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1.
Zhonghua Xue Ye Xue Za Zhi ; 45(5): 453-461, 2024 May 14.
Article in Chinese | MEDLINE | ID: mdl-38964919

ABSTRACT

Objective: To investigate the impact of donor human leukocyte antigen (HLA) -Bw4 expression on natural killer (NK) cell reconstitution and transplant outcomes in recipients undergoing haploidentical hematopoietic stem cell transplantation (HSCT) from maternal or related donors without ex vivo T-cell depletion. Methods: This study prospectively enrolled 32 patients who received T-replete haploidentical HSCT from maternal or collateral donors (cohort 1) to evaluate the facilitating effect of donor HLA-Bw4 expression on NK cell reconstitution. Furthermore, a retrospective analysis was conducted on 278 patients who underwent T-replete haploidentical HSCT from maternal or collateral donors (cohort 2) to analyze the impact of donor HLA-Bw4 expression on HSCT outcomes. Thus, a comparison was made between the effects of donor HLA-Bw4 expression on HSCT outcomes in patients receiving or not receiving post-transplant cyclophosphamide (PT-Cy) conditioning. Results: Donors expressing HLA-Bw4 alleles facilitated NK cell reconstitution and functional recovery, which remained unaffected by PT-Cy. Donors with HLA-Bw4 expression were associated with reduced transplant-related mortality (TRM), particularly mortality related to infections. The use of PT-Cy did not impact the ability of donor HLA-Bw4 to decrease TRM. Conclusion: In haploidentical HSCT from maternal or related donors without ex vivo T-cell depletion, the presence of donor HLA-Bw4 expression promotes rapid NK cell reconstitution and functional recovery and is significantly associated with lower TRM, especially infection-related mortality. These findings underscore the clinical significance of donor HLA-Bw4 expression in patients who underwent HSCT. Hence, the consideration of donor HLA-Bw4 in recipient selection and HSCT strategies holds important clinical implications.


Subject(s)
HLA-B Antigens , Hematopoietic Stem Cell Transplantation , Killer Cells, Natural , Transplantation, Haploidentical , Humans , Killer Cells, Natural/immunology , Adult , Female , Male , Hematopoietic Stem Cell Transplantation/methods , Young Adult , Adolescent , Middle Aged , HLA-B Antigens/genetics , Retrospective Studies , Prospective Studies , Tissue Donors , Child , Alleles , Child, Preschool , Transplantation Conditioning/methods
2.
Zhonghua Yi Xue Za Zhi ; 104(11): 843-849, 2024 Mar 19.
Article in Chinese | MEDLINE | ID: mdl-38462360

