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1.
Zhonghua Nei Ke Za Zhi ; 59(5): 347-352, 2020 May 01.
Artigo em Chinês | MEDLINE | ID: mdl-32370462

RESUMO

Objective: To investigate the efficacy and safety of daratumumab in relapsed and refractory multiple myeloma (RRMM). Methods: The efficacy and adverse events (AEs) of daratumumab based regimens were retrospectively analyzed in 37 patients with RRMM from Peking University People's Hospital, Beijing Hospital and Fu Xing Hospital affiliated to Capital Medical University in China. The deadline for inclusion was December, 2019. Results: Among the 37 patients, 35 patients were available for response evaluation. The overall response rate (ORR) was 68.6%, which was better in patients receiving 16 mg/kg daratumumab than in those with fixed doses of 800 mg daratumumab [ORR: 78.3%(18/23) vs. 40.0%(4/10)]. The percentage of infusion related reactions of daratumumab was 27.0%(10/37). The most common hematological AEs were lymphocytopenia and thrombocytopenia, with the incidences of grade 3 or more severe 59.5%(22/37) and 43.2%(16/37) respectively. Pulmonary infections(37.8%, 14/37) were the most common non-hematological AEs. One patient with positive hepatitis B surface antigen (HBsAg) and two patients dependent on dialysis were safely treated with daratumumab. Conclusion: Daratumumab is highly effective in relapsed and refractory multiple myeloma. Adverse reactions are mild and well tolerable.

2.
Zhonghua Xue Ye Xue Za Zhi ; 41(4): 308-312, 2020 Apr 14.
Artigo em Chinês | MEDLINE | ID: mdl-32447935

RESUMO

Objective: To retrospectively analyzed the impact of splenomegaly on outcomes in patients with chronic myelomonocytic leukemia (CMML) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Clinical data of 25 patients with CMML receiving allo-HSCT at Peking University Institute of Hematology from 2004-2018 were retrospectively analyzed. Engraftment, graft versus host disease (GVHD) , relapse, survival were compared between patients with or without splenomegaly before transplantation. Results: There were 15 splenomegaly patients including 8 males and 7 females with a median age of 45 (23-61) years, and 10 non-splenomegaly patients including 5 males and 5 females with a median age of 39 (12-56) years. Clinical characteristics at baseline were comparable in two groups (P>0.05) . The neutrophil engraftment rates in splenomegaly and non-splenomegaly patients were 93.3% (14/15) and 100.0% (10/10) , and with a median time of 17 (11-20) days and 14 (11-18) days respectively (χ(2)=5.303, P=0.021) . The platelet engraftment rates in splenomegaly and no-splenomegaly patients were 80.0% (12/15) and 90.0% (9/10) (P=0.212) , and the median time of engraftment was 17 (12-33) days and 15 (12-19) days respectively (χ(2)=0.470, P=0.493) . Five patients with splenomegaly developed acute GVHD (aGVHD) (4 patients with grade Ⅰ/Ⅱ, 1 with grade Ⅲ/Ⅳ) , and 6 patients developed aGVHD in non-splenomegaly group (5 with grade Ⅰ/Ⅱ, 1 with grade Ⅲ/Ⅳ) (χ(2)=0.204, P=0.652) . The cumulative incidences of aGVHD at 100 days between two groups were 33.3% (95%CI 14.9%-51.7%) and 20.0% (95%CI 2.8%-37.2%) respectively (P=0.635) . Five patients in splenomegaly group developed chronic GVHD (cGVHD) including 3 patients with extensive cGVHD. None in non-splenomegaly group reported cGVHD (P=0.041) . The 3-year cumulative incidences of relapse in splenomegaly and non-splenomegaly patients were (42.7±2.6) % and (11.1±1.2) % (P=0.122) , and the 3-year overall survival rates were (61.5±13.5) % and (68.6±15.1) % (χ(2)=0.351, P=0.554) . In addition, the leukemia-free survival rates were (56.3±14.8) % and (80.0±17.9) % respectively (χ(2)=1.148, P=0.284) . Conclusion: In CMML patients receiving allo-HSCT, splenomegaly may have an impact on the time of neutrophil engraftment, but not affecting disease relapse and survival.

