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1.
J Transl Med ; 22(1): 275, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38481248

RESUMEN

BACKGROUND: The prognostic significance of myelofibrosis (MF) grade in patients with myelodysplastic syndrome (MDS) following an allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains elusive. METHODS: We retrospectively analyzed data from 153 patients with MDS who underwent allo-HSCT and divided the patients into the MF-0/1 (N = 119) and MF-2/3 (N = 34) cohorts to explore the impact of MF on outcomes of allo-HSCT. RESULTS: The 2-year rates of relapse, non-relapse mortality (NRM), overall survival (OS), and progression-free survival (PFS) were 10.9% (95% confidence interval [CI] 5.9%-17.7%), 16.3% (95% CI 10.2%-23.6%), 76.6% (95% CI 69.0%-85.1%), and 72.8% (95% CI 65.0%-81.5%) in the MF-0/1 cohort, and 16.9% (95% CI 5.8%-32.9%), 14.7% (95% CI 5.3%-28.7%), 71.8% (95% CI 57.6%-89.6%), and 68.4% (95% CI 53.6%-87.2%) in the MF-2/3 cohort, respectively. No significant difference in the outcomes of allo-HSCT was observed between the two cohorts. Both univariate and multivariate analyses confirmed that MF-2/3 in patients with MDS had no effect on the prognosis of transplantation. In addition, major/bidirectional ABO blood type between donors and recipients was an independent risk factor for OS (hazard ratio [HR], 2.55; 95% CI 1.25-5.21; P = 0.010) and PFS (HR, 2.21; 95% CI 1.10-4.42; P = 0.025) in the multivariate analysis. In the subgroup of patients diagnosed with MDS with increased blasts (MDS-IB), it was consistently demonstrated that the clinical outcomes of the MF-2/3 cohort were comparable with those of the MF-0/1 cohort. The risk factors for OS and PFS in patients with MDS-IB were non-complete remission at transplantation and major/bidirectional ABO blood type. CONCLUSIONS: In conclusion, MF grade had no significant effect on prognosis of allo-HSCT in patients diagnosed with MDS. Major/bidirectional ABO blood type should be carefully considered in the context of more than one available donor.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Síndromes Mielodisplásicos , Mielofibrosis Primaria , Humanos , Mielofibrosis Primaria/complicaciones , Mielofibrosis Primaria/terapia , Estudios Retrospectivos , Trasplante Homólogo , Síndromes Mielodisplásicos/terapia
2.
Cell Transplant ; 33: 9636897231225821, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38270130

RESUMEN

KMT2A rearrangement (KMT2A-r) in patients with acute myeloid leukemia (AML) is associated with poor outcomes; the prognostic factors after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain unclear. We investigated 364 adults with AML who underwent allo-HSCT between April 2016 and May 2022, and 45 had KMT2A-r among them. Propensity score analysis with 1:1 matching and the nearest neighbor matching method identified 42 patients in KMT2A-r and non-KMT2A-r cohorts, respectively. The 2-year overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and non-relapsed mortality rates of patients with KMT2A-r (n = 45) were 59.1%, 49.6%, 41.5%, and 8.9%, respectively. Using propensity score matching, the 2-year OS rate of patients with KMT2A-r (n = 42) was lower than that of those without KMT2A-r (n = 42; 56.1% vs 88.1%, P = 0.003). Among patients with KMT2A-r (n = 45), the prognostic advantage was exhibited from transplantation in first complete remission (CR1) and measurable residual disease (MRD) negative, which was reflected in OS, RFS, and CIR (P < 0.001, P < 0.001, and P = 0.002, respectively). Furthermore, patients with AF6 had poorer outcomes than those with AF9, ELL, and other KMT2A-r subtypes (P = 0.032, P = 0.001, and P = 0.001 for OS, RFS, and CIR, respectively). However, no differences were found in the OS, RFS, and CIR between patients with KMT2A-r with and without mutations (all P > 0.05). Univariate and multivariate analyses revealed that achieving CR1 MRD negative before HSCT was a protective factor for OS [hazard ratio (HR) = 0.242, P = 0.007], RFS (HR = 0.350, P = 0.036), and CIR (HR = 0.271, P = 0.021), while AF6 was a risk factor for RFS (HR = 2.985, P = 0.028) and CIR (HR = 4.675, P = 0.004). The prognosis of patients with KMT2A-r AML was poor, particularly those harboring AF6-related translocation; however, it is not associated with the presence of mutations. These patients can benefit from achieving CR1 MRD negative before HSCT.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Adulto , Humanos , Pronóstico , Análisis por Conglomerados , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Análisis Multivariante
4.
Risk Manag Healthc Policy ; 16: 2907-2913, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38155846