ABSTRACT

Objective: To investigate the effects of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients with haploidentical stem cell transplantation (haplo-SCT). Methods: Fifteen consecutive patients who received haplo-SCT and pre-transplant donor specific anti-human leukocyte antigen (HLA) antibody (DSA) positive [mean fluorescence intensity (MFI)≥2 000] in the Institute of Hematological Diseases from November 2021 to March 2023 were retrospectively recruited into the desensitized group. There were 4 males and 11 females, with a median age [M(Q1, Q3)] of 48 (37, 59) years. All patients were desensitized with sirolimus combined with anti-CD20 monoclonal antibody. The non-desensitized group included 29 patients with haplo-SCT who had not received desensitization treatment from August 2012 to June 2016. There were 12 males and 17 females with a median age of 42 (26, 50) years. Up to October 1, 2023, the median follow-up time was 13 (9, 18) months in the study group and 23 (14, 29) months in the control group. The changes of MFI before and after desensitization treatment and the prognosis of patients in the desensitized group were compared, including the incidence of primary implantation failure (pGF), neutrophil implantation time, platelet implantation time, grade Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) and chronic GVHD incidence, non-recurrence related mortality, event-free survival rate, disease-free survival rate and overall survival rate. The survival curve was drawn by Kaplan-Meier method, and the survival rate between groups was compared with Log-rank test. Results: After desensitization treatment, the level of DSA MFI in the desensitized group decreased from 8 879 (7 544, 11 495) to 3 781 (1 638, 4 165) after desensitization treatment (P<0.01). All of the patients achieved hematopoietic recovery, and the median time for neutrophil and platelet engraftment were 14 (11, 15) and 20 (18, 25) days, respectively. The incidence of pGF in the desensitized group was 0, which was lower than that in the non-desensitized group (34.5%, 10/29) (P=0.011). The expected 1-year disease-free survival rate and overall survival rate in the desensitized group were 100% (15/15) and 100% (15/15) respectively, while those in the non-desensitized group were 75.9% (22/29) and 75.9% (22/29) respectively, the difference was not statistically significant (both P>0.05). The one-year event-free survival rate in the desensitized group was expected to be 100% (15/15), which was higher than that in the non-desensitized group (51.3%, 15/29) (P=0.002). Conclusion: Sirolimus combined with anti-CD20 monoclonal antibody desensitization therapy can reduce the DSA level of haplo-SCT recipients, promote hematopoietic engraftment after transplantation, and avoid the occurrence of pGF after transplantation.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Male , Female , Humans , Sirolimus/therapeutic use , Retrospective Studies , Hematopoietic Stem Cell Transplantation/adverse effects , Prognosis , Graft vs Host Disease/etiology , Antibodies, Monoclonal , Transplantation Conditioning/adverse effects , Transplantation Conditioning/methods
3.
Braz J Biol ; 83: e275635, 2023.
Article in English | MEDLINE | ID: mdl-38126635

ABSTRACT

Bioavailability of nutrients, the scarcity of synthetic fertilisers, and the rising cost of fuel have all contributed to an increase in production costs, which has in turn reduced crop productivity and led scientists to seek out new methods to ensure high-quality output. In this context, various cytokinins dosages were tested in Peru to see whether they affected the quality of caigua, in an effort to address these issues. To mitigate these problems, a pot experiment was carried out to check the effects of various doses of cytokinin in the quality of caigua in Peru. The experiment consisted of 5 treatments including (0, 50, 100, 150 and 200 mL of cytokinin) by using (Anthesis Plus per 200 L of water) as a source, each with three replicates and placed following a randomized complete block design (RCBD). Treatment with 100 mL of cytokinins foliar analysis resulted in a caigua length of 18.9 cm, an increase in diameter of 5.65 cm, and an improvement in pulp thickness of 7.60 millimeters. Physiological parameters of caigua plants taken after 45 days of sowing were considerably improved with the same treatment. Similarly, N, K and Zn concentration in leaf was higher in case of 100 mL of cytokinins foliar analysis. Therefore, policymakers must advise using the recommended quantity of cytokinins to bring about regime transition, and formers can gain by injecting 100 mL of cytokinins to boost production and the economy. It was concluded that the adequate dose of cytokinins is in treatment T3, which raised value of potassium concentration in leaves, this influenced optimal development, strengthening against environmental stress and therefore quality. For this reason, research was carried out on the comparative study of cytokinin doses in the quality of caigua in Peru; the objective was to determine the appropriate dose to obtain higher quality fruit. Likewise, it was underlined that the objective was to employ an ecological alternative of plant origin such as the usage of phytohormone that stimulates the growth of the plant and consequently the quality of the fruit. The obtained the results were served as a recommendation for farmers in the area.


