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1.
Zhonghua Xue Ye Xue Za Zhi ; 41(1): 16-22, 2020 Jan 14.
Artigo em Chinês | MEDLINE | ID: mdl-32023749

RESUMO

Objective: To probe the prognostic value of consolidation chemotherapy in non-favorable acute myeloid leukemia (AML) patients who were candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT) with first complete remission (CR(1)) and negative minimal residual disease (MRD(-)) . Methods: A retrospective analysis was conducted on 155 patients with non-favorable AML who received allo-HSCT in CR(1)/MRD(-) from January 2010 to March 2019. The survival data were compared between patients who received and those not received pre-transplant consolidation chemotherapy. Results: A total of 102 patients received pre-transplant consolidation chemotherapy (consolidation group) , and 53 cases directly proceeded to allo-HSCT when CR(1)/MRD(-) was achieved (nonconsolidation group) . The median ages were 39 (18-56) years old and 38 (19-67) years old, respectively. Five-year post-transplant overall survival [ (59.3±7.5) % vs (62.2±6.9) %, P=0.919] and relapse-free survival [ (53.0±8.9) % vs (61.6±7.0) %, P=0.936] were not significantly different between the two groups (consolidation vs nonconsolidation) . There was a weak relationship between consolidation therapy and cumulative incidence of relapse [consolidation: (21.9±5.4) % vs nonconsolidation: (18.3±6.0) %, P=0.942], as well as non-relapse mortality [consolidation: (22.4±4.3) % vs nonconsolidation: (28.4±6.5) %,P=0.464]. Multivariate analysis indicated that pre-transplant consolidation and the consolidation courses (< 2 vs ≥2 courses) did not have an impact on allo-HSCT outcomes. Conclusion: Allo-HSCT for candidate patients without further consolidation when CR(1)/MRD(-) was attained was feasible.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Adolescente , Adulto , Idoso , Humanos , Leucemia Mieloide Aguda/terapia , Pessoa de Meia-Idade , Neoplasia Residual , Prognóstico , Estudos Retrospectivos , Transplante Homólogo , Adulto Jovem
2.
Ann Hematol ; 99(1): 73-82, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31768677

RESUMO

For acute myeloid leukemia (AML) with nucleophosmin 1 mutation (NPM1m), multiparameter flow cytometry (FCM) and real-time quantitative polymerase chain reaction (RQ-PCR) are used to monitor minimal residual disease (MRD). However, the results of the two methods are sometimes inconsistent. This study was designed to analyze how to address the discordant results of FCM and RQ-PCR in AML patients undergoing chemotherapy, especially when positive FCM (FCM+) and negative NPM1m (NPM1m-) results are detected in the same sample. Our study included 93 AML patients with NPM1m positive (NPM1m+) who received chemotherapy but did not undergo hematopoietic stem cell transplantation. We monitored NPM1m and leukemia-associated immunophenotypes (LAIPs) by RQ-PCR and FCM, respectively, to assess MRD after each chemotherapy course. After each course of chemotherapy, all patients were classified into four groups based on the results of FCM and RQ-PCR: both negative (group 1, FCM-NPM1m-), single positive (group 2, FCM-NPM1m+; group 3, FCM+NPM1m-), or both positive (group 4, FCM+NPM1m+). The results showed that there was not a significant difference in the 2-year cumulative incidence of relapse (CIR) after each course of chemotherapy between group 2 and group 3. Furthermore, patients in groups 2 and 3 had a lower 2-year CIR than those in group 4 and a significantly higher 2-year CIR than those in group 1 after the first two courses. The patients in group 4 had a significantly higher 2-year CIR than those in group 1 after the first two courses. These results suggested that in the MRD monitoring process of AML patients, when the results of FCM and RQ-PCR are inconsistent (especially when FCM is positive and NPM1m is negative), these single-positive results still have predictive significance for relapse.


