| Objective: To analyze the therapeutic effect of different consolidation therapy after induction towards the acute B lymphoblastic leukemia of Ph negative adolescent and young adults. And to study the prognostic effect of different risk factors. Detecting the bone marrow of patients with acute B lymphoblastic leukemia and analyze the mutation frequency through next generation sequencing.Methods: 80 Ph negative B-ALL patients of 16-39 years old, admitted by the hematology department of 301 (65 cases) and 309 (15 cases) hospitals from 1999 to 2016, are retrospectively analyzed. Patients obtained remission after combined induction chemotherapy of four or five chemotherapeutic drugs (VDCLP/ VDLP/ DOLP/ IOLP), and then went through consolidation therapy of pediatric-inspired protocols and Allo-HSCT or Haplo-HSCT afterwards. The median follow-up time is 29 (6-153) months. Detected the Minimal Residual Disease of 20 pediatric-inspired protocol patients and 30 HSCT patients by 4 colour FCM. 18 B-ALL patients admitted by the hematology department of 301 from 2015.8 to 2017.4 was detected mutations by Annoroad Next Generation Sequence including 111 hematological tumor related genes.Results: HSCT were carried out after CR1. The 5-year OS, EFS, of Allo-HSCT group(n=29)is (73±16)%,(67±17)%,respectively, while those of Haplo-HSCT group(n=20) is (53±22)%,(53±22)%,respectively and those of pediatric-inspired protocols(n=31) is (63±17)%,(50±18)%, respectively. There is no significantly difference between the OS and the EFS of three group,(P>0.05). The re-remission rate of recurrent patients is (50±23)%. On the one side, the Cumulate Incidence of TRM of Pediatric-inspired protocol is better than HSCT,(P<0.05). On the other side, the CIR of Pediatric-inspired protocol is poorer than HSCT, yet without significant difference, (P>0.05). The median remission time of CR2 patients is 14(2-36) months. Univariate and Multivariate analysis are performed in 65 patients. The result showed an abnormal result of CD13 or CD33 positive, CD22 negative, indicating a poorer prognosis(P<0.05). The patient that minimal residual disease (MRD) after CR is negative in 3 months is better than the patient MRD positive, (P<0.05). The patient that minimal residual disease (MRD) after CR is negative for 1 year is better than the patient MRD positive (P<0.05). And the patient that MRD pre-HSCT is negative is better than the positive,but there is no significant difference, (P>0.05).There were 11 gene mutations detected by Next Generation Sequence involving 7 patients,including TP53, TPMT, KRAS, NRAS, IKZF1, PTPN11, PHF6, KIT and EZH2. The highest incidence of Ph-like mutations, TP53, TPMT mutation was 11.1%, detected by next generation sequencing. KRAS, NRAS, IKZF1, PTPN11 belongs to Ph-like mutations, and the incidence of them is 5.6%. And PHF6, KIT and EZH2 was 5.6%. Three patient was detected more than 2 different mutations. And 2 patients were detected multisite mutations.Conclusion: The Ph negative adolescent and young adult patients performed in pediatric-inspired protocols could have a similar survival time with those in Allo-HSCT group.However, more prospective clinical research of RCT should be studied. After CR, the patient that MRD become negative early, and sustains negative for 1 year is better than the patient that MRD is positive. There are characteristic mutations in B-ALL, such as Ph-like ALL mutations (RAS, IKZF1, PTPN11), TP53, TPMT, but we need more cases to analysis for accurate treatment. |
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