Subject(s)
Cytokinins , Plant Growth Regulators , Cytokinins/pharmacology , Peru , Plant Growth Regulators/pharmacology , Plant Leaves/physiology , Stress, Physiological
4.
Braz J Biol ; 83: e275698, 2023.
Article in English | MEDLINE | ID: mdl-37937631

ABSTRACT

The pandemic and the geopolitical conflict between Russia and Ukraine are events that have caused economic instability in Peru. Reason that was investigated on the analysis of the biological and chemical characteristics of cabbage fed with compost based on sugarcane residues. The objective was to analyze the physical, chemical and biological characteristics of cabbage from the adequate dose of compost based on sugarcane residues and distance between plants. It is based on the methodology applied with an experimental approach, for which the Completely Random Block Design with a 4x 2 factorial arrangement was used, which consisted of 3 blocks and 8 treatments that were the combination: F1 with 0, F2 with 8, T3 with 10 and F4 with 12 t/ha and spacing (D1) with 0.30 m between plants and 0.60 m between rows and (D2) with 0.35 m between plants and 0.60 m between rows. The physical characteristics of cabbage were evaluated and processed by analysis of variance, nutrient concentrations in leaves and stomatal density were analyzed. The results determined that T7 stood out in plant height with 41.88 cm, yield with 26.76 tn/ha and T6 in root length with 20.22 cm. In chemical analysis of leaves T1 stood out in nitrogen, phosphorus, potassium and T4 in calcium, magnesium and sulfur. In T7 stomata density with 977 stomata/mm2. It concludes that at an adequate dose and greater distance that T7 stands out in the concentration of nutrients that are within normal values and high density of stomata; Therefore, these characteristics influenced the optimal biochemical reactions, which obtained good development and yield that differed at 51.39% and 32.17% with respect to the controls T1 and T5.


Subject(s)
Brassica , Composting , Saccharum , Brassica/chemistry , Russia
5.
bioRxiv ; 2023 Sep 13.
Article in English | MEDLINE | ID: mdl-37745319

ABSTRACT

Changes in daylight amount (photoperiod) drive pronounced alterations in physiology and behaviour1,2. Adaptive responses to seasonal photoperiods are vital to all organisms - dysregulation is associated with disease, from affective disorders3 to metabolic syndromes4. Circadian rhythm circuitry has been implicated5,6 yet little is known about the precise neural and cellular substrates that underlie phase synchronization to photoperiod change. Here we present a previously unknown brain circuit and novel system of axon branch-specific and reversible neurotransmitter deployment that together prove critical for behavioural and sleep adaptation to photoperiod change. We found that the recently defined neuron type called mrEn1-Pet17 located in the mouse brainstem Median Raphe Nucleus (MRN) segregates serotonin versus VGLUT3 (here proxy for the neurotransmitter glutamate) to different axonal branches innervating specific brain regions involved in circadian rhythm and sleep/wake timing8,9. We found that whether measured during the light or dark phase of the day this branch-specific neurotransmitter deployment in mrEn1-Pet1 neurons was indistinguishable; however, it strikingly reorganizes on photoperiod change. Specifically, axonal boutons but not cell soma show a shift in neurochemical phenotype upon change away from equinox light/dark conditions that reverses upon return to equinox. When we genetically disabled the deployment of VGLUT3 in mrEn1-Pet1 neurons, we found that sleep/wake periods and voluntary activity failed to synchronize to the new photoperiod or was significantly delayed. Combining intersectional rabies virus tracing and projection-specific neuronal silencing in vivo, we delineated a Preoptic Area-to-mrEn1Pet1 connection responsible for decoding the photoperiodic inputs, driving the neurochemical shift and promoting behavioural synchronization. Our results reveal a previously unrecognized brain circuit along with a novel form of periodic, branch-specific neurotransmitter deployment that together regulate organismal adaptation to photoperiod changes.

