Donor CHIP and Allogeneic HSCT Outcome

Study Overview
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Brief Summary
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Current data on the impact of donor CHIP on long-term recipient outcome remain largely speculative. Data on the impact of donor CHIP including on allograft function, immunologic dysfunction, graft versus host disease (GVHD), disease relapse and survival across various donor populations are scarce. This is a retrospective-prospective cohort study designed to determine the association between donor gene mutations and outcome following allogeneic HSCT.

Detailed Description
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This is a single centre prospective and retrospective cohort study. This study involves allo-HSCT recipients and their donors at Queen Mary Hospital, Hong Kong. Information on the presence of gene mutations in donor peripheral blood or bone marrow sample; gene mutations in recipient peripheral blood or bone marrow post-allo-HSCT; and donor and recipient outcome will be collected in either prospective, partial-prospective/retrospective or retrospective manner. The information will be used to determine the association between the presence of clonal haematopoiesis in the donor and recipient outcome following allo-HSCT. Data will be collected through routine clinical visits and/or reviewing medical records. Data will be collected at the time of peripheral blood stem cells (PBSC) or bone marrow stem cells donation, at the time of allo-HSCT, one month post-allo-HSCT and every 6 months thereafter until death/study termination. Genetic profile of donors will be collected at the time of PBSC or BM stem cell donation. Genetic profile of recipients will be collected at 1-month, 6-month, 12-month post-HSCT and at time of relapse or occurrence of leukaemia. Gene mutations and pathogenic gene fusion will be determined in the peripheral blood and/or marrow samples by next-generation sequencing (NGS) using a myeloid-gene panel and nanopore long-read sequencing.

Official Title
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Impact of Donor Clonal Haematopoiesis of Indeterminate Potential (CHIP) on Recipient Outcome Following Allogeneic Haematopoietic Stem Cell Transplantation (Allo-HSCT)

Conditions
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Clonal Hematopoiesis

Intervention / Treatment
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* Diagnostic Test: Next generation sequencing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult aged 18 year or above Donor and recipient of allo-HSCT In prospective and partial prospective/retrospective case, subjects who have provided a signed written informed consent. In retrospective case, subjects who had provided a previously signed written informed consent on: voluntary provision of clinical data, and voluntary provision of archived/remaining specimens for genetic analysis, and authorizing storage and usage of archived/remaining specimens for any further analysis Exclusion Criteria: 1. Autologous peripheral blood stem cells or bone marrow stem cell donors for autologous HSCT

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Allogeneic HSCT recipients and donors<br> | Diagnostic Test: Next generation sequencing<br>* Genetic profile of donors will be collected at the time of PBSC or BM stem cell donation. Genetic profile of recipients will be collected at 1-month, 6-month, 12-month post-HSCT and at time of relapse or occurrence of leukaemia. Gene mutations and pathogenic gene fusion will be determined in the peripheral blood and/or marrow samples by next-generation sequencing (NGS) using a myeloid-gene panel and nanopore long-read sequencing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) of the recipient. | This is defined as the time (in months) from the date of allo-HSCT to death from any cause (event), latest follow-up (censor) or study termination. | 5 years | 
| Progression-free survival (PFS) of the recipient. | This is defined as the time (in months) from the date of allo-HSCT to relapse/progression (event), death, latest follow-up or study termination. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute and chronic GVHD | The occurrence of acute and/or chronic graft-versus-host disease | 5 years | 
| Leukemia of donor origin | The occurrence of donor cell derived MDS/AML in the recipient following allogeneic HSCT | 5 years | 
| Cardiac complications | The occurrence of arrthymias, pericardial disease, coronary artery disease, myocardial dysfunction, pulmonary hypertension | 5 years | 
| Pulmonary complications | The occurrence of bronchiolitis obliterans, bronchiolitis obliterans with organizing pneumonia. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Donor clonal hematopoiesis, Allogeneic hematopoiectic stem cell transplantation, Outcome