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Severe cytokine release syndrome (sCRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) have limited the widespread use of chimeric antigen receptor T (CAR T)-cell therapy. We designed a novel anti-CD19 CAR (ssCART-19) with a small hairpin RNA (shRNA) element to silence the interleukin-6 (IL-6) gene, hypothesizing it could reduce sCRS and ICANS by alleviating monocyte activation and proinflammatory cytokine release. In a post hoc analysis of two clinical trials, we compared ssCART-19 with common CAR T-cells (cCART-19) in relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). Among 87 patients, 47 received ssCART-19 and 40 received cCART-19. Grade ≥3 CRS occurred in 14.89% (7/47) of the ssCART-19 group versus 37.5% (15/40) in the cCART-19 group (p = 0.036). ICANS occurred in 4.26% (2/47) of the ssCART-19 group (all grade 1) compared to 15% (2/40) of the cCART-19 group. Patients in the ssCART-19 group showed comparable rates of treatment response (calculated with rates of complete remission and incomplete hematological recovery) were 91.49% (43/47) for ssCART-19 and 85% (34/40) for cCART-19 (p = 0.999). With a median follow-up of 21.9 months, cumulative nonrelapse mortality was 10.4% for ssCART-19 and 13.6% for cCART-19 (p = 0.33). Median overall survival was 37.17 months for ssCART-19 and 32.93 months for cCART-19 (p = 0.40). Median progression-free survival was 24.17 months for ssCART-19 and 9.33 months for cCART-19 (p = 0.23). These data support the safety and efficacy of ssCART-19 for r/r B-ALL, suggesting its potential as a promising therapy.
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Over past two years, a total of 39,918 hematopoietic stem cell transplantation (HSCT) cases were reported, with 18,194 and 21,714 transplants performed in 2022 and 2023, respectively. Autologous HSCT accounted for 6562 cases (31%) in 2022, while allogeneic HSCT comprised 12,632 cases (69%). In 2023, the number of allogeneic HSCTs exceeded 15,000, maintaining a 69% share. Participation in the 2022 and 2023 surveys included 193 and 212 transplantation teams, respectively, from 27 provinces, municipalities, or autonomous regions. The leading indication of HSCT was acute leukemia, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and mixed phenotype acute leukemia, with a total of 17,421 cases. AML was the most common disease (10,339, 38%) for allogeneic HSCT, which was followed by ALL (5925 cases, 21%). Peripheral blood emerged as the primary source of stem cell grafts, utilized in 54% of matched sibling donor transplants and 77% of haploidentical donor transplants. The BuCy-based conditioning regimen was the most prevalent, used in 53% of allogeneic HSCT cases in the past two years. This survey offers a comprehensive overview of the current HSCT landscape and serves as a valuable resource for clinical practice.
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The consensus in 2018 from The Chinese Society of Haematology (CSH) on the monitoring, treatment, and prevention of leukaemia relapse after allogeneic haematopoietic stem cell transplantation (HSCT) facilitated the standardization of clinical practices in China and progressive integration with the world. To integrate recent developments and further improve the consensus, a panel of experts from the CSH recently updated the following consensus: (1) integrate risk-adapted, measurable residual disease (MRD)-guided strategy on modified donor lymphocyte infusion (DLI) and interferon-α into total therapy, which was pioneered and refined by Chinese researchers; (2) provide additional evidence of the superiority of haploidentical HSCT (the dominant donor source in China) to matched HSCT for high-risk populations, especially for pre-HSCT MRD-positive patients; (3) support the rapid progress of techniques for MRD detection, such as next-generation sequencing (NGS) and leukaemia stem cell-based MRD detection; and (4) address the role of new targeted options in transplant settings. In conclusion, the establishment of a "total therapy" strategy represents a great step forward. We hope that the consensus updated by Chinese scholars will include the latest cutting-edge developments and inspire progress in post-HSCT relapse management.