6.
Zhonghua Xue Ye Xue Za Zhi ; 44(12): 1010-1015, 2023 Dec 14.
Article in Chinese | MEDLINE | ID: mdl-38503524

ABSTRACT

Objective: This study aimed to observe the dynamic changes of NUP98::NSD1 expression before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Moreover, the clinical value of measurable residual disease (MRD) was analyzed. Methods: Sixteen AML patients who were diagnosed with the NUP98::NSD1 fusion gene and received allo-HSCT at Peking University People's Hospital were included. The NUP98::NSD1 fusion gene and leukemia-associated immunophenotype (LAIP) were monitored before and after transplantation to evaluate their MRD status. Results: The median follow-up time for all patients was 526 days (139-1136 days) , with four patients (25.0%) experiencing hematological recurrence at a median of 474 days (283-607 days) after transplantation. Three patients (18.8%) died, two of whom (12.5%) died of leukemia recurrence. The median expression level of NUP98::NSD1 in newly diagnosed patients with complete data was 78.5% (18.9%-184.4%) at the time of initial diagnosis. The recurrence rate was higher in NUP98::NSD1-positive patients after transplantation, with 44.4% of patients experiencing recurrence, whereas no recurrence occurred in NUP98::NSD1-negative patients after transplantation. The area under the receiver operating characteristic curve predicted by the NUP98::NSD1 level after transplantation was 1.000 (95% confidence interval: 1.000-1.000, P=0.003) . Among the four patients with recurrence, NUP98::NSD1 was more sensitive than flow cytometry residual (FCM) and Wilms' tumor gene 1 (WT1) . Conclusions: The NUP98::NSD1 fusion gene can be used to evaluate the MRD status of allo-HSCT. NUP98::NSD1-positive patients after transplantation have a high relapse rate and poor prognosis. NUP98::NSD1 was more sensitive than FCM and WT1 in predicting posttransplant relapse.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Nuclear Pore Complex Proteins , Humans , Clinical Relevance , Transplantation, Homologous , Recurrence , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/therapy , Chronic Disease , Neoplasm, Residual , Prognosis , Histone-Lysine N-Methyltransferase
7.
Zhonghua Xue Ye Xue Za Zhi ; 43(3): 221-228, 2022 Mar 14.
Article in Chinese | MEDLINE | ID: mdl-35405780

ABSTRACT

Objective: To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . Methods: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (n=788) or underwent MSDT (n=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Results: Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% CI 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% CI 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% CI 15.0% -19.7% ) and 13.8% (95% CI 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% CI 66.1% -72.1% ) and 73.0% (95% CI 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (n=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [n=716, 31.6% (95% CI 25.8% -37.5% ) vs 14.3% (95% CI 11.4% -17.2% ) , P<0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (n=219) had a lower 3-year CIR than that of cases who underwent MSDT [n=63, 27.2% (95% CI 21.0% -33.4% ) vs 47.0% (95% CI 33.8% -60.2% ) , P=0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (n=716) , cases with Pre-MRD<0.01% group (n=46) , cases with Pre-MRD 0.01% -<0.1% group (n=117) , cases with Pre-MRD 0.1% -<1% group (n=87) , and cases with Pre-MRD≥1% group (n=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (n=40) had a lower CIR than that of MSDT [n=6, 10.0% (95% CI 0.4% -19.6% ) vs 32.3% (95% CI 0% -69.9% ) , P=0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (n=81) also had a lower 3-year CIR than that of MSDT [n=36, 20.4% (95% CI 10.4% -30.4% ) vs 47.0% (95% CI 29.2% -64.8% ) , P=0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (n=163) was performed, the results showed that cases received haplo-HSCT (n=121) experienced lower 3-year CIR [16.0% (95% CI 9.4% -22.7% ) vs 40.5% (95% CI 25.2% -55.8% ) , P<0.001], better 3-year LFS [78.2% (95% CI 70.6% -85.8% ) vs 47.6% (95% CI 32.2% -63.0% ) , P<0.001] and OS [80.5% (95% CI 73.1% -87.9% ) vs 54.6% (95% CI 39.2% -70.0% ) , P<0.001] than those of MSDT (n=42) , but comparable in 3-year NRM [5.8% (95% CI 1.6% -10.0% ) vs 11.9% (95% CI 2.0% -21.8% ) , P=0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (HR=0.248, 95% CI 0.131-0.472, P<0.001) , and superior LFS (HR=0.275, 95% CI 0.157-0.483, P<0.001) and OS (HR=0.286, 95% CI 0.159-0.513, P<0.001) . Conclusion: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, B-Cell , Leukemia, Lymphocytic, Chronic, B-Cell , Precursor Cell Lymphoblastic Leukemia-Lymphoma , B-Lymphocytes , HLA Antigens/genetics , Haplotypes , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Leukemia, B-Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Neoplasm, Residual , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Recurrence , Retrospective Studies , Siblings
8.
J Neonatal Perinatal Med ; 15(2): 317-325, 2022.
Article in English | MEDLINE | ID: mdl-34719446