3.
Zhonghua Xue Ye Xue Za Zhi ; 41(2): 93-99, 2020 Feb 14.
Artigo em Chinês | MEDLINE | ID: mdl-32135623

RESUMO

Objective: To explore the efficacy and prognosis of nilotinib or dasatinib as second- or third-line treatment in patients with chronic myeloid leukemia (CML) in the chronic phase (CP) and accelerated phase (AP) . Methods: From January 2008 to November 2018, the data of CML patients who failed first- or second-line tyrosine kinase inhibitor (TKI) -therapy received nilotinib or dasatinib as second-line and third-line therapy were retrospectively reviewed. Results: A total of 226 patients receiving nilotinib or dastinib as second-line (n=183) and third-line (n=43) therapy were included in this study. With a median follow-up of 21 (range, 1-135) months, the cumulative rates of complete hematological response (CHR) , complete cytogenetic response (CCyR) and major molecular response (MMR) were 80.4%, 56.3%and 38.3%, respectively in those receiving TKI as second-line TKI therapy. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 78.7%and 93.1%, respectively. Multivariate analyses showed that Sokal high risk, female gender, the best response achieved

Assuntos
Dasatinibe/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva , Pirimidinas/uso terapêutico , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento
4.
Zhonghua Xue Ye Xue Za Zhi ; 41(2): 106-111, 2020 Feb 14.
Artigo em Chinês | MEDLINE | ID: mdl-32135625

RESUMO

Objective: To analyze the risk factors of steroid resistant acute graft- versus-host disease (aGVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The clinical data of adult patients with acute myeloid leukemia (AML) /Myelodysplastic syndrome (MDS) who developed aGVHD after haplo-HSCT in Peking University Institute of Hematology from January 1st, 2010 to December 31st, 2012 were retrospectively reviewed. Results: A total of 85 patients were enrolled in the study, including 55 males and 30 females, with a median age of 30 (19-67) years. After steroid therapy, there were 53 (62.4%) , 6 (7.1%) and 26 (30.6%) patients achieved complete remission (CR) , partial remission (PR) and non-remission (NR) , respectively. The CR rates of the grade Ⅰ/Ⅱ and Ⅲ/Ⅳ aGVHD by steroid therapy were 66.2% (51/77) vs 25.0% (2/8) (χ(2)=3.639, P=0.048) , respectively. The CR rates of the patients with aGVHD involving 1 target organ and 2 target organs were 77.4% (48/62) vs 21.7% (5/23) (χ(2)=22.157, P<0.001) . The CR rates of patients with standard risk (SR) and high risk (HR) Minnesota risk score was 67.5% (52/77) vs 12.5% (1/8) (χ(2)=7.153, P=0.004) . The mononuclear cells≥8.33×10(8)/kg and the HR Minnesota risk score were independent risk factors for steroid-resistant aGVHD in multivariate analysis. Between Minnesota risk score SR (77 cases) and HR (8 cases) groups, the OS rates at 22 months after transplantation were (90.3±3.8) %vs (75.0±15.3) % (χ(2)=2.831, P=0.092) . After steroid treatment for aGVHD, the OS rates at 22 months in the CR group (53 cases) and non-CR group (32 cases) were (95.2±3.4) %vs (78.6±7.9) % (χ(2)=5.287, P=0.021) respectively. Conclusion: The Minnesota risk score and mononuclear cells count are effective tool for predicting steroid-resistant aGVHD after haplo-HSCT.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Doença Aguda , Adolescente , Adulto , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
5.
Eur Rev Med Pharmacol Sci ; 24(1): 213-221, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31957834

