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1.
Virol Sin ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38914259

RESUMO

Next-generation sequencing (NGS) has significantly improved the accuracy and efficiency of pathogen diagnosis for a wide range of diseases. In this study, viral metagenomics analysis was conducted on fecal and tissue samples from a 13-year-old recipient of hematopoietic stem cell transplantation (HSCT) afflicted with severe lingual papillomatosis. The analysis revealed a high abundance of adeno-associated virus 2 (AAV2), alongside potential helper viruses, herpesvirus type 1 (HSV-1), and the uncommon adenovirus serotype 18 (AdV18). Although a direct causal relationship was not definitively established, the concurrence of these viruses indicated a plausible link to the development of severe lingual papillomatosis in immunocompromised individuals. Notably, the study generated a complete genome sequence of AdV18, offering insights into adenovirus genetic variability, origin, and pathogenicity. Noteworthy findings include three amino acid substitutions in the polymerase and one in the hexon, distinguishing them from previously published strains of AdV18. Phylogenetic analysis unveiled a close relationship between both the polymerase and hexon regions of AdV18 in our study and previously reported AdV18 sequences. This study underscores the pivotal role of comprehensive viral scrutiny in elucidating infections among HSCT patients with lingual papillomatosis.

2.
Cell Rep Med ; 5(5): 101551, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38697104

RESUMO

Accurate diagnosis and prognosis prediction are conducive to early intervention and improvement of medical care for natural killer/T cell lymphoma (NKTCL). Artificial intelligence (AI)-based systems are developed based on nasopharynx magnetic resonance imaging. The diagnostic systems achieve areas under the curve of 0.905-0.960 in detecting malignant nasopharyngeal lesions and distinguishing NKTCL from nasopharyngeal carcinoma in independent validation datasets. In comparison to human radiologists, the diagnostic systems show higher accuracies than resident radiologists and comparable ones to senior radiologists. The prognostic system shows promising performance in predicting survival outcomes of NKTCL and outperforms several clinical models. For patients with early-stage NKTCL, only the high-risk group benefits from early radiotherapy (hazard ratio = 0.414 vs. late radiotherapy; 95% confidence interval, 0.190-0.900, p = 0.022), while progression-free survival does not differ in the low-risk group. In conclusion, AI-based systems show potential in assisting accurate diagnosis and prognosis prediction and may contribute to therapeutic optimization for NKTCL.


Assuntos
Inteligência Artificial , Imageamento por Ressonância Magnética , Humanos , Prognóstico , Imageamento por Ressonância Magnética/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Linfoma Extranodal de Células T-NK/diagnóstico por imagem , Linfoma Extranodal de Células T-NK/patologia , Linfoma Extranodal de Células T-NK/mortalidade , Linfoma Extranodal de Células T-NK/diagnóstico , Idoso
3.
mSystems ; 9(6): e0138523, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38752789

RESUMO

A dysfunction of human host genes and proteins in coronavirus infectious disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key factor impacting clinical symptoms and outcomes. Yet, a detailed understanding of human host immune responses is still incomplete. Here, we applied RNA sequencing to 94 samples of COVID-19 patients with and without hematological tumors as well as COVID-19 uninfected non-tumor individuals to obtain a comprehensive transcriptome landscape of both hematological tumor patients and non-tumor individuals. In our analysis, we further accounted for the human-SARS-CoV-2 protein interactome, human protein interactome, and human protein complex subnetworks to understand the mechanisms of SARS-CoV-2 infection and host immune responses. Our data sets enabled us to identify important SARS-CoV-2 (non-)targeted differentially expressed genes and complexes post-SARS-CoV-2 infection in both hematological tumor and non-tumor individuals. We found several unique differentially expressed genes, complexes, and functions/pathways such as blood coagulation (APOE, SERPINE1, SERPINE2, and TFPI), lipoprotein particle remodeling (APOC2, APOE, and CETP), and pro-B cell differentiation (IGHM, VPREB1, and IGLL1) during COVID-19 infection in patients with hematological tumors. In particular, APOE, a gene that is associated with both blood coagulation and lipoprotein particle remodeling, is not only upregulated in hematological tumor patients post-SARS-CoV-2 infection but also significantly expressed in acute dead patients with hematological tumors, providing clues for the design of future therapeutic strategies specifically targeting COVID-19 in patients with hematological tumors. Our data provide a rich resource for understanding the specific pathogenesis of COVID-19 in immunocompromised patients, such as those with hematological malignancies, and developing effective therapeutics for COVID-19. IMPORTANCE: A majority of previous studies focused on the characterization of coronavirus infectious disease 2019 (COVID-19) disease severity in people with normal immunity, while the characterization of COVID-19 in immunocompromised populations is still limited. Our study profiles changes in the transcriptome landscape post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hematological tumor patients and non-tumor individuals. Furthermore, our integrative and comparative systems biology analysis of the interactome, complexome, and transcriptome provides new insights into the tumor-specific pathogenesis of COVID-19. Our findings confirm that SARS-CoV-2 potentially tends to target more non-functional host proteins to indirectly affect host immune responses in hematological tumor patients. The identified unique genes, complexes, functions/pathways, and expression patterns post-SARS-CoV-2 infection in patients with hematological tumors increase our understanding of how SARS-CoV-2 manipulates the host molecular mechanism. Our observed differential genes/complexes and clinical indicators of normal/long infection and deceased COVID-19 patients provide clues for understanding the mechanism of COVID-19 progression in hematological tumors. Finally, our study provides an important data resource that supports the increasing value of the application of publicly accessible data sets to public health.