ABSTRACT

BACKGROUND: Currently there is limited information to guide health professionals regarding the optimal time frame to initiate safe and effective oral feedings to preterm infants. The study aims to revise and validate a streamlined version of the Traditional Chinese-Preterm Oral Feeding Readiness Assessment Scale, the TC-POFRAS®, and evaluate its construct validity in the clinical decisions regarding feeding readiness of preterm infants. METHODS: Eighty-one clinically stable preterm infants were assessed using the TC-POFRAS for oral feeding readiness. Item-total correlation analysis was used to check if any item was inconsistent with the averaged TC-POFRAS scores. Cronbach's α coefficient was used to evaluate the inter-item consistency. Exploratory factor analysis was used to determine the coherence of variables to reorganize assessment domains. The revised version of TC-POFRAS (TC-POFRAS®) was developed and a new cut-off score based on discriminant accuracy was established. RESULTS: Based on the results from statistical analysis, five items ("lips posture," "tongue posture," "biting reflex," "gag reflex," and "tongue cupping") were deleted from the original TC-POFRAS to form the TC-POFRAS®. The TC-POFRAS®'s global accuracy was 92.1%. The cut-off value of 19 was the one that presented the most optimization of sensitivity based on specificity. The TC-POFRAS® was reconstructed into corrected gestational age and five behavioral domains. CONCLUSIONS: The TC-POFRAS® is considered a valid, safe, and accurate objective instrument to assist health professionals to initiate oral feeding of preterm infants.


Subject(s)
Infant, Premature , Humans , Infant , Infant, Newborn
11.
BJS Open ; 5(5)2021 09 06.
Article in English | MEDLINE | ID: mdl-34672342

ABSTRACT

BACKGROUND: The study aimed to assess the correlation between long-term survival and treatment in very young women with breast cancer. METHODS: Data on women with breast cancer were retrieved from the Taiwan Cancer Registry between 2004 and 2014. Patients who did not undergo surgery or who had stage 0 or IV disease were excluded. Survival analysis was conducted. The participants were divided into very young (20-29.9 years), young (30-39.9 years), and adult (40-50.0 years) groups. RESULTS: Among 104 115 women, 24 474 (572 very young, 5565 young, and 18 337 adult) were eligible for the study. Median follow-up was 79.5 (range 24-158) months. The mortality rates in the very young, young, and adult groups were 12.9, 10.0, and 8.2 per cent respectively (P < 0.001). Very young patients had higher histological grade, unfavourable subtype, higher TNM stage, and received more breast-conserving surgery (BCS). Kaplan-Meier survival analysis showed that very young patients had the poorest long-term survival. Very young patients with stage II disease had the worst prognosis. In the multivariable regression model, radiotherapy was associated with decreased local recurrence but not with improved overall, cancer-specific, or disease-free survival for stage II disease in the very young group. Surgery type and chemotherapy were not associated with significant improvement in overall survival. CONCLUSION: Very young patients with stage II disease had poor long-term outcomes. BCS had no detrimental effects on long-term outcomes.