RESUMEN

Objective: In the first half of 2022, Shanghai faced the challenge of an emerging wave of epidemics caused by the Omicron variant. In response, 48 hospitals, spanning municipal and district levels, were rapidly converted into designated hospitals. This case study focuses on the South Branch of Renji Hospital, School of Medicine, Shanghai Jiaotong University, as one such designated hospital. Methods: Facing unprecedented challenges without prior experience, we devised a strategic approach to deploy ICU nurses effectively. This approach involved crisis event gradation, establishing a human resources pool, and classifying nursing staff based on qualifications and proficiencies. Results: By May 11, 2022, all 48 designated hospitals were operational. The South Branch of Renji Hospital treated 3310 Omicron-infected patients between April 7 and June 21, 2022, including 115 critically ill patients in a 38-bed ICU. We meticulously assigned 136 nurses, distributed as follows: Grade A 12.5%, Grade B 12.5%, Grade C 40%, and Grade D 35%, with three specialized nursing managers. Nurses worked tirelessly in 4-hour shifts, wearing full protective gear. Remarkably, the hospital maintained a flawless record, with no nursing-related adverse events and zero patient mortality in the ICU. Conclusion: Effective management of ICU nursing personnel is associated with patient safety. Strategic rostering and placement of ICU nurses in designated hospitals optimize resource utilization, enhancing service effectiveness and working conditions. This technique is a crucial resource for hospitals facing unforeseen public health crises requiring rapid ICU nurse resource allocation and management.

5.
Sci Rep ; 13(1): 15901, 2023 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-37741848

RESUMEN

Recent studies have shown great performance of Transformer-based models in long-term time series forecasting due to their ability in capturing long-term dependencies. However, Transformers have their limitations when training on small datasets because of their lack in necessary inductive bias for time series forecasting, and do not show significant benefits in short-time step forecasting as well as that in long-time step as the continuity of sequence is not focused on. In this paper, efficient designs in Transformers are reviewed and a design of decomposing residual convolution neural networks or DRCNN is proposed. The DRCNN method allows to utilize the continuity between data by decomposing data into residual and trend terms which are processed by a designed convolution block or DR-Block. DR-Block has its strength in extracting features by following the structural design of Transformers. In addition, by imitating the multi-head in Transformers, a Multi-head Sequence method is proposed such that the network is enabled to receive longer inputs and more accurate forecasts are obtained. The state-of-the-art performance of the presented model are demonstrated on several datasets.

7.
Br J Haematol ; 202(3): 608-622, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37306071

RESUMEN

Most events that limit life expectancy after allogeneic haematopoietic stem cell transplantation (allo-HSCT) occur within the first 2 years; however, treatment outcomes in long-term survivors who survive for at least 2 years post-HSCT without relapse are yet to be elucidated. To explore the life expectancy trends and late complications and to assess the main mortality-related factors, we investigated the characteristics of patients who received allo-HSCT for haematological malignancies from 2007 to 2019 in our centre and survived in remission for 2 years. A cohort of 831 patients was enrolled; of these, 508 received grafts from haploidentical-related donors (61.1%). The estimated overall survival rate at 10 years was 91.9% (95% confidence interval [CI], 89.8-93.5), which was affected by prior grade III-IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 2.98; 95% CI, 1.47-6.03; p = 0.002) and severe chronic GVHD (HR, 3.60; 95% CI, 1.93-6.71; p < 0.001). The probability of late relapse and non-relapse mortality at 10 years was 8.7% (95% CI, 6.9-10.8) and 3.6% (95% CI, 2.5-5.1) respectively. The top cause of late mortality was relapsed (49.0%). Projected long-term survival in 2-year disease-free survivors following allo-HSCT was excellent. Strategies should be implemented to minimise the late death-specific hazards in recipients.