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Subunidade alfa 2 de Fator de Ligação ao Core , Leucemia Mieloide Aguda , Humanos , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Estudos Retrospectivos , Pontuação de Propensão , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Proteína 1 Parceira de Translocação de RUNX1RESUMO
It was previously believed that patients with Ph-like ALL had poorer prognosis compared with other B-ALL subgroups due to resistance to conventional chemotherapy and lack of targeted drugs. CAR-T therapy has been successfully applied in the treatment of relapsed and refractory B-ALL. Currently, there are few data on whether CAR-T therapy can alter the outcome of Ph-like ALL. Here we included 17 Ph-like, 23 Ph+ and 51 other B-ALL patients, who received autologous CAR T-cell therapy and subsequently allogenic stem cell transplantation. Patients in the Ph-like group and B-ALL-others group were younger that those in the Ph+ group (P=0.001). Ph-like and Ph+ ALL patients showed higher white blood cell counts at diagnosis (P=0.025). The percentage of patients with active disease before receiving CAR T-cells infusion was 64.7%, 39.1% and 62.7% in the Ph-like, Ph+ and B-ALL-others groups. The response rates to CAR-T therapy were 94.1% (16/17), 95.6% (22/23) and 98.0% (50/51) in the Ph-like, Ph+ and B-ALL-others groups. Measurable residual disease negative CR was achieved in 64.7% (11/17), 60.9% (14/23) and 54.9% (28/51) in the Ph-like, Ph+ and B-ALL-others groups, respectively. The estimated rates of 3-year overall survival (65.9%±16.5%, 59.7%±10.5% and 61.6%±7.3%, P=0.758) and 3-year relapse-free survival (59.8%±14.8%, 63.1%±10.5% and 56.3%±7.1%, P=0.764) were comparable among the Ph-like, Ph+ and B-ALL-others groups. Estimated 3-year cumulative relapse rate was 7.8%±0.6%, 23.4%±0.9% and 29.0%±0.4% (P=0.241). Our findings suggest that CART followed by allo-HSCT results in a comparable prognosis in Ph-like ALL and other high-risk B-ALL.Trial registration ClinicalTrials. gov, NCT03275493, Registered on September 7, 2017, prospectively registered and NCT03614858, Registered on August 3, 2018, prospectively registered.
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Between 2020 and 2021, 31,525 hematopoietic stem cell transplantations (HSCTs) were reported to the Chinese Blood and Marrow Transplantation Registry Group throughout mainland China. In this report, we describe the activity and current trends for HSCT in China during the SARS-CoV-2 pandemic. In 2020, a total of 13,415 cases of HSCT were reported from 166 transplantation teams, and 75% (10,042 cases) were allogeneic HSCTs. In 2021, a total of 18,110 cases of HSCT were reported from 174 transplantation teams, and 70% (12,744 cases) were allogeneic HSCTs. Haploidentical donor (HID) transplantation accounted for 63% (7977 cases) of allogeneic HSCTs in 2021. The most common indications for allogeneic HSCT for malignant disease were acute myeloid leukemia (37%) and acute lymphoblastic leukemia (23%), and the largest proportion of nonmalignant disease comprised aplastic anemia (13%). The peripheral blood stem cell source accounted for 41% of HIDs and 75% of matched sibling donors. The BuCy-based regimen (57%) was the most popular conditioning regimen for allogeneic HSCT, followed by the BuFlu-based regimen (28%) and total body irradiation-based regimen (11%). This survey provides comprehensive information about the current activities and might benefit clinical physicians' decision planning for HSCT.