Subject(s)
Breast Neoplasms , Breast Neoplasms/surgery , Breast Neoplasms/therapy , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Mastectomy, Segmental , Prognosis
12.
Zhonghua Nei Ke Za Zhi ; 60(7): 644-649, 2021 Jul 01.
Article in Chinese | MEDLINE | ID: mdl-34619842

ABSTRACT

Objective: To investigate the incidences and risk factors of poor hematopoietic reconstitution (PHR) in patients with hematological diseases who underwent haploidentical allograft and were treated with rituximab for desensitization. Methods: Eight-three donor specific anti-HLA antibody (DSA, 2000 ≤MFI<10 000) positive patients who underwent haploidentical allograft were prospectively enrolled. Rituximab (375 mg/m2) was used for desensitization day-3 of conditioning regimen. Incidence and factors associated with PHR, including primary poor graft function and prolonged thrombocytopenia, were investigated. Results: There were 22 males and 61 females with a median age of 39(range: 1-65) years. Kaplan-Meier analysis showed that the 100 day cumulative incidences of neutrophil and platelet engraftment were 93.0% and 90.7%, respectively. The incidences of PHR were 14.7%. The 3-year relapse rate, non-relapse mortality (NRM) rate, event-free survival (EFS), leukemia-free survival (DFS) and overall survival (OS) were 6.5%, 15.1%, 70.8%, 79.4% and 79.4%, respectively. Patients with DSA MFI<5 000 (group A, n=46) experienced lower PHR (4.4% vs. 27.5%, P=0.003), and higher 3-year EFS (79.5% vs. 59.8%, P=0.020) compared to those with DSA MFI≥5 000 (group B, n=37). Multivariate analysis showed that DSA MFI≥5 000 was correlated with PHR (HR=6.101, P=0.021). PHR was associated with higher NRM (HR=4.110, P=0.026), lower DFS (HR=3.656, P=0.019) and OS (HR=3.656, P=0.019). Conclusion: Our data suggest that high pre-transplant DSA level is a risk factor for PHR in patients with hematological diseases receiving haploidentical allograft and rituximab for desensitization.


Subject(s)
Hematologic Diseases , Hematopoietic Stem Cell Transplantation , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Hematologic Diseases/therapy , Humans , Infant , Male , Middle Aged , Neoplasm Recurrence, Local , Rituximab/therapeutic use , Tissue Donors , Young Adult
13.
Zhonghua Nei Ke Za Zhi ; 60(10): 868-874, 2021 Oct 01.
Article in Chinese | MEDLINE | ID: mdl-34551474

ABSTRACT

Objective: To investigate the dynamic change and clinical impact of DEK-NUP214 fusion gene in patients with acute myeloid leukemia (AML) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Real-time quantitative polymerase chain reaction (RQ-PCR) and multicolor flow cytometry (FCM) were used to detect DEK-NUP214 gene expression and leukemia-associated immunophenotype (LAIP) in 15 newly diagnosed patients with positive DEK-NUP214 and receiving allo-HSCT from September 2012 to September 2017 at Peking University People's Hospital. The clinical outcome was analyzed using Kaplan-Meier survival curves. The impact of DEK-NUP214 expression was analyzed by log-rank test. Results: The subjects were followed-up with a median period of 657 (62-2 212) days. The median DEK-NUP214 expression level at diagnosis was 488% (274%-1 692%). Thirteen patients achieved complete remission before allo-HSCT. Thirteen patients had a residual DEK-NUP214 expression of 0.38% (0.029%-738.9%) before allo-HSCT. After allo-HSCT, DEK-NUP214 expression in 9/13 patients remained positive, which dropped by around 500 folds (5.7-5 663.0 folds) within a month post-transplant. Five patients died and 2 patients relapsed. The 3-year cumulative incidence of relapse in patients with positive DEK-NUP214 before transplant was 17.5%±11.3% and the 3-year overall survival was 60.5%±13.8%. After allo-HSCT, DEK-NUP214-negative patients had a better outcome. Conclusion: Quantitative monitor of DEK-NUP214 fusion gene could be a sensitive indicator of MRD status after allo-HSCT.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Chromosomal Proteins, Non-Histone/genetics , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/therapy , Neoplasm, Residual , Nuclear Pore Complex Proteins , Oncogene Proteins/genetics , Poly-ADP-Ribose Binding Proteins/genetics , Prognosis , Transplantation, Homologous
14.
Zhonghua Xue Ye Xue Za Zhi ; 42(2): 116-123, 2021 Feb 14.
Article in Chinese | MEDLINE | ID: mdl-33858041

