[Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience].

Objective: To explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven+AZA) in previously untreated patients unfit for standard chemotherapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in China. Methods: A retrospective study was conducted in 60 previously untreated patients unfit for standard chemotherapy and patients with R/R AML who received Ven+ AZA (venetoclax, 100 mg D1, 200 mg D2, 400 mg D3-28; azacitidine, 75 mg/m(2) D1- 7) at the Peking University Institute of Hematology from June 1, 2019 to May 31, 2021. The incidence of adverse events, complete remission (CR) /CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR) , and minimal residual disease (MRD) status in patients with different risk stratification and gene subtypes were analyzed. Results: The median age of the patients was 54 (18-77) years, 33 (55.0%) were males, and the median follow-up time was 4.8 (1.4-26.3) months. Among the 60 patients, 24 (40.0%) were previously untreated patients unfit for standard chemotherapy, and 36 (60.0%) were R/R patients. The median mumber cycles of Ven+AZA in the two groups were both 1 (1-5) . According to the prognostic risk stratification of the National Comprehensive Cancer Network, it was divided into 8 cases of favorable-risk, 2 cases of intermediate risk, and 14 cases of poor-risk. In previously untreated patients unfit for standard chemotherapy, after the first cycle of Ven+AZA, 17/24 (70.8%) cases achieved CR/CRi, 3/24 (12.5%) achieved partial remission (PR) , and the ORR was 83.3%. Among them, nine patients received a second cycle chemotherapy and two received a third cycle. Among CR/CRi patients, 8/17 (47.1%) achieved MRD negativity after two cycles of therapy. In the R/R group, after the first cycle of Ven+AZA, 21/36 (58.3%) cases achieved CR/CRi (7/21 achieved MRD negativity) , 3 achieved PR, and the ORR was 66.7%. Among R/R patients, 12 were treated for more than two cycles. There were no new CR/CRi patients after the second treatment cycle, and 14 cases (66.7%) achieved MRD negativity. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 in the poor-risk group (CR to hematological recurrence<18 months, no remission after one cycle of therapy, and no remission after two or more cycles of therapy) . Eleven of 24 (45.8%) cases achieved CR/CRi after one cycle of Ven+AZA in the poor-risk R/R group, and 10 of 12 (83.3%) achieved CR/CRi in the favorable-risk R/R group, which was significantly superior to the poor-risk group (P=0.031) . After one cycle of treatment, 13 patients with IDH1/2 mutations and 4 that were TP53-positive all achieved CR/CRi. The CR/CRi rate of 18 patients with NPM1 mutations was 77.8%. Five patients with RUNX1-RUNX1T1 combined with KIT D816 mutation (two initial diagnoses and three recurrences) had no remission. Ven+ AZA was tolerable for AML patients. Conclusion: Ven+AZA has acceptable safety in previously untreated patients unfit for standard chemotherapy, patients with R/R AML can achieve a high response rate, and some patients can achieve MRD negativity. It is also effective in NPM1-, IDH1/IDH2-, and TP53-positive patients. The long-term efficacy remains to be observed.

[Observation on the efficacy of consolidation chemotherapy combined with allogeneic natural killer cell infusion in the treatment of low and moderate risk acute myeloid leukemia].

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.

[Analysis of induction efficacy and prognostic factors in FLT3-ITD positive acute myeloid leukemia in the real world].

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.

[Minimal residual disease in adults with Philadelphia chromosome negative acute lymphoblastic leukemia in high-risk].