Assuntos
COVID-19 , Hospedeiro Imunocomprometido , SARS-CoV-2 , Transcriptoma , Humanos , COVID-19/genética , COVID-19/imunologia , COVID-19/virologia , Transcriptoma/genética , SARS-CoV-2/genética , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/imunologia , Masculino , Feminino , Mapas de Interação de Proteínas/genética , Pessoa de Meia-Idade , Perfilação da Expressão Gênica/métodos
4.
Int Immunol ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38778574

RESUMO

BACKGROUND: Lymphocyte trafficking via chemokine receptors such as CCR5 and CXCR3 plays a critical role in the pathogenesis of aGVHD. Our previous studies showed that addition of CCR5 or CXCR3 antagonist could only slightly alleviate the development of aGVHD. Given the specificity of T lymphocytes bearing CXCR3 and CCR5, we investigated whether combined CCR5 and CXCR3 blockade could further attenuate murine aGVHD. METHODS: A mouse model of aGVHD was established to assess the efficacy of CCR5 or/and CXCR3 blockade on the development of aGVHD. The distribution of lymphocytes was calculated by quantification of immunostaining cells. The immunomodulatory effect on T cells were assessed by evaluating T- cell proliferation, viability, and differentiation. RESULTS: Using murine allo-HSCT model, we demonstrated that blockade of both CCR5 and CXCR3 could efficiently alleviate the development of aGVHD. Further investigation on the immune mechanisms for this prophylactic effect showed that more T cells were detained into secondary lymphoid organs (SLOs), which may lead to reduced infiltration of T cells into GVHD target organs. Our study also showed that T cells detained into SLOs dampened the activation, suppressed the polarization toward Th1 and Tc1, and induced the production of Treg cells. CONCLUSION: These data suggest that concurrent blockade of CCR5 and CXCR3 attenuates murine aGVHD through modulating donor-derived T cell distribution and function, and this might be applicable for aGVHD prophylaxis in clinical settings.

6.
Brief Bioinform ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38279649

RESUMO

The identification of human-herpesvirus protein-protein interactions (PPIs) is an essential and important entry point to understand the mechanisms of viral infection, especially in malignant tumor patients with common herpesvirus infection. While natural language processing (NLP)-based embedding techniques have emerged as powerful approaches, the application of multi-modal embedding feature fusion to predict human-herpesvirus PPIs is still limited. Here, we established a multi-modal embedding feature fusion-based LightGBM method to predict human-herpesvirus PPIs. In particular, we applied document and graph embedding approaches to represent sequence, network and function modal features of human and herpesviral proteins. Training our LightGBM models through our compiled non-rigorous and rigorous benchmarking datasets, we obtained significantly better performance compared to individual-modal features. Furthermore, our model outperformed traditional feature encodings-based machine learning methods and state-of-the-art deep learning-based methods using various benchmarking datasets. In a transfer learning step, we show that our model that was trained on human-herpesvirus PPI dataset without cytomegalovirus data can reliably predict human-cytomegalovirus PPIs, indicating that our method can comprehensively capture multi-modal fusion features of protein interactions across various herpesvirus subtypes. The implementation of our method is available at https://github.com/XiaodiYangpku/MultimodalPPI/.


