Total Lymphoid Irradiation as Conditioning for Pediatric Haploidentical Hematopoietic Stem Cell Transplantation

In this comparative study, the investigators aim to compare prospective pediatric patients who receive total lymphoid irradiation (TLI) using tomotherapy with age- and disease-matched controls who receive conventional total body irradiation (TBI) as part of conditioning for haploidentical hematopoietic stem cell transplantation (HSCT) for both malignant and non-malignant diseases. The investigators shall evaluate graft failure-free, graft-versus-host disease (GVHD)-free survival, overall survival, frequency of rejection, GVHD, relapse of malignancy, adverse effects and post-transplant immunoreconstitution.

Study Overview

• Status: Recruiting
• Conditions: Hematopoietic Organs; Disorder
• Intervention / Treatment: Radiation: Total lymphoid irradiation

Detailed Description

Radiotherapy at a dose of 6Gy divided into 3 equal fractions (2Gy per fraction) to all lymphoid organs (TLI) over 2 days using tomotherapy will be given to participants as part of the conditioning treatment before haploidentical hematopoietic stem cell transplantation (HSCT). Retrospective patients who are age- and disease-matched with the recruited patients and had received radiotherapy to the whole body (TBI) with or without lung shielding at a total dose of 2-12 Gy delivered as 1-6 equal fractions by conventional opposed fields radiotherapy as part of conditioning will be compared for the outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 23
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Daniel Cheuk; Phone Number: 852-35136049; Email: cheukkld@gmail.com

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Hong Kong Children's Hospital
    • Contact: Daniel Cheuk; Phone Number: 852-35136049; Email: cheukkld@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 0-18 years who requires allogeneic HSCT, has no human leukocyte antigen (HLA)-matched sibling donor but has an HLA-haploidentical donor.
• Adequate organ function to tolerate the conditioning chemotherapy and radiotherapy
• Karnofsky or Lansky performance status score ≥50

Exclusion Criteria:

• Pregnant or lactating woman
• HIV infection
• Patients for whom alternative treatment is deemed more appropriate by treating physician
• Patients who are unlikely to benefit from haploidentical hematopoietic stem cell transplantation, e.g., terminal malignancy with multiorgan failure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Total lymphoid irradiation (TLI)	Radiation: Total lymphoid irradiation; Total lymphoid irradiation (TLI) 6Gy by tomotherapy as part of conditioning treatment before haploidentical hematopoietic stem cell transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Graft failure-free, GVHD-free survival	From the date of treatment start until the date of graft failure or GVHD or death from any cause, whichever comes first, assessed up to 1 year	up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients who develop relapse among those with malignant diseases	Relapse is defined as reappearance of biopsy-proven malignant disease after complete remission	up to 1 year
Proportion of patients who develop graft failure	Graft failure is defined as donor cells <5% in whole blood	up to 1 year
Proportion of patients who develop acute graft-versus-host disease	Acute graft-versus-host disease is defined by MAGIC criteria	up to 1 year
Proportion of patients who develop chronic graft-versus-host disease	Chronic graft-versus-host disease is defined by NIH criteria	up to 1 year
Blood T lymphocyte count at 3 months	Mean T lymphocyte count in blood among evaluable patients	at 3 months
Blood T lymphocyte count at 1 year	Mean T lymphocyte count in blood among evaluable patients	at 1 year
Overall survival	From the date of treatment start until the date of death from any cause, whichever comes first, assessed up to 1 year	up to 1 year
Proportion of patients who develop adverse events not mentioned in outcomes 4-6	Adverse events are graded according to Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events version 5 (CTCAEv5)	up to 1 year

Collaborators and Investigators

• Sponsor: Hong Kong Children's Hospital
• Collaborators: The University of Hong Kong; Hong Kong Sanatorium & Hospital
• Investigators: Principal Investigator: Daniel Cheuk, Hong Kong Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: October 4, 2023
• First Submitted That Met QC Criteria: October 4, 2023
• First Posted (Actual): October 10, 2023

Study Record Updates

• Last Update Posted (Estimated): September 10, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: PAED-2023-020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No