Pediatric-inspired regimen for adolescent and adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia: a prospective study from China

Several international centers have used and reported pediatric-inspired regimens for adolescent and adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL). However, there is a lack of prospective data on the Chinese population. Herein, we performed a prospective study with a pediatric-inspired regimen (IH-2014 regimen) in treating adolescent and adult Ph- ALL patients in our center. From 2014 to 2021, a total of 415 patients aged between 14 and 65 years (median age, 27) were included in this study. After a median follow-up of 40.8 months, the 5-year overall survival, disease-free survival, and event-free survival rates were 53.8%, 51.1% and 45.0%, respectively. The regimen was generally well tolerated and safe, and the overall chemotherapy-related mortality was 3.6%. Age ≥ 40 years and persistent detectable minimal residual disease (MRD) post-induction were independent prognostic factors. Traditional risk factors for adult patients combined with MRD post-induction exhibit predictive significance for survival and relapse, which is helpful in the selection of subsequent treatment. Patients with high risk factors who can achieve deep MRD response after induction do not derive benefit from allogeneic hematopoietic stem cell transplantation

High-Dose Cytarabine in Acute Myeloid Leukemia Treatment: A Systematic Review and Meta-Analysis

<div><p>The optimal dose, scheme, and clinical setting for Ara-C in acute myeloid leukemia (AML) treatment remain uncertain. In this study, we performed a meta-analysis to systematically assess the impact of high-dose cytarabine (HDAC) on AML therapy during the induction and consolidation stages. Twenty-two trials with a total of 5,945 <i>de</i><i>novo</i> AML patients were included in the meta-analysis. Only patients less than 60 year-old were included in the study. Using HDAC in induction therapy was beneficial for RFS (HR = 0.57; 95% CI, 0.35–0.93; <i>P</i> = 0.02) but not so for CR rate (HR = 1.01; 95% CI, 0.93–1.09; <i>P</i> = 0.88) and OS (HR = 0.83; 95% CI, 0.66–1.03; <i>P</i> = 0.1). In consolidation therapy, HDAC showed significant RFS benefits (HR = 0.67; 95% CI, 0.49–0.9; <i>P</i> = 0.008) especially for the favorable-risk group (HR = 0.38; 95% CI, 0.21–0.69; <i>P</i> = 0.001) compared with SDAC (standard dose cytarabine), although no OS advantage was observed (HR = 0.84; 95% CI, 0.55–1.27; <i>P</i> = 0.41). HDAC treatment seemed less effective than auto-BMT/allo-BMT treatment (HR = 1.66, 95% CI, 1.3–2.14; <i>P</i><0.0001) with similar OS. HDAC treatment led to lower relapse rate in induction and consolidation therapy than SDAC treatment, especially for the favorable-risk group. Auto-BMT/allo-BMT was more beneficial in prolonging RFS than HDAC.</p></div

Effect of HDAC versus SDAC in induction therapy.

<p><b>A</b>: Effect of HDAC versus SDAC in induction therapy on CR rate. <b>B</b>: Overall survival benefit of HDAC in induction therapy. <b>C</b>: Relapse free survival benefit of HDAC in induction therapy.</p

Relapse free survival benefit of HDAC in consolidation therapy.

<p><b>A</b>: Total relapse free survival benefit of HDAC in consolidation therapy. <b>B</b>: Relapse free survival benefit of different subgroups of HDAC in consolidation therapy.</p

Effect of HDAC versus BMT on overall survival.

<p>Effect of HDAC versus BMT on overall survival.</p

Characteristics of Included Studies for consolidation therapy.

<p>Note: ▴ S. Miyawaki et al, 2011 repeated the same trial of S, Ohtake et al, 2011.</p><p>BMT randomized trials were defined that if the patients didn’t have donors, they were randomized into auto-BMT and high-dosed Ara-C groups.</p><p>★analyze analyze <60 years the patients in each trial.</p><p>Abbreviations: NR, not reported; IDA, idarubicin; Ara-c, cytarabin; VP-16, etoposide; DNR, daunorubicin MCT, multiagent chemotherapy;</p><p>CTX, cyclophosphamide; MTZ, mitoxantrone; AZQ, diaziquone; 6-TG, thioguanine; AMS, amsacrine.</p><p>Characteristics of Included Studies for consolidation therapy.</p

Characteristics of included Studies for induction therapy.

<p>Note: ▴ T. Büchner et al, 2009 repeated the same trial of T. Büchner et al, 2006.</p><p>analyze <60 years patients in each trial.</p><p>Abbreviations: NR, not reported; IDA, idarubicin; Ara-c, cytarabin; VP-16, etoposide; DNR, daunorubicin.</p><p>Characteristics of included Studies for induction therapy.</p

Effect of HDAC versus BMT on relapse free survival.

<p>Effect of HDAC versus BMT on relapse free survival.</p

Distinct genetic alteration profiles of acute myeloid leukemia between Caucasian and Eastern Asian population

Abstract Racial and ethnic disparities in malignancies attract extensive attention. To investigate whether there are racial and ethnic disparities in genetic alteration between Caucasian and Eastern Asian population, data from several prospective AML trials were retrospectively analyzed in this study. We found that there were more patients with core binding factor (CBF) leukemia in Eastern Asian cohorts and there were different CBF leukemia constitutions between them. The ratios of CBF leukemia are 27.7, 22.1, 21.1, and 23.4%, respectively, in our (ChiCTR-TRC-10001202), another Chinese, Korean, and Japanese Eastern Asian cohorts, which are significantly higher than those in ECOG1900, MRC AML15, UK NCRI AML17, HOVON/SAKK AML-42, and German AML2003 (15.5, 12.5, 9.3, 10.2, and 12%, respectively). And CBFbeta-MYH11 occurred more prevalently in HOVON/SAKK AML- 42 and ECOG1900 trials (50.0 and 54.3% of CBF leukemia, respectively) than in Chinese and Japanese trials (20.1 and 20.8%, respectively). The proportion of FLT3-ITD mutation is 11.2% in our cohort, which is lower than that in MRC AML15 and UK NCRI AML17 (24.6 and 17.9%, respectively). Even after excluding the age bias, there are still different incidence rates of mutation between Caucasian and Eastern Asian population. These data suggest that there are racial and ethnic disparities in genetic alteration between Caucasian and Eastern Asian population