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1.
Anal Biochem ; 614: 114063, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33306976

RESUMO

Many diseases, including cancers, AIDS, diabetes, asthma, Parkinson's, and lymphoma, are associated with the immune cell responses of patients suffering from them. Identifying the underlying immune response in such diseases is critical to correctly diagnose their root cause and determine the correct medications to target that root cause for personal therapy and immunotherapy. This work focuses on small molecular CF dyes to conjugate with antibodies, such as CD4 and CD19, for their application in flow cytometry. The CF dyes enable the expansion of flow cytometry reagent panels to support high dimensional flow cytometry analysis of the resulting emissions of 30-40 fluorescent colors, a record in flow cytometry. The CF dyes can be used along with existing flow cytometry dyes to provide a quick, accurate, and cost-effective method for the diagnosis and immunology treatment of diseases such as minimal residual disease (MRD) after cancer therapy. The CF dyes will also be an effective tool for the clinical studies of immune response to SARS-CoV-2 and the related vaccine development.


Assuntos
/diagnóstico , Citometria de Fluxo , Corantes Fluorescentes/química , Imunidade Celular/imunologia , /virologia , Separação Celular , Fluorescência , Humanos , Neoplasia Residual/diagnóstico , Neoplasia Residual/imunologia , Neoplasia Residual/patologia , /isolamento & purificação
2.
Medicine (Baltimore) ; 99(50): e23569, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327316

RESUMO

The SET nuclear proto-oncogene (SET)-nucleoporin (NUP) 214 fusion gene (SET-NUP214) is a rare leukemia fusion gene. Due to the limited number of samples with SET-NUP214 fusion gene in previous studies, the significance of SET-NUP214 for measurable residual disease (MRD) monitoring in patients with acute leukemia (AL) is still unclear. Our study aimed to observe the dynamic changes in SET-NUP214 expression before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and analyzed whether SET-NUP214 could be used to evaluate MRD status. Our study included 24 AL patients who were newly diagnosed with SET-NUP214 fusion gene and they all received allo-HSCT. Their MRD was evaluated by monitoring SET-NUP214 fusion gene and leukemia-associated immunophenotype (LAIP). The median follow-up time was 501 days (56-2208 days). Of the enrolled patients, 6 (25%) patients died, including 3 (12.5%) patients died of leukemia relapse. Total 5 (20.8%) patients experienced hematological relapse at a median of 225 days (56-1057 days) post-transplantation. The SET-NUP214 median expression level at diagnosis was 405.1% (14.6%-1482.4%). SET-NUP214 gene expression generally became positive prior to flow cytometry results. In addition, the Kaplan-Meier survival curves analysis showed that those who had SET-NUP214 positive (SET-NUP214+) post-transplantation had a higher 2-year cumulative incidence of leukemia relapse (CIR) of 43.7 ±â€Š18.8% (P < .05). However, there was no significant difference between SET-NUP214 positive and SET-NUP214 negative patients with regard to their 2-year overall survival (OS) (82.5 ±â€Š11.3 vs 64.6 ±â€Š17.5%, respectively, P = .271). ROC curve analysis turned out that the area under the ROC curve (AUC) was 0.916 (95% CI: 0.784-1.0; P = .005). In conclusion, SET-NUP214 fusion gene determined by real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR) could be used to evaluate MRD status after allo-HSCT. Patients with positive SET-NUP214 expression after transplantation will have a poor prognosis.


Assuntos
Proteínas de Ligação a DNA/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Chaperonas de Histonas/genética , Leucemia/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Fusão Oncogênica/genética , Adolescente , Adulto , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Estimativa de Kaplan-Meier , Leucemia/diagnóstico , Leucemia/mortalidade , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Prognóstico , Curva ROC , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(6): 1831-1836, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33283706