Asunto(s)
Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Humanos , Recurrencia Local de Neoplasia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/etiología , Neoplasias Hematológicas/complicaciones , Modelos de Riesgos Proporcionales , Supervivencia sin Enfermedad , Estudios Retrospectivos
8.
Front Pediatr ; 11: 1057574, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37063666

RESUMEN

Gaucher disease (GD) is an inherited lysosomal storage disease caused by mutations in the glucocerebrosidase gene. The decrease of glucocerebrosidase activity in lysosomes results in the accumulation of its substrate glucocerebroside in the lysosomes of macrophages in organs such as the liver, spleen, bones, lungs, brain and eyes, and the formation of typical storage cells, namely "Gaucher cells", leading to lesions in the affected tissues and organs. Hepatosplenomegaly, bone pain, cytopenia, neurological symptoms, and other systemic manifestations are common in clinical practice. Most pediatric patients have severe symptoms. Early diagnosis and treatment are crucial to improve the curative effect and prognosis. However, due to the low incidence of this disease, multi-system involvement in patients, and diverse clinical manifestations, multidisciplinary teamwork is needed for comprehensive evaluation, diagnosis and treatment. In this study, we reported 2 cases of different types of GD who were diagnosed, treated and followed up by multidisciplinary collaboration in infancy.

9.
Bone Marrow Transplant ; 58(7): 801-810, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37072477

RESUMEN

Relapse remains the leading cause of death in acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem-cell transplantation (allo-HSCT), limiting the efficacy of allo-HSCT. Thus, the ability to identify high-risk patients in a manner that permits early intervention has the potential to improve survival outcomes. We retrospectively enrolled 414 younger patients (aged 14-60 years) with AML who received allo-HSCT between January 2014 and May 2020. From June 2020 to June 2021, 110 consecutive patients were included prospectively in the validation cohort. The primary outcome was early relapse (relapse within 1 year). The cumulative incidence of early relapse after allo-HSCT was 11.8%. The overall survival rate for patients who relapsed within 1-year was 4.1% at 3 years after relapse. After multivariable adjustment, statistically significant associations between primary resistance, pre-transplantation measurable residual disease, DNMT3A mutation, or white blood cell count at diagnosis and early relapse were observed. An early relapse prediction model was developed based on these factors and the model performed well. Patients deemed to have a high risk or a low risk of early relapse had early relapse rates of 26.2% and 6.8%, respectively (P < 0.001). The prediction model could be used to help identify patients at risk for early relapse and to guide personalized relapse prevention.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Estudios Retrospectivos , Trasplante Homólogo , Enfermedad Crónica , Recurrencia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia Mieloide Aguda/genética
10.
Infect Drug Resist ; 15: 6893-6905, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36465805

RESUMEN

Background: Bloodstream infection (BSI) is a common and serious complication that may lead to high mortality during the different phases after hematopoietic stem cell transplant (HSCT). We investigated BSI in patients undergoing HSCT to provide an appropriate clinical anti-infection experience and improve the prognosis of recipients with BSI after HSCT. Methods: A total of 105 patients with BSI after HSCT at our center from January 2015 to June 2020 were included in this retrospective study. We analyzed the clinical and microbiological data, and the risk factors for mortality at 3 months after BSI. Results: Of the 1141 HSCT recipients, 105 (9.2%) patients presented with 122 episodes of BSI, of which we isolated 85 (65.9%) gram-negative bacteria, 32 (24.8%) gram-positive bacteria and 12 (9.3%) fungi. Multidrug-resistant bacteria (MDR) were more than 70% of all pathogens and carbapenem-resistant organisms (CRO) were 25.6%. There were 55 episodes of BSI in the pre-engraftment phase and 67 episodes in the post-engraftment phase. The mortality of post-engraftment BSI was significantly higher than that of pre-engraftment (56.7% vs 32.7%, p = 0.005). Through multivariate analysis, the independent risk factors for all-cause mortality at 3 months after BSI were higher levels of procalcitonin (PCT), failure to cover appropriate antibiotics timely, and CRO BSI in pre-engraftment period or multidrug-resistant gram-negative bacteria (MDRGNB) BSI in post-engraftment period. Conclusion: Although the incidence of BSI was lower after HSCT, MDR-dominated BSI had a high mortality rate. Rapid identification of infection or pathogens' classification with various testing methods and the more sensible and timely antibiotic cover are critical to the outcome of BSI after HSCT.

