Analysis of induction efficacy and prognostic factors in FLT3-ITD positive acute myeloid leukemia in the real world / 中华血液学杂志

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 (χ2=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.

Efficacy and safety of decitabine in combination with G-CSF, low-dose cytarabine and aclarubicin in MDS-EB and AML-MRC / 中华血液学杂志

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/m2 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/m2 for 5 days and lower-dose CAG regimen (cytarabine of 10 mg/m2 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 (χ2=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 (χ2=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 (χ2=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 (χ2=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.

Age-related clinical characteristics and prognosis in non-senile adults with acute myeloid leukemia / 中华血液学杂志

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.

Outcomes of adult patients with de novo acute myeloid leukemia received idarubicin plus cytarabine regimen as induction chemotherapy / 中华血液学杂志

Objective@#To explore outcomes in adult with de novo acute myeloid leukemia (AML) received IA10 (10 mg/m2 d1-3 idarubicin plus cytarabine 100 mg/m2 d1-7) regimen as induction chemotherapy.@*Methods@#From January 2008 to February 2016, data of consecutive newly-diagnosed AML (non-M3) 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 ≥ 1×109/L and PLT ≥ 100×109/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.

Factors associated with early treatment response in adults with acute myeloid leukemia / 中华血液学杂志

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 ≥ 1×109/L and PLT ≥ 100×109/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<30×109/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 ≥30×109/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 / 中华血液学杂志

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<100×109/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 / 中华血液学杂志

Objective@#To explore prognostic significance of blood count at the time of achieving first morphologic leukemia-free state[complete remission (CR, ANC ≥1×109/L and PLT ≥100×109/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 / 中华血液学杂志

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<100×109/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.

Outcome of patients with adult acute lymphoblastic leukemia between 2000 and 2013: experience from single center / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the outcomes of patients with adult acute lymphoblastic leukemia (ALL) over the last 14 years by taking 2006 as the demarcation point.</p><p><b>METHODS</b>From January 2000 to December 2013, 477 consecutive hospitalized patients with adult ALL were retrospectively analyzed, including 276 (57.9%) with Ph negative B-ALL (Ph⁻-B-ALL) B-ALL, 69 (14.5%) with T-ALL and 132 (27.7%) with Ph positive ALL (Ph⁺-ALL); 111 (23.3%) before 2006 and 366 (76.7%) after 2006. Among 435 patients who achieved complete remission (CR), 248 (57.0%) received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 187 remained on chemotherapy.</p><p><b>RESULTS</b>With a median follow-up period of 19 months in all patients and 35 months in living patients, overall CR rate was 92.0%. Of 435 CR patients, the cumulative incidences of 5-year relapse, disease-free survival( DFS) and overall survival (OS) rates were 42.5%, 46.2% and 47.6%, respectively. Compared with the patients hospitalized before 2006: ① the Ph+-ALL patients hospitalized after 2006 achieved a higher overall CR rate (P=0.036). There was no difference for CR rates of Ph--B-ALL and T-ALL patients between before and after 2006. ②The CR patients hospitalized after 2006 had higher 5-year DFS and OS rates (P=0.001; P < 0.001), including higher 5-year OS rate in Ph⁻-B-ALL patients (P=0.046), and higher 5-year DFS and OS rates in both T-ALL (P=0.013; P=0.036) and Ph⁺-ALL patients (P=0.003; P < 0.001) , especially in those Ph⁺-ALL patients who received imatinib from the beginning of the induction chemotherapy (P < 0.001; P < 0.001) ③The patients who received allo-HSCT after 2006 had higher 5-year DFS and OS rates (P=0.001; P < 0.001), but there was no difference for the outcomes in those who remained on chemotherapy before and after 2006. After 2006, Ph⁺-ALL patients who received imatinib from the beginning of the induction chemotherapy had the highest 5-year DFS and OS rates compared with Ph⁻-B-ALL and T-ALL patients (P=0.009; P=0.001) . Multivariate analysis showed that allo-HSCT and imatinib were two important factors affecting the outcomes of ALL patients.</p><p><b>CONCLUSION</b>The outcomes of ALL patients improved significantly over the last 14 years, especially in Ph⁺-ALL ones.</p>