Assuntos
Citometria de Fluxo , Leucemia Mieloide Aguda , Mutação , Proteínas de Neoplasias , Proteínas Nucleares , Reação em Cadeia da Polimerase em Tempo Real , Adolescente , Adulto , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/genética , Neoplasia Residual , Proteínas Nucleares/sangue , Proteínas Nucleares/genética , Valor Preditivo dos Testes , Estudos Retrospectivos
3.
BJOG ; 127(3): 377-387, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31631477

RESUMO

OBJECTIVE: To assess the long-term risk factors predicting residual/recurrent cervical intraepithelial neoplasia (CIN 2-3) and time to recurrence after large loop excision of the transformation zone (LLETZ). DESIGN: Retrospective study. SETTING: Colposcopy clinic. POPULATION: 242 women with CIN 2-3 treated between 1996 and 2006 and followed up until June 2016. METHODS: Age, margins, and high-risk human papillomavirus (HR-HPV) were estimated using Cox proportional hazard and unconditional logistic regression models. The cumulative probability of treatment failure was estimated by Kaplan-Meier analysis. MAIN OUTCOME MEASURE: Histologically confirmed CIN 2-3, HR-HPV, margins, age. RESULTS: CIN 2-3 was associated with HR-HPV (HR = 30.5, 95% confidence interval [CI] = 3.80-246.20), age >35 years (HR = 5.53, 95% CI = 1.22-25.13), and margins (HR = 7.31, 95% CI = 1.60-33.44). HR-HPV showed a sensitivity of 88.8% and a specificity of 80%. Ecto+ /endocervical+ (16.7%), uncertain (19.4%) and ecto- /endocervical+ margins (9.1%) showed a higher risk of recurrence (odds ratio [OR] = 13.20, 95% CI = 1.02-170.96; OR = 15.84, 95% CI = 3.02-83.01; and OR = 6.60, 95% CI = 0.88-49.53, respectively). Women with involved margins and/or who were HR-HPV positive had more treatment failure than those who were HR-HPV negative or had clear margins (P-log-rank <0.001). CONCLUSIONS: HR-HPV and margins seem essential for stratifying post-LLETZ risk, and enable personalised management. Given that clear margins present a lower risk, a large excision may be indicated in older women to reduce the risk. TWEETABLE ABSTRACT: After LLETZ for CIN 2-3, recurrences appear more often in women with positive HR-HPV and involved margins and aged over 35.


Assuntos
Neoplasia Intraepitelial Cervical , Efeitos Adversos de Longa Duração , Margens de Excisão , Recidiva Local de Neoplasia/diagnóstico , Neoplasia Residual/diagnóstico , Infecções por Papillomavirus , Traquelectomia , Neoplasias do Colo do Útero , Transformação Celular Neoplásica , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasia Intraepitelial Cervical/patologia , Neoplasia Intraepitelial Cervical/cirurgia , Colo do Útero/patologia , Colo do Útero/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Efeitos Adversos de Longa Duração/diagnóstico , Efeitos Adversos de Longa Duração/epidemiologia , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Estudos Retrospectivos , Medição de Risco/métodos , Espanha/epidemiologia , Traquelectomia/efeitos adversos , Traquelectomia/métodos , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia
4.
Recent Results Cancer Res ; 214: 71-91, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31473849

RESUMO

Bispecific T cell engagers are antibody constructs directed to a tumor-specific target on the one hand and to CD3-positive T cells on the other hand. Blinatumomab is a compound with specificity for the pan-B cell marker CD19. Clinical activity was tested in relapsed and refractory (R/R) non-Hodgkin's Lymphoma (NHL), R/R acute lymphoblastic leukemia (ALL), and ALL patients with minimal residual disease. Trials have already been started in de novo ALL. The most clinically relevant toxicities are neurologic events and cytokine release syndrome as with other T cell-activating therapies. The mechanisms of resistance are not fully understood. Higher leukemia load and later stage disease represent unfavorable factors. Besides, an upregulation of regulatory T cells and inhibitory molecules like PD-1/PD-L1 may have a role as the loss of target by several mechanisms. The future will show whether the use of bispecifics in ALL can change the standard treatment algorithms and whether bispecific T cell engagers will also be successfully used in other malignant entities.