RESUMO

OBJECTIVE: To investigate the consistency between FCM and PCR on the detecting of MRD in TCF3-PBX1+ ALL, and to investigate the prognosis value of these 2 methods. METHODS: 55 cases of paediatric TCF3-PBX1+ ALL patients from April 2008 to April 2015 were enrolled and analyzed. The FCM and PCR was used to detect the MRD in 239 bone marrow samples of 55 patients. All statistical analyses were carried out by using SPSS software version 16. RESULTS: Among the 55 children with TCF3-PBX1+ ALL, there were 30 male and 25 female. The median age was 5 (1-14) years. 20 patients relapsed during follow-up. The MRD results from PCR and FCM showed a strong correlation between both methods (K=0.774, P<0.001). There was no significant difference in 5-years DFS and OS between the patients in PCR+ and PCR- groups on day 15 or day 33. The 5 year DFS rate between the patients in FCM- and FCM+ was 63.9%±7.0% and 0; the 5 year OS rate was 66.5%±7.9% and 0. Combined with the result of FCM and PCR, at the d 33 of treatment, the 5-year DFS rate in FCM-/PCR- and single positive group was 65.4%±7.2% and 25.0%±15.3% (P<0.01). CONCLUSION: The detection result of MRD in TCF3-PBX1 detect by FCM and PCR shows better consistency. MRD positivity detected by FCM at the end of induction therapy (day 33) predicts a high risk of relapse in TCF3-PBX1 ALL patients.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Medula Óssea , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Neoplasia Residual , Proteínas de Fusão Oncogênica/genética , Prognóstico , Recidiva
4.
Nat Commun ; 11(1): 6175, 2020 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-33268821

RESUMO

To elucidate the effects of neoadjuvant chemotherapy (NAC), we conduct whole transcriptome profiling coupled with histopathology analyses of a longitudinal breast cancer cohort of 146 patients including 110 pairs of serial tumor biopsies collected before treatment, after the first cycle of treatment and at the time of surgery. Here, we show that cytotoxic chemotherapies induce dynamic changes in the tumor immune microenvironment that vary by subtype and pathologic response. Just one cycle of treatment induces an immune stimulatory microenvironment harboring more tumor infiltrating lymphocytes (TILs) and up-regulation of inflammatory signatures predictive of response to anti-PD1 therapies while residual tumors are immune suppressed at end-of-treatment compared to the baseline. Increases in TILs and CD8+ T cell proportions in response to NAC are independently associated with pathologic complete response. Further, on-treatment immune response is more predictive of treatment outcome than immune features in paired baseline samples although these are strongly correlated.


Assuntos
Antígeno B7-H1/genética , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Terapia Neoadjuvante/métodos , Antraciclinas/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/mortalidade , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/imunologia , Carcinoma Ductal de Mama/mortalidade , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/imunologia , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Docetaxel/uso terapêutico , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/imunologia , Feminino , Perfilação da Expressão Gênica , Humanos , Imunidade Inata , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/imunologia , Estudos Longitudinais , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Neoplasia Residual , Receptor ErbB-2/genética , Receptor ErbB-2/imunologia , Trastuzumab/uso terapêutico , Resultado do Tratamento , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
5.
Dis Colon Rectum ; 63(9): 1328-1333, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-33216502

RESUMO

BACKGROUND: Perineal reconstructive surgery is an effective procedure to decrease the morbidity associated with extensive abdominoperineal resection in the treatment of advanced low rectal and anal malignancies. Rectus abdominis myocutaneous flaps are often utilized in perineal reconstruction with excellent results. However, the main disadvantages are donor-site morbidity and the need for an open procedure after laparoscopic resection, requiring larger incisions with a resultant increase in postoperative pain. Herein, we describe a modified oblique rectus abdominis myocutaneous flap technique that allows sparing of the rectus sheath and the linea alba. TECHNIQUE: We followed the 3 stages regularly described for the procedure: 1) abdominoperineal resection with simultaneous abdominal and perineal team approach, and removal of the specimen through the perineal wound; 2) right oblique rectus abdominis myocutaneous flap with inferior epigastric pedicle, and release of the rectus muscle from its aponeurotic sheath through the skin paddle incision and transposition of the oblique rectus abdominis myocutaneous flap through an incision in the transversalis fascia; and 3) perineal reconstruction by sutures of the skin paddle to the perineal wound skin edges. RESULTS: Release of the rectus muscle within its sheath through the incision in the skin paddle turned out to be a simple surgical procedure, without the need of specialized surgical instruments or additional incisions. There were no complications during the postoperative recovery. Our patient was pain-free 1 month after the surgery, with a well-healed flap and abdominal scar. CONCLUSION: Performance of an oblique rectus abdominis myocutaneous flap that is specifically fitted for the perineal defect after abdominoperineal resection, with muscle dissection performed through the skin paddle incision and transposition into the pelvis through the transversalis fascia, offers good functional outcome while minimizing damage to the abdominal wall.


