In vitro chemosensitivity by MTT assay and clinical outcomes in childhood leukemia

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We investigated the relationship between in vitro sensitivity and clinical outcomes in 196 children with newly diagnosed ALL.We explored whether the sensitivity to a combination of four drugs DPAV (Dex, Pred, Asp, VCR) predicted induction failure and early relapse (IF/e.rel). [Patients and Methods] Eligible were children (age 0-16 years) with non-B cell ALL,newly diagnosed between 1989 and 1995. BM samples were sent for in vitro drug tests. There were 142 samples of common ALL (cALL), 21 of T-ALL,28 of mixed lineage ALL (mix ALL) and 5 of undifferentiated ALL (uALL). All patients (pts) were treated with the ALL protocol of Pred, Asp and VCR for standard risk, plus CPA and DNR for high risk, as induction therapy. In vitro tests were carried out with a four-day culture and MTT assay. We tested 16 drugs and calculated LD70 for 14 drugs, and LCS for Dex and Pred.For each single drug, pts were classified into two groups, as either S (lower than median LD70 or LCS) or R (higher than median L … More D70 or LCS).[Statistics] The Kaplan-Meier method for EFS,log rank test, Fisher's PLSD,and contingency table analysis for multi-variate comparison were conducted using Stat View-J4.5 (Abacus Concepts).[Results] EFS (3 yrs) of pts with cALL,T-ALL,mix ALL,uALL were 0.727,0.560,0.534,0.600 respectively. S group pts for Pred, VP16, VCR and MIT had superior EFS to R group pts (p<0.05). When we classified pts into three groups (S,I,R) by sensitivity to four drugs (DPAV), EFS (3 yrs) of S group (n=41) was 0.833, that of I (n=78) was 0.752, and that of R (n=74) was 0.546 (p=0.0011). Then we investigated whether the drug sensitivity of S or R was related to three prognostic groups (CCR,IF/e.rel, late relapse). S groups of Pred, BLM,VP16, VCR,MIT were significantly related to CCR,and R to IF/e.rel (p<0.05). When we used S,I and R for DPAV sensitivity, S and I pts tended to maintain CCR,and R pts tended to undergo IF/e. rel and late relapse (p=0.004). [Conclusion] In vitro drug sensitivity testing together with immunological marker testing provides prognostic information for childhood ALL. Less