Assuntos
Anticorpos Biespecíficos/farmacologia , Linfoma não Hodgkin/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Linfócitos T/citologia , Antígenos CD19 , Ensaios Clínicos como Assunto , Humanos , Neoplasia Residual/terapia
5.
Recent Results Cancer Res ; 215: 163-180, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31605229

RESUMO

The clinical implications of being able to accurately detect tumor-derived DNA in the circulation, termed circulating tumor DNA (ctDNA), could be enormous. Already, a plethora of clinical applications is under validation that include detection of minimal residual disease and predicting recurrence, monitoring response and resistance to treatment, identifying targets for therapies, and early detection. ctDNA is only a fraction of the total cell-free DNA (cfDNA) which confounds its detection and sometimes conceals its properties. To use ctDNA as a cancer biomarker with confidence, we need to understand its nature. Its characteristics, including size, half-life, and amount, are critical for the development of tests for its detection and discrimination from the rest of the cfDNA. Technological advances have enabled the detection and quantification of individual fragments of cfDNA, which is pivotal for clinical applications. Understanding the causes, the source of and the mechanisms of release of ctDNA are important for the interpretation of test results. Despite the many advances in understanding the nature and biology of ctDNA, we do not yet have a clear appreciation of the processes that govern its presence and levels in the circulation. ctDNA is not detectable in the blood of every cancer patient, and there is not a directly proportional relationship to tumor type, size, or stage. It is not clear if the lack of correlation with these specific clinical parameters is strictly due to technical or biological challenges. Better understanding of the pathophysiology of ctDNA is therefore important for the improvement of clinical applications and interpretation of their results.


Assuntos
DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/metabolismo , Neoplasias/genética , Neoplasias/patologia , Humanos , Neoplasia Residual/sangue , Neoplasia Residual/genética
6.
Recent Results Cancer Res ; 215: 263-273, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31605234

RESUMO

An accurate profiling of the genomic landscape is mandatory to establish the best clinical and therapeutic approach for patients with solid malignancies. Moreover, tumor cells constantly adapt to external pressures-i.e., systemic treatment-with the selection and expansion of resistant subclones and the emergence of heterogeneous overlapping genomic alterations of resistance. The current standard for molecular characterization in cancer is the performance of a tissue tumor biopsy at the time of diagnosis and, when possible, a re-biopsy at the time of progression. However, tissue biopsy is not always feasible or practical and may underestimate tumor heterogeneity and clonal dynamics. Circulating DNA fragments carrying tumor-specific sequence alterations (circulating tumor DNA, ctDNA) are released from cancer cells into the bloodstream, representing a variable and generally small fraction of the total circulating cell-free DNA. Tumor genotyping in ctDNA (liquid biopsy) offers potential advantages versus the standard tumor tissue biopsy, including non-invasiveness and representation of molecular heterogeneity. Technical advances in sequencing platforms have led to dramatic improvements in variant detection sensitivity and specificity that allow for the detection and quantification of low levels of ctDNA. This provides valuable information on both actionable mutations and captures real-time variations in tumor dynamics. Liquid biopsy clinical applications include molecular diagnosis, determination of tumor load as a surrogate marker of early response, monitoring of mutations of resistance to targeted therapy and detection of minimal residual disease after cancer surgery. The aim of this chapter is to provide an overview of the biological rational and technical background of ctDNA analysis, as well as on the main clinical applications of liquid biopsy in dynamic treatment stratification in solid tumors. Special emphasis will be made on the current and potential benefits of the implementation of ctDNA in clinical practice, mainly in melanoma, lung, and colorectal cancer.


Assuntos
DNA Tumoral Circulante/genética , Biópsia Líquida , Neoplasias/genética , Neoplasias/terapia , DNA Tumoral Circulante/análise , DNA Tumoral Circulante/sangue , Humanos , Mutação , Neoplasia Residual/sangue , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Neoplasias/sangue , Neoplasias/diagnóstico
7.
J Clin Pathol ; 73(1): 42-46, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31471466

RESUMO

AIMS: In previous studies, skin retraction of dermato-pathological specimens after the surgical excision of tumours was calculated at 30% for the surface, with approximately 20% for the length and 15% for the width. The aim of this study was to analyse the retraction of the specimens and the retraction of the lesion and the margins. METHODS: Patients who underwent excision of a skin tumour between January 2013 and July 2014 were randomly included. RESULTS: A total of 104 patients was included. There were 52% male with a mean age of 68.3 years. Seventy-eight per cent of the lesions were malignant (51% were basal cell carcinoma, 10% squamous cell carcinoma). The retraction of the area of the specimen (29%) was significantly greater than the retraction of the tumour (21%). On multivariate analysis, the localisation and the duration of fixation were independent predictors of the specimen area retraction. The retraction of the specimen was 17% in length and 15% in width. The retraction of the margins was calculated at 19% in length and 12% in width. The surgeon correctly evaluated the localisation of the smallest margin in 55% of cases. CONCLUSIONS: Our study provided additional data regarding the retraction of the tumours and margins. The guidelines for surgical excision of skin cancers recommend a clinical margin before excision, but the evaluation of the sufficiency of the margins is based on histological measurement. Our data are useful for the interpretation of the sufficiency of the margins.


