Donor CHIP and Allogeneic HSCT Outcome

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест Next generation sequencing
  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.

Первичные конечные точки

• Overall survival (OS) of the recipient. [Срок оценки: 5 years]
• Progression-free survival (PFS) of the recipient. [Срок оценки: 5 years]

Вторичные конечные точки (4)

• Acute and chronic GVHD [Срок оценки: 5 years]
• Leukemia of donor origin [Срок оценки: 5 years]
• Cardiac complications [Срок оценки: 5 years]
• Pulmonary complications [Срок оценки: 5 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

1\. Autologous peripheral blood stem cells or bone marrow stem cell donors for autologous HSCT

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Гонконг · 1 центр

• The University of Hong Kong — Гонконг

Публикации

• Steensma DP, Bejar R, Jaiswal S, Lindsley RC, Sekeres MA, Hasserjian RP, Ebert BL. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015 Jul 2;126(1):9-16. doi: 10.1182/blood-2015-03-631747. Epub 2015 Apr 30. PMID 25931582
• Steensma DP, Ebert BL. Clonal hematopoiesis as a model for premalignant changes during aging. Exp Hematol. 2020 Mar;83:48-56. doi: 10.1016/j.exphem.2019.12.001. Epub 2019 Dec 12. PMID 31838005
• Steensma DP. Clinical Implications of Clonal Hematopoiesis. Mayo Clin Proc. 2018 Aug;93(8):1122-1130. doi: 10.1016/j.mayocp.2018.04.002. Epub 2018 Jul 4. PMID 30078412
• Steensma DP. Clinical consequences of clonal hematopoiesis of indeterminate potential. Blood Adv. 2018 Nov 27;2(22):3404-3410. doi: 10.1182/bloodadvances.2018020222. PMID 30482770
• Shlush LI, Zandi S, Mitchell A, Chen WC, Brandwein JM, Gupta V, Kennedy JA, Schimmer AD, Schuh AC, Yee KW, McLeod JL, Doedens M, Medeiros JJ, Marke R, Kim HJ, Lee K, McPherson JD, Hudson TJ; HALT Pan-Leukemia Gene Panel Consortium; Brown AM, Yousif F, Trinh QM, Stein LD, Minden MD, Wang JC, Dick JE. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature. 2014 Feb 20;5 PMID 24522528
• Gibson CJ, Kennedy JA, Nikiforow S, Kuo FC, Alyea EP, Ho V, Ritz J, Soiffer R, Antin JH, Lindsley RC. Donor-engrafted CHIP is common among stem cell transplant recipients with unexplained cytopenias. Blood. 2017 Jul 6;130(1):91-94. doi: 10.1182/blood-2017-01-764951. Epub 2017 Apr 26. PMID 28446434
• Frick M, Chan W, Arends CM, Hablesreiter R, Halik A, Heuser M, Michonneau D, Blau O, Hoyer K, Christen F, Galan-Sousa J, Noerenberg D, Wais V, Stadler M, Yoshida K, Schetelig J, Schuler E, Thol F, Clappier E, Christopeit M, Ayuk F, Bornhauser M, Blau IW, Ogawa S, Zemojtel T, Gerbitz A, Wagner EM, Spriewald BM, Schrezenmeier H, Kuchenbauer F, Kobbe G, Wiesneth M, Koldehoff M, Socie G, Kroeger N, Bu PMID 30403573
• Wong WH, Bhatt S, Trinkaus K, Pusic I, Elliott K, Mahajan N, Wan F, Switzer GE, Confer DL, DiPersio J, Pulsipher MA, Shah NN, Sees J, Bystry A, Blundell JR, Shaw BE, Druley TE. Engraftment of rare, pathogenic donor hematopoietic mutations in unrelated hematopoietic stem cell transplantation. Sci Transl Med. 2020 Jan 15;12(526):eaax6249. doi: 10.1126/scitranslmed.aax6249. PMID 31941826

Идентификаторы

NCT: NCT04689750 · CHIP001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