RESUMO

OBJECTIVE: To uncover the role of circ0021205 in the progression of non-small cell lung cancer (NSCLC) and its molecular mechanism. PATIENTS AND METHODS: The expression level of circ0021205 in NSCLC tissues and cells was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between circ0021205 level and the pathological indexes of NSCLC was analyzed by the Chi-square test. The Kaplan-Meier curves were depicted for evaluating the influence of circ0021205 on the survival of NSCLC patients. After altering circ0021205 level in A549 and PC9 cells, the changes in the proliferative, migratory, and invasive abilities were assessed. The interaction among circ0021205, miRNA-16-5p, and the vascular endothelial growth factor A (VEGFA) was verified by Dual-Luciferase Reporter Gene Assay and the Spearman correlation test. At last, the role of circ0021205/miRNA-16-5p/VEGFA axis in regulating the progression of NSCLC was identified. RESULTS: Circ0021205 was upregulated in NSCLC tissues and cells. Its level was positively correlated to tumor size, tumor node metastasis (TNM) staging, and distant metastasis of NSCLC. Upregulation of circ0021205 predicted worse prognosis of NSCLC patients. The overexpression of circ0021205 in A549 and PC9 cells accelerated proliferative, migratory, and invasive abilities. Moreover, circ0021205 could bind to miRNA-16-5p to further mediate VEGFA level. The overexpression of miRNA-16-5p or knockdown of VEGFA could reverse the role of the overexpressed circ0021205 in regulating the cellular behaviors of NSCLC. CONCLUSIONS: Circ0021205 aggravates the malignant progression of NSCLC by binding to miRNA-16-5p to regulate the VEGFA level.

6.
Zhonghua Xue Ye Xue Za Zhi ; 40(11): 889-894, 2019 Nov 14.
Artigo em Chinês | MEDLINE | ID: mdl-31856435

RESUMO

Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People's Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories' results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion: The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.


Assuntos
Leucemia Mieloide Aguda , China , Subunidade alfa 2 de Fator de Ligação ao Core , Humanos , Proteína 1 Parceira de Translocação de RUNX1 , Reação em Cadeia da Polimerase em Tempo Real , Transcrição Genética , Proteínas WT1
7.
Zhonghua Xue Ye Xue Za Zhi ; 40(11): 924-931, 2019 Nov 14.
Artigo em Chinês | MEDLINE | ID: mdl-31856442

RESUMO

Objectives: To compare the efficacy and safety of Chinese generic imatinib with branded imatinib as frontline therapy in adults with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) (Frontline group) , and to explore the efficacy and safety of Chinese generic imatinib in CML-CP patients switching from branded imatinib (Switching group) . Methods: Frontline group: Data of adults with newly diagnosed CML-CP receiving Chinese generic imatinib (Xinwei(®)) or branded imatinib (Glivec(®)) between October 2013 and August 2018 were retrospectively collected and analyzed. Switching group: Data of adults diagnosed with CML-CP who received branded imatinib and then switched to Chinese generic imatinib after achieving at least complete cytogenetic response (CCyR) were retrospectively collected and analyzed. Results: Frontline group: In total, 409 adult patients receiving Chinese generic imatinib (n=201) or Glivec (n=208) were included in this study. Median age was 42 years (range, 18-83 years) . Comparison of baseline showed significant difference on demographic characteristics among two cohorts: lower education level (P<0.001) , and divorced or widowed status (P=0.004) and rural household registration (P<0.001) were more common in the generic imatinib cohort than those in the Glivec cohort. There was no significant difference on age, gender, Sokal risk score, WBC and HGB between the 2 cohorts. With a median follow-up of 25 months (range, 3-62 months) , there was no significant difference on the 3-year cumulative incidence of achieving CCyR (97.5% vs 94.5%, P=0.592) , major molecular response (MMR) (84.3% vs 93.1%, P=0.208) , molecular response(4.0) (MR(4.0)) (42.7% vs 41.7%, P=0.277) , molecular response(4.5) (MR(4.5)) (25.4% vs 33.0%, P=0.306) as well as the 3-year probabilities of failure free survival (FFS) (76.7% vs 81.0%, P=0.448) , progression free survival (PFS) (91.8% vs 96.3%, P=0.325) and overall survival (OS) (95.8% vs 98.5%, P=0.167) between the generic and branded imatinib cohorts. Multivariate analysis showed the type of imatinib was not associated with treatment responses and outcomes. The incidences of adverse effects were comparable in the 2 cohorts. Switching group: In total, 39 patients switching from branded imatinib to Chinese generic imatinib after achieving at least CCyR were included in this study. Median age was 42 years (range, 23-80 years) . With a median follow-up of 39 months (range, 6-63 months) , molecular responses were maintained in 23 (58.9%) patients and improved in 12 (39.8%) patients. Adverse effects were tolerable. Conclusion: Demographic characteristics might influence the choice of the type of TKI used in CML-CP patients. There was a comparable efficacy and safety between the Chinese generic imatinib and the branded imatinib in adults with newly diagnosed CML-CP under standard management and closely monitoring. Patients could safely switch from the branded imatinib to the Chinese generic imatinib.