Assuntos
Margens de Excisão , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Tempo , Fixação de Tecidos/métodos , Resultado do Tratamento , Adulto Jovem
8.
Medicine (Baltimore) ; 98(50): e18355, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852138

RESUMO

BACKGROUND: The use of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery has been extensively studied in patients with peritoneal carcinomatosis from various malignancies. However, the effectiveness of HIPEC for ovarian cancer is still controversial. Therefore, we performed this meta-analysis to identify patients with ovarian cancer who can obtain survival benefit from HIPEC. METHODS: Articles regarding HIPEC in the MEDLINE, EMBASE, and Cochrane Library were searched till December 2018. In total, 13 case-control studies and two randomized controlled trials were included in this meta-analysis. We investigated the effect of HIPEC on disease-free survival (DFS) and overall survival (OS), and performed subgroup analyses based on the study design, adjustment of confounding variables, and quality of the study. RESULTS: HIPEC improved both DFS (hazard ratio [HR], 0.603; 95% confidence interval [CI], 0.513-0.709) and OS (HR, 0.640; 95% CI, 0.519-0.789). In cases of primary disease, HIPEC improved DFS (HR, 0.580; 95% CI, 0.476-0.706) and OS (HR, 0.611; 95% CI, 0.376-0.992). Subgroup analyses revealed that HIPEC did not improve OS but improved DFS of patients with residual tumors ≤1 cm or no visible tumors. In cases of recurrent disease, HIPEC was associated with better OS (HR, 0.566; 95% CI, 0.379-0.844) but not with DFS. Subgroup analyses also revealed similar tendencies. However, HIPEC improved DFS of patients with residual tumors ≤1 cm or no visible tumors, while it improved OS of only those with residual tumors ≤1 cm. CONCLUSIONS: HIPEC may improve DFS of patients with ovarian cancer when residual tumors were ≤1 cm or not visible. It may also improve OS of only patients with recurrent disease whose residual tumors were ≤1 cm.


Assuntos
Hipertermia Induzida/mortalidade , Neoplasias Ovarianas/terapia , Seleção de Pacientes , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Resultado do Tratamento
9.
Ann Hematol ; 98(12): 2769-2780, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31748925

RESUMO

Difficulty in regularly analyzing marrow myeloma cells (MMCs) and low frequency of circulating myeloma cells (CMCs) in blood presents challenges for monitoring minimal residual disease (MRD) in multiple myeloma (MM). We have developed a set of method for enrichment of CMCs by immunomagetic beads (IMB) combined with flow cytometry (IMB-FCM) based on CD38-APC/CD138-APC antibodies in U266-spiked samples and in 122 patient samples. U266 cell capture efficiency of CD38/CD138-IMB-FCM (6.960, 2.574) was 6- and 2-fold higher than that of FCM (1.032), and the sensitivity of FCM and IMB-FCM was 0.01% and 0.001%, respectively. In MM cohort, the positive rate of CMCs by IMB-FCM increased from 60.5~70.0 to 85~87.2% in newly diagnosed/relapsed and partial remission (PR) patients compared with by FCM (P < 0.05). Two complete remission (CR) patients contain certain amounts of CMCs by IMB-FCM while no CMCs and MMCs were detectable by FCM. Patients exhibiting PR and CR upon therapy had much lower CMC and MMC counts than newly diagnosed/relapsed patients (P < 0.005). Based on MRD measurement in BM and PB samples, all FCM-negative BM samples were also paired with FCM/IMB-FCM-negative PB samples among newly diagnosed, relapsed, and PR patients, and FCM-positive BM samples were accompanied by IMB-FCM-positive results in 88% of corresponding PB samples. CMCs strongly associated with other clinical biomarkers of disease burden, including elevated MMCs, ß2-MG, sCrea, and DS and ISS stages, and more serious anemia, bone destruction, and renal impairment (P < 0.05). Logistic regression analysis revealed that elevated ß2-MG and moderate-to-more anemia were significant risk factors for the presence of CMCs (P < 0.05). As a noninvasive "liquid biopsy" of monitoring MRD, the potential of IMB-FCM for CMC detection may complement or minimize bone marrow aspiration in future treatment of MM patients.