Assuntos
Benchmarking , Citomegalovirus , Humanos , Aprendizado de Máquina , Processamento de Linguagem Natural
8.
Leuk Lymphoma ; 65(3): 353-362, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38069781

RESUMO

Unfit acute myeloid leukemia and high-risk myelodysplastic syndrome patients with prolonged neutropenia demand coadministration of venetoclax and azoles. However, venetoclax dosing under drug-drug interaction with azoles remains controversial. Therapeutic drug monitoring (TDM) is expected to guide drug dosage adjustments. We retrospectively enrolled 17 patients under this coadministration and TDM. Venetoclax dosages were interfered when inappropriate drug concentrations appeared. The primary endpoints were objective response and adverse events. Venetoclax concentration outliers were more frequently evaluated before than after dose adjustment (Cmax 60.87% vs. 0.00%, p < .0001). MRD negativity rate was higher in patients staying within reference range than those having outliers (90.91% vs. 33.33%, p = .028). Objective response rate was 100%. Hematologic adverse events included neutropenia (93.3%), febrile neutropenia (53.3%), and thrombocytopenia (81.3%). Median time to neutropenia and thrombocytopenia recovery was 20 (14-32) and 16.5 (6-34) days, respectively. No invasive fungal and other life-threatening infections were observed.


Assuntos
Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Neutropenia , Sulfonamidas , Trombocitopenia , Humanos , Antifúngicos/efeitos adversos , Estudos Retrospectivos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/induzido quimicamente , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Neutropenia/induzido quimicamente , Neutropenia/diagnóstico , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/tratamento farmacológico , Azóis/uso terapêutico , Trombocitopenia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
9.
Ann Hematol ; 103(1): 153-162, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37749319

RESUMO

The purpose is to ascertain the clinical impact of Castleman disease (CD) by reassessment of the real-world data from Peking University First Hospital (PKUFH). The results will contribute to the standardization of diagnosis and treatment on CDs. Based on the last 15-year retrospective real-world data from Peking University First Hospital (PKUFH), we reclassified and re-evaluated the clinical and pathological information of patients with pathologically suspected diagnosis of CD. A total of 203 patients were included in our study, in which the diagnosis of CD was confirmed in 189 cases, including 118 patients with unicentric CD (UCD, n = 118, 62.4%) and 71 patients with multicentric CD (MCD, n = 71, 37.6%). A total of 44.1% (n = 52) of UCDs in our cohort were complicated with paraneoplastic pemphigus (PNP). The treatment of UCD is primarily surgical, with a 5-year overall survival (OS) of 88.1%. Patients with PNP had a poorer prognosis than those without PNP (82.9% (95% CI 123-178) vs 92.8% (95% CI 168-196), log-rank p = 0.041). The rate of concurrent systemic symptoms was 74.6% (n = 53), and renal involvement occurred in 49.3% (n = 35) MCD patients. The MCD treatments were mainly chemotherapy regimens, with a 5-year OS of 77.6% (95% CI, 143-213). Patients with UCD demonstrate a better overall prognosis than patients with MCD. But the prognosis of those complicated with PNP was poor. The differential diagnosis of MCD is extensive. MCD treatment in China is heterogeneous. The inaccessibility of anti-IL-6-targeted drugs in China may contribute to the poor prognosis for patients with MCD.A preprint has previously been published (Guo et al. 34).


Assuntos
Hiperplasia do Linfonodo Gigante , Humanos , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/epidemiologia , Hiperplasia do Linfonodo Gigante/terapia , Estudos Retrospectivos , Pequim/epidemiologia , Prognóstico , China/epidemiologia
10.
Cancer Med ; 12(24): 21592-21604, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38062912