Assuntos
Músculos Abdominais Oblíquos/transplante , Neoplasias do Ânus/cirurgia , Carcinoma de Células Escamosas/cirurgia , Laparoscopia/métodos , Retalho Miocutâneo/transplante , Períneo/cirurgia , Protectomia/métodos , Procedimentos Cirúrgicos Reconstrutivos/métodos , Reto do Abdome/transplante , Adulto , Quimiorradioterapia , Feminino , Humanos , Neoplasia Residual , Vagina/cirurgia
9.
Zhonghua Bing Li Xue Za Zhi ; 49(11): 1169-1173, 2020 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-33152824

RESUMO

Objective: To explore the relationship between the expression of human epidermal growth factor receptor 2 (HER2) in core needle biopsy (CNB) specimens before neoadjuvant chemotherapy (NAC) and post NAC Residual Cancer Burden (RCB) classification in breast cancer. Methods: This retrospective study included 150 patients with CNB proven invasive breast carcinoma in the Fourth Hospital of Hebei Medical University from January 2013 to January 2014. Immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) was used to detect the expression of HER2 in the CNB specimens. RCB was used to assess the chemotherapy response of patients. SPSS 21.00 and GraphPad Prism 8.0.1 were used for data statistics; Chi square test and Fisher's exact test for correlation analysis, and Cox regression for survival analysis. P<0.05 was considered statistically significant. Results: Among the 150 patients, there were 38 RCB-0, 12 RCB-Ⅰ, 61 RCB-Ⅱ and 39 RCB-Ⅲ post NAC. RCB-0 meant pathological complete response (PCR). Statistical analysis found that the pre NAC HER2 expression was related to PCR and RCB classification after surgery (r1=‒0.217,r2=‒0.282;P<0.05). Further analysis demonstrated that in the HER2-positive group, PCR was associated with prolonged OS and DFS (HR=2.939, 2.359; P<0.05); the differences of OS and DFS in RCB classifications were more significant (P<0.05) in the HER2 positive than HER2 negative groups. Conclusion: There is a correlation between pre NAC HER2 expression and PCR and RCB classification after treatment. In HER2-positive patients, the prognostic stratification of RCB classification is more obvious, suggesting that pre NAC HER2 overexpression combined with RCB classification after surgery can more accurately predict the prognosis.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Humanos , Hibridização in Situ Fluorescente , Neoplasia Residual , Prognóstico , Receptor ErbB-2/genética , Estudos Retrospectivos , Resultado do Tratamento
10.
Cancer Treat Rev ; 91: 102106, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33049623

RESUMO

In this article, we broadly review the application of cfDNA analysis to the diagnosis and management of lymphoma. We introduce the advantages of cfDNA measurement over conventional tissue biopsy and describe how cfDNA may be utilized for both genotyping and detection of minimal residual disease. First, we discuss genotyping, beginning with differences in identifying mutations from the blood plasma vs. from circulating cells. We review the technical distinctions between PCR- and NGS-based assays and describe two important applications of NGS-based cfDNA tests, namely the identification of resistance mutations and classification of disease subtype. We discuss difficulties in genotyping diseases with low burden of tumor cells and the application of cfDNA assays in these contexts. Second, we describe the utility of ctDNA measurement in assessing MRD. We cover recent advances in the assessment of pre-treatment disease burden as a prognostic biomarker, detection of molecular response to therapy, and early detection of relapsing disease. Third, we explore select emerging areas of research in ctDNA technologies that show promise in boosting the performance of existing ctDNA-based assays. These include cell-free DNA fragment structure analysis or 'fragmentomics', epigenetic modifications, and novel circulating analytes such as tumor-educated platelets and extracellular vesicular DNA. We also discuss alternative analytes to blood plasma for tumor detection, such as urine, saliva, and stool. Finally, we present a case that highlights potential applications of ctDNA approaches to the management of patients with lymphoma, while also defining important prerequisite advances before this can be fully realized. We close with a look to the future of cfDNA applications, outlining one potential timeline and path forward towards routine clinical application.