Assuntos
Citometria de Fluxo , Separação Imunomagnética , Mieloma Múltiplo/sangue , Células Neoplásicas Circulantes/metabolismo , Adulto , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Neoplasia Residual , Células Neoplásicas Circulantes/patologia
10.
Clin Ter ; 170(5): e352-e356, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612192

RESUMO

OBJECTIVE: Multiparameter flow cytometry is considered the gold standard to evaluate minimal residual disease in multiple myeloma (MM) and patients in complete remission can achieve "Flow MRD-negative" status (i.e. immunophenotypically abnormal plasma cells not detectable). In the current study we report the usefulness of an eight-color flow cytometric method with a 10-5 sensitivity, using monoclonal antibodies in dried formulation. MATERIALS AND METHODS: Forty-six patients with MM were treated with bortezomib-based regimens and, when eligible, with autologous stem cell transplantation. Response to therapy was assessed according to the criteria validated by the International Myeloma Working Group. Multiparameter flow cytometry was carried out with an 8-color panel validated by the Euroflow Consortium. A commercially available single 8-color tube in dried formulation was used and almost 2,000,000 events were acquired, in order to obtain a 10-5 sensitivity. RESULT: Sixteen patients achieved stringent complete remission and another three patients achieved complete remission. In these groups of patients, the "Flow MRD-negative" status was achieved in sixteen cases. In patients who had a different degree of response (very good partial response, partial response, minimal response) immunophenotypically abnormal plasma cells were always detected. CONCLUSION: Using a single eight-color tube in dried formulation, and an acquisition strategy able to obtain a 10-5 sensitivity, not only is it possible to detect a deep response to modern therapy in patients who obtained at least complete remission, but it is also always possible to detect minimal residual disease in patients with either complete remission or stringent complete remission.


Assuntos
Citometria de Fluxo/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Neoplasia Residual/terapia , Adulto , Anticorpos Monoclonais/uso terapêutico , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Neoplasia Residual/diagnóstico , Indução de Remissão , Transplante Autólogo
11.
Zhonghua Xue Ye Xue Za Zhi ; 40(9): 713-719, 2019 Sep 14.
Artigo em Chinês | MEDLINE | ID: mdl-31648470

RESUMO

Objective: To explore clinical features and severity of chronic graft- versus- host disease (cGVHD) after chemotherapy plus donor lymphocyte infusion (Chemo-DLI) in a consecutive cohort of acute leukemia patients who were minimal residual disease (MRD) positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: The global scoring system proposed by National Institutes of Health (NIH) Consensus Conference was used to identify the characteristics and severity of cGVHD in patients who MRD positive after Chemo-DLI. Results: 54 (59.3%) patients were diagnosed with cGVHD after Chemo-DLI, with the median time of onset of 70 (13-504) days. There were 6 cases (6.6%) of mild cGVHD, 21 cases (23.1%) of moderate cGVHD and 27 cases (29.7%) of severe cGVHD.The 5-year cumulative incidence of relapse after Chemo-DLI was 61.9% (95%CI 45.3%-78.5%) , 15.1% (95%CI 1.1%-29.1%) , and 26.6% (95%CI 9.2%-44.0%) (χ(2)=18.901, P<0.001) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. The 5-year cumulative incidence of relapse after Chemo-DLI was 61.9% (95%CI 45.3%-78.5%) , 19.9% (95%CI 8.1%-31.7%) , and 28.6% (95%CI 0.0%-65.0%) (χ(2)=18.307, P<0.001) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. cGVHD was not associated with non-relapse morality after Chemo-DLI. Probabilities of 5-year leukemia-free survival (LFS) after Chemo-DLI were 24.0% (95%CI 9.1%-38.9%) , 77.2% (95%CI 60.8%-93.6%) , and 64.9% (95%CI 45.7%-84.1%) (χ(2)=24.447, P<0.001) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. Probabilities of 5-year LFS after Chemo-DLI were 24.0% (95%CI 9.1%-38.9%) , 75.5% (95%CI 62.7%-88.3%) , and 42.9% (95%CI 1.8%-84.0%) (χ(2)=25.665, P<0.001) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. Probabilities of 5-year overall survival (OS) after Chemo-DLI were 50.0% (95%CI 31.1%-68.9%) , 87.9% (95%CI 74.7%-100.0%) , and 71.0% (95%CI 52.0%-90.0%) (χ(2)=9.517, P=0.009) in non-cGVHD, mild to moderate cGVHD, and severe cGVHD groups, respectively. Probabilities of 5-year OS after Chemo-DLI were 50.0% (95%CI 31.1%-68.9%) , 83.9% (95%CI 72.8%-95.0%) , and 51.4% (95%CI 6.2%-96.6%) (χ(2)=10.673, P=0.005) in non-cGVHD, classical cGVHD, and overlap syndrome groups, respectively. In multivariate analysis, patients receiving allo-HSCT in first complete remission stage and classical cGVHD after Chemo-DLI were associated with lower relapse risk and better survival. Conclusions: These findings highlight the close relation between cGVHD and the graft-versus-leukemia effect in patients who were MRD positive and received Chemo-DLI after allo-HSCT. However, overlap syndrome could not improve the clinical outcomes of these patients.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Transfusão de Linfócitos , Linfócitos , Neoplasia Residual , Prognóstico , Transplante Homólogo
12.
Zhonghua Xue Ye Xue Za Zhi ; 40(9): 720-725, 2019 Sep 14.
Artigo em Chinês | MEDLINE | ID: mdl-31648471

