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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Hematopoietic Organs; Disorder

Intervention / Treatment
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* Radiation: Total lymphoid irradiation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 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 | 
| 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 | 
| 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 |