Assuntos
DNA Tumoral Circulante/análise , Biópsia Líquida/métodos , Linfoma/diagnóstico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Humanos , Linfoma/genética , Linfoma/metabolismo , Mutação , Neoplasia Residual , Medicina de Precisão
11.
J Surg Oncol ; 122(8): 1761-1769, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33125715

RESUMO

BACKGROUND: The impact of length of time to surgery (TTS) on oncologic outcomes following neoadjuvant chemotherapy (NAC) in breast cancer patients is unclear. We investigated the relationship between TTS on residual cancer burden (RCB) score and oncologic outcomes. METHODS: Patients with breast cancer receiving NAC from 2011 to 2017 were identified. The association of TTS with recurrence-free survival (RFS), overall and disease-specific survival (OS, DSS), and RCB score was examined with Kaplan-Meier and Cox proportional hazards analysis, adjusting for relevant clinicopathologic factors. RESULTS: We identified 463 patients. Median TTS was 29 days (range 11-153). Median follow-up was 57 months (range, 2-93 months). Five-year local recurrence-free survival, locoregional RFS, OS, and DSS was 86%, 96%, 89%, and 91%, respectively. On multivariate analysis, TTS >6 weeks was independently associated with worse RFS (HR [hazard ratio] 3.45; p < .001) and DSS (HR 2.82; p < .05), while TTS >6 weeks was independently associated with a positive size of the effect on RCB score of 0.59 (p < .0001). CONCLUSION: Prolonged TTS is a modifiable risk factor for adverse oncologic outcomes following NAC for breast cancer, possibly mediated by increasing RCB score overtime after NAC. In the absence of contraindications, surgery should be performed within 6 weeks following NAC for optimal oncologic outcomes.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/mortalidade , Carcinoma Ductal/mortalidade , Terapia Neoadjuvante/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasia Residual/mortalidade , Tempo para o Tratamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal/tratamento farmacológico , Carcinoma Ductal/patologia , Carcinoma Ductal/cirurgia , Quimioterapia Adjuvante/mortalidade , Feminino , Seguimentos , Humanos , Mastectomia , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/patologia , Neoplasia Residual/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1631-1636, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067965

RESUMO

OBJECTIVE: To investigate the influence of MRD status in newly diagnosed MM patients with VGPR and above after treatment on clinical prognosis. METHODS: Clinical data of 210 newly diagnosed MM patients with VGPR and above after treatment in Fifth People's Hospital of Chendu city. from January 2010 to January 2018 were collected and retrospectively analyzed. The patients were divided into 2 groups: group A (152 patients with MRD-) and group B (58 patients with MRD+). The influencing factors of progression free survival and overall survival of patients were analyzed, and the correlation between MRD status and high-risk cytogenetic abnormalities, treatment plan and response to treatment were evaluated. RESULTS: There were no significant difference in clinical characteristics between the patients in 2 groups (P>0.05). Single factor analysis showed that ASCT and MRD status were related with progression free survival of patients with newly diagnosed MM (P<0.05). Multivariate analysis by Cox regression model showed that MRD+ persistence was the independent risk factor for progression free survival of patients with newly diagnosed MM (P<0.05). The cumulative progression free survival rate in 2-year with follow-up of patients in group A was significantly higher than that in B group (P<0.05). The median progression free survival time and overall survival time of patients with persistent MRD- were significantly longer than those of MRD+ (P<0.05). The single factor analysis showed that MRD- maintenance time was the influencing factor of PFS and OS time of newly diagnosed MM patients (P<0.05). The cumulative overall survival rate in 2-year with follow-up of patients with MRD- maintenance for 6 months was significantly higher than that of patients with MRD- maintenance for<6 months (P<0.05). The cumulative progression free survival rate and overall survival rate in 2 years with follow-up of patients with MRD- maintenance for ≥12 months were significantly higher than those of MRD-maintenance for <12 months(P<0.05). The median progression free survival time of patients with MRD- was significantly longer than that of patients with MRD+ who had≥ one kind of high-risk cytogenetic abnormality (P<0.05). The MRD- rate of patients received ASCT was significantly higher than that of patients without ASCT (P<0.05). The median progression free survival time of patients with MRD- was significantly longer than that of patients with MRD+ (P<0.05). The maintenance time of MRD- in patients with bortezomib treatment was significantly longer than that of patients without bortezomib treatment in population with MRD- (P<0.05). The median progression free survival time of patients with bortezomib treatment was significantly longer than patients without bortezomib treatment (P<0.05). CONCLUSION: MRD+ maintenance in newly diagnosed MM patients with VGPR and above after treatment closely relates with poor long-term prognosis, however, the MRD- maintenance time can be used for prognosis evaluation. MRD+ suggests that patients possess the possibility of early recurrence, and dynamic monitoring of MRD status in treatment can be helpful to clinical determination of treatment opportunity for relapsed MM patients.