RESUMO

Objective: To evaluate the prognostic significance of minimal residual disease (MRD) monitoring by 10-color flow cytometry in multiple myeloma (MM) patients after treatment. Methods: 150 patients with MM who were admitted to the First Affiliated Hospital of Soochow University from July 2015 to July 2017 were retrospectively analyzed. Clinical data, MRD data monitoring by 10-color flow cytometry and prognosis were analyzed. Results: 39.1% (34/87) patients were MRD negative after induction chemotherapy, and 49.3% (34/69) patients were MRD negative within 1 year after autologous hematopoietic stem cell transplantation (ASCT) . MRD-negative patients after induction chemotherapy or after transplantation have better progress-free survival (PFS) than MRD-positive patients (P=0.022 and P<0.001) . According to the changes of MRD pre-ASCT and after ASCT, the patients were divided into 4 groups: patients with MRD continued negativity,improved from MRD positive to MRD negative, MRD continued positivity, transformed from MRD negative to MRD positive. The two-year PFS of the four groups were 83%, 82%, 44%, 0, respectively, (P=0.002) . Multivariate analysis showed that the level of MRD after induction chemotherapy was an independent factor for PFS (P=0.002) , HR=4.808 (95%CI 1.818-12.718) . Conclusion: Patients with MRD negative after treatment is a better prognosis marker than complete remission or even the best marker, which can evaluate prognosis by combining R-ISS and cytogenetic changes.


Assuntos
Mieloma Múltiplo , Citometria de Fluxo , Humanos , Mieloma Múltiplo/diagnóstico , Neoplasia Residual , Prognóstico , Estudos Retrospectivos , Transplante Autólogo
15.
Gynecol Oncol ; 155(2): 280-282, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31522838

RESUMO

BACKGROUND: Prophylactic salpingectomy has been heavily promoted based on the theory that serous tubal intraepithelial carcinoma is a precursor lesion for serous ovarian carcinoma. However, the validity of prophylactic salpingectomy has yet to be proven through adequate research. The purpose of this study is to evaluate the completeness of salpingectomy intended for ovarian cancer risk reduction. MATERIALS AND METHODS: Women without a history of ovarian cancer who were undergoing salpingoophorectomy at a single institution in Honolulu, Hawaii were enrolled in this study. Salpingectomy was performed prior to oophorectomy. A blinded pathologist then examined the ovaries for the presence of residual salpingeal tissue. Data collected included type of surgery (minimally invasive or laparotomy) and level of surgeon (attending or resident). Data were analyzed using Fisher's exact test. RESULTS: A total of 107 ovaries were examined. Following salpingectomy, 5.6% (n = 6/107) of ovaries had residual salpingeal tissue present and 94.4% (n = 101/107) of ovaries were absent of salpingeal tissue. Of the ovaries with residual salpingeal tissue, there was no difference in level of surgeon (attending n = 3/107, resident n = 3/107, p = 1.0) or type of surgery (minimally invasive n = 5/107, laparotomy n = 1/107, p = 0.42). DISCUSSION: This is the largest blinded study ever conducted to examine ovaries for residual salpingeal tissue after salpingectomy. In addition, this is the only study to compare learner versus attending outcomes in this setting. This study found that over 94% of salpingectomies resulted in complete removal of salpingeal tissue. Of the ovaries with residual salpingeal tissue, there wasn't a difference among surgeon level and surgery type, but the study was not powered to detect this. This study supports the continued clinical practice of prophylactic salpingectomy for ovarian cancer risk reduction.