Objective: To explore the significance of minimal residual disease (MRD) in predicting prognosis and guiding therapy of adults with Philadelphia-chromosome negative acute lymphoblastic leukemia (Ph(-) ALL) in high-risk. Methods: Data of newly diagnosed adults with Ph(-) ALL in high-risk who achieved CR were reviewed. Variables associated with outcome were identified by COX regression model and Landmark analysis. Results: A total of 177 patients, 99 (56%) cases male with a median age of 40 years (range, 16-65 years) were included in this study. Of them, 95 (54%) patients received allo-HSCT in CR(1). Multivariate analyses showed that MRD negativity after the first cycle of consolidation (HR=0.52, 95%CI 0.30-0.89, P=0.017) and achieving CR within 4 weeks (HR=0.43, 95%CI 0.24-0.79, P=0.006) were the factors significantly-associated with longer DFS, and allo-HSCT was associated with both longer DFS (HR=0.13, 95%CI 0.08-0.22, P<0.001) and OS (HR=0.24, 95%CI 0.15-0.41, P<0.001) . Landmark analysis was performed on 121 patients, of 85 patients achieving MRD negativity after the first cycle of consolidation, multivariate analyses showed that MRD negativity after the third cycle of consolidation was significantly-associated with longer DFS (HR=0.18, 95%CI 0.05-0.64, P=0.008) and OS (HR=0.14, 95%CI 0.04-0.50, P=0.003) . For the patients achieving MRD negativity after both the first and the third cycles of consolidation, the 3-year DFS rate in the allo-HSCT cohort had a higher trend compared with that in the chemotherapy cohort (75.2% vs 51.3%, P=0.082) , however, the 3-year OS rates in the 2 cohorts were similar (72.7% vs 68.7%, P=0.992) . In those with MRD positivity after the first and/or the third cycle of consolidation, 3-year DFS (64.8% vs 33.3%, P=0.006) and OS (77.0% vs 33.3%, P=0.028) rates in the allo-HSCT cohort were significantly higher than those in the chemotherapy cohort, and similar to those in the cohort achieving MRD negativity after both the first and the third cycles of consolidation and receiving allo-HSCT. Conclusions: MRD negativity after the first cycle of consolidation was a predictor for better outcome in adults with Ph(-) ALL in high-risk. The survival advantage of the allo-HSCT cohort was not pronounced compared with that in the chemotherapy cohort even in those with high-risk features but achieving MDR negativity after both the first and third cycles of consolidation. However, allo-HSCT could be a good option for the patients with MRD positivity after the first and/or the third cycle of consolidation.

[Efficacy and safety of decitabine in combination with G-CSF, low-dose cytarabine and aclarubicin in MDS-EB and AML-MRC].

Objective: To evaluate the clinical efficacy and safety of decitabine in combination with lower-dose CAG regimen (G-CSF, cytarabine and aclarubicin; D-CAG regimen) in the treatment of myelodysplastic syndromes with excess blasts (MDS-EB) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), compared to standard CAG regimen. Methods: A total of 42 patients with newly diagnosed MDS-EB and AML-MRC from May 2011 to March 2017 were included in the retrospective study. 21 cases were initially treated with G-CSF for priming, in combination with cytarabine of 10 mg/m(2) q12h for 14 days and aclarubicin of 20 mg/d for 4 days (CAG regimen) and the other 21 cases were initially treated with decitabine of 20 mg/m(2) for 5 days and lower-dose CAG regimen (cytarabine of 10 mg/m(2) q12h for 7 days, aclarubicin of 10 mg/d for 4 days, and G-CSF for priming (D-CAG regimen). After two cycles of induction chemotherapy, the patients who obtained complete remission(CR) received consolidation chemotherapy or hematopoietic stem cell transplantation (HSCT). Results: Among a total of 42 patients, the median age was 52.5 years (18-65 years) and 64.3% of them were male. Baseline characteristics of patients between D-CAG group and CAG group showed no significant differences. The CR for patients in D-CAG group was 81.0% (17/21), compared to 52.4% (11/21) in CAG group after 2 cycles of therapy (χ(2)=3.857, P=0.050). The overall response rate (ORR) for patients in D-CAG group and CAG group was 85.7% (18/21) and 76.2% (15/21) respectively, without significant difference (χ(2)=1.273, P=0.259). By December 2017, the median follow-up of D-CAG group and CAG group was 13(6-32) months and 15(2-36) months respectively. Finally, 10 patients in D-CAG group and 7 patients in CAG group received HSCT respectively. Except patients receiving HSCT, the median leukemia-free survival (LFS) time for patients in D-CAG group and CAG group was 18.0 (95%CI 6.6-29.4) months and 11.0 (95%CI 0-23.9) months respectively. Probabilities of 12 months LFS for D-CAG group and CAG group were (63.6±14.5)% and (50.0±13.4)% respectively, without difference (χ(2)=0.049, P=0.824). Except patients receiving HSCT, there were 2 deaths in D-CAG group and 7 deaths in CAG group respectively. The cumulative probabilities of 12 months OS for non-HSCT patients in D-CAG group and CAG group were (90.9±8.7)% and (61.5±13.5)% respectively, without significant difference (χ(2)=1.840, P=0.175). The incidences of side effects between D-CAG group and CAG group did not show significant differences (P=0.479), and the main side effects included cytopenias, pneumonia, infections of skin and soft tissues, neutropenic patients with fever, liver dysfunction. Conclusion: The decitabine in combination with lower-dose CAG regimen improved CR for patients with MDS-EB and AML-MRC, and was a promising choice.