Assuntos
Mieloma Múltiplo , Humanos , Neoplasia Residual , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
13.
Lancet Haematol ; 7(11): e816-e826, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33091355

RESUMO

BACKGROUND: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable activity in patients with refractory or relapsed acute lymphocytic leukaemia. Various anti-CD19 CAR T-cell constructs have been trialled and responses vary widely among different studies. We aimed to systematically analyse the outcomes of patients with acute lymphocytic leukaemia treated with anti-CD19 CAR T cells and identify factors associated with differences in outcomes. METHODS: We did a systematic review and meta-analysis of published and unpublished clinical trials that reported data on the outcomes of adult or paediatric patients that were treated with anti-CD19 CAR T cells for relapsed or refractory B-cell acute lymphocytic leukaemia, reported between Jan 1, 2012, and April 14, 2020. Studies with two patients or fewer were excluded and summary data were extracted from the reports. The primary outcome was the number of patients who had complete remission at any time after anti-CD19 CAR T-cell infusion. This study is not registered in PROSPERO. FINDINGS: From 1160 studies, we identified 40 potentially appropriate studies, 35 (88%) of which met the eligibility criteria and were included in the final analysis (n=953 patients). The pooled complete remission was 80% (95% CI 75·5-84·8) and heterogeneity between studies was moderate (I2=56·96%). In the prespecified subgroup analyses, 195 (75% [95% CI 66·9-82·9, I2=35·22%]) of 263 patients in adult studies and 242 (81% [72·9-87·2, I2=54·45%]) of 346 patients in paediatric studies achieved complete remission, p=0·24. The pooled complete remission did not significantly differ with anti-CD19 CAR T-cell construct type or single-chain variable fragment clone, but was higher with autologous T-cell origin (727 [83%, 78·5-86·5, I2=44·34%] of 901 patients), compared with allogeneic T-cell origin (29 [55%, 30·6-79·0, I2=62·64%] of 52 patients; p=0·018). 242 (26% [95% CI 18·5-34·1]) of 854 patients developed grade 3 or worse cytokine release syndrome and 97 (12% [6·6-19·2]) of 532 developed grade 3 or worse neurotoxicity. There was no difference in the proportion of patients who achieved complete remission or who had cytokine release syndrome or neurotoxicity between different anti-CD19 CAR T-cell constructs. The risk of bias was assessed as low in 17 studies and moderate in 18 studies. INTERPRETATION: The high response rates after anti-CD19 CAR T-cell therapy can be used to guide the use of therapy in patients with relapsed or refractory acute lymphocytic leukaemia. Comparison studies are required to further determine differences in efficacy between different anti-CD19 CAR T-cell constructs in the setting of relapsed or refractory acute lymphocytic leukaemia. FUNDING: National Cancer Institute, National Comprehensive Cancer Network, Mayo Clinic K2R Research Pipeline, and Mayo Clinic Center for Individualized Medicine.