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COVID-19 , Transplante de Células-Tronco Hematopoéticas , Humanos , SARS-CoV-2 , Medula Óssea , População do Leste Asiático , Pandemias , COVID-19/epidemiologia , Sistema de RegistrosRESUMO
Mixed phenotype acute leukemia (MPAL) is a subtype of leukemia in which lymphoid and myeloid markers are co-expressed. Knowledge regarding the genetic features of MPAL is lacking due to its rarity and heterogeneity. Here, we applied an integrated genomic and transcriptomic approach to explore the molecular characteristics of 176 adult patients with MPAL, including 86 patients with T-lymphoid/myeloid MPAL (T/My MPAL-NOS), 42 with Ph+ MPAL, 36 with B-lymphoid/myeloid MPAL (B/My MPAL-NOS), 4 with t(v;11q23), and 8 with MPAL, NOS, rare types. Genetically, T/My MPAL-NOS was similar to B/T MPAL-NOS but differed from Ph+ MPAL and B/My MPAL-NOS. T/My MPAL-NOS exhibited higher CEBPA, DNMT3A, and NOTCH1 mutations. Ph+ MPAL demonstrated higher RUNX1 mutations. B/T MPAL-NOS showed higher NOTCH1 mutations. By integrating next-generation sequencing and RNA sequencing data of 89 MPAL patients, we defined eight molecular subgroups (G1-G8) with distinct mutational and gene expression characteristics. G1 was associated with CEBPA mutations, G2 and G3 with NOTCH1 mutations, G4 with BCL11B rearrangement and FLT3 mutations, G5 and G8 with BCR::ABL1 fusion, G6 with KMT2A rearrangement/KMT2A rearrangement-like features, and G7 with ZNF384 rearrangement/ZNF384 rearrangement-like characteristics. Subsequently, we analyzed single-cell RNA sequencing data from five patients. Groups G1, G2, G3, and G4 exhibited overexpression of hematopoietic stem cell disease-like and common myeloid progenitor disease-like signatures, G5 and G6 had high expression of granulocyte-monocyte progenitor disease-like and monocyte disease-like signatures, and G7 and G8 had common lymphoid progenitor disease-like signatures. Collectively, our findings indicate that integrative genomic and transcriptomic profiling may facilitate more precise diagnosis and develop better treatment options for MPAL.
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Leucemia Mieloide Aguda , Transcriptoma , Humanos , Doença Aguda , Fenótipo , GenômicaRESUMO
Background: Ocular graft-versus-host disease (oGVHD) is one of the complications after allogeneic hematopoietic stem cell transplantation (HSCT), which impairs the quality of life and may indicate poor prognosis. In this retrospective study, the aim was to investigate the characteristics of ocular surface after HSCT, and analyze the risk factors related to the severity of ocular surface lesions. Methods: 248 post-HSCT patients were enrolled in this retrospective study. Subjects were divided into no lesion group, mild lesion group and severe lesion group, according to the severity of ocular surface lesions. The correlations between grades of ocular surface lesions and gender, age, primary disease, donor source, human leukocyte antigen (HLA) type, kinship, donor-recipient relationship, blood type, source of stem cell and systemic GVHD were analyzed. Results: The median scores of corneal epitheliopathy, lid margin lesions and meibomian gland loss were 3, 6 and 2 points, respectively. The grade of corneal epitheliopathy was related to donor source (P<0.001), kinship (P=0.033), HLA-matching (P<0.001), and systemic GVHD (P=0.007), especially oral GVHD (P<0.001) and liver GVHD (P=0.002). The grade of lid margin lesions was related to donor source (P=0.019), HLA-matching (P=0.006), and systemic GVHD (P=0.013), especially skin GVHD (P=0.019) and oral GVHD (P=0.019). The grade of meibomian gland loss was related to age (P=0.035) and gastrointestinal GVHD (P=0.007). The grade of corneal epitheliopathy after HSCT was related to the lid margin lesion score (P<0.001). Conclusions: The occurrence and development of ocular GVHD are mostly accompanied by the history of systemic GVHD. While in few cases, ocular surface lesions related to GVHD can be observed prior to the rejection of other tissues and organs. Severe corneal epitheliopathy occurs in patients with severe lid margin lesions in ocular GVHD. The lesions of corneal epithelium and lid margin are milder in HLA partially matching transplantation.