[Outcomes of adult patients with de novo acute myeloid leukemia received idarubicin plus cytarabine regimen as induction chemotherapy].

Objective: To explore outcomes in adult with de novo acute myeloid leukemia (AML) received IA10 (10 mg/m(2) d1-3 idarubicin plus cytarabine 100 mg/m(2) d1-7) regimen as induction chemotherapy. Methods: From January 2008 to February 2016, data of consecutive newly-diagnosed AML (non-M(3)) adults treated with IA10 who achieved morphologic leukemia-free state (MLFS) but not accepted allogeneic hematopoietic stem cell transplantation (allo-HSCT) were assessed retrospectively. Results: A total of 198 patients were included in this study with 96 (48.5%) male and a median age of 42 years old (range, 18-62 years old). Using the SWOG cytogenetic classification, 45 (22.7%), 104 (52.5%), 24 (12.1%) and 25 (12.6%) patients belonged to favorable, intermediate, unfavorable and unknown categories, respectively. 6 (3.0%) patients had monosomal karyotype, and 28 (14.1%) positive FLT3-ITD mutation. A complete remission (CR, defined as MLFS with ANC ≥ 1×10(9)/L and PLT ≥ 100×10(9)/L) achieved in 168 (84.8%) patients, a CRp (defined as MLFS with incomplete PLT recovery) in 16 (8.1%) and a CRi (defined as MLFS with incomplete ANC and PLT recovery) in 14 (7.1%). With a median follow-up period of 15 months (range, 1 to 70 months) in survivors, the probabilities of cumulative incident of relapse (CIR), disease free survival (DFS) and overall survival (OS) rates at 2-year were 45.2%, 46.9% and 62.9%, respectively; the median durations of relapse, DFS and OS were 34, 20 and 37 months respectively. At the time of achieving first MLFS, multivariate analyses showed that positive FLT3-ITD mutation and CRi were common adverse factors affecting CIR, DFS and OS; unfavorable-risk of SWOG criteria was an adverse factor affecting CIR and DFS; monosomal karyotype was associated with shorter OS. After first consolidation therapy, FLT3-ITD mutation positive and unfavorable-risk of SWOG criteria had negatively impact on CIR, DFS and OS; peripheral blasts ≥ 0.50 and positive MRD (defined as RQ-PCR WT1 mRNA ≥ 0.6% or any level of abnormal blast population detected by flow cytometry) after first consolidation therapy were common adverse factors affecting CIR and DFS; CRi was an adverse factor affecting DFS and OS. Conclusions: In adult with de novo AML received IA10 regimen as induction regimen, unfavorable molecular markers or cytogenetics at diagnosis and CRi independently predicted poor outcome. In addition, a higher percentage of peripheral blasts, monosomal karyotype and positive MRD after first consolidation therapy had negatively impact on outcomes.

[Age-related clinical characteristics and prognosis in non-senile adults with acute myeloid leukemia].