11.
Nat Commun ; 13(1): 6683, 2022 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-36335142

RESUMEN

Studies at the molecular level demonstrate that dietary amino acid intake produces substantial effects on health and disease by modulating metabolism. However, how these effects may manifest in human food consumption and dietary patterns is unknown. Here, we develop a series of algorithms to map, characterize and model the landscape of amino acid content in human food, dietary patterns, and individual consumption including relations to health status, covering over 2,000 foods, ten dietary patterns, and over 30,000 dietary profiles. We find that the type of amino acids contained in foods and human consumption is highly dynamic with variability far exceeding that of fat and carbohydrate. Some amino acids positively associate with conditions such as obesity while others contained in the same food negatively link to disease. Using linear programming and machine learning, we show that these health trade-offs can be accounted for to satisfy biochemical constraints in food and human eating patterns to construct a Pareto front in dietary practice, a means of achieving optimality in the face of trade-offs that are commonly considered in economic and evolutionary theories. Thus this study may enable the design of human protein quality intake guidelines based on a quantitative framework.


Asunto(s)
Aminoácidos , Dieta , Humanos , Conducta Alimentaria , Obesidad , Programación Lineal
12.
Transpl Immunol ; 72: 101598, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35381344

RESUMEN

Chronic graft-versus-host disease (cGVHD) is a major late complication of hematopoietic stem cell transplantation (HSCT). Polymyositis (PM) has been reported to be an uncommon presentation of cGVHD. Myocarditis is an even rarer manifestation of cGVHD-associated PM. Here, we report a 38-year-old male patient developed cGVHD-related PM twelve years post-transplantation, which was confirmed by muscle biopsy and immunological study. The presence of pain in the chest area, dynamic changes in the electrocardiogram, as well as elevated troponin and myocardial enzyme levels with improvement after immunotherapy all pointed to cardiac involvement. Ruxolitinib in combination with tachlimus and methylprednisolone successfully treated cGVHD associated PM with myocarditis. The literature on cGVHD-related PM and myocarditis is briefly reviewed.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Miocarditis , Polimiositis , Adulto , Enfermedad Crónica , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Miocarditis/diagnóstico , Miocarditis/etiología , Miocarditis/terapia , Polimiositis/complicaciones , Polimiositis/tratamiento farmacológico
13.
Front Oncol ; 11: 741341, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34722293

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of standard or low-dose chemotherapy followed by HLA-mismatched allogeneic T-cell infusion (allo-TLI) for the treatment of elderly patients with acute myeloid leukemia (AML) and patients with intermediate-2 to high-risk myelodysplastic syndrome (MDS). METHODS: We carried out a prospective, multicenter, single-arm clinical trial. Totally of 25 patients were enrolled, including 17 AML patients and 8 MDS patients. Each patient received four courses of non-ablative chemotherapy, with HLA-mismatched donor CD3+ allo-TLI 24 h after each course. AML patients received chemotherapy with decitabine, idarubicin, and cytarabine, and MDS patients received decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor. RESULTS: A total of 79 procedures were performed. The overall response rates of the AML and MDS patients were 94% and 75% and the 1-year overall survival rates were 88% (61-97%) and 60% (13-88%), respectively. The overall 60-day treatment-related mortality was 8%. Compared with a historical control cohort that received idarubicin plus cytarabine (3 + 7), the study group showed significantly better overall response (94% vs. 50%, P=0.002) and overall survival rates (the 1-year OS rate was 88% vs. 27%, P=0.014). Post-TLI cytokine-release syndrome (CRS) occurred after 79% of allo-TLI operations, and 96% of CRS reactions were grade 1. CONCLUSION: Elderly AML patients and intermediate-2 to high-risk MDS patients are usually insensitive to or cannot tolerate regular chemotherapies, and may not have the opportunity to undergo allogeneic stem cell transplantation. Our study showed that non-ablative chemotherapy followed by HLA-mismatched allo-TLI is safe and effective, and may thus be used as a first-line treatment for these patients. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/showproj.aspx?proj=20112.