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Corneal perforation is a rare and serious complication of ocular graft-versus-host disease (oGVHD) patients. This study was to retrospectively report seven corneal perforation patients after allogeneic hematopoietic stem cell transplantation (HSCT). Demographic, hematologic, and ophthalmological data of patients were clarified in detail. Nine eyes of seven corneal perforation patients were clarified (Cases 3 and 6 were bilateral and the others are unilateral). All the cases had other affected GVHD organs, especially skin involvement. The duration between HSCT and corneal perforation was usually long with 21 (17-145) months as median interval, whereas the duration between oGVHD diagnosis and corneal perforation was relatively shorter with 4 (2-81) months as median interval. Most patients presented to ophthalmology department with poor visual acuity, BUT and Schirmer's test. Eyelid marginal hyperemia and irregularity were observed in most corneal perforation eyes. Keratoplasty or conjunctival flap covering (CFC) surgeries was performed after corneal perforation. After a long-term follow-up for most patients (median 21 months, range: 2-86 months), only two eyes of two patients (22.22%) had a final BCVA of 20/100 or better. Patients involved in both cutaneous GVHD and blepharitis indicate the aggressive development of oGVHD. Early diagnosis, long-term follow-up, and effective multi-disciplinary treatments for oGVHD patients are essential. Corticosteroids and immunosuppressor remain essential, whereas the use of topical corticosteroids should be carefully considered in corneal ulceration patients. In addition, appropriate surgeries should be performed to control oGVHD development in time.
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The 7 + 3 regimen is the front-line induction chemotherapy in patients with newly diagnosed acute myeloid leukemia, with a response rate of 60-80%. But it's not suitable for all patients especially old/unfit patients because of a higher treatment related toxicity. Therefore, safer and more effective induction therapies are required. In this retrospective study, 50 patients with newly diagnosed acute myeloid leukemia received decitabine combined with HAAG (homoharringtonine, aclarubicin, low-dose cytarabine and G-CSF) as induction chemotherapy. Complete remission (CR) rate was 96% (48/50) and overall response rate was 100%. Of note, All 7 patients harboring FLT3-ITD mutation achieved CR. The median overall survival (OS) was 40.0 months (range 2.0, 58.0). The OS at 1, 3, and 5 years were 75.3%, 54.2%, and 49.3%. The median relapse free survival (RFS) was 38.0 months (range 2.0, 58.0). The RFS at 1, 3, and 5 years were 67.3%, 48.9%, and 45.1%. The OS and RFS of patients who received hematopoietic stem cell transplantation (HSCT) were significantly higher than those who did not undergo HSCT (p=0.017; 0.016). The incidence of grade 3-4 neutropenia and thrombocytopenia was 84% and 88%. Meanwhile, the incidence of grade 3-4 infection and bleeding was only 16% and 6%. There was no early death. In conclusion, DAC+HAAG regimen is effective and well-tolerated as induction therapy in patients with newly diagnosed AML.
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Patients with relapsed/refractory acute myeloid leukemia (R/R AML) often show resistance to chemotherapy and have dismal outcomes. Therefore, it is urgent to develop new treatment strategies to address this problem. With tremendous achievement of chimeric antigen receptor T cells (CAR-T) therapy against B-cell malignancies, many efforts have been devoted to developing CAR-T therapy for R/R AML but with limited success, in part owing to a lack of specific targets. C-type lectin-like molecule-1 (CLL-1) is highly expressed on AML blasts with no expression on normal hematopoietic stem cells, which makes it an ideal target of immunotherapy for AML. Here, we report 2 R/R AML patients who relapsed after allogeneic stem cell transplantation and failed multiline salvage therapies including anti-CD38 CAR-T therapy, but were successfully treated with PD-1 silenced anti-CLL-1 CAR-T therapy. Both patients achieved molecular complete remission with incomplete hematologic recovery at 28 days of evaluation after CLL-1 CAR-T cell infusion. Cytokine release syndrome in cases 1 and 2 were grade 1 and 2, respectively. At the last follow-up, cases 1 and 2 had maintained continuous remission for 8 and 3 months, respectively. Our results demonstrated that CLL-1 CAR-T cells might be an effective and safe salvage therapy for AML patients with posttransplant relapse.
