Anticuerpos Biespecíficos/efectos adversos , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Niño , Preescolar , Terapia Combinada , Quimioterapia de Consolidación/efectos adversos , Supervivencia sin Enfermedad , Terminación Anticipada de los Ensayos Clínicos , Femenino , Humanos , Lactante , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recurrencia , Adulto Joven
8.
JAMA ; 325(9): 843-854, 2021 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-33651091

RESUMEN

Importance: Blinatumomab is a CD3/CD19-directed bispecific T-cell engager molecule with efficacy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). Objective: To evaluate event-free survival in children with high-risk first-relapse B-ALL after a third consolidation course with blinatumomab vs consolidation chemotherapy before allogeneic hematopoietic stem cell transplant. Design, Setting, and Participants: In this randomized phase 3 clinical trial, patients were enrolled November 2015 to July 2019 (data cutoff, July 17, 2019). Investigators at 47 centers in 13 countries enrolled children older than 28 days and younger than 18 years with high-risk first-relapse B-ALL in morphologic complete remission (M1 marrow, <5% blasts) or with M2 marrow (blasts ≥5% and <25%) at randomization. Intervention: Patients were randomized to receive 1 cycle of blinatumomab (n = 54; 15 µg/m2/d for 4 weeks, continuous intravenous infusion) or chemotherapy (n = 54) for the third consolidation. Main Outcomes and Measures: The primary end point was event-free survival (events: relapse, death, second malignancy, or failure to achieve complete remission). The key secondary efficacy end point was overall survival. Other secondary end points included minimal residual disease remission and incidence of adverse events. Results: A total of 108 patients were randomized (median age, 5.0 years [interquartile range {IQR}, 4.0-10.5]; 51.9% girls; 97.2% M1 marrow) and all patients were included in the analysis. Enrollment was terminated early for benefit of blinatumomab in accordance with a prespecified stopping rule. After a median of 22.4 months of follow-up (IQR, 8.1-34.2), the incidence of events in the blinatumomab vs consolidation chemotherapy groups was 31% vs 57% (log-rank P < .001; hazard ratio [HR], 0.33 [95% CI, 0.18-0.61]). Deaths occurred in 8 patients (14.8%) in the blinatumomab group and 16 (29.6%) in the consolidation chemotherapy group. The overall survival HR was 0.43 (95% CI, 0.18-1.01). Minimal residual disease remission was observed in more patients in the blinatumomab vs consolidation chemotherapy group (90% [44/49] vs 54% [26/48]; difference, 35.6% [95% CI, 15.6%-52.5%]). No fatal adverse events were reported. In the blinatumomab vs consolidation chemotherapy group, the incidence of serious adverse events was 24.1% vs 43.1%, respectively, and the incidence of adverse events greater than or equal to grade 3 was 57.4% vs 82.4%. Adverse events leading to treatment discontinuation were reported in 2 patients in the blinatumomab group. Conclusions and Relevance: Among children with high-risk first-relapse B-ALL, treatment with 1 cycle of blinatumomab compared with standard intensive multidrug chemotherapy before allogeneic hematopoietic stem cell transplant resulted in an improved event-free survival at a median of 22.4 months of follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT02393859.


Asunto(s)
Anticuerpos Biespecíficos/uso terapéutico , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Inmunoterapia , Leucemia de Células B/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Anticuerpos Biespecíficos/efectos adversos , Antineoplásicos/efectos adversos , Niño , Preescolar , Terapia Combinada , Quimioterapia de Consolidación/efectos adversos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Estimación de Kaplan-Meier , Leucemia de Células B/mortalidad , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recurrencia , Factores de Riesgo , Tasa de Supervivencia
9.
Zhonghua Yi Xue Za Zhi ; 101(13): 926-933, 2021 Apr 06.
Artículo en Chino | MEDLINE | ID: mdl-33789373