Objective: To explore age-related clinical characteristics, early responses and outcomes in non-senile adults with de novo acute myeloid leukemia (AML). Methods: Data of consecutive cases of 18-65 years adults with de novo AML (non-acute promyelocytic leukemia) were reviewed retrospectively. Clinical characteristics at diagnosis, early responses and outcomes across different age groups of patients were analyzed. Results: 1 097 patients were enrolled. 591 (53.9%) were male. Median age was 42 years. Increasing age was significantly associated with decreasing WBC count (P=0.003), increasing PLT count (P=0.034), lower blast proportions in bone marrow (P=0.021). The incidence of NPM1(+)/FLT3-ITD(-) increased with age (P<0.001). Multivariate analyses showed that increasing age was associated with low probabilities of achieving morphologic leukemia free state (MLFS) (P=0.053) and complete remission (CR) (P=0.004) and poor overall survival (OS) (P=0.070) in the whole patients population. However, increasing age was not associated with low MLFS rate and poor OS, except low CR rate (P=0.075) in those receiving standard induction regimen instead of low-intensity regimen. Conclusions: There were significant differences on clinical characteristics, cytogenetics and molecular genetics across different age groups in non-senile adults with de novo AML. In the patients receiving standard induction regimen, age was not associated with MLFS rate and OS.

[Clinical features and early treatment effects in intermediate risk and poor risk acute myeloid leukemia with EVI1 positive].

OBJECTIVE: To investigate the clinical biological characteristics of EVI1 positive acute myeloid leukemia (AML) and its effect on early chemotherapy. METHODS: The clinical and biological cha-racteristics of 33 AML patients with EVI1 positive were retrospectively analyzed in 361 AML patients who were diagnosed and treated in our institute from March 2015 to July 2016, and the clinical and biological features, and rates of the induced remission were compared between the intermediate risk and poor risk with EVI1 positive AML, moreover, the influential factors on complete remission (CR) were analyzed. The expression of EVI1/ABL was tested in 32 healthy donors to confirm the abnormal threshold of EVI1 expression. RESULTS: The definition of EVI1 positive was that the quantitative expression of EVI1/ABL was more than 8.0%. The 33 AML patients with EVI1 positive were found in 361 newly diagnosed AML patients, in which the female and male patients were 17 and 16 respectively, the median age was 45 (18-67) years, with a median follow-up of 6.6 (0.7-13.2) months. Intermediate karyotype was found in 17 patients(including 9 patients with normal karyotypes,1 patient with +8);unfavorable karyotype was found in 14 patients [including 7 patients with -7/7q-,4 patients with t (v;11q23),3 patients with inv(3)/t(3;3), and 2 patients without mitotic figures]. The rate of CR in the first induction chemotherapy was 42.4%, and the rate of total CR was 60.6%. According to the NCCN, 16 intermediate risk patients and poor risk patients were divided, without favorable risk patients. The rate of CR in the first induction chemotherapy were 68.8% and 17.6% (P=0.005) in the intermediate risk and poor risk respectively, that of total CR were 81.3% and 41.2%(P=0.032), and the rates of relapse were 7.7% and 14.3%.Univariable analysis revealed that unfavorable karyotype could affect the rate of CR in the first reduction chemotherapy and that of total CR (P=0.004, 0.029). The poor risk patients had higher mortality (41.2% vs. 6.3%, P=0.039) and lower overall survival (OS)(P=0.012). CONCLUSION: EVI1 may be not an independent prognostic factor for the AML patients considering the appea-rance in the intermediate and poor risk patients. It predicts poor outcome in the EVI1 positive AML patients who have unfavorable karyocytes, such as -7/7q-, t(v;11q23), and inv(3)/t(3;3), and also a low rate of both CR in the first induction chemotherapy and total CR. It also has a low rate of long-term survival and high mortality in the AML patients with EVI1 positive, who may benefit from allogeneic bone marrow transplantation as soon as possible.

[Factors associated with early treatment response in adults with acute myeloid leukemia].