Assuntos
Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos , Demografia , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
8.
Zhonghua Xue Ye Xue Za Zhi ; 40(10): 812-817, 2019 Oct 14.
Artigo em Chinês | MEDLINE | ID: mdl-31775478

RESUMO

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.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Quimioterapia de Consolidação , Humanos , Células Matadoras Naturais , Leucemia Mieloide Aguda/terapia , Prognóstico , Indução de Remissão
9.
Zhonghua Xue Ye Xue Za Zhi ; 40(10): 831-836, 2019 Oct 14.
Artigo em Chinês | MEDLINE | ID: mdl-31775482

RESUMO

Objective: To investigate the characteristic and prognostic significance of leukemia stem cells associated antigens expressions including CD34, CD38, CD123, CD96 and TIM-3 in t (8;21) AML. Methods: Bone marrow samples of 47 t (8;21) AML patients were collected at diagnosis from October 2015 to April 2018 in Peking University Peoples' Hospital, then flow cytometry method was performed to detect the expression frequencies of CD34, CD38, CD123, CD96 and TIM-3 to analyze the relationship between leukemia stem cells associated antigens expressions and relapse. Results: Of 47 t (8;21) AML patients tested, the median percentages of CD34(+)CD38(-), CD34(+) CD38(-)CD123(+), CD34(+)CD38(-) CD96(+) and CD34(+) CD38(-) TIM-3(+) cells among nucleated cells were 2.37%, 0.24%, 0.27% and 0.06%, respectively. All the frequencies of CD34(+)CD38(-), CD34(+)CD38(-)CD123(+), CD34(+)CD38(-)CD96(+) and CD34(+) CD38(-)TIM-3(+) cells had no impact on the achievement of CR after the first course of induction. All higher frequencies of CD34(+)CD38(-), CD34(+)CD38(-)CD123(+), CD34(+)CD38(-)CD96(+) cells were related to higher 2-year CIR rate. Whereas, the frequency of CD34(+) CD38(-) TIM-3(+) cells had no impact on CIR rate. Both high frequency of CD34(+) CD38(-) cells and the high level of minimal residual diseases (patients with <3-log reduction in the RUNX1-RUNX1T1 transcript level after the second consolidation therapy) were independent poor prognostic factors of CIR[P=0.025, HR=6.9 (95%CI 1.3-37.4) ; P=0.031, HR=11.1 (95%CI 1.2-99.2) ]. Conclusion: Different leukemia stem cells associated antigens had distinct prognostic significance in t (8;21) AML. High frequencies of CD34(+) CD38(-), CD34(+) CD38(-) CD123(+) and CD34(+)CD38(-)CD96(+) cells at diagnosis predicted relapse in patients with t (8;21) AML.


Assuntos
Leucemia Mieloide Aguda , ADP-Ribosil Ciclase 1 , Antígenos CD , Citometria de Fluxo , Humanos , Subunidade alfa de Receptor de Interleucina-3 , Células-Tronco Neoplásicas , Prognóstico , Células-Tronco
10.
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
14.
Beijing Da Xue Xue Bao Yi Xue Ban ; 51(3): 409-413, 2019 Jun 18.
Artigo em Chinês | MEDLINE | ID: mdl-31209410