Assuntos
Neoplasias Ovarianas/prevenção & controle , Salpingectomia/métodos , Feminino , Humanos , Laparoscopia/métodos , Neoplasia Residual/patologia , Neoplasias Ovarianas/patologia , Ovário/patologia , Estudos Retrospectivos , Comportamento de Redução do Risco , Salpingectomia/estatística & dados numéricos , Salpingo-Ooforectomia/métodos , Salpingo-Ooforectomia/estatística & dados numéricos
16.
Ann Hematol ; 98(12): 2719-2727, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31486880

RESUMO

Aberrant promoter methylation of RASSF6 and RASSF10 occurs at a high frequency in acute lymphoblastic leukemia (ALL). Because of the complexity of the current minimal residual disease (MRD) detecting-methods, the DNA methylation status of the RASSF6 and RASSF10 genes could potentially become biomarkers for the assessment of MRD levels in ALL patients. The promoter methylation status of RASSF6 and RASSF10 was assessed by using methylation-specific PCR (MSP) in the DNA isolated from 280 peripheral blood (PB) samples taken at the time of diagnosis, day 14, 28, and from the subsequent 30-month follow-ups of 45 adult ALL patients. The relative methylation level obtained during the follow-ups by MSP was compared to the MRD results obtained by the amplification of IG/TCR clonal rearrangements using the allele-specific quantitative-PCR (ASO-PCR) assay. Frequently, RASSF6 was methylated in B-ALL, and RASSF10 was methylated in T-ALL. The applicability and accuracy of the assays were increased when these markers were combined (91.1% and 93.8%, respectively). When a cutoff was defined for the PCR-MRD level, results of the 30 months of MRD detection showed a significant correlation between the PCR and MSP techniques (r = 0.848; p < 0.001). Due to the high applicability, the non-invasiveness, and promising prospect of longitudinal assessment, the DNA methylation status of the RASSF6 and RASSF10 genes could be potential biomarkers for the assessment of residual disease in PB of patients with ALL.


Assuntos
Biomarcadores Tumorais , Metilação de DNA , DNA de Neoplasias , Proteínas Monoméricas de Ligação ao GTP , Leucemia-Linfoma Linfoblástico de Células Precursoras , Regiões Promotoras Genéticas , Proteínas Supressoras de Tumor , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , DNA de Neoplasias/sangue , DNA de Neoplasias/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Monoméricas de Ligação ao GTP/sangue , Proteínas Monoméricas de Ligação ao GTP/genética , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Supressoras de Tumor/sangue , Proteínas Supressoras de Tumor/genética
18.
World Neurosurg ; 132: e399-e402, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31476462

RESUMO

OBJECTIVE: The effectiveness of tumor control after Gamma Knife radiosurgery (GKS) for intracranial meningioma is well established. Moreover, GKS is an alternative to reduce surgical-remnant meningioma recurrence. Nevertheless, the tumor can recur even after GKS and is associated with its histologic malignancy. We here investigated the risk factors associated with recurrence from remnant lesions after GKS, assessing recurrence patterns according to histological grades. METHODS: From January 2007 to January 2017, 218 patients underwent GKS for surgical-remnant lesions. To evaluate post-GKS lesion recurrence, pre-GKS magnetic resonance images were compared with those at follow-up. We retrospectively analyzed the histologic classification of meningioma and patients' clinical characteristics (sex, age, tumor location, target volume, and prescription dose). RESULTS: Of the 218 patients, 13 (5.9%) developed post-GKS recurrence within a mean follow-up period of 37.4 months. The recurrence patterns were as follows: adjacent to the 50% marginal-dose field (9 patients); within the 50% marginal-dose field (2 patients); and outside the field (2 patients). Six of 196 World Health Organization grade I meningioma cases, 6 of 20 grade II cases, and 1 of 2 grade III cases developed recurrence. Thus 32% of high-grade meningioma cases (grades II and III) developed recurrence during the follow-up period. Histologic grade was significantly associated (P < 0.001) with recurrence. CONCLUSIONS: The study findings indicate that the post-GKS meningioma recurrence likelihood is high when the meningioma has malignant histologic features. In addition, considering the recurrence patterns, it is important to define a precise target for GKS.