RESUMEN

Objective: To classify and quantify IKZF1 mutant transcripts in B-cell acute lymphoblastic leukemia (B-ALL) by RNA sequencing (RNA-seq) and bioinformatics analysis. Methods: A cohort of 263 B-ALL cases was enrolled at Hebei Yanda Ludaopei Hospital from September 2018 to September 2020. An integrated bioinformatics pipeline was developed to adapt the classification and quantification of IKZF1 transcripts from RNA-seq and was applied to sequencing data of these cases. The IKZF1 mutant transcripts classified by RNA-seq analysis were compared with the qualitative reverse transcription PCR (RT-PCR). Results: IKZF1 mutant transcripts were identified in 53 B-ALL patients by RT-PCR and Sanger sequencing, among which IK6 and IK10 transcripts accounted for 67.9% (36/53) and 28.3% (15/53) respectively. Additionally, 2 patients were double positive for IK6 and IK10. RNA-seq analysis identified 51 patients with IKZF1 mutant transcripts. Compared with the RT-PCR result, the detection sensitivity and specificity of RNA-seq analysis reached 94.3% (50/53) and 99.5% (209/210), respectively. Among the 50 patients with IKZF1 mutant transcripts both in RNA-seq and RT-PCR analysis, the ratio of mutant transcripts to total IKZF1 transcripts in 6 patients was 0.14 (0.11, 0.35), which was significantly lower than that of the other 44 patients [0.88 (0.35, 0.97), Z=-3.945,P<0.001]. IKZF1 mutations mostly occurred in Ph+and Ph-like B-ALL, characterized by abnormal JAK-STAT pathway, and B-ALL with PAX5 translocation. Conclusions: Through the optimized bioinformatics analysis process, RNA-seq data can be used to classify and quantitatively analyze IKZF1 transcripts in B-ALL. Furthermore, the relative expression of mutant IKZF1 transcripts was found to cluster into two groups, and IKZF1 mutation was found often accompanied with PAX5 translocations.


Asunto(s)
Factor de Transcripción Ikaros , Leucemia-Linfoma Linfoblástico de Células Precursoras , Linfocitos B/metabolismo , Humanos , Factor de Transcripción Ikaros/genética , Factor de Transcripción Ikaros/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pronóstico , Isoformas de Proteínas , Transcriptoma
10.
Bone Joint J ; 103-B(3): 589-596, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33641424

RESUMEN

AIMS: Osteonecrosis (ON) can cause considerable morbidity in young people who undergo treatment for acute lymphoblastic leukaemia (ALL). The aims of this study were to determine the operations undertaken for ON in this population in the UK, along with the timing of these operations and any sequential procedures that are used in different joints. We also explored the outcomes of those patients treated by core decompression (CD), and compared this with conservative management, in both the pre- or post-collapse stages of ON. METHODS: UK treatment centres were contacted to obtain details regarding surgical interventions and long-term outcomes for patients who were treated for ALL and who developed ON in UKALL 2003 (the national leukaemia study which recruited patients aged 1 to 24 years at diagnosis of ALL between 2003 and 2011). Imaging of patients with ON affecting the femoral head was requested and was used to score all lesions, with subsequent imaging used to determine the final grade. Kaplan-Meier failure time plots were used to compare the use of CD with non surgical management. RESULTS: Detailed information was received for 85 patients who had developed ON during the course of their ALL treatment. A total of 206 joints were affected by ON. Of all joints affected by ON, 21% required arthroplasty, and 43% of all hips affected went on to be replaced. CD was performed in 30% of hips affected by ON. The majority of the hips were grade 4 or 5 at initial diagnosis of ON. There was no significant difference in time to joint collapse between those joints in which CD was performed, compared with no joint-preserving surgical intervention. CONCLUSION: There is a high incidence of surgery in young people who have received treatment for ALL and who have developed ON. Our results suggest that CD of the femoral head in this group of patients does not delay or improve the rates of femoral head survival. Cite this article: Bone Joint J 2021;103-B(3):589-596.


