Improved prognosis with additional medium-dose VP16 to CY/TBI in allogeneic transplantation for high risk ALL in adults.
Yasuyuki AraiTadakazu KondoAkio ShigematsuJunji TanakaKazuteru OhashiTakahiro FukudaMichihiro HidakaNaoki KobayashiKoji IwatoToru SakuraMakoto OnizukaYukiyasu OzawaTetsuya EtoMineo KurokawaKaoru KahataNaoyuki UchidaYoshiko AtsutaShuichi MizutaShinichi KakoPublished in: American journal of hematology (2017)
Allogeneic hematopoietic stem cell transplantation (HSCT) with the conventional cyclophosphamide and total body irradiation (CY/TBI) regimen is an essential therapeutic strategy for acute lymphoblastic leukemia (ALL) in adults. Medium-dose etoposide (VP16, 30-40 mg/kg) can be added to intensify this CY/TBI regimen and reduce relapse; however, differences in prognosis between the VP16/CY/TBI and CY/TBI regimens have not yet been fully analyzed. We conducted a retrospective cohort study using a Japanese transplant registry database to compare the prognosis between the VP16/CY/TBI (VP16, total 30-40 mg/kg) (N = 376) and CY/TBI (N = 1178) regimens in adult patients with ALL transplanted at complete remission (CR) between January 1, 2000 and December 31, 2014. Our analyses indicated that VP16/CY/TBI significantly reduced relapse compared with CY/TBI (risk ratio, 0.75; 95% confidence interval [CI], 0.56-1.00; P = .05) with a corresponding improvement in leukemia-free survival (hazard ratio [HR], 0.76; 95%CI, 0.62-0.93; P = .01), particularly in patients transplanted at CR1 with advanced-risk (positive minimal residual disease, presence of poor-risk cytogenetics, or an initial elevated leukocyte count) (HR, 0.75; 95%CI, 0.56-1.00; P = .05) or those transplanted beyond CR2 (HR, 0.58; 95%CI, 0.39-0.88; P = .01). The addition of VP16 did not increase post-transplant complications or nonrelapse mortality (HR, 0.88; 95%CI, 0.65-1.18; P = .38). This study is the first to reveal the efficacy of the addition of medium-dose VP16 to CY/TBI in high-risk ALL. To establish new myeloablative conditioning regimens including VP16, a large-scale prospective study is necessary.
Keyphrases
- traumatic brain injury
- severe traumatic brain injury
- mild traumatic brain injury
- disease virus
- allogeneic hematopoietic stem cell transplantation
- acute lymphoblastic leukemia
- free survival
- acute myeloid leukemia
- stem cell transplantation
- bone marrow
- emergency department
- risk factors
- cardiovascular events
- rheumatoid arthritis
- high dose
- systemic lupus erythematosus
- radiation induced
- single cell
- dna methylation
- prognostic factors
- mesenchymal stem cells
- disease activity