Modified TBF Regimen as Conditioning Regimen Prior to Allo-HSCT for T-ALL/LBL
Status:
Recruiting
Trial end date:
2025-09-01
Target enrollment:
Participant gender:
Summary
T cell acute lymphoblastic leukemia (T-ALL)/Lymphoblastic lymphoma (LBL) is a hematological
malignancy caused by malignant transformation and clonal expansion of T-lineage precursor
cells. The long-term cure rate of pediatric patients with T-ALL/LBL reaches 90%, but
long-term survival of adult patients is less than 60%. Moreover, patients with high-risk
factors such as PTEN/NRAS gene mutation, early T cell precursor (ETP) phenotype or positive
minimal residual disease (MRD) have high rates of chemoresistance and dismal outcome.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can significantly improve the
prognosis of high-risk T-ALL/LBL. Total body irradiation (TBI)-based conditioning
chemotherapy regimen is the preferred regimen for allo-HSCT in children and young adults with
ALL because of lower relapse rates and satisfactory survival. Different from children, the
non-relapse-related mortality (NRM) after TBI-based preconditioning in adults (especially
those >35 years old) was reported as high as 38%. In addition, serious sequelae after TBI
seriously affect the quality of life and non-radiation conditioning chemotherapy regimens are
urgently needed for T-ALL/LBL. The reported recurrence rates after BUCY (busulfan +
cyclophosphamide) conditioning regimen for T-ALL as 41.2%. -56.7% and long-term survival was
only 30-50%. Thiotepa is an ethyleneimine alkylating agent with anti-tumor effects and
immunosuppressive effects, thus is widely used in conditioning regimen before HSCT.
Retrospective paired analysis from EBMT indicated conditioning regimen thiotepa achieved
similar relapse rates, long-term survival and faster granulocyte and platelet engraftment
than TBI regimen. A recent retrospective study of childhood ALL from Turkey also reported
that the TBF(thiotepa + fludarabine + busulfan) regimen had a recurrence rate of only 11.9% ,
a non-relapse mortality rate of 14.0% and a long-term survival of 79.1%. Data from a large
retrospective paired study suggested TBF regimen can significantly reduce the relapse rate of
acute myeloid leukemia after the first remission (HR=0.4, CI 0.2-0.7, P = .02) without
increasing treatment related deaths compared with the traditional BUCY regimen. Based on
these data, we modified the TBF regimen with additional cytarabine for allo-HSCT in T-ALL/LBL
with expection to reduced disease relapse and improved long-term survival.