| BackgroundCyclin-dependent kinase inhibitor 2(CDKN2)deletion occurs frequently in many lymphoid malignancies,accounting for 21-48.6%and holding nearly 50%morbidity in acute lymphoblastic leukemia(ALL).The value of CDKN2 deletion in ALL remains controversial.Emerging reports draw the adverse prognostic value of CDKN2 deletion in ALL,including our previous single center’s study,suggesting CDKN2 deletion as a poor prognostic predictor involved in the progression of adult B-lineage ALL(B-ALL).The role of allogeneic hematopoietic cell transplant(allo-HCT)on ALL with CDKN2 deletion is still under debate.Some studies suggested that allo-HCT could improve outcomes of ALL with CDKN2 deletion,while other studies draw the opposite conclusion.Here,in order to figure out the value of CDKN2 deletion in B-ALL and whether B-ALL with CDKN2 deletion might benefit from allo-HCT,we screened five medical centers’ data in China to take the analysis.MethodsThe patients with adult B-ALL underwent more than two courses of chemotherapy with cytogenetic data were enrolled in the multicenter retrospective study.Follow up until 2020-12,relapse and survival were analyzed by Stata 15.0.ResultsA total of 1712 cases of B-ALL met the age criteria after retrieval from five institutes.After screening,1336 cases of B-ALL were enrolled in this study.The median age at diagnosis was 30.5 years,including 295 patients with CDKN2 deletion and 1041 wild-type(WT).The complete remission(CR)rates were 83.8%and 88.2%(P=0.232),the rate of minimal residual disease(MRD)nagetive post-induction were 51.0%and 61.1%(P=0.008)after induction chemotherapy in patients with CDKN2 deletion and WT,respectively.The median follow-up time was 25.0 months(range 2.6 to 116.9 months).Five hundred and fifty-nine cases survived and 777 cases died.There is no statistical difference in baseline data,including gender,age,WBC count,BCR/ABL,MLL rearranged,hypodip-loidy,complex karyotype,and high-risk stratification,the 5-year cumulative relapse post-CR were 56%(95%CI,52-68)and 43%(95%CI,40-51)(P<0.001),5-year disease-free survival(DFS)were 30%(95%Cl,24-36)and 41%(95%CI,39-46)(P<0.001),and 5-year overall survival(OS)were 35%(95%CI,28-39)and 47%(95%CI,44-49)(P<0.001)in the two groups,respectively.Subgroup analysis revealed that the 5-year cumulative relapse were 89.3%(95%CI,83.0-96.5)and 68.4%(95%CI,60.2-72.5)(P<0.001),5-year DFS were 4.9%(95%CI,1.8-10.4)and 22.7%(95%CI,18.0-27.7)(P<0.001),and 5-year OS were 6.9%(95%CI,3.1-12.9)and 23.4%(95%CI,18.7-28.6)(P<0.001)in CDKN2 deletion and WT groups undergoing chemotherapy alone,respectively,while there were not different in terms of 5-year cumulative relapse(38.1%vs 34.3%,P=0.211),DFS(48.4%vs 52.2%,P=0.325)and OS(54.5%vs 56.3%,P=0.483)between those with CDKN2 deletion and WT undergoing allo-HCT.Univariate analysis showed that CDKN2 deletion,high-risk stratification,MRD positive after induction chemotherapy,and not receiving allo-HCT were risk factors for relapse.And 15-39 years old,CDKN2 wild-type,standard-risk stratification,MRD negative after induction chemotherapy,allo-HCT were protective factors for DFS and OS.Multivariate analysis showed that CDKN2 deletion,high-risk stratification and MRD positive after induction chemotherpy were risk factors for relapse,DFS and OS,while allo-HCT was a protective factor.ConclusionsCDKN2 deletion might be a poor prognostic predictor of adult B-ALL.Adult B-ALL with CDKN2 deletion might benefit from allo-HCT. |
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