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Patients with relapsed/refractory early T-cell precursor lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) respond poorly to traditional therapy and have dismal prognosis. CD7 is a promising therapeutic targets for chimeric antigen receptor modified T cell therapy (CART) due to its widely expression in almost all T-cell malignancies. Here we present the anti-CD7 CART therapy in a 11-year-old male with TP53 mutated relapsed/refractory ETP-ALL/LBL. The patient suffered second relapse after haploidentical hematopoietic stem cell transplantation, showing resistance to 4 lines salvage therapies including venetoclax. Nanobody derived CD7-CART cells were manufactured by co-transducing CAR-T cells with a CD7 protein expression blocker. 70.5% of blasts (CD7 expression: 92.6%) and extensive extramedullary disease (mediastinal mass, enlarged lymph nodes and spleen) were observed prior to CD7-CART-cell therapy. A total of 5 × 106/kg donor-derived CD7-CART-cells were infused. Hematological and extramedullary remission were both achieved, with persistence of CD7-CART-cells be detected until the last followup at 96th days after the infusion. Reversible adverse effects including grade 3 cytokine release syndrome and macrophage activation syndrome were observed. This case demonstrated that CD7-CART was a potent and safe salvage therapy in relapsed/refractory ETP-ALL/LBL patient with high tumor burden.Trial registration: ClinicalTrials. gov, NCT04785833 , Registered on March 8, 2021, prospectively registered.
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OBJECTIVE: To investigate the characteristics of platelet antibody in patients with hematological diseases, so as to research the effect of immunized platelet transfusion refractoriness (PTR) on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recepients with malignant hematological diseases patients. METHODS: The clinical data of platelet antibody positive patients tested by Capture-P in the First Affiliated Hospital of Soochow University from July 1, 2014 to July 1, 2019 were retrospectively analyzed, including sex, age, disease, platelet transfusion assessments, CD34+ cells, transplant prognosis, and so on. RESULTS: In 5 years, 913 (7.28%) hematologic patients with platelet antibody positive were identified, the detection rate of females (513 cases) were higher than males (400 cases). Among the 913 patients, the antibody positive rates of 520 patients with malignant hematological diseases (acute myeloid leukemia, acute lymphoblastic leukemia and myelodysplastic syndrome) showed significantly statistical different (10.27%, 8.01%, and 7.20%) (P<0.01), and the positive rate of the acute myeloid leukemia of those patients was higher than myelodysplastic syndrome patients(α<0.0125). There were 35 cases diagnosed as immunized PTR before allo-HSCT, the platelet increments, 14 h correct count increment, progression-free survival rate and overall survival rate of those patients were significantly lower than those in negative transfusion effective patients (P<0.01), while the percentage of ABO matching was significantly higher (α<0.0125). CONCLUSION: The positive rate of platelet antibody identification is high in females and acute myeloid leukemia patients, and immunized PTR caused by antibody is a risk factor for poor prognosis of allo-HSCT in malignant hematological disease patients.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Feminino , Humanos , Masculino , Transfusão de Plaquetas , Estudos RetrospectivosRESUMO
EP300-ZNF384-positive B cell acute lymphoblastic leukemia (B-ALL) patients are reported to have a unique immunophenotype with high expression of CD19 and CD22, weak expression of CD20 and aberrant expression of CD13 and/or CD33, sensitivity to chemotherapy and a favorable outcome. To date, the cases of only 53 patients have been reported, albeit few reports on salvage therapy when conventional chemotherapies failed. Here, we describe two relapsed and refractory adult B-ALL patients with EP300-ZNF384 who achieved second remission through tandem CD19/CD22 CAR T-cell therapy. Grade 3 and 2 cytokine release syndrome were observed in cases 1 and 2, respectively. No immune effector cell-associated neurotoxicity syndrome was detected. Both patients underwent consolidate haploidentical hematopoietic stem cell transplantation (HSCT), and each maintained measurable residual disease-negative remission for 14 and 13 months, respectively. Our study suggests that CD19/CD22 CAR T-cell therapy bridging to allogeneic HSCT may be a viable option for EP300-ZNF384-positive B-ALL.