RESUMO

OBJECTIVE: X-linked adrenoleukodystrophy (ALD) is a severe inherited disorder leading to rapid neurological deterioration and premature death. Allogeneic hematopoietic stem cell transplantation (HSCT) is still the only treatment that halts the neurologic symptoms in ALD. However, many patients lack suitable human leukocyte antigen (HLA) matched related donors and must rely on alternative donors for a source of stem cells. The purpose of this study was to explore the outcomes of haploidentical allogeneic stem cell transplantation for ALD patients. METHODS: Between December 2014 and December 2018, eight children with ALD lacking HLA matched related or unrelated donors were treated with haploidentical allogeneic hematopoietic stem cell transplantation. The patients received conditioning regimen with busulfan 9.6 mg/kg, cyclophosphamide 200 mg/kg and fludarabine 90 mg/m2. Graft-versus-host disease (GVHD) prophylaxis consisted of anti-human thymocyte globulin, cyclosporine A, mycophenolate mofetil and short course of methotrexate. RESULTS: All the 8 children received allogeneic stem cell transplants from their fathers. The median age of the recipients was 8 (range: 5-12) years. The median age of the donors was 36 (range: 32-40) years. All the recipients received granulocyte colony-stimulating factor (G-CSF) mobilized bone marrow and peripheral blood-derived stem cells. The median number of total mononuclear cells dose and CD34+ dose was 10.89 (range: 9.40-12.16)×108/kg and 7.06 (range: 0.74-7.80)×106/kg, respectively. Neutrophil engraftment occurred a median of 11 days (range:8-13 days) after transplantation. Platelet engraftment occurred a median of 10 days (range:8-12 days) after transplantation. All the patients achieved complete donor chimerism at the time of engraftment. Four patients had grades II-IV acute GVHD and 1 had chronic graft-versus-host disease. No severe chronic GVHD occurred. Among all the children, 2 had cytomegalovirus (CMV) DNAemia and 2 Epstein-Barr virus (EBV) DNAemia. Overall, seven of them survived and had no major complications related to transplantation. One died of cerebral hernia after epilepsy 125 days after transplantation. CONCLUSION: The preliminary observation demonstrates that haploidentical allogeneic stem cell transplantation with this novel regimen could successfully achieve full donor chimerism in ALD patients. According to our experience, haploidentical allogeneic hematopoietic stem cell transplantation is safe and feasible in the treatment of X-linked adrenoleukodystrophy.


Assuntos
Adrenoleucodistrofia , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adrenoleucodistrofia/terapia , Adulto , Transplante de Medula Óssea , Criança , Pré-Escolar , Cromossomos Humanos X , Humanos , Condicionamento Pré-Transplante
16.
Zhonghua Xue Ye Xue Za Zhi ; 40(5): 398-403, 2019 May 14.
Artigo em Chinês | MEDLINE | ID: mdl-31207705

RESUMO

Objective: To investigate the efficacy and prognostic factors of induction therapy in FLT3-ITD(+) acute myeloid leukemia (AML) in the real world data. Methods: From January 2013 to December 2016, 114 de novo patients with FLT3-ITD(+)AML were enrolled in this study. Out of 114 cases, 75 were male, and 39 were female. The median age was 42 years old (ranged from 14 to 72 years old) . The chemotherapy regimens were used for induction therapy and all cases were followed up. The treatment response was evaluated by MICM and the comparison of the ratio were analyzed by chi-square test and the survival was estimated by Kaplan-Meier analysis and Cox proportional hazards model was used to identify independent prognostic factors. Results: There were 52 FLT3-ITD(+)AML patients with favorable prognosis genes (46 cases with NPM1, 5 cases with RUNX1-RUNX1T1, 1 case with CEBPA double mutation) and 62 patients with other types of FLT3-ITD(+)AML at diagnosis. All patients completed at least one cycle of induction therapy and the clinical curative effect was evaluated, complete remission (CR) rate was 50.0% (57/114) in one cycle and total CR rate was 72.5% (74/104) in two cycles. The CR rate of the FLT3-ITD(+) AML patients with favorable prognosis genes was 67.3% (35/52) in one cycle and 83.3% (40/48) in two cycles; for the other types FLT3-ITD(+)AML patients, the CR rate was 35.5% (22/62) in one cycle and 64.8% (35/54) in two cycles. There was a significant difference in CR rate between the FLT3-ITD(+)AML patients with and without favorable prognosis genes (P<0.05) . This indicates that the FLT3-ITD(+)AML patients with favorable prognosis gene had relatively good therapeutic effect. Among other types of FLT3-ITD(+)AML patients who did not achieve remission from one cycle of chemotherapy, 9 patients were given sorafenib plus chemotherapy and 6 cases (66.7%) achieved CR; 23 patients were given conventional chemotherapy and 7 cases (30.4%) achieved CR. There was a significant difference between sorafenib plus chemotherapy and conventional chemotherapy groups (χ(2)=4.47, P<0.05) and this indicates that sorafenib plus chemotherapy can significantly improve the CR rate of FLT3-ITD(+)AML patients. Comparing overall survival (OS) and disease free survival (DFS) , there was no significant difference between sorafenib plus chemotherapy and conventional chemotherapy groups (P values were 0.641 and 0.517, respectively) . Conclusion: The overall prognosis of FLT3-ITD(+)AML patients is poor, and the stratification therapeutic efficacy of FLT3-ITD(+)AML without favorable prognosis gene can be improved by sorafenib combined with chemotherapy.