Objective: To explore the factors influencing early treatment responses in adult with de novo acute myeloid leukemia (AML) . Methods: Data of consecutive newly-diagnosed AML (non-acute promyelocytic leukemia) adults were analyzed retrospectively. To assess the impact of clinical characteristics at diagnosis and induction regimen on achieving morphologic leukemia-free state (MLFS) , blood counts and minimal residual leukemia (MRD, positive MRD defined as RQ-PCR WT1 mRNA ≥0.6% and/or any level of abnormal blast population detected by flow cytometry) at the time of achieving MLFS. Results: 739 patients were included in this study. 406 (54.9%) patients were male, with a median age of 42 years (range, 18-65 years) . In the 721 evaluable patients, MLFS was achieved in 477 (66.2%) patients after the first induction regimen and 592 (82.1%) within two cycles. A total of 634 patients (87.9%) achieved MLFS, including 534 (84.2%) achieving a complete remission (CR, defined as MLFS with ANC ≥ 1×10(9)/L and PLT ≥ 100×10(9)/L) , 100 (15.8%) achieving a CRi (defined as MLFS with incomplete ANC or PLT recovery) , respectively. 260 (45.9%) patients of 566 (89.3%) who detected MRD at the time of achieving MLFS had positive MRD. Multivariate analyses showed that female gender, favorable-risk of SWOG criteria, IA10 and HAA/HAD as induction regimen were factors associated with achieving early MLFS. In addition, low bone marrow blasts, HGB ≥ 80 g/L, PLT counts<30×10(9)/L and mutated NPM1 without FLT3-ITD were factors associated with achieving MLFS after the first induction regimen; Negative FLT3-ITD mutation was factor associated with achieving MLFS within two cycles. PLT counts ≥30×10(9)/L and IA10, IA8 or HAA/HAD as induction chemotherapy were factors associated with achieving CR. Female gender, favorable-risk of SWOG criteria, FLT3-ITD mutation negative, mutated NPM1 without FLT3-ITD were factors associated with negative MRD. Conclusions: Female gender, favorable molecular markers or cytogenetics, and standard-dose induction regimen were key factors associated with higher probability of early and deep responses in adults with AML.

[Minimal residual disease level predicts outcomes in the non-favorable risk patients with acute myeloid leukemia].

Objective: To explore impact of minimal residual leukemia (MRD) on outcomes in the non-favorable risk adults with de novo acute myeloid leukemia (AML) . Methods: From January 2008 to February 2016, data of consecutive newly-diagnosed non-favorable risk adults with AML (non-APL) according to SWOG criteria who achieved morphologic leukemia-free state (MLFS) and received continuous chemotherapy were assessed retrospectively. Results: 292 AML patients were enrolled, 150 (51.4%) were male. Median age was 46 years (range, 18-65 years) . Using the SWOG cytogenetic classification, 186 (63.7%) , 49 (16.8%) and 57 (19.5%) patients belonged to intermediate, unfavorable and unknown categories, respectively. With a median follow-up period of 15 months (range, 1 to 94 months) in survivors, the probabilities of cumulative rates of relapse (CIR) , disease free survival (DFS) and overall survival (OS) at 2-years were 51.6%, 42.6% and 60.0%, respectively. Multivariate analyses showed that MRD positive (defined as Q-PCR WT1 mRNA ≥0.6% or any level of abnormal blast population detected by flow cytometry) after achieving MLFS and PLT<100×10(9)/L were common adverse factors affecting CIR and DFS. In addition, positive FLT3-ITD mutation and CRp/CRi had negatively impact on CIR, DFS and OS. Monosomal karyotype was adverse factors affecting CIR and OS. Age ≥44 years and unfavorable-risk of SWOG criteria were associated with shorter DFS. Conclusions: MRD level after achieving MLFS had prognostic significance on outcomes in non-favorable adults with AML who received continuous chemotherapy after achieving MLFS.

[Prognostic significance of blood count at the time of achieving morphologic leukemia-free state in adults with acute myeloid leukemia].