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OBJECTIVE: To explore the role of chidamide, decitabine plus priming regimen in the salvage treatment of relapsed/refractory acute myeloid leukemia. METHODS: A clinical trial was conducted in relapsed/refractory acute myeloid leukemia patients using chidamide, decitabine, cytarabine, idarubicin, and granulocyte-colony stimulating factor, termed CDIAG, a double epigenetic priming regimen. RESULTS: Thirty-five patients were recruited. Three patients received 2 treatment cycles. In 32 evaluable patients and 35 treatment courses, the completed remission rate (CRR) was 42.9%. The median OS time was 11.7 months. The median OS times of responders were 18.4 months, while those of nonresponders were 7.4 months (P = 0.015). The presence of RUNX1 mutations was associated with a high CRR but a short 2-year OS (P = 0.023) and PFS (P = 0.018) due to relapse after treatment. The presence of IDH mutations had no effect on the remission rate (80.0% vs. 73.3%), but showed a better OS (2-year OS rate: 100.0% vs. 28.9%). Grade 3/4 nonhematological adverse events included pneumonia, hematosepsis, febrile neutropenia, skin and soft tissue infection and others. CONCLUSION: The double epigenetic priming regimen (CDIAG regimen) showed considerably good antileukemia activity in these patients. Adverse events were acceptable according to previous experience. The study was registered as a clinical trial. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/, identifier:NCT03985007.
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The consensus recommendations in 2018 from The Chinese Society of Hematology (CSH) on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation (allo-HSCT) facilitated the standardization of clinical practices of allo-HSCT in China and progressive integration with the world. There have been new developments since the initial publication. To integrate recent developments and further improve the consensus, a panel of experts from the CSH recently updated the consensus recommendations, which are summarized as follows: (1) there is a new algorithm for selecting appropriate donors for allo-HSCT candidates. Haploidentical donors (HIDs) are the preferred donor choice over matched sibling donors (MSDs) for patients with high-risk leukemia or elderly patients with young offspring donors in experienced centers. This replaces the previous algorithm for donor selection, which favored MSDs over HIDs. (2) Patients with refractory/relapsed lymphoblastic malignancies are now encouraged to undergo salvage treatment with novel immunotherapies prior to HSCT. (3) The consensus has been updated to reflect additional evidence for the application of allo-HSCT in specific groups of patients with hematological malignancies (intermediate-risk acute myeloid leukemia (AML), favorable-risk AML with positive minimal residual disease, and standard-risk acute lymphoblastic leukemia). (4) The consensus has been updated to reflect additional evidence for the application of HSCT in patients with nonmalignant diseases, such as severe aplastic anemia and inherited diseases. (5) The consensus has been updated to reflect additional evidence for the administration of anti-thymocyte globulin, granulocyte colony-stimulating factors and post-transplantation cyclophosphamide in HID-HSCT.
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Seleção do Doador/métodos , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , China/epidemiologia , Neoplasias Hematológicas/epidemiologia , Humanos , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Sociedades Médicas , Transplante Homólogo/métodosRESUMO
PURPOSE: Genetic changes have prognostic significance in cytogenetically normal acute myeloid leukemia (CN-AML). We set out to evaluate the prognostic of 6 gene mutations in CN-AML. METHODS: We performed a mutational analysis and evaluated prognostic findings of six genes (NPM1, CEBPA, DNMT3A, FLT3-ITD, FLT3-TKD, and C-KIT) in 428 CN-AML patients at our center over 10 years. RESULTS: A total of 282 patients (65.9%) had at least one gene mutation, and the mutation frequencies were as follows: 29.7% (NPM1), 24.1% (CEBPA), 20.1% (FLT3-ITD), 4.0% (FLT3-TKD), 11.9% (DNMT3A), and 4.7% (C-KIT). Multivariate analysis indicated that FLT3-ITDmut and CEBPAwt were independent risk factors correlated with poor overall survival (OS) and disease-free survival (DFS) of CN-AML. Compared with patients who received chemotherapy as consolidation, hematopoietic stem cell transplantation (HSCT) significantly improved OS of CN-AML patients. For standard/high risk patients, HSCT improved both OS and DFS. Combined analysis showed that patients with CEBPAmut/FLT3-ITDwt had the best prognosis, and patients with CEBPAwt/FLT3-ITDmut had the worst OS, with 3-year OS of only 44%. In 212 patients who received HSCT, FLT3-ITD/CEBPA mutations and minimal residual disease (MRD) were correlated with OS and DFS in univariate analysis. CONCLUSIONS: We found that HSCT significantly improves the prognosis of standard/high risk CN-AML patients with superior OS and DFS. Molecular marker analyses, especially combined analysis of the FLT3-ITD and CEBPA status revealed a correlation with the prognosis of CN-AML. For patients who have received HSCT, MRD before transplantation was a strong prognostic marker predicting patient outcome.