ABSTRACT

Objective: To explore the different values of minimal residual disease (MRD) detection by multiparameter flow cytometry (MFC) and real-time quantitative polymerase chain reaction (RQ-PCR) before hematopoietic stem cell transplantation (HSCT) for predicting relapse, leukemia-free survival (LFS) , and overall survival (OS) in Philadelphia chromosome-positive ALL (Ph(+) ALL) . Methods: A retrospective study (n=280) was performed. MRD was determined using multiparameter flow cytometry and RQ-PCR. Results: MRD analysis with MFC and RQ-PCR of the BCR-ABL fusion transcript showed a strong correlation before transplantation. The positive rates of MRD detected by MFC and RQ-PCR before transplantation were 25.7% (72/280) and 60.7% (170/280) , respectively. MFC MRD-positive (MRDpos) Ph(+) ALL patients had a higher 3 year cumulative incidences of relapse (CIR) than did MFC MRD-negative (MRDneg) Ph(+) ALL patients (23.6%vs 8.6%; P<0.001) . However, the RQ-PCR MRDpos group had similar rates of 3 year OS, LFS, and NRM compared with those in the RQ-PCR MRDneg group. Moreover, patients with RQ-PCR MRD ≥1% experienced higher 3 year CIR (23.1%vs 11.4%; P=0.032) , lower LFS (53.8%vs 74.4%; P=0.015) , and OS (57.7% vs 79.1%; P=0.009) compared with the RQ-PCR MRD<1% group. Multivariate analyses confirmed the association of MFC MRD status and RQ-PCR MRD ≥1% with outcomes (P<0.05) . The sensitivity, specificity, positive predictive value (PPV) , and negative predictive value (NPV) of MFC detection MRD to predict recurrence were 48.50%, 77.56%, 23.62%, and 87.16%, respectively. Moreover, the sensitivity, specificity, PPV, and NPV were 23.00%, 88.59%, 17.15%, and 91.84%, respectively, when RQ-PCR MRD ≥1% was used to predict recurrence. Additionally, the sensitivity, specificity, PPV, and NPV were 54.29%, 73.88%, 45.7% and 91.87%, respectively, when MRD-positive status before transplantation (MFC MRDpos or RQ-PCR MRD ≥1%) was used to predict recurrence after transplantation. Conclusions: Both MFC and RQ-PCR detection of pretransplant MRD levels can predict the prognosis of Ph(+) B-ALL patients receiving allogeneic HSCT. MFC MRD-positive status before transplantation is the risk factor of leukemia recurrence after transplantation. The combined use of the two methods (MFC MRDpos or RQ-PCR MRD ≥1%) can improve the sensitivity, PPV, and NPV of predicting recurrence and help to better screen high-risk patients for intervention, thereby improving clinical efficacy.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, B-Cell , Flow Cytometry , Humans , Neoplasm, Residual , Philadelphia Chromosome , Prognosis , Real-Time Polymerase Chain Reaction , Retrospective Studies , Transplantation, Homologous
18.
Zhonghua Xue Ye Xue Za Zhi ; 40(10): 812-817, 2019 Oct 14.
Article in Chinese | MEDLINE | ID: mdl-31775478