RESUMO

BACKGROUND: Chromosomal translocations involving core binding factor (CBF) genes account for 15% of adult acute myeloid leukemia (AML) cases in China. Despite being classified as favorable-risk by European Leukemia Net (ELN), CBF-AML patients have a 40% relapse rate. This study aims to analyze clinical characteristics and prognosis of CBF-AML, compare its subtypes (inv(16) and t(8;21)), and validate prognostic factors. METHODS: Retrospective analysis of 149 AML patients (75 CBF-AML, 74 non-CBF) at Peking University First Hospital (March 2012-March 2022). RESULTS: CBF-AML patients have significantly lower disease-free survival (DFS) (p = 0.005) and higher non-relapse mortality (NRM) (p = 0.028) compared to non-CBF AML. inv (16) and t(8;21) show distinct co-occurring gene mutation patterns, with inv(16) being prone to central nervous system (CNS) leukemia. Multivariate analysis identifies age as a risk factor for overall survival (OS) and disease free survival (DFS), kinase mutation as a risk factor for DFS and Recurrence, while WT1 mutation as a risk factor for OS and non relapse mortality (NRM) risk in t(8;21) AML. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) improves prognosis in low-risk t(8;21). CONCLUSION: Prognosis of CBF-AML is poorer than ELN guidelines suggest. inv(16) and (8;21) are separate entities with relatively poor prognoses, requiring rational risk stratification strategies. Allo-HSCT may benefit low-risk t(8;21), but further research is needed for conclusive evidence.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Adulto , Humanos , Prognóstico , Estudos Retrospectivos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Fatores de Ligação ao Core/genética , Recidiva , Fatores de Risco
11.
Front Immunol ; 14: 1274492, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37928518

RESUMO

Background: The widespread adoption of Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) has significantly improved the survival rates of patients with hematological malignancies. However, Graft-Versus-Host Disease (GVHD) remains a formidable complication, threatening patient prognosis. Recent research has indicated that decitabine (DAC), known for its hypomethylating properties may also exhibit immune-regulatory capabilities and a potential for reducing GVHD incidence and enhancing survival. Methods: We retrospectively reviewed data from AML/MDS patients who underwent Allo-HSCT at our center from January 2010 to January 2023. From a total of 251 patients with complete data, we employed propensity score matching (PSM) to create 100 matched pairs (200 patients) for comprehensive trial analysis. Patients receiving low-dose DAC-containing regimen were matched with those who did not receive DAC. Results: Patients in the DAC group exhibited a significantly lower incidence of grade II-IV acute GVHD (aGVHD) compared to non-DAC group (21% vs. 38%, P=0.013). Univariable and multivariable logistic regression analysis demonstrated DAC intervention as a protective factor against grade II-IV aGVHD (P=0.017, OR=0.47, 95% CI 0.23-0.81; P=0.018, OR=0.46, 95% CI 0.24-0.87). Multivariate competing risk regression further supported administration of decitabine as a protective factor against grade II-IV aGVHD (P=0.038, SHR=0.53, 95%CI 0.29-0.97). There was no significant difference between both groups concerning chronic GVHD, infection, disease relapse, overall survival, disease-free survival and GVHD free, relapse free survival. In MRD negative or intermediate risk subgroup, the grade II-IV aGVHD ameliorating effect of DAC was confirmed as well. Conclusion: Low-dose DAC-intensified modified conditioning regimen could improve prognosis in AML/MDS Patients treated with allogeneic hematopoietic stem cell transplantation.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Decitabina/uso terapêutico , Estudos Retrospectivos , Transplante Homólogo , Recidiva Local de Neoplasia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Leucemia Mieloide Aguda/patologia
13.
Ann Hematol ; 102(11): 3061-3074, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37667046

RESUMO

Acute myeloid leukemia (AML) is a malignant lymphohematopoietic tumor that ranks among the most frequent indications for allogeneic hematopoietic stem cell transplantation (allo-HSCT). This article aims to provide a comprehensive analysis of the application of allo-HSCT for AML and identify prognostic factors to enhance future treatment effect. This retrospective study collected data from 323 patients diagnosed with AML at Peking University First Hospital who underwent allo-HSCT between September 2003 and July 2022. The annual number of transplantations has steadily increased. Our center has observed a rise in the proportion of cytogenetic high-risk and measurable residual disease (MRD) positive patients since 2013, as well as an increase in the number of haploidentical transplantations. The overall leukocyte engraftment time has decreased over the past 20 years. Furthermore, both overall survival (OS) and disease-free survival (DFS) have significantly improved, while non-relapse mortality (NRM) has significantly decreased since 2013. Multivariate analysis identified transplantation before 2013, patients in complete remission (CR) 2 or non-CR, and recipients older than 50 years as risk factors for NRM, while patients in non-CR and patients with positive MRD are risk factors for recurrence. These findings offer insights into AML treatment outcomes in China, highlighting changes in transplantation practices and the need to reduce post-transplant relapse. Effective interventions, such as MRD monitoring and risk stratification schemes, are crucial for further enhancing transplant outcomes.