Assuntos
Leucemia Mieloide Aguda , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas de Fusão Oncogênica , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Adulto Jovem , Tirosina Quinase 3 Semelhante a fms
18.
Zhonghua Xue Ye Xue Za Zhi ; 40(4): 281-287, 2019 Apr 14.
Artigo em Chinês | MEDLINE | ID: mdl-31104438

RESUMO

Objectives: To explore the incidence and factors of severe leukopenia and/or thrombocytopenia in newly diagnosed patients with chronic myeloid leukemia (CML) to probe their impacts on cytogenetic and molecular responses, progression free survival (PFS) and overall survival (OS) . Methods: Data of newly diagnosed patients with CML in the chronic phase (CP) and/or accelerated phase (AP) were retrospectively collected and analyzed. Results: 855 CML patients [including 744 (87%) in the CP and 111 (13.0%) in the AP] were included in this study. 523 (61.2%) patients were male with a median age of 39 years (range, 14-87 years) . 749 (87.6%) patients received imatinib, 93 (10.9%) nilotinib, and 13 (1.5%) dasatinib, respectively as front-line therapy. At a median treatment of 1 month (range, 0.1-7.0 months) , 137 (16.0%) developed ≥grade 3 leukopenia and/or thrombocytopenia and recovered 0.6 month (range, 0.3-6.5 months) . Multivariate analysis showed that female gender (OR=1.5, 95%CI 1.0-2.2, P=0.033) , WBC ≥100×109/L (OR=1.9, 95%CI 1.3-2.8, P=0.001) , CP in Sokal high-risk (OR=2.2, 95%CI 1.2-3.9, P=0.005) , AP with ≥15% blast cells in blood or bone marrow (OR=5.1, 95%CI 1.9-13.3, P=0.001) were factors associated with higher incidence of ≥grade 3 leukopenia and/or thrombocytopenia. Severe leukopenia and/or thrombocytopenia with time of drug discontinuance >2 weeks was associated with lower probabilities of achieving complete cytogenetic (OR=0.4, 95%CI 0.3-0.6, P<0.001) , severe leukopenia and/or thrombocytopenia, no matter the time of drug discontinuance >2 weeks or ≤2 weeks, were associated with lower probabilities of achieving major molecular responses (OR=0.3, 95%CI 0.2-0.5, P<0.001; OR=0.7, 95%CI 0.5-1.0, P=0.036) and MR4.5 (OR=0.2, 95%CI 0.1-0.5, P=0.002; OR=0.7, 95%CI 0.4-1.1, P=0.110) ; however, those had no impacts on PFS and OS. Conclusions: Severe leukopenia and/or thrombocytopenia were common adverse events during TKI therapy. Female patients, WBC ≥100×109/L at diagnosed, CP in Sokal high-risk, CML-AP with ≥15% blast cells in blood or bone marrow were at high risk for higher incidence of severe leukopenia and/or thrombocytopenia. Those severe adverse events had impacts on lower cytogenetic and molecular response.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Dasatinibe , Feminino , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases , Proteínas Tirosina Quinases , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
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