Objective: To explore prognostic significance of blood count at the time of achieving first morphologic leukemia-free state[complete remission (CR, ANC ≥1×10(9)/L and PLT ≥100×10(9)/L) , CR with incomplete PLT recovery (CRp) and CR with incomplete ANC and PLT recovery (CRi) ]in adult patients with de novo acute myeloid leukemia (AML) . Methods: From January 2008 to February 2016, data of consecutive newly-diagnosed AML (non-APL) adults who received continuous chemotherapy in our hospital were analyzed retrospectively. Results: 352 patients were included in the study. 179 (50.9%) were male. Median age was 44 (17-65) years. Using the SWOG cytogenetic classification, 87 (24.7%) , 171 (48.6%) , 46 (13.1%) and 48 (13.6%) patients belonged to favorable, intermediate, unfavorable and unknown categories, respectively. 16 (4.5%) had monosomal karyotype and 41 (11.6%) had FLT3-ITD mutation positive. Best response achieved at the time of achieving first morphologic leukemia-free state was CR in 299 (84.9%) patients, CRp in 26 (7.4%) and CRi in 27 (8.1%) . With a median follow-up period of 16 (2-94) months in survivors, the probabilities of cumulative incident of relapse (CIR) rate, disease free survival (DFS) and overall survival (OS) at 30 months were 47.5%, 46.0% and 58.6%, respectively. Multivariate analyses showed that non-CR (CRp or CRi) , was associated with high relapse rate, shorter DFS and OS. In addition, intermediate or high risk of SWOG cytogenetic classification and FLT3-ITD positive were common unfavorable factors affecting CIR, DFS and OS. Peripheral blast ≥60% at diagnosis was adverse factors affecting DFS. Age ≥48 years and bone marrow blasts ≥67% were associated with shorter OS. Conclusion: Blood count at the time of achieving morphologic leukemia-free state was one of the key markers associated with treatment outcomes in adults with AML.

[Prognostic significance of early assessment of minimal residual disease in acute myeloid leukemia with mutated NPM1 patients].

Objective: To explore prognostic significance of early assessment of minimal residual leukemia (MRD) in adult patients with de novo acute myeloid leukemia (AML) with mutated NPM1. Methods: The response, NPM1 mutated transcript level after induction chemotherapy and the first 2 cycles of consolidation chemotherapy, disease-free survival (DFS) and overall survival (OS) in 137 patients with AML with NPM1 mutations of A, B and D were retrospectively analyzed. Results: Data of 137 patients were collected, 67 were male, the median age was 49 years (16-67 years) , 107 (78.1%) had normal karyotype, 57 (41.6%) had positive FLT3-ITD mutation, the median NPM1 mutated transcript level at diagnosis was 84.1%. Among the 134 evaluable patients, 115 (85.8%) achieved a complete remission (CR) . Multivariate analyses revealed that WBC<100×10(9)/L (OR=0.3, 95% CI 0.1-0.9, P=0.027) and first induction therapy with "IA10" protocol (OR=0.3, 95% CI 0.1-0.8, P=0.015) were factors associated with achieving a CR. With a median follow-up period of 24 months (range, 2 to 91 months) in 77 survived CR patients, the probabilities of DFS and OS at 3 years were 48.0% and 63.9%, respectively. Multivariate analyses showed that positive FLT3-ITD (HR=3.2, 95% CI 1.6-6.7, P=0.002) , high MRD level after 2 cycles of consolidation chemotherapy (NPM1 mutation transcript level <3-log reduction from the individual baseline, HR=23.2, 95% CI 7.0-76.6, P<0.001) and chemotherapy or autologous hematopoietic stem cell transplantation (auto-HSCT) rather than allogeneic HSCT (allo-HSCT) (HR=2.6, 95% CI 1.0-6.6, P=0.045) were the unfavorable factors affecting DFS, high MRD level at the time of achieving the first CR (NPM1 mutation transcript level <2-log reduction from the individual baseline, OR=2.5, 95% CI 1.0-6.1, P=0.040) and after 2 cycles of consolidation chemotherapy (HR=4.5, 95% CI 2.0-10.3, P<0.001) were the unfavorable factors affecting OS. Furthermore, DFS and OS rates at 3 years in those receiving chemotherapy or auto-HSCT were 39.7% and 59.1%, respectively; positive FLT3-ITD and high MRD level after 2 cycles of consolidation chemotherapy were independent factors associated with both shorter DFS (HR=3.5, 95% CI 1.6-7.6, P=0.002 and HR=8.9, 95% CI 3.8-20.7, P<0.001) and OS (HR=2.7, 95% CI 1.1-6.9, P=0.036 and HR=3.1, 95% CI 1.2-8.0, P=0.021) ; meanwhile, high MRD level at the time of achieving the first CR associated with shorter OS (HR=3.1, 95% CI 1.2-8.0, P=0.022) . Conclusion: Positive FLT3-ITD mutation and high MRD level after induction or consolidation chemotherapy associated with poor outcomes in AML patients with mutated NPM1.