14.
Ann Hematol ; 102(11): 3185-3193, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37700194

RESUMO

The aim of this study is to evaluate the survival benefit of consolidative autologous hematopoietic stem cell transplantation (ASCT) in patients with peripheral T-cell lymphomas (PTCL). In this retrospective study, the ASCT group underwent consolidative ASCT after first-line therapy at 14 transplantation centers in China between January 2001 and December 2019. Data were collected over the same time frame for the non-ASCT group from the database of lymphoma patient records at Peking University Cancer Hospital & Institute. A total of 120 and 317 patients were enrolled in the ASCT and non-ASCT groups, respectively, and their median ages were 43 years and 51 years, respectively. In the ASCT group, 101 patients had achieved complete remission (CR) and 19 patients had achieved partial remission at the time of ASCT. The median follow-up time was 40.2 months and 68 months, and the 3-year overall survival (OS) rate was 80.6% and 48.9% (p < 0.001) for the ASCT and non-ASCT groups, respectively. The beneficial effect of ASCT for OS remained even after propensity score-matched (PSM) analysis (81.6% vs 68.3%, p = 0.001). Among the 203 patients who were aged ≤ 65 years and achieved CR, ASCT conferred a significant survival benefit (3-year progression-free survival [PFS]: 67.4% vs 47.0%, p = 0.004; 3-year OS: 84.0% vs 74.1%, p = 0.010), and this was also maintained after PSM analysis (3-year PFS: 66.6% vs 48.4%, p = 0.042; 3-year OS: 84.8% vs 70.5%, p = 0.011). Consolidative ASCT improved the survival outcome of PTCL patients, even those who achieved CR after first-line therapy.

15.
Transplant Proc ; 55(7): 1706-1714, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37385841

RESUMO

BACKGROUND: Diagnosis of acute graft-vs-host disease (aGVHD) based on clinical symptoms and biopsy of involved organ was not satisfactory; reliable plasma biomarkers or their panels would be of great value to increase the sensitivity and specificity for such a fatal complication. METHOD: One hundred two patients who received allogeneic hematopoietic stem cell transplantation in our center were included in this study. Systemic biomarkers of ST2, IP10, IL-2Rα, TNFR1, and organ-specific biomarkers of Elafin, REG-3α, and KRT-18F in plasma were tested by ELISA. The correlation of each biomarker or selected panel of some systemic and organ-specific biomarker with aGVHD was investigated. RESULTS: The level of each systemic biomarker in aGVHD patients was significantly higher than that in patients without aGVHD. Organ-specific biomarker of Elafin, REG-3α, and KRT-18F also had predictive value for aGVHD of skin, gastrointestinal tract, and liver, respectively. Combination of ST2 with one of the 3 organ-specific biomarkers could provide more accurate prediction for aGVHD with skin, gastrointestinal tract, and liver, respectively. CONCLUSIONS: All the biomarkers tested in our study correlated with the severity and clinical course of aGVHD. Combination of each systemic biomarker with organ-specific biomarker could increase the sensitivity and specificity for the diagnosis of aGVHD, whereas ST2 with organ-specific biomarker is more sensitive for the diagnosis of organ-specific aGVHD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Elafina , Proteína 1 Semelhante a Receptor de Interleucina-1 , Biomarcadores , Sensibilidade e Especificidade , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Aguda
16.
Lancet Reg Health West Pac ; 34: 100720, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37283978

RESUMO

Background: Castleman disease (CD) is a group of rare and heterogenous lymphoproliferative disorders including unicentric CD (UCD), human herpesvirus-8(HHV-8)-associated multicentric CD (HHV8-MCD), and HHV-8-negative/idiopathic multicentric CD (iMCD). Knowledge of CD mainly comes from case series or retrospective studies, but the inclusion criteria of these studies vary because the Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD and UCD were not available until 2017 and 2020, respectively. Further, these criteria and guidelines have not been systematically evaluated. Methods: In this national, multicenter, retrospective study implementing CDCN criteria, we enrolled 1634 CD patients (UCD, n = 903; MCD, n = 731) from 2000 to 2021 at 40 Chinese institutions to depict clinical features, treatment options, and prognostic factors of CD. Findings: Among UCD, there were 162 (17.9%) patients with an MCD-like inflammatory state. Among MCD, there were 12 HHV8-MCD patients and 719 HHV-8-negative MCD patients, which included 139 asymptomatic MCD (aMCD) and 580 iMCD meeting clinical criteria. Of 580 iMCD patients, 41 (7.1%) met iMCD-TAFRO criteria, the others were iMCD-NOS. iMCD-NOS were further divided into iMCD-IPL (n = 97) and iMCD-NOS without IPL (n = 442). Among iMCD patients with first-line treatment data, a trend from pulse combination chemotherapy toward continuous treatment was observed. Survival analysis revealed significant differences between subtypes and severe iMCD (HR = 3.747; 95% CI: 2.112-6.649, p < 0.001) had worse outcome. Interpretation: This study depicts a broad picture of CD, treatment options and survival information in China and validates the association between the CDCN's definition of severe iMCD and worse outcomes, requiring more intensive treatment. Fundings: Beijing Municipal Commission of Science and Technology, CAMS Innovation Fund and National High Level Hospital Clinical Research Funding.

