ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION, Chemotherapy, T-Cell Lymphocytic Leukemia, Total Body Irradiation
Conditions
Brief summary
T-cell acute lymphoblastic leukemia (T-ALL), a hematological malignant neoplasm of immature T cells, accounting for a morbidity of 10-15% among pediatric and 20-25% among adult patients of ALL. Despite the application of improved intensive therapies, the overall survival (OS) of T-ALL patients is still unsatisfactory, with a 5-year OS rate of less than 60% in adults and 85% in children. Over the past few decades, allogeneic hematopoietic stem-cell transplantation (allo-HSCT) has emerged as a potential and the most likely curative treatment for patients with high-risk hematological malignant neoplasms, and it has been proven that allo-HSCT could hold the potential to improve the prognosis of T-ALL patients and may even cure T-ALL. The two most common myeloablative conditioning regimens for T-ALL patients with allo-HSCT were total body irradiation (TBI) plus cyclophosphamide (TBI-Cy) and busulfan (Bu) plus cyclophosphamide (BuCy). The most common use conditioning regimen for ALL patients is the TBI-Cy conditioning regimen over other hematological malignancy patients because TBI possess potent and distinct anti-leukemic effects, particularly in organs not easily affected by systemic chemotherapy and intense immunosuppressive effects. However, TBI-based conditioning regimens may cause a high risk of cataracts, interstitial pneumonitis (IP), engraftment failure and even subsequent malignant neoplasms (SMNs). To avoid these disadvantages, intravenous Bu replaced TBI as a part of conditioning. Extensive studies have shown that allo-HSCT with conditioning regimens based on TBI could benefit survival compared with conditioning regimens based on chemotheraphy in treating ALL. We retrospectively analyzed post-10-year data from T-ALL patients from two transplant centers, and all the databases were used to eliminate confounding factors via PSM. We demonstrated that the TBI-Cy conditioning regimen had inferior efficacy to the BuCy conditioning regimen, especially for T-ALL patients who were children, refractory, had extramedullary disease before transplantation, had active disease or an MRD-positive status at allo-HSCT, or who received haplo-HSCT.
Interventions
BIOLOGICALTBICy
The TBI-Cy group was administered 250 mg/m2/d oral Me-CCNU on day -8. A total of 12 Gy TBI was for each patient and fractionated dose was 2 Gy twice daily or 4Gy once daily on days -8 to -6. Occluding of the lung fields during TBI, the corresponding irradiation dose reduced to a total of 8 Gy. On day -5, the schedule was intravenous 2 g/m2 Ara-C every 12 hours. Then intravenous 1.8 g/m2 CTX once per day from days -4 to -3.
BIOLOGICALBuCy
The BuCy group received oral Me-CCNU 250 mg/m2/d twice daily on day -8, intravenous cytosine arabinoside (Ara-C) 2 g/m2 twice daily on day -7, intravenous Bu 3.2 mg/kg/d from days -6 to -4, and intravenous cyclophosphamide (CTX) 1.8 g/m2/d from days -3 to -2. There were no patients accepted oral Bu.
Sponsors
Children's Hospital of Soochow University
Ruijin Hospital
Nanfang Hospital, Southern Medical University
Fujian Medical University Union Hospital
First Affiliated Hospital Xi'an Jiaotong University
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Zhejiang University
Anhui Provincial Hospital
The First Affiliated Hospital of Soochow University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. T-ALL patients aged \> 2 years and ≤55 years; 2. For the first time accept allo-HSCT; 3. With Eastern Cooperative Oncology Group (ECOG) performance status of 0-3; 4. Signing an informed consent form, having the ability to comply with study and follow-up procedures.
Exclusion criteria
1. With other malignancies; 2. With a previous history of autologous hematopoietic cell transplantation, allogeneic hematopoietic cell transplantation or chimeric antigen receptor T cell therapy; 3. With uncontrolled infection intolerant to haploidentical hematopoietic cell transplantation; 4. With severe organ dysfunction; 5. In pregnancy or lactation period; 6. With any conditions not suitable for the trial (investigators' decision).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival | 2 years after randomization | estimated progression-free survival at 2 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 2 years after randomization | estimated overall survival at 2 year |
| Cumulative incidence of relapse | 2 years after randomization | estimated cumulative incidence of relapse at 2 year |
| Non-relapse mortality | 2 years after randomization | estimated non-relapse mortality at 2 year |
| Adverse events | 2 years after randomization | Number of participants with adverse events. Frequencies of toxicities based on Common Terminology Criteria for Adverse Events (CTCAE) will be tabulated. |
Countries
China
Contacts
Primary ContactYang Xu
Outcome results
None listed