BuCy Vs. TBICy for Allo-HSCT in T-ALL Patients

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.

Conditions

• T-Cell Lymphocytic Leukemia
• ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION
• Total Body Irradiation
• Chemotherapy

Interventions

BIOLOGICAL

TBICy

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.

BIOLOGICAL

BuCy

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 & Collaborators

• Children's Hospital of Soochow University

  collaborator OTHER

• Ruijin Hospital

  collaborator OTHER

• Nanfang Hospital, Southern Medical University

  collaborator OTHER

• Fujian Medical University Union Hospital

  collaborator OTHER

• First Affiliated Hospital Xi'an Jiaotong University

  collaborator OTHER

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  collaborator OTHER

• Zhejiang University

  collaborator OTHER

• Anhui Provincial Hospital

  collaborator OTHER_GOV

• The First Affiliated Hospital of Soochow University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

2 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-12-01

Primary Completion

2029-11-30

Completion

2029-11-30

Countries

• China

Study Locations