Assuntos
Antígenos CD19/imunologia , Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Síndrome da Liberação de Citocina/etiologia , Humanos , Imunoterapia Adotiva/efeitos adversos , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Intervalo Livre de Progressão , Receptores de Antígenos Quiméricos/uso terapêutico , Indução de Remissão , Transplante Autólogo
14.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5482-5485, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019220

RESUMO

Acute leukemia often comes with life-threatening prognosis outcome and remains a critical clinical issue today. The implementation of measurable residual disease (MRD) using flow cytometry (FC) is highly effective but the interpretation is time-consuming and suffers from physician idiosyncrasy. Recent machine learning algorithms have been proposed to automatically classify acute leukemia samples with and without MRD to address this clinical need. However, most prior works either validate only on a small data cohort or focus on one specific type of leukemia which lacks generalization. In this work, we propose a transfer learning approach in performing automatic MRD classification that takes advantage of a large scale acute myeloid leukemia (AML) database to facilitate better learning on a small cohort of acute lymphoblastic leukemia (ALL). Specifically, we develop a knowledge-reserved distilled AML pre-trained network with ALL complementary learning to enhance the ALL MRD classification. Our framework achieves 84.5% averaged AUC which shows its transferability across acute leukemia, and our further analysis reveals that younger and elder ALL patient samples benefit more from using the pre-trained AML model.


Assuntos
Neoplasias Hematológicas , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Idoso , Destilação , Humanos , Leucemia Mieloide Aguda/diagnóstico , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico
15.
Am J Clin Pathol ; 154(6): 816-827, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-32880627

RESUMO

OBJECTIVES: Autologous stem cell transplant with lenalidomide maintenance therapy has greatly improved the relapse-free and overall survival rates of patients with multiple myeloma but also has been associated with an increased risk of secondary B-lymphoblastic leukemia/lymphoma (B-ALL). METHODS: We report a comprehensive review of the clinicopathologic features of 2 patients with multiple myeloma who developed secondary B-ALL during lenalidomide maintenance. RESULTS: Our observations showed that the disease may initially present with subtle clinical, morphologic, and flow-cytometric findings. The flow cytometry findings in such cases may initially mimic an expansion of hematogones with minimal immunophenotypic variation. Both patients achieved complete remission of secondary B-ALL after standard chemotherapy; however, one patient continues to have minimal residual disease, and the other experienced relapse. Next-generation sequencing of the relapse specimen showed numerous, complex abnormalities, suggesting clonal evolution. CONCLUSIONS: Our findings suggest the need for increased awareness and further study of this unique form of secondary B-ALL.


Assuntos
Fatores Imunológicos , Lenalidomida/efeitos adversos , Mieloma Múltiplo/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/induzido quimicamente , Adulto , Antineoplásicos/uso terapêutico , Medula Óssea/química , Medula Óssea/patologia , Análise Citogenética , Evolução Fatal , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lenalidomida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Recidiva , Indução de Remissão , Transplante de Células-Tronco
16.
J Pediatr Hematol Oncol ; 42(7): 415-419, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32976349

RESUMO

INTRODUCTION: Mixed-phenotype acute leukemia (MPAL) accounts for 1.2% to 5% of acute leukemia across age groups with intermediate prognosis. We evaluated clinicoepidemiologic profiles and outcomes of MPAL. METHODS: Records of children younger than 15 years of age with acute leukemia from January 2010 to December 2016 were reviewed on the basis of the MPAL WHO 2008 criteria. Treatment was uniform with a modified MCP-841 protocol. Descriptive analysis tools were used. Outcomes were measured by the Kaplan-Meier method on MedCalc, version 14.8.1. RESULTS: Among 3830 children with acute leukemia in the study period, 2892 received treatment from our center, of whom 24 (0.83%) had MPAL, median age 9 years, with a male:female ratio of 3:1, and median white blood cell of 13.4×10/L. Common immunophenotypes were B/myeloid-12 (50%), T/myeloid-9 (37.5%), and B/T-lymphoid-3 (12.5%). Some B/myeloid cases had abnormal cytogenetics. Seventeen patients were evaluable for outcome. Sixteen patients underwent postinduction bone marrow and 13 (81%) achieved morphologic remission. Thirteen patients underwent flow cytometry-based minimal residual disease evaluation; 9 (69%) were <0.01% (4 postinduction, 5 postconsolidation), and 67% of these had sustained remission till the last follow-up. None underwent bone marrow transplant. The projected 3-year event-free and overall survival rates were 40% and 48%, respectively (median follow-up: 22 mo). CONCLUSION: MPAL represented <1% of childhood acute leukemia. acute lymphoblastic leukemia-type chemotherapy that incorporated high-dose cytarabine was effective in achieving an minimal residual disease-negativity rate of 69% in evaluated patients, which was also predictive of better outcome.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasia Residual/epidemiologia , Neoplasia Residual/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Doença Aguda , Adolescente , Criança , Pré-Escolar , Clorambucila/administração & dosagem , Citarabina/administração & dosagem , Feminino , Seguimentos , Humanos , Índia/epidemiologia , Masculino , Mitoxantrona/administração & dosagem , Neoplasia Residual/diagnóstico , Fenótipo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prednisolona/administração & dosagem , Prognóstico , Taxa de Sobrevida
17.
Clin Adv Hematol Oncol ; 18(7): 413-422, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32903253