Asunto(s)
Necrosis de la Cabeza Femoral/cirugía , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Adolescente , Niño , Descompresión Quirúrgica , Femenino , Humanos , Masculino , Clasificación del Tumor , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Reino Unido , Adulto Joven
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 38-42, 2021 Feb.
Artículo en Chino | MEDLINE | ID: mdl-33554794

RESUMEN

OBJECTIVE: To analyze the outcomes of the children suffered from philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) treated with tyrosine kinase inhibitor (TKI) plus chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: 21 cases of firstly diagnosed Ph+ALL patients aged <12 year treated with Chinese Childhood Leukemia Group ALL 2008 (CCLG-ALL 2008) protocol form January 2008 and April 2015 were retrospectively analyzed.The patients were divided into two groups, one group was TKI+ chemotherapy group, the other group was allo-HSCT group. RESULTS: Among 21 patients, 17 were male and 4 were female with a median age of 8 years old (range, 4-12 years), the median follow-up time was 30 moths (range, 10-133 months). All the patients were treated with chemotherapy induced by the high-risk project of CCLG-ALL 2008. Among 14 patients treated with TKI plus chemotherapy, nine patients achieved complete remission. During 3 months after treatment, patients without complete molecular response or with the second complete remission and intensity desire of transplantation were treated with allo-HSCT, among 9 patients with allo-HSCT, six patients achieved long term survival. CONCLUSION: At TKI era, TKI combined with strong chemotherapy can make Ph+ ALL children achieve 5 years event-free survival as campared those treated with allo-HSCT. However, for the patients without complete molecular response persistently and relapsed they can still benefit from allo-HSCT.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Anciano , Niño , Femenino , Humanos , Lactante , Masculino , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inhibidores de Proteínas Quinasas , Estudios Retrospectivos
13.
Ann Hematol ; 100(4): 1003-1012, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33587155

RESUMEN

Chimeric antigen receptor (CAR) T cell therapy improves the remission rate of refractory/relapsed B-acute lymphoblastic leukemia (R/R B-ALL) patients, but the relapse rate remains high. Recent studies suggest patients who underwent post-chimeric antigen receptor T cell therapy hematopoietic stem cell transplantation (post- HSCT) would achieve durable remission and better survival, but this remains controversial. To this end, we conducted a meta-analysis to assess the role of post-HSCT in R/R B-ALL. The Cochrane Library, Embase, and PubMed were used to identify relevant studies; the latest search update was on July 05, 2020. We used the Cochran Q test and I-squared statistics to test for heterogeneity among the studies analyzed. The fixed model and random model were used to combine results when appropriate. We performed all statistical analyses with Stata 12, and P < 0.05 was considered statistically significant. We included 18 studies with 758 patients in the meta-analysis. Our results indicated that post-HSCT was associated with lower relapse rate (RR: 0.40, 95% CI: 0.32-0.50, P = 0.000), better overall survival (HR: 0.37, 95% CI: 0.19-0.71, P = 0.003), better leukemia-free survival (HR: 0.20, 95% CI: 0.10-0.40, P = 0.000). However, post-HSCT did not influence OS in Caucasians, and CAR-T cells with CD28 co-stimulation factor bridged to HSCT did not influence OS. Post-HSCT decreased the relapse rate and improved the long-term survival of R/R B-ALL patients. R/R B-ALL patients would benefit from post-HSCT after CAR-T cell therapy.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Inmunoterapia Adoptiva , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Terapia Recuperativa , Antígenos CD19/inmunología , Grupo de Ascendencia Continental Asiática , Supervivencia sin Enfermedad , Estudios Epidemiológicos , Grupo de Ascendencia Continental Europea , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnología , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Pronóstico , Recurrencia , Inducción de Remisión , Resultado del Tratamiento
14.
Int J Nanomedicine ; 16: 1127-1141, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33603372

