Evolving paradigms in the treatment of adult ALL include the application of intense pediatric
regimens to the treatment of adolescents and young adults (AYA) and the optimization of
allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the cure of patients. The
Cancer and Leukemia Group B (CALGB) and the Children's Cancer Group (CCG) first asked whether
AYA between the ages of 16 and 20 fared differently whether they were treated on pediatric
protocols. The results of this study demonstrated that although the complete remission rates
were identical for the AYAs treated on the CALGB and CCG trials, the AYAs had a 63%
event-free survival (EFS) and 67% OS at 7 years on the CCG trials compared with 34% and 46%,
respectively, on the CALGB trials.
High relapse and transplantation-related-mortality still remains great challenge for HSCT of
adult ALL, which both range between 25% and 30%. Recently, risk-adapted indication and
optimization of conditioning regimen are highlighted, which aiming to reduce TRM and relapse
rate, respectively.City of Hope National Medical Center studied the substitution of etoposide
(VP-16) for CY in the treatment of ALL patients receiving HCT. The result suggested that
etoposide and TBI are associated with a decreased relapse rate following transplantation for
ALL, compared with those receiving CY and TBI. Japanese and Germany reports pronounced the
advantage of VP-16 in intensified regimen for adult ALL. On the same time, the investigators
previous researches have confirmed the effect and safety of FA-intensified conditioning
regimen on relapse and refractary leukemia.
Based on mentioned above, the investigators speculate that VP-16-intensified conditioning
regimen could improve the outcome for adult ALL. The potential mechanism will be attributed
to reduce MRD and promote GVL effect via providing enough time-window for
immuno-reconstitution by high-dose preparative regimen.