RESUMO

Measurable residual disease (MRD) quantification is an essential component of caring for patients with acute lymphoblastic leukemia (ALL). Many studies in pediatric and adult populations have validated the prognostic significance of MRD early in and throughout the course of treatment for ALL, and it is generally accepted that achievement of MRD less than 10[-4] (0.01%) is a critical milestone. ALL is uniquely amenable to quantification of MRD by multiple techniques, including multiparameter flow cytometry, various allele-specific and mutation-specific quantitative polymerase chain reaction methods, and more recently amplicon-based next-generation sequencing. Quantification of MRD with these high-sensitivity methods not only facilitates risk stratification, but also is used to determine appropriateness of intensified therapy, such as allogeneic hematopoietic cell transplant, as well as MRD-targeted therapy with blinatumomab. We review the data supporting the use of MRD quantification in ALL to guide clinical decision-making.


Assuntos
Citometria de Fluxo , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Humanos , Neoplasia Residual
18.
Clin Nucl Med ; 45(12): 948-953, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32969911

RESUMO

PURPOSE: Evaluation of utility of cervical ultrasound (US) for detection of thyroid remnants (ThR) in patients after thyroidectomy for differentiated thyroid cancer. METHODS: Included were 154 consecutive patients (17-89 years, 123 female and 31 male patients), without known cancer residues or cervical lymph nodes metastases, admitted for ThR ablation with I, 14 to 20 weeks after surgery. Neck uptake of I (Tup) and thyroglobulin were determined, and location and volume of ThR detected by cervical US were recorded. On days 3 to 4 after ablation (1.7-4.6GBq, 46-124.3 mCi I), neck SPECT/CT was performed, and I uptake foci were assigned to one of the regions as described below. The anterior neck was divided into 2 compartments: superior and inferior to lower margin of thyroid cartilage, and each compartment was subdivided into middle and lateral regions (in SPECT/CT, posterolateral and anterolateral regions were also marked out). I uptake sites and ThR detected by US, if congruent with SPECT/CT, were counted and analyzed. RESULTS: In total, 341 I uptake foci were found in 150 patients (97.4%) by SPECT/CT and 213 corresponding ThR in 118 patients (76.6%) by US. Ultrasound detected 30% to 46% of I uptake foci in superior lateral regions, 49% in pyramidal lobe/thyroglossal duct area (both P < 0.05), 74% to 77% in inferior lateral regions, and 22% in isthmus (both P > 0.05). Correlation between ThR volume and Tup was strong (r = 0.79), and that between ThR volume and thyroglobulin was weak (r = 0.24). CONCLUSIONS: Ultrasound is less sensitive than I posttherapy scans for ThR detection in patients after thyroidectomy, especially for remnants located above the lower margin of thyroid cartilage.