15.
Am J Hematol ; 96(11): 1429-1440, 2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34370319

RESUMEN

The aim of our study was to evaluate the most optimal donor for young acute leukemia (AL) patients with multiple donors available for allogeneic hematopoietic stem cell transplantation (allo-HSCT), including HLA-matched sibling donors (MSDs), HLA-matched unrelated donors (URDs), haploidentical parental donors (HPDs), and haploidentical sibling donors (HSDs). From March 2008 to December 2016, 430 AL patients ≤ 35 years of age were included in the discovery, retrospective study. Patients who received transplantation from a MSD or a HSD had better 5-year OS rates compared with patients who received transplantation from a URD or a HPD. A superior graft-versus-leukemia effect was observed for high-risk patients undergoing HSD-HSCT with a lower relapse rate (p = 0.014) and a higher disease-free survival (DFS) rate (p = 0.029) compared with those undergoing MSD-HSCT. Outcomes of high-risk patients receiving an URD or HPD were equivalent. For intermediate/standard-risk patients, either a MSD or HSD may be the front-line donor selection with comparable outcomes. HLA-matched unrelated donors were preferred over HPDs with reduced non-relapse mortality and higher overall survival (OS) and DFS rates. We further conducted an independent prospective randomized study to evaluate the survival advantage with the new donor hierarchy. Two hundred and fifty patients were randomly assigned to follow our new donor hierarchy or the traditional donor hierarchy at a 2:1 ratio. The new donor hierarchy contributed to significantly superior 2-year OS and DFS rates (OS: 76.2% vs. 67.8%, p = 0.046; DFS: 71.8% vs. 64.5%, p = 0.039).


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Factores de Edad , Niño , Selección de Donante , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Estudios Retrospectivos , Análisis de Supervivencia , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/métodos , Resultado del Tratamiento , Adulto Joven
16.
Front Oncol ; 11: 665217, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34195075

RESUMEN

INTRODUCTION: We analyzed different patient subgroups to determine optimal maintenance therapy in newly diagnosed multiple myeloma (NDMM) patients. METHODS: A total of 226 NDMM patients in our center were included in the study. The characteristics, survival, and adverse reactions were compared among patients who received maintenance therapy or not, and patients who received proteasome inhibitors (PIs) or immunomodulators (IMiDs) maintenance. The survival of different maintenance durations of bortezomib-based regimens was also analyzed. RESULTS: The maintenance therapy not only upgraded more patient responses (34.3 vs 13.3%, P = 0.006), but also significantly prolonged their progression-free survival (PFS) (median PFS: 41.1 vs 10.5 months, P < 0.001) and overall survival (OS) (median OS: not reached vs 38.6 months, P < 0.001). Compared with IMiDs, the PFS (median PFS: 43.7 vs 38.5 months, P = 0.034) and OS (median OS: not reached vs 78.5 months, P = 0.041) were both enhanced by PIs maintenance. Patients younger than 65 years who received PIs had a significantly prolonged OS (P = 0.032). Patients achieving only a partial response (PR) after induction and consolidation therapy had significantly longer PFS and OS after PIs maintenance compared to IMiDs (P = 0.007, 0.002). High-risk patients (ISS 2-3, DS 2-3, and RISS 2-3) given PIs maintenance benefit from a prolonged PFS (P = 0.002, 0.02, 0.06) and OS (P = 0.059, 0.047, 0.044, respectively) compared with IMiDs therapy. OS was significantly prolonged in patients who received ≥ 12 months of bortezomib-based maintenance therapy compared to those who were treated for < 12 months (P < 0.001), but no difference was observed in OS between patients who received 12 to 24 or ≥ 24 months of bortezomib-based maintenance therapy (P = 0.292). CONCLUSION: PIs maintenance was superior to IMiDs in overall PFS and OS. The beneficial effect was most evident in patients achieving PR after induction and consolidation therapy, and in high-risk patients. Moreover, younger patients also benefited from PIs maintenance with an increased OS. A bortezomib-based maintenance therapy duration of 12 to 24 months after induction and consolidation therapy produced satisfactory OS.

17.
Biomark Res ; 9(1): 53, 2021 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-34229751

RESUMEN

Myelodysplastic syndrome with myelofibrosis (MDS-MF) has been associated with an inferior prognosis compared with MDS without MF. However, MDS-MF is not listed independently as a subtype of MDS, and its clinical and genetic characteristics remain poorly understood. We retrospectively compared 53 patients with MDS-MF (44 MF grade 1/MF1; 9 MF grade 2-3/MF2 - 3) and 31 with de novo MDS without MF (MDS). The leukemic transformation risks of both MDS-MF2 - 3 and MDS-MF1 were increased compared with the MDS group. To identify the potential mechanisms responsible for the leukemic transformation of MDS-MF, we performed single-cell sequencing for one MDS-MF2 - 3 patient before and after leukemic transformation to explore the variations in gene expression levels. In addition to upgraded expression levels of acute myeloid leukemia-related genes during leukemic transformation, expression levels of some inflammation-related genes (such as S100s, RNASE3, and CYBB) were also increased, and inflammation-related pathways were up-regulated. These results suggest that inflammation-related genes and pathways may play an important role in the leukemic transformation of MDS-MF.