Comparison of 10 mg/m² or 8 mg/m² idarubicin plus cytarabine regimen as induction chemotherapy for adult patients with newly diagnosed acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the efficacy and toxicity of 10 mg/m² or 8 mg/m² idarubicin (Ida) combined with cytarabine (IA"3+7"regimen) as induction chemotherapy for adult patients with newly diagnosed acute myeloid leukemia (AML).</p><p><b>METHODS</b>From June 2004 to October 2013, 335 adult AML (non acute promyelocytic leukemia) patients receiving the IA regimen as induction chemotherapy were enrolled, including 198 cases with 10 mg/m² Ida and 137 cases with 8 mg/m² Ida for 3 days. We compared the hematologic response, hematologic side effects and prognosis between the two regimens.</p><p><b>RESULTS</b>Except for 4 early deaths, the complete remission (CR) rate after the first cycle of induction chemotherapy was 72.5%, 10.0% partial remission (PR) and 82.5% overall remission (OR) rate. The CR and OR rates were higher in the 10 mg/m² Ida group than the 8 mg/m² Ida group (CR: 78.9% vs 63.5%, P=0.003; OR: 88.2% vs 75.4%, P=0.007). Multivariate analysis showed that female, HGB≥100 g/L, FLT3-ITD mutation negative and 10 mg/m² Ida were favorable factors for CR. All patients presented cytopenias of grade Ⅳ. There was no differences on the recovery time of ANC≥0.5×10⁹/L and PLT≥20×10⁹/L after induction chemotherapy. Within a median follow-up of 14 (1-118) months, 98 (29.3%) patients relapsed, 92 (27.5%) died. The disease-free survival (DFS) and overall survival (OS) at 3 years were 53.2% and 58.9%, respectively. DFS and OS at 3-year were 34.2% and 37.4% in the chemotherapy cohort, 74.5% and 81.2% in the transplant cohort. 10 mg/m² Ida was an independent favorite factor for DFS (P=0.040) and OS (P=0.007).</p><p><b>CONCLUSION</b>As compared to 8 mg/m², 10 mg/m² Ida significantly improved the CR, with the same extent of hematological side effects, and was an independent favorite factor for DFS and OS.</p>

Prognostic factors of adult Philadelphia chromosome negative acute lymphoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the prognostic factors in adult Philadelphia chromosome negative acute lymphoblastic leukaemia (Ph⁻ ALL).</p><p><b>METHODS</b>From December 1999 to December 2013, 353 consecutive hospitalized 18-65-year-old adult Ph⁻ ALL patients were retrospectively analyzed. Induction therapy was CODP±L-asparaginase (L-Asp) regimen, and consolidation therapy included CODP and high dose methotrexate or revised Hyper-CVAD A and B regimens for 8 cycles. 178 patients (50.4%) performed allo-HSCT after three to five cycles of consolidation treatment, and 172 patients didn't receive allo-HSCT. The median follow-up was 39.9 months (2.0 to 171.0 months) for the 184 survivors.</p><p><b>RESULTS</b>Three patients (0.85%) happened early death. CR rate after the first cycle of induction chemotherapy was 77.4% (271/350) among evaluated 350 patients. Overall CR rate was 92.9% (325/350). WBC ≥ 100.0 × 10⁹/L (P=0.010) and hepatomegaly/splenomegaly/lymphadenopathy (P=0.036) were independent adverse factors for overall CR. Among the 325 CR patients, 117 patients developed relapse, cumulative incidence of relapse (CIR) at 5 years was 43.2%, disease-free survival (DFS) and overall survival (OS) rates at 5 years were 44.7% and 45.6% respectively. Multivariate analysis showed that harboring central nervous system leukaemia (CNSL) at diagnose (P=0.004, P=0.002, P<0.001, respectively), induction regimen without L-Asp (P=0.023, P=0.009, P=0.004, respectively), time to CR more than 4 weeks (P=0.034, P=0.024, P=0.003, respectively), and non-allo-HSCT (P<0.001, P<0.001, P<0.001, respectively) were adverse factors of relapse, DFS and OS. In addition, high WBC count at diagnosis (≥ 30.0 × 10⁹/L for B lineage and ≥ 100.0 × 10⁹/L for T lineage) was poor factor of DFS (P=0.044). Based on the four adverse prognostic factors of DFS above mentioned (including WBC at diagnose, harboring CNSL at diagnose, induction regimen with or without L-Asp, time to CR more than 4 weeks), patients were grouped into low risk (no factor), intermediate risk (one factor), and high risk (at least two factors). Non-allo-HSCT and allo-HSCT had similar outcomes in low risk subgroup. Allo-HSCT significantly improved OS and DFS in intermediate and high risk subgroups rather than non-allo-HSCT (all P values < 0.001).</p><p><b>CONCLUSION</b>In adult Ph- ALL patients, high WBC count at diagnosis (≥ 30.0 × 10⁹/L for B lineage and ≥ 100.0 × 10⁹/L for T lineage), CNSL at diagnosis, induction regimen without L-Asp, time to CR more than 4 weeks and non-allo-HSCT were adverse prognostic factors. Allo-HSCT improved OS and DFS in patients with more than one of the first four adverse prognosis factors.</p>

