Dataset Information

Role of CD19 and specific KIT-D816 on risk stratification refinement in t(8;21) acute myeloid leukemia induced with different cytarabine intensities.

ABSTRACT: High-dose cytarabine (Ara-C) has been reported with increased treatment-related mortality, whereas few data are available concerning intermediate-dose Ara-C for induction of acute myeloid leukemia (AML) with t(8;21) translocation. We retrospectively analyzed factors impacting complete remission (CR), event-free survival (EFS), cumulative incidence of relapse (CIR), and overall survival (OS) in 197 adults with t(8;21) AML, of whom 107 cases were induced with intermediate-dose and 90 with standard-dose Ara-C (as part of 3 + 7 protocol). After a single induction course, the overall CR rate was 87.6% (170/194), with a significant difference between the standard-dose (83/105, 79.0%) and intermediate-dose (87/89, 97.8%) groups (p < 0.001). Rather than general KITmut, the specific KIT-D816 independently led to a lower probability of achieving CR (HR = 3.29 [1.18-9.24], p = 0.023), worse EFS (HR = 3.53 [1.82-6.84], p < 0.001), and OS (HR = 5.45 [1.77-16.84], p = 0.003) in the standard-dose group, but not in the intermediate-dose group. CD19(+) represented the only independent factor predicting lower CIR both in the standard-dose group (HR = 0.32 [0.10-1.00], p = 0.050) and in the intermediate-dose group (HR = 0.11 [0.03-0.40], p = 0.001). When combined, KIT(+) plus CD19(-) conferred the most increased relapse risk (3-year CIR 60%; SE 0.12). Specific KIT-D816, instead of general KITmut, may be incorporated in prognostication model for t(8;21) AML. Combination of CD19 with KIT provides a more definite risk stratification profile for t(8;21) AML.

SUBMITTER: Wang B

PROVIDER: S-EPMC7897948 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Role of CD19 and specific KIT-D816 on risk stratification refinement in t(8;21) acute myeloid leukemia induced with different cytarabine intensities.

Wang Biao B Yang Bin B Ling Yun Y Zhang Jihong J Hua Xiaoying X Gu Weiying W Yan Feng F

Cancer medicine 20201231 3

High-dose cytarabine (Ara-C) has been reported with increased treatment-related mortality, whereas few data are available concerning intermediate-dose Ara-C for induction of acute myeloid leukemia (AML) with t(8;21) translocation. We retrospectively analyzed factors impacting complete remission (CR), event-free survival (EFS), cumulative incidence of relapse (CIR), and overall survival (OS) in 197 adults with t(8;21) AML, of whom 107 cases were induced with intermediate-dose and 90 with standard ...[more]

