Analysis Of Clinical Efficacy Of Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia In Adolescents And Young Adults

Objective: We retrospectively analyzed the clinical features,outcome and prognostic factors on Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and young adults.Methods: The study retrospectively analyzed 118 Ph-AYA ALL patients who are newly diagnosed,admitted to Department of Hematology in the Hospital of Jilin University from January 2010 to August 2017.The patients were divided into standared-risk group and high-risk group according to WBC count,immunophenotype,cytogenetics,molecular biological characteristics and early treatment reaction.The patients treated with CCLG-2008 protocol were classified as children's protocol treatment group and patients treated with CALLG-2008 or Hyper CVAD(MDACC)protocol were classified as adult's regien treatment group.We aimed at early mortality rate,morphological remission rate in d14,complete response(CR)rate,minimal residual disease negative conversion rate,long-term survival and prognostic factors.All subjects or their immediate relatives were fully informed and signed informed consent.The research was approved by the Ethics Committee in the Hospital of Jilin University.Results: 1.The overall CR rate was 91.5%(108/118).Early mortality rate and CR rate have no significant difference between children's protocol group and adute regien treatment group(1.7% vs 1.7%,94.8% vs 88.3%,P=1.000,P=0.205).The patients have good early morphological remission rate in d14 and MRD negative conversion rate in the children's protocol group than in the adult's regien treatment group(87.3% vs 69.0%,72.2% vs 41.8%,P=0.019,P=0.001).2.Long-term survival analysis suggested that with a median follow-up of 35(5-90.5)months,1-year overall survival(OS)and relapse-free survival(RFS)rate were 93.9% and 68.5%,respectively.OS and RFS rates in 3-year were 65.9% and 53.1%,respectively.OS and RFS rates in 5-year were 61.1% and 47.8%,respectively.The difference between the two group have significance(81.2% vs 43.4%,67.0% vs 31.3%,P=0.002,P=0.001).3.The univariate analysis showed that risk stratification,blast level at d14,protocol,and MRD at CR and 3 months after treatment were associated with OS.Blast level at d14,protocol,and MRD at CR and 3 months after treatment were associated with RFS.The univariate analysis showed that allo-HSCT was not associated with OS or RFS,which was associated with OS and RFS in patients with high risk stratification(P=0.011,P=0.022).4.Multvariate analysis indicated that traditional risk stratification(HR=2.764,95% CI 1.087~7.033,P=0.033)and MRD level at the time point of CR(HR=4.704,95% CI 2.037~10.867,P<0.000)were associated with OS independently.Protocol(HR=2.506,95% CI 1.223~5.137,P=0.012)and MRD at 3 months after treatment(HR=5.336,95% CI 2.534 ~ 11.239,P < 0.000)were associated with RFS independently.Conclusions: 1.The overall CR rate was 91.5% in our study.The children's protocol improved early response and MRD conversion rate,but not the early mortality rate or CR rate.2.The univariate analysis and multvariate analysis showed that the traditional risk stratification indicate long-term survival in a way,but it was lack of evidence to indicate relapse.As a new risk stratification index,MRD was important to guide the next treatment which was not affected by other elements.3.With Ph-AYA ALL long-term survival prolonged under children's protocol,patients of high risk stratification benefit from allo-HSCT.