Assuntos
Técnicas de Ablação , Radioisótopos do Iodo , Linfonodos/diagnóstico por imagem , Neoplasia Residual/diagnóstico por imagem , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pescoço/diagnóstico por imagem , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Ultrassonografia
19.
Zhonghua Er Ke Za Zhi ; 58(9): 758-763, 2020 Sep 02.
Artigo em Chinês | MEDLINE | ID: mdl-32872717

RESUMO

Objective: To analyse the long-term efficacy in childhood T-cell acute lymphoblastic leukemia (T-ALL) cases enrolled in the national protocol of childhood leukemia in China-acute lymphoblastic leukemia (NPCLC-ALL) 2008. Methods: Clinical data of 96 patients diagnosed as T-ALL and treated with NPCLC-ALL2008 protocol between January 2009 and December 2017 in the Department of Hematology-Oncology, the Children's Hospital, Zhejiang University School of Medicine were analyzed retrospectively. Predictive value of minimal residual disease (MRD) monitored by flow cytometry was analyzed. Kaplan-Meier method was used for long-term survival analysis. Results: A total of 96 evaluable patients with newly diagnosed T-ALL were analysed, including 72 males and 24 females. The age was 9.5 (ranged from 1.0 to 16.0) years. The follow-up time was 5.7 (ranged from 1.0 to 9.7) years. Among 96 patients, 92 (96%) achieved complete remission. The 5-year event free survival (EFS) and overall survival (OS) rates were (61±6) % and (70±5) %, respectively. Relapse occurred in 18 cases and the 5-year cumulative incidence of relapse was (27±6) %. Twenty-four patients died. The 5-year OS rates of patients with MRD>5% on day 15 of induction therapy was significantly worse than those with MRD≤5% ((60±12) % vs. (72±6) %, χ(2)=3.904, P=0.048) . The 5-year EFS and OS rates were obviously lower in patients with MRD>10% before the consolidation therapy ((50±35) %). The 5-year OS rates of patients with relapsed disease was significantly worse than those without ((26±13) % vs. (81±5) %, χ(2)=18.411, P<0.01). The earlier the relapse, the worse the prognosis. The 5-year OS rates for patients relapsed within 6 months, within 3 years and more than 3 years, were (25±22) %, (30±14) % and (50±35) % respectively (χ(2)=13.207, P<0.01). Conclusions: NPCLC-ALL2008 protocol is effective for childhood T-ALL. The MRD guided accurate risk stratification and individualized treatment can reduce the relapse and improve the survival rate of pediatric T-ALL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , China , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Linfócitos T , Resultado do Tratamento
20.
Ann Hematol ; 99(11): 2599-2609, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32935190

RESUMO

Methods to estimate bone marrow plasma cells (BMPC) basically include histopathology, cytomorphology, and flow cytometry. The present study compares the outcomes of these methods with special focus on the impact of BMPC-specific characteristics on their recovery by either method. Laboratory reports of diagnostic samples from 238 consecutive patients with suspected or known plasma cell disease were retrospectively analyzed. The median (IQR) proportion of BMPC was 30.0% (15.0-70.0%) by histological review (hBMPC), 7.0% (2.0-16.0%) by smear review (sBMPC), and 3.0% (0.8-10.0%) by flow cytometry (fBMPC). The disparity of results between core biopsy and aspirate smear was enhanced in case of poor quality of the smear, increased BM fiber content, higher grade cell atypia, expression of CD56 (all P < 0.0001), the number of cytogenetic aberrations (P = 0.0002), and abnormalities of the MYC gene (P = 0.0002). Conversely, expression of CD19 and a non-clonal plasma cell phenotype were associated with a lower difference between hBMPC and sBMPC (both P < 0.0001). The disparity between the percentages of sBMPC and fBMPC was associated with the quality of the smear (P = 0.0007) and expression of CD56 (P < 0.0001). Our results suggest that the recovery of BMPC in aspirate specimens not only is a matter of sampling quality but also depends on biological cell properties. Aspiration failure due to malignant type features of BMPC may lead to misclassification of plasma cell disorders and represent a bias for the detection of minimal residual disease after therapy.


Assuntos
Antígenos CD19/biossíntese , Células da Medula Óssea , Antígeno CD56/biossíntese , Mieloma Múltiplo , Proteínas de Neoplasias/biossíntese , Plasmócitos , Adulto , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/classificação , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Neoplasia Residual , Plasmócitos/metabolismo , Plasmócitos/patologia , Estudos Retrospectivos
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