Abstract
The outcomes of adult acute lymphoblastic leukemia (ALL) patients with chemotherapy or autologous hematopoietic stem cell transplantation (HSCT) are unsatisfactory. Therefore, allogeneic (allo) HSCT has been applied to those patients in first complete remission (CR1), and has shown a long-term survival rate of approximately 50 %. In terms of myeloablative conditioning (MAC) regimen, higher dose of cyclophosphamide (CY) and total body irradiation (TBI) (the standard CY + TBI) has been generally applied to allo HSCT. Other MAC regimens such as busulfan-based or etoposide-based regimens have also been used. Among those, medium-dose etoposide (ETP) in addition to the standard CY + TBI conditioning regimen appears to be promising for allo HSCT in adult ALL when transplanted in ALL patients aged under 50 years in CR1 and also in CR2, showing an excellent outcome without increasing relapse or transplant-related mortality (TRM) rates. By contrast, reduced-intensity conditioning (RIC) regimens have also been applied to adult ALL patients and favorable outcomes have been obtained; however, relapse and TRM rates remain high. Therefore, an allo HSCT conditioning regimen which deserves further study for adult ALL patients aged under 50 years in CR1 and CR2 appears to be medium-dose ETP + CY + TBI and RIC is suitable for patients aged over 50 years or for younger patients with comorbid conditions. On the contrary, new therapeutic strategies for adult ALL patients are increasingly utilized with better outcomes; namely, various tyrosine kinase inhibitors for Philadelphia chromosome (Ph)-positive ALL, human leukocyte antigen-haploidentical HSCT, and pediatric-inspired regimens for Ph-negative ALL. Therefore, the optimal treatment modality should be selected considering patient’s age, Ph-positivity, donor availability, risk classification, efficacy, and safety.
Highlights
Adult acute lymphoblastic leukemia (ALL) is a type of intractable hematological malignancies, showing a longterm survival rate of approximately 30 % with a high incidence of relapse when treated with intensive chemotherapies [30, 53, 70, 74]
Almost comparable outcomes were observed in patients with allo hematopoietic stem cell transplantation (HSCT) and those without allo HSCT, the survival in patients with minimal residual disease (MRD) (≧1−3) at 6 weeks after induction initiation was longer in the allo HSCT cohort than in the no HSCT cohort. These results indicate standard risk ALL patients aged < 40– 45 years with MRD (
In allo HSCT, the medium-dose ETP + CY + total body irradiation (TBI) regimen is promising for high-risk ALL patients aged < 50 years in CR1 and for standard-risk patients in CR2, resulting in an excellent outcome without higher transplant-related mortality (TRM) and relapse rates
Summary
Adult acute lymphoblastic leukemia (ALL) is a type of intractable hematological malignancies, showing a longterm survival rate of approximately 30 % with a high incidence of relapse when treated with intensive chemotherapies [30, 53, 70, 74]. A standard conventional MAC regimen for allo HSCT in patients with ALL is 120 mg/kg cyclophosphamide (CY) plus 12 to 13.2 gray (Gy) fractionated total body irradiation (TBI) With this regimen, a 3-Y overall survival (OS) or DFS rate of approximately 50 % was obtained when transplanted in CR1 [58, 70]. In a retrospective analysis in which 37 ALL patients in 28 CR1, 7 CR2, and 2 non-CR were treated with allo HSCT by a medium-dose ETP (15 mg/kg × 2) + CY (60 mg/kg × 2) + TBI (2 Gy × 6) regimen, a 3-Y OS, relapse, and transplant-related mortality (TRM) rate were 89 %, 8 %, and 5 %, respectively [59].
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