The relationship between induction chemotherapy cycles and prognosis in patients with acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the relationship between induction chemotherapy cycles to achieve complete remission (CR) and prognosis in patients with acute myeloid leukemia(AML).</p><p><b>METHODS</b>From April 2004 to December 2013, 397 adult patients with newly diagnosed AML (acute promyelocytic leukemia excluded) received the idarubicin combined with cytarabine (IA)"3+7" regimen as the first induction chemotherapy were enrolled in the study. Therapeutic effect, relapse and survival of these patients were discussed. Patients underwent continuous consolidation chemotherapy, and some eligible patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the first complete remission.</p><p><b>RESULTS</b>Of 397 patients, 347 evaluable patients achieved CR after 1-4 cycles induction chemotherapy.The median follow-up was 18.0 (2.4-115.4) months in survivors, the cumulative incidence of relapse (CIR), disease-free survival (DFS) and overall survival (OS) at 3 years were 33.0%, 58.6% and 67.1%, respectively. Multivariate analysis revealed that unfavorable cytogenetics, more cycles to achieve CR and post-remission treatment without allo-HSCT were independent risk factors affecting DFS and OS. FLT3-ITD mutation positive was another independent risk factor affecting DFS. There was no statistic difference between patients who achieved CR after one cycle (n=255) and two cycles (n=73) treatment in DFS and OS (P>0.05). DFS and OS in patients who achieved CR after 3 or 4 cycles(n=19)were significantly lower than the above two groups (P<0.05). Multivariate analysis among 183 patients who received consistent chemotherapy showed that achieving CR within 2 cycles was the favorable factor affecting DFS and OS (P=0.001, P=0.035).</p><p><b>CONCLUSION</b>Achieving CR within 2 cycles of induction chemotherapy was associated with better prognosis among adult CR patients with AML.</p>

Bortezomib improves progression-free survival in multiple myeloma patients overexpressing preferentially expressed antigen of melanoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Significant efforts have been made to identify factors that differentiate patients treated with novel therapies, such as bortezomib in multiple myeloma (MM). The exact expression pattern and prognostic value of the cancer/testis antigen preferentially expressed antigen of melanoma (PRAME) in MM are unknown and were explored in this study.</p><p><b>METHODS</b>The transcript level of PRAME was detected in bone marrow specimens from 100 newly diagnosed MM patients using real-time quantitative polymerase chain reaction, and the prognostic value of PRAME was determined through retrospective survival analysis. PRAME expression higher than the upper limit of normal bone marrow was defined as PRAME overexpression or PRAME (+).</p><p><b>RESULTS</b>Sixty-two patients (62.0%) overexpressed PRAME. PRAME overexpression showed no prognostic significance to either overall survival (n = 100) or progression-free survival (PFS, n = 96, all P > 0.05) of patients. The patients were also categorized according to regimens with or without bortezomib. PRAME overexpression tended to be associated with a lower two-year PFS rate in patients treated with non-bortezomib-containing regimens (53.5% vs. 76.9%, P = 0.071). By contrast, it was not associated with the two-year PFS rate in patients with bortezomib-containing regimens (77.5% vs. 63.9%, P > 0.05). When the patients were categorized into PRAME (+) and PRAME (-) groups, treatment with bortezomibcontaining regimens predicted a higher two-year PFS rate in PRAME (+) patients (77.5% vs. 53.5%, P = 0.027) but showed no significant effect on two-year PFS rate in PRAME (-) patients (63.9% vs. 76.9%, P > 0.05).</p><p><b>CONCLUSION</b>PRAME overexpression might be an adverse prognostic factor of PFS in MM patients treated with non-bortezomib-containing regimens. Bortezomib improves PFS in patients overexpressing PRAME.</p>

Bortezomib-based combination therapy for newly diagnosed multiple myeloma / 中华内科杂志

Objective To study retrospectively the response and side effects in two groups of patients with untreated multiple myeloma receiving bortezomib-based regimen(VD/VT)and vincristine combined with adriamycin and dexamethasone(VAD).Methods Eighteen patients were enrolled in a group of VD or VT,receving bortezomib 1.0 mh/m2 or 1.3 mg/m2 on days 1,4,8 and 11,along with dexamethasone 20-40 mg on days 1-4(12 cases);or thalidomide 100 mg/d continuously(6 cases). Twenty-four patients treated with VAD entered into a control group,receiving vincristine 0.4 mg/d on days 1- 4,adriamycin 9 mg·m-2·d-1 on days 1-4 and dexamethasone on days 1-4,9-12,17-20,with 28 days as a cycle.Results After bortezomib-based combinations,16 of with 18 patients(88.9%)achieved at least a partial response,including complete response and near complete response in 7 patients(38.9%).Side effects in the VD/VT group were predictable and manageable;they were mainly haematologic, gastrointestinal,and peripheral neuropathic and were more evident during early cycles.The main side reactions in the VAD group were infections.loss of hair and phlebitis.Conclusion Bortezomib-based combinations therapy is an effective and safe induction regimen for newly diagnosed multipli myeloma patients and appears significantly superior to VAD,yielding high response rates even in patients with poor prognostic features.