RESUMEN

Background: Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children. It requires a long and rigorous course of chemotherapy treatments. 6-Mercaptopurine (6-MP) is one of the primary drugs used in chemotherapy. Unfortunately, its efficacy has been limited due to its insolubility, poor bioavailability and serious adverse effects. To overcome these drawbacks, we constructed 6-mercaptopurine (6-MP)-loaded nanomedicines (6-MPNs) with biodegradable poly(lactide-co-glycolide) (PLGA) to enhance the anticancer efficacy of 6-MP. Methods: We prepared the 6-MPNs using a double-emulsion solvent evaporation method, characterizing them for the physicochemical properties. We then investigated the plasma, intestinal region and other organs in Sprague Dawley (SD) rats for pharmacokinetics. Additionally, we evaluated its anticancer efficacy in vitro on the human T leukemia cell line Jurkat and in vivo on the ALL model mice. Results: The 6-MPNs were spherical in shape with uniform particle size and high encapsulation efficiency. The in vitro release profile showed that 6-MPNs exhibited a burst release that a sustained release phase then followed. The apoptosis assay demonstrated that 6-MPNs could improve the in vitro cytotoxicity in Jurkat cells. Pharmacokinetics profiles revealed that 6-MPNs had improved oral bioavailability. Tissue distribution experiments indicated that 6-MPNs increased the duodenum absorption of 6-MP, at the same time having a low accumulation of the toxic metabolites of 6-MP. The in vivo pharmacodynamics study revealed that 6-MPNs could prolong the survival time of the ALL model mice. The prepared 6-MPNs, therefore, have superior properties in terms of anticancer efficacy against ALL with reduced systemic toxicity. Conclusion: Our nanomedicines provide a promising delivery strategy for 6-MP; they offer a simple preparation method and high significance for clinical translation.


Asunto(s)
Mercaptopurina/química , Mercaptopurina/farmacocinética , Nanomedicina , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Administración Oral , Animales , Apoptosis , Proliferación Celular , Femenino , Humanos , Mercaptopurina/administración & dosificación , Ratones , Ratones Endogámicos NOD , Ratones SCID , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Ratas , Ratas Sprague-Dawley , Distribución Tisular , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
15.
Medicine (Baltimore) ; 100(6): e24630, 2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33578579

RESUMEN

RATIONALE: Mucormycosis is a rare fungal infection that typically occurs in immunosuppressed patients following chemotherapy or hematopoietic stem cell transplantation. PATIENT CONCERNS: An 11-year-old child with newly developed acute lymphoblastic leukemia suffered from the paroxysmal left chest pain, fever, and hemoptysis. DIAGNOSES: We made a histopathologic diagnosis aided by bronchoscopy techniques, which indicated invasive fungal hyphae that are characteristic of mucormycosis. INTERVENTIONS: The patient was treated with oral posaconazole and repeated bronchoscopy interventions for 4 months. OUTCOMES: The patient's clinical signs and symptoms and signs were no longer present. The prior lung lesions were also no longer observable using radiologic methods, and a 3-month follow-up with the patient showed no signs of mucormycosis recurrence. Finally, the patient was cured, when the cancer chemotherapy was stopped. Close follow-up for another 2 years showed no evidence of recurrence. LESSONS: Mucormycosis diagnosis is difficult as clinical and imaging findings vary. This case demonstrates that posaconazole monotherapy combined with bronchoscopy interventions may be a safe and effective treatment option for pediatric pulmonary mucormycosis.


Asunto(s)
Huésped Inmunocomprometido , Enfermedades Pulmonares Fúngicas/diagnóstico , Mucormicosis/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras , Administración Oral , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , Niño , Diagnóstico Diferencial , Fiebre/etiología , Humanos , Enfermedades Pulmonares Fúngicas/complicaciones , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Enfermedades Pulmonares Fúngicas/patología , Masculino , Mucormicosis/complicaciones , Mucormicosis/tratamiento farmacológico , Mucormicosis/patología , Triazoles/administración & dosificación , Triazoles/uso terapéutico
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