ABSTRACT

Objective: To evaluate the efficacy of consolidation chemotherapy combined with allogeneic natural killer (NK) cell infusion in the treatment of low or intermediate-risk (LIR) acute myeloid leukemia (AML) . Methods: A cohort of 23 LIR AML patients at hematologic complete remission (CR) received NK cell transfusion combined with consolidation chemotherapy after 3 consolidation courses from January 2014 to June 2019 were reviewed. Control group cases were concurrent patients from Department of Hematology, and their gender, age, diagnosis, risk stratification of prognosis, CR and the number of courses of consolidate chemotherapy before NK cell transfusion were matched with LIR AML patients. Results: A total of 45 times of NK cells were injected into 23 LIR AML patients during 4 to 7 courses of chemotherapy. The median NK cell infusion quantity was 7.5 (6.6-8.6) ×10(9)/L, and the median survival rate of NK cells was 95.4% (93.9%-96.9%) . Among them, the median CD3(-)CD56(+) cell number was 5.0 (1.4-6.4) ×10(9)/L, accounting for 76.8% (30.8%-82.9%) ; The number of CD3(+) CD56(+) cells was 0.55 (0.24-1.74) ×10(9)/L, accounting for 8.8% (4.9%-20.9%) . Before NK cell infusion, the number of patients with positive MRD in the treatment and control groups were 9/23 (39.1%) and 19/46 (41.3%) (χ(2)=0.030, P=0.862) respectively. After NK infusion, There was no significant difference in terms of MRD that went from negative to positive between the treatment and the control groups (14.3% vs 22.2%, χ(2)=0.037, P=0.847) . In the treatment group, 66.7% (6/9) of the MRD were converted from positive to negative, which was significantly higher than that in the control group (10.5%, 2/19) (χ(2)=6.811, P=0.009) . Morphological recurrence occurred in 1 case of MRD negative in the treatment group and 2 cases of MRD positive in the control group. By the end of follow-up, the median follow-up was 35 (10-59) months, the number of patients with morphological recurrence in the treatment group was 30.4% (7/23) , which was significantly lower than that in the control group (50.2%, 24/46) (χ(2)=2.929, P=0.087) , although there was no statistically significant difference between the two groups. There was no significant difference on MRD-negative between the treatment and the control groups (43.5% vs 43.5%, χ(2)=1.045, P=0.307) . The 3-year leukemia-free survival was better in the treatment group [ (65.1±11.1) %] than that in the control group [ (50.0±7.4) %] (P=0.047) . The 3-year overall survival in the treatment and control groups were (78.1±10.2) % and (65.8±8.0) % (P=0.212) , respectively. Conclusion: The consolidation of chemotherapy combined with allogeneic NK cell infusion contributed to the further remission of patients with LMR AML and the reduction of long-term recurrence.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Consolidation Chemotherapy , Humans , Killer Cells, Natural , Leukemia, Myeloid, Acute/therapy , Prognosis , Remission Induction
20.
Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 32(23): 1810-1812, 2018 Dec 05.
Article in Chinese | MEDLINE | ID: mdl-30550215

ABSTRACT

Objective: To evaluate the effect of the application of functional parotid surgery for removal of benign parotid tumors and the prevention of Frey syndrome. Method: One hundred and fifty-six cases with benign tumor were underwent functional regional parotidectomy. All tumors were smaller than 4 cm in diameter. The safe surgical margin was 5 mm when the tumors were less than 2 cm in diameter, while the safety margin was 1 cm for the tumors diameter between 2-4 cm. 156 cases were assigned to two groups(A and B). The absorbable hemostatic sponge was placed between the surface of parotid gland and skin flap after tumor resection in group A,while no sponge was placed in group B. Postoperative followup was 12-24 months. Result: No compression bandage was performed. No patient had recurrence or salivary fistula. There were 3 cases of temporary facial paralysis, of which 2 cases recovered from the mandibular marginal branch injury within 1 month and 1 case recovered from the facial nerve trunk injury within 6 months. Compared with group B 15.38%(12/78),the incidence of Frey syndrome was significantly decreased in group A 3.85%(3/78).χ2=5.728, P<0.05. Conclusion: The removal of benign parotid tumors by functional parotid surgery can effectively preserve the function of residual gland and reduce complication. Intraoperative implantation of absorbable hemostatic sponge between parotid gland and skin flap can reduce the incidence of Frey syndrome.

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