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Proteínas Estimuladoras de Ligação a CCAAT/genética , Transplante de Células-Tronco Hematopoéticas/mortalidade , Leucemia Mieloide Aguda/mortalidade , Mutação , Neoplasia Residual/mortalidade , Sequências de Repetição em Tandem , Tirosina Quinase 3 Semelhante a fms/genética , Adolescente , Adulto , Idoso , Citogenética , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/genética , Neoplasia Residual/patologia , Neoplasia Residual/terapia , Nucleofosmina , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Transplante Homólogo , Adulto JovemRESUMO
OBJECTIVE: To investigate the prognosis of patients with adult B-cell acute lymphoblastic leukemia (B-ALL) accompanied with Ikaros family zinc finger 1 (IKZF1) mutation, and to explore the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in improving the clinical outcome of patients. METHODS: The clinical data of 164 adult B-ALL patients who received IKZF-1 mutation detection by capillary electrophoresis of bone marrow were collected, and the relationship between the IKZF-1 gene mutation and the prognosis of adult B-ALL patients was analyzed. RESULTS: Among 164 adult B-ALL patients, the patients with IKZF-1 mutation (IKZF-1+) were 80 cases, while the patients without IKZF-1 mutation (IKZF-1-) were 84 cases. Among 80 IKZF-1 positive patients, according to the treatment method after complete remission these patients were divided into HSCT group (48 cases) and chemotherapy group (32 cases). Analysis showed that the 3-year overall survival (OS) and leukemia-free survival (LFS) rates in the IKZF1+ group were much lower. The OS and LFS rate in transplantation group were 50.3%±8.3%, 41.6%±8.5%; the OS and LFS rates in the chemotherapy group were 33.7%±12.8%, 31.5%±9.5%, which were lower than those in the IKZF1- group (the transplantation group: 79.5%±7.6%, 64.0%±8.4%; the chemotherapy group: 54.4%±9.9%, 40.6%±9.6% respectirely (Pï¼0.05). Among 80 B-ALL patients with IKZF-1- mutation, the 3-year OS and LFS rates were significantly higher in the transplantation group (55.3%±7.5%, 48.3%±7.6%) than those in the chemotherapy group (32.9%±11.8%, 28.4%±10.3%) with IKZF1 mutation (Pï¼0.05). CONCLUSION: IKZF1 mutation is an adverse prognostic factor for adult B-ALL patients, However, allo-HSCT significantly improves the OS and LFS of patients and also their clinical outcomes.
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Fator de Transcrição Ikaros/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Linfócitos B , Transplante de Células-Tronco Hematopoéticas , Humanos , Mutação , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Prognóstico , Estudos Retrospectivos , Dedos de ZincoRESUMO
Background: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is associated with high rates of treatment failure and poor outcome. Activation of ABL/Src family kinases is found in ~10% of Ph-like ALL, which can be therapeutically targeted by tyrosine kinase inhibitors. LYN is a member of the ABL/Src-tyrosine kinase family. Somatic LYN rearrangements are found in 5 cases of hematopoietic malignancies so far, although none of them were treated with tyrosine kinase inhibitors. Case presentation: A 6-year-old boy with relapsed B-ALL had no response to reinduction chemotherapy. He was then treated with the ABL1 tyrosine kinase inhibitor dasatinib and achieved complete remission within 2 weeks. Haploidentical allogenic stem cell transplantation (allo-HSCT) was subsequently performed and maintenance therapy with dasatinib initiated 8 weeks post-transplantation. He has been in minimal residual disease negative remission for 10 months after allo-HSCT. Result: His bone marrow karyotype showed a balanced translocation between chromosomes 8 and 17, leading to a NCOR1-LYN fusion gene confirmed with sequencing. Conclusion: Although LYN overexpression is described in many AML and B-ALL patients, intragenic LYN rearrangement is a rare event. For the first time, we present evidence that dasatinib is effective in treating a pediatric B-ALL with NCOR-LYN fusion.