19.
J Hematol Oncol ; 13(1): 128, 2020 09 25.
Artículo en Inglés | MEDLINE | ID: mdl-32977829

RESUMEN

BACKGROUND: Acute myeloid leukemia (AML) is a fatal hematopoietic malignancy and has a prognosis that varies with its genetic complexity. However, there has been no appropriate integrative analysis on the hierarchy of different AML subtypes. METHODS: Using Microwell-seq, a high-throughput single-cell mRNA sequencing platform, we analyzed the cellular hierarchy of bone marrow samples from 40 patients and 3 healthy donors. We also used single-cell single-molecule real-time (SMRT) sequencing to investigate the clonal heterogeneity of AML cells. RESULTS: From the integrative analysis of 191727 AML cells, we established a single-cell AML landscape and identified an AML progenitor cell cluster with novel AML markers. Patients with ribosomal protein high progenitor cells had a low remission rate. We deduced two types of AML with diverse clinical outcomes. We traced mitochondrial mutations in the AML landscape by combining Microwell-seq with SMRT sequencing. We propose the existence of a phenotypic "cancer attractor" that might help to define a common phenotype for AML progenitor cells. Finally, we explored the potential drug targets by making comparisons between the AML landscape and the Human Cell Landscape. CONCLUSIONS: We identified a key AML progenitor cell cluster. A high ribosomal protein gene level indicates the poor prognosis. We deduced two types of AML and explored the potential drug targets. Our results suggest the existence of a cancer attractor.


Asunto(s)
Examen de la Médula Ósea/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Leucemia Mieloide Aguda/patología , Análisis de la Célula Individual/métodos , Linaje de la Célula , Células Clonales , Sistemas de Computación , ADN Mitocondrial/genética , ADN de Neoplasias/genética , Regulación Leucémica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Leucemia Monocítica Aguda/genética , Leucemia Monocítica Aguda/patología , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Proteínas de Neoplasias/genética , Células Madre Neoplásicas/química , Células Madre Neoplásicas/patología , Fenotipo , Pronóstico , ARN Mensajero/análisis , ARN Neoplásico/análisis , Recurrencia , Proteínas Ribosómicas/genética , Factores de Transcripción/fisiología
20.
Ann Hematol ; 99(11): 2639-2648, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32889611

RESUMEN

Extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) continues to remain a clinical challenge. The data on EMR in acute lymphoblastic leukemia (ALL) are currently limited. Herein, a retrospective analysis of 268 adult ALL patients who underwent allo-HSCT in our center between March 2008 and December 2017 was performed to analyze post-HSCT EMR. Ninety patients (33.58%) experienced relapse; 51(19.03%) experienced bone marrow relapse (BMR), whereas 39 (14.55%) experienced EMR. The 5-year cumulative EMR incidence (CEMRI) revealed that matched sibling donor (MSD)-HSCTs were more likely to develop EMR than unrelated donor (URD)- and haploidentical-related donor (HRD)-HSCTs (CEMRI: 24.02%, 7.69%, and 14.69% for MSD, URD, and HRD, respectively). Notably, MSD-HSCTs (URD vs MSD hazard ratio (HR) = 0.26, p = 0.015; HRD vs MSD HR = 0.46, p = 0.032), history of extramedullary disease (EMD) (HR = 2.45, p = 0.041), and T cell ALL (HR = 2.80, p = 0.012) were independent risk factors for EMR in the multivariate analysis. The median overall survival (OS) for all patients was 15.23 months. However, the OS of EMR patients was significantly longer (19.50 months) than that of BMR patients (12.90 months) (p = 0.003). Multivariate analyses revealed that the leading risk factors for post-relapse deaths were shorter intervals between HSCT and relapse (> 12 months vs ≤ 12 months, HR = 0.30, p < 0.001) and BMR (HR = 0.41, p = 0.002). In conclusion, EMR patients have better survival than BMR patients. ALL patients with allo-HSCT from MSDs, a history of EMD, and the T cell type were significantly associated with EMR.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia
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