[Non-Hodgkin's lymphoma mimicking Mikulicz disease: a case report].

IgG4-related disease is a systemic disorder involving a spectrum of multiple indications, and various histopathological features are shared among different IgG4-related disease subtypes, which challenge diagnosis, although certain syndromes have organ-specific involvement. Among them, Mikulicz's disease affecting the salivary and lacrimal glands, distinguished by often elevated levels of serum IgG4, infiltration of IgG4+ plasma cells into target tissues, and diffuse swelling, mass formation, or fibrosis of affected organs. However, there are several diseases, which could manifest as salivary gland swelling, mimicking Mikulicz's disease, such as Sjogren's syndrome, mumps virus infection, obstruction of parotid duct, non-Hodgkin's lymphoma (NHL), and so on. So differential diagnosis is important and essential as to the salivary gland swelling. In this paper, we analyzed a case of a 59-year-old male with symmetric salivary gland swelling. Mikulicz's disease was misdiagnosed at the beginning without biopsy. Prednisone treatment ever seemed to be effective and antibiotics had no effect. Besides salivary involvement, the patient also manifested as testicle swelling and severe pancytopenia with the development of the disease, which rarely appeared in Mikulicz's disease. Physical examination showed skin, sclera yellow dye, swollen submandibular, sublingual and lacrimal gland and splenomegaly. As a result, biopsy of right submandibular gland was made, and mucosa-associated lymphoid tissue lymphoma was confirmed by morphology and immunohistochemistry. Bone marrow biopsy also confirmed that lymphoma cells were found in the bone marrow. Finally, the diagnosis of mucosa-associated lymphoid tissue lymphoma (Phase IVE, Group A) was made on the patient, who was transferred to the hematology department for the treatment. NHL, especially, primary extranodal lymphoma usually involves the salivary gland, and painless swelling of the salivary gland is a common manifestation, similar with Mikulicz's disease. So although salivary gland swelling is often associated with autoimmune diseases such as Sjogren's syndrome and IgG4-related disease, the awareness and suspicion of a possibility of NHL are essential for rheumatologists. Biopsy is a necessary examination to decrease or avoid misdiagnosis.

[The prognostic significance of proportion of blasts in bone marrow on day 14 during induction chemotherapy in patients with adult Ph-negative acute lymphoblastic leukemia].

OBJECTIVE: To investigate the prognostic significance of proportion of the blasts in bone marrow on day 14 (D14) during induction chemotherapy in patients with adult Ph-negative acute lymphoblastic leukemia (Ph (-) ALL). METHODS: Newly diagnosed Ph (-) ALL patients with bone marrow morphology analysis on day 14 during induction chemotherapy were analyzed retrospectively. The proportion of the D14 blasts which had an impact on achieving a CR by the first induction chemotherapy and outcomes were determined by ROC curve. RESULTS: 166 ALL patients including 94 male and 72 female were analyzed. The median age was 32 years (range, 18-64 years). The CR rate by the first induction chemotherapy was 74.7% with a total CR rate as 93.3%. By ROC analysis, 7.5% of the D14 blasts had the best sensitivity and specificity. The patients with D14 blasts ≥7.5% had lower CR rates after the first and overall induction chemotherapy compared with those with D14 blasts <7.5% (42.7% vs 85.9%, P<0.001 and 75.9% vs 95.6%, P=0.001 respectively). The probabilities of 5-year disease free survival (DFS) and 5-year overall survival (OS) were higher in the patients with D14 blasts<7.5% than those with D14 blasts ≥7.5% (49.8% vs 29.6%, P=0.006 and 52.4% vs 32.6%, P=0.010 respectively). Multivariate analysis showed that higher WBC or central nervous system leukemia at diagnosis, D14 blasts ≥7.5%, no CR after the first induction chemotherapy and receiving consolidation and maintenance chemotherapy rather than transplant were associated with poor outcomes. CONCLUSIONS: Higher proportion of D14 blasts in bone marrow during the first induction therapy indicated poor prognosis in adult Ph(-) ALL.