17.
Am J Hematol ; 98(9): 1394-1406, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37366294

RESUMO

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mielomonocítica Crônica , Humanos , Prognóstico , Transplante Homólogo/efeitos adversos , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia
19.
Int Immunopharmacol ; 120: 110299, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37201405

RESUMO

Donor-specific anti-HLA antibody (DSA) is a significant obstacle to successful haploidentical hematopoietic stem cell transplantation (haplo-HSCT) and is associated with poor engraftment rates. DSA strongly positive patients with a mean fluorescence intensity (MFI) over 5000 have a primary poor graft function (PGF) rate of over 60%. Currently, there is no consensus on the desensitization of DSA, and existing strategies are complex and have limited effectiveness. To address this issue, we conducted a retrospective study on 19 patients with strongly positive DSA (MFI over 5000) who underwent haplo-HSCT and were treated with intravenous immunoglobulin (IVIg)-based therapy. We also included 38 baseline-matched patients with DSA-negative as controls. Our findings revealed that the cumulative incidence of engraftment, PGF, graft-versus-host disease (GVHD), virus infection, overall survival (OS), disease-free survival (DFS), relapse, and non-relapse mortality (NRM) in the DSA strongly positive group after desensitization were comparable to those in the DSA negative group (P > 0.05). Our multivariable analysis showed that disease remission was a protective factor against PGF (P = 0.005, OR = 0.019, 95% CI 0.001-0.312). Subgroup analysis revealed that the desensitization efficacy was equal regardless of DSA type against HLA-I or II, and MFI value over 5000 or not. In conclusion, we propose a simple and effective DSA desensitization strategy based on immunoglobulin to ensure successful engraftment and improve patient prognosis.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Transplante Haploidêntico , Humanos , Estudos Retrospectivos , Doadores de Tecidos , Imunoglobulinas Intravenosas/uso terapêutico , Soro Antilinfocitário , Antígenos HLA
20.
Int J Hematol ; 118(2): 231-241, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37247070

RESUMO

Light chain amyloidosis is a plasma cell dyscrasia characterized by deposition of misfolded amyloid fibrils in tissues, leading to multi-organ dysfunction. We retrospectively analyzed 335 patients (median age, 60 years) with systemic light chain amyloidosis in the First Hospital of Peking University from 2011 to 2021. Involved organs were the kidney (92.8%), heart (57.9%), liver (12.8%) and peripheral nervous system (6.3%). Chemotherapy was administered to 55.8% (187/335) of patients, among whom 94.7% received novel agent-based regimens. Hematologic response (≥ very good partial response) was achieved in 63.4% of patients who received chemotherapy. Only 18.2% of patients received autologous hematopoietic stem cell transplant (ASCT). Among transplant-eligible patients, the overall survival of ASCT recipients was better than those who received chemotherapy only. The median overall survival of the patients with light chain amyloidosis was 77.5 months. Estimated glomerular filtration rate and Mayo 2012 stage were independent prognostic factors for overall survival in multivariate analysis. Although the younger age and high ratio of renal involvement might contribute to the favorable prognosis of this cohort, the role of novel agents and ASCT is also discernible. This study will provide a comprehensive perspective on progress in treatment of light chain amyloidosis in China.


Assuntos
Amiloidose , Transplante de Células-Tronco Hematopoéticas , Amiloidose de Cadeia Leve de Imunoglobulina , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , População do Leste Asiático , Resultado do Tratamento , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Prognóstico , Transplante Autólogo
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