PMID: 33382538

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Project description:ObjectiveWe aimed to retrospectively discern the heterogeneity of outcomes from clinicopathological characteristics and next-generation sequencing (NGS) data in adult patients with NPM1-mutated (NPM1mut ) acute myeloid leukemia (AML) induced with standard-dose (SD, 100-200 mg/m2 ) and intermediate-dose (ID, 1000-2000 mg/m2 ) cytarabine arabinose (Ara-C).MethodsIn the entire cohort and FLT3-ITD subgroups, multivariate Logistic and Cox regression analyses were used to analyze the comprehensive complete remission (cCR) rate after one or two induction cycles, event-free survival (EFS), and overall survival (OS).ResultsAmong a total of 203 NPM1mut patients evaluable for clinical outcome, 144 (70.9%) received a first SD-Ara-C induction and 59 (29.1%) received ID-Ara-C induction. Early death was recorded in seven (3.4%) after one or two cycles of induction. Focusing analysis on the NPM1mut /FLT3-ITD(-) subgroup, independent factors showing inferior outcome were presence of TET2 mutation [cCR rate, OR = 12.82 (95%CI 1.93-85.28), p = 0.008; EFS, HR = 2.92 (95%CI 1.46-5.86), p = 0.003], increasing age [EFS, HR = 1.49 (95%CI 1.10-2.02), p = 0.012 by every 10-years elevation], white blood cell count ≥60 × 109 /L [EFS, HR = 3.30 (95%CI 1.63-6.70), p = 0.001], and ≥4 mutated genes at initial diagnosis [OS, HR = 5.54 (95%CI 1.77-17.33), p = 0.003]. In contrast, when focusing on the NPM1mut /FLT3-ITD(+) subgroup, factors showing superior outcome were ID-Ara-C induction [cCR rate, OR = 0.20 (95%CI 0.05-0.81), p = 0.025; EFS, HR = 0.27 (95%CI 0.13-0.60), p = 0.001] and allo-transplantation [OS, HR = 0.45 (95%CI 0.21-0.94), p = 0.033]. Factors showing inferior outcome included CD34(+) [cCR rate, OR = 6.22 (95%CI 1.86-20.77), p = 0.003; EFS, HR = 2.01 (95%CI 1.12-3.61), p = 0.020] and ≥5 mutated genes [OS, HR = 2.85 (95%CI 1.33-6.10), p = 0.007].ConclusionWe conclude that TET2(+) , age, and white blood cell count convey an outcome risk modulation for AML with NPM1mut /FLT3-ITD(-) , as does CD34 and ID-Ara-C induction for NPM1mut /FLT3-ITD(+) . The findings permit re-stratification of NPM1mut AML into distinct prognostic subsets to guide risk-adapted individualized treatment.

Project description:BackgroundPatients with different karyotypes had different prognosis in t(8;21) acute myeloid leukemia (AML). Cytarabine (Ara-C) plays an important role as consolidation therapy in t(8;21) AML. T(8;21) AML patients with different karyotypes responded differently to post-remission therapy with Ara-C. However, the optimum dose of Ara-C in patients with different karyotypes remains unclear.MethodsFrom January 2002 to September 2018, a total of 188 younger adult (14-60 years) patients with t(8;21) AML were enrolled in this retrospective study. Cytogenetic analysis and aberration descriptions followed the International System for Human Cytogenetic Nomenclature. All the patients achieved first complete remission (CR1) after induction chemotherapy. Patients received low-dose Ara-C [LDAC (<1 g/m2)], intermediate-dose Ara-C [IDAC (1-1.5 g/m2)], or high-dose Ara-c [HiDAC (2-3 g/m2)] regimens as consolidation therapy after CR1. All patients were followed for survival or relapse until death, or study completion. We analyzed the prognosis of LDAC, IDAC, and HiDAC regimens as consolidation therapy in patients with different karyotypes. The primary endpoint was overall survival (OS) and the secondary endpoint was relapse-free survival (RFS).ResultsThe results showed IDAC significantly improved OS compared with LDAC [hazard rate (HR) =0.55, P=0.0375] when the clinical factors were adjusted. However, no significant difference between HiDAC and IDAC was found. Subgroup analysis further showed that the OS advantage of IDAC was focused on patients with additional cytogenetic abnormalities, including loss of X chromosome (-X), del(9q), or complex karyotype (group B, HR =0.21, P=0.0125), but not on patients with t(8;21)-only or additional loss of Y chromosome (-Y) cytogenetics (group A, HR =0.77, P=0.4804) in multivariate analysis. Similarly, better OS was shown after IDAC than LDAC consolidation in patients in group B, whether they received allogeneic hematopoietic stem cell transplantation (allo-HSCT) or not, but not in group A.ConclusionsIDAC was suitable for patients with additional -X, del(9q), or complex karyotype, while LDAC might be sufficient for patients with t(8;21)-only or additional -Y cytogenetics. It suggested that t(8;21) AML patients with different karyotypes should use different consolidation regimens.

Dataset Information

Role of CD19 and specific KIT-D816 on risk stratification refinement in t(8;21) acute myeloid leukemia induced with different cytarabine intensities.

Publications

Role of CD19 and specific KIT-D816 on risk stratification refinement in t(8;21) acute myeloid leukemia induced with different cytarabine intensities.

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