Assuntos
Neoplasias Meníngeas/patologia , Meningioma/patologia , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/patologia , Neoplasia Residual/cirurgia , Radiocirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Adulto Jovem
19.
Radiol Med ; 124(12): 1315-1323, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31473928

RESUMO

PURPOSE: To evaluate whether perfusion and diffusion parameters from staging MR in ovarian cancer (OC) patients may predict the presence of residual tumor at surgery and the progression-free survival (PFS) in 12 months. MATERIALS AND METHODS: Patients who are from a single institution, candidate for OC to cytoreductive surgery and undergoing MR for staging purposes were included in this study. Inclusion criteria were: preoperative MR including diffusion-weighted imaging (DWI) and perfusion dynamic contrast-enhanced (DCE) sequence; cytoreductive surgery performed within a month from MR; and minimum follow-up of 12 months. Patients' characteristics including the presence of residual tumor at surgery (R0 or R1) and relapse within 12 months from surgery were recorded. DWI parameters included apparent diffusion coefficient (ADC) of the largest ovarian mass (O-ADC) and normalized ovarian ADC as a ratio between ovarian ADC and muscle ADC (M-ADC). DCE quantitative parameters included were descriptors of tumor vascular properties such as forward and backward transfer constants, plasma volume and volume of extracellular space. Statistical analysis was performed, and p values < 0.05 were considered significant. RESULTS: Forty-nine patients were included. M-ADC showed a slightly significant association with the presence of residual tumor at surgery. None of the other functional parameters showed either difference between R0 and R1 patients or association with PFS in the first 12 months. CONCLUSIONS: This preliminary study demonstrated a slightly significant association between normalized ovarian ADC and the presence of residual tumor at surgery. The other perfusion and diffusion parameters were not significant for the endpoints of this study.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Ovarianas/diagnóstico por imagem , Adulto , Idoso , Meios de Contraste , Procedimentos Cirúrgicos de Citorredução , Feminino , Seguimentos , Gadolínio , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasia Residual , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Prognóstico , Intervalo Livre de Progressão , Estudos Prospectivos , Fatores de Tempo
20.
Cancer Sci ; 110(10): 3255-3266, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31402561

RESUMO

Tyrosine kinase inhibitor (TKI) administration after allogeneic hematopoietic stem cell transplantation (HSCT) may carry a survival benefit in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Therefore, we investigated whether TKI prophylaxis for negative-minimal residual disease (MRD) after HSCT would improve patient outcomes in this nationwide retrospective cohort study. We included patients with Ph+ ALL who underwent their first allogeneic HSCT between 2001 and 2016, received TKI before HSCT, and achieved negative-MRD status within 180 days after HSCT. Of 850 patients for inclusion, 50 patients received TKI prophylaxis, mostly imatinib or dasatinib (median dose: 400 mg with imatinib and 40 mg with dasatinib). In a multivariate analysis, disease status at HSCT was the sole risk factor for relapse (hazard ratio, 3.58; P < .001 for positive-MRD with complete remission [CR] and hazard ratio, 6.13; P < .001 for active disease). TKI prophylaxis was not associated with a decreased risk of relapse or superior overall survival in either the whole cohort or in the analysis limited to negative-MRD or positive-MRD with CR1 at HSCT. Meanwhile, TKI prophylaxis limited to dasatinib might be associated with a decreased risk of relapse (hazard ratio, 0.34; P = .140), unlike imatinib. Alternative strategies using new-generation TKI for high-risk patients are warranted to improve the outcomes after allogeneic HSCT.


Assuntos
Proteínas de Fusão bcr-abl/genética , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Inibidores de Proteínas Quinases/administração & dosagem , Adolescente , Adulto , Idoso , Terapia Combinada , Dasatinibe/administração & dosagem , Dasatinibe/farmacologia , Feminino , Proteínas de Fusão bcr-abl/efeitos dos fármacos , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/farmacologia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Inibidores de Proteínas Quinases/farmacologia , Indução de Remissão , Estudos Retrospectivos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
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