Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Adult Patients with T-Cell Acute Lymphoblastic Leukemia: A Survey From the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT)
Authors: Cahu Xavier , Labopin Myriam , Giebel Sebastian , Socie Gerard , Beelen Dietrich , Arnold Renate , Michallet Mauricette , Milpied Noel , Sucak Gulsan , Gurman Gunhan , Kyrcz-Krzemien Slawomira , Passweg Jakob R. , Yakoub-Agha Ibrahim , Stelljes Matthias , Esteve Jordi , Mohty Mohamad 
Published: October 2019

Abstract
Abstract 356

Background:
T-cell acute lymphoblastic leukemia (T-ALL) comprises about 25% of all adult ALL. Although allogeneic hematopoietic stem cell transplantation (allo-SCT) exerts a graft versus leukemia effect, very few large series exist on the outcome of adult T-ALL patients allografted with a myeloablative conditioning regimen.

Patients and methods:
adult cases of T-ALL patients who underwent related or unrelated (6/6) allo-SCT with a myeloablative regimen between 2000 and 2010 were extracted from the EBMT registry. Patients with a prior autologous or allogeneic SCT and those who received cord blood allo-SCT were excluded from analysis. Primary goal of the study was to evaluate overall survival (OS), leukemia-free survival (LFS), non-relapse mortality (NRM) and relapse incidence (RI) for T-ALL patients in first (CR1), second or subsequent remission (CR2+) and in relapse or refractory disease (advanced).

Results:
886 patients were included in this study. The median follow-up was 43 months. The median age was 29 (range: 18–63) and 649 patients (73%) were males. Allo-SCT characteristics are described in table 1.
Among patients (n=561) allografted in CR1, 25% had a white blood cell count (WBC) ≥100 G/L, and a complex karyotype was identified in 43 cases (16%, available data = 268). 4-year OS and 4-year LFS were 58% (standard deviation (SD) 2%) and 55% (SD 2%), respectively, whereas 4-year NRM and RI were 19% (SD 2%) and 26% (SD 2%), respectively. In univariate analysis, age < median age (60% versus 50%, p = 0.02) and use of total-body-irradiation (TBI) (57% versus 42%, p = 0.04) were associated with an improved 4-year LFS. In a multivariate analysis including age, use of TBI, donor type and donor sex, age <median age (Hazard Ratio (HR)= 0.71 [95% CI: 0.55–0.92], p=0.01) and use of TBI (HR = 0.67 [0.48–0.93], p=0.02) were associated with an improved LFS.
In the CR2+ T-ALL group (n=151), 4-year OS and 4-year LFS were 25% (SD 4%) and 24% (SD 4%), respectively. 4-year NRM was 27% (SD 4%) whereas 4-year RI was 49% (SD 4%). In univariate analysis, use of TBI was associated with an improved 4-year LFS (29% versus 8%, p = 0.02). In a multivariate analysis including age, patient sex, use of TBI and donor type, use of TBI was associated with an improved LFS (HR = 0.57 [0.37–0.88], p=0.01).
Finally, in the advanced T-ALL group (n=174), 4-year OS and 4-year LFS were 15% (SD 3%) and 12% (SD 3%), respectively. 4-year NRM was 30% (SD 4%), whereas 4-year RI was 58% (SD 4%). In univariate analysis, use of TBI was associated with an improved 4-year LFS (16% versus 3%, p= 0.002). In a multivariate analysis including age, use of TBI and donor type, use of TBI was again associated with an improved LFS (HR=0.56 [0.38–0.82], p=0.003).

Conclusion:
This large series demonstrates that myeloablative conditioning allo-SCT is followed by a relatively favorable outcome in patients with T-ALL transplanted in CR1, and might be an option for subgroups of patients in more advanced phase of the disease. Of note, use of TBI as part of the conditioning regimen is associated with an improved LFS in all disease stages.

Disclosures:
No relevant conflicts of interest to declare.