Germline predisposition traits in allogeneic hematopoietic stem-cell transplantation for myelodysplastic syndromes: a survey-based study and position paper on behalf of the Chronic Malignancies Working Party of the EBMT.
Carmelo Gurnari
(1, 2)
,
Marie Robin
(3)
,
Lucy A. Godley
(4)
,
Joanna Drozd-Sokołowska
(5)
,
Marcin W. Włodarski
(6)
,
Kavita Raj
(7)
,
Francesco Onida
(8)
,
Nina Worel
(9)
,
Fabio Ciceri
(10)
,
Selim Carbacioglu
(11)
,
Michelle Kenyon
(12)
,
Mahmoud Aljurf
(13)
,
Carmen Bonfim
,
Hideki Makishima
(14)
,
Charlotte Niemeyer
(15)
,
Pierre Fenaux
(3)
,
Armin Zebisch
(16)
,
Nada Hamad
(17)
,
Yves Chalandon
(18)
,
Eva Hellström-Lindberg
(19)
,
Maria Teresa Voso
(2)
,
Cristina Mecucci
(20)
,
Fernando Barroso Duarte
(21)
,
Marie Sebert
(3)
,
Flore Sicre de Fontbrune
(3)
,
Jean Soulier
(3)
,
Akiko Shimamura
(22)
,
R. Coleman Lindsley
(22)
,
Jarosław P. Maciejewski
(1)
,
Rodrigo T. Calado
(23)
,
Ibrahim Yakoub-Agha
(24)
,
Donal P. Mclornan
(7)
1
Cleveland Clinic
2 Università degli Studi di Roma Tor Vergata [Roma, Italia] = University of Rome Tor Vergata [Rome, Italy] = Université de Rome Tor Vergata [Rome, Italie]
3 AP-HP - Hopital Saint-Louis [AP-HP]
4 University of Chicago
5 Medical University of Warsaw - Poland
6 St Jude Children's Research Hospital
7 UCLH - University College London Hospitals NHS Foundation Trust [London, UK]
8 Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
9 Medizinische Universität Wien = Medical University of Vienna
10 IRCCS Ospedale San Raffaele [Milan, Italy]
11 University Hospital Regensburg
12 KCH - King's College Hospital
13 KFSHRC - King Faisal Specialist Hospital and Resarch Centre [Riyadh, Saudi Arabia]
14 Kyoto University
15 Albert-Ludwigs-Universität Freiburg = University of Freiburg
16 Medical University of Graz = Medizinische Universität Graz
17 St. Vincent's Hospital, Sydney
18 UNIGE - Université de Genève = University of Geneva
19 Karolinska University Hospital [Stockholm]
20 Perugia General Hospital
21 UFC - Universidade Federal do Ceará = Federal University of Ceará
22 Dana-Farber Cancer Institute [Boston]
23 USP - Universidade de São Paulo = University of São Paulo
24 LIRIC - Lille Inflammation Research International Center - U 995
2 Università degli Studi di Roma Tor Vergata [Roma, Italia] = University of Rome Tor Vergata [Rome, Italy] = Université de Rome Tor Vergata [Rome, Italie]
3 AP-HP - Hopital Saint-Louis [AP-HP]
4 University of Chicago
5 Medical University of Warsaw - Poland
6 St Jude Children's Research Hospital
7 UCLH - University College London Hospitals NHS Foundation Trust [London, UK]
8 Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
9 Medizinische Universität Wien = Medical University of Vienna
10 IRCCS Ospedale San Raffaele [Milan, Italy]
11 University Hospital Regensburg
12 KCH - King's College Hospital
13 KFSHRC - King Faisal Specialist Hospital and Resarch Centre [Riyadh, Saudi Arabia]
14 Kyoto University
15 Albert-Ludwigs-Universität Freiburg = University of Freiburg
16 Medical University of Graz = Medizinische Universität Graz
17 St. Vincent's Hospital, Sydney
18 UNIGE - Université de Genève = University of Geneva
19 Karolinska University Hospital [Stockholm]
20 Perugia General Hospital
21 UFC - Universidade Federal do Ceará = Federal University of Ceará
22 Dana-Farber Cancer Institute [Boston]
23 USP - Universidade de São Paulo = University of São Paulo
24 LIRIC - Lille Inflammation Research International Center - U 995
Résumé
The recent application of whole exome or whole genome sequencing unveiled a plethora of germline variants predisposing to myeloid disorders, particularly myelodysplastic neoplasms. The presence of such variants in patients with myelodysplastic syndromes has important clinical repercussions for haematopoietic stem-cell transplantation, from donor selection and conditioning regimen to graft-versus-host disease prophylaxis and genetic counselling for relatives. No international guidelines exist to harmonise management approaches to this particular clinical scenario. Moreover, the application of germline testing, and how this informs clinical decisions, differs according to the expertise of individual clinical practices and according to different countries, health-care systems, and legislations. Leveraging the global span of the European Society for Blood and Marrow Transplantation (EBMT) network, we took a snapshot of the current European situation on these matters by disseminating an electronic survey to EBMT centres experienced in myelodysplastic syndromes transplantation. An international group of haematologists, transplantation physicians, paediatricians, nurses, and experts in molecular biology and constitutional genetics with experience in myelodysplastic syndromes contributed to this Position Paper. The panel met during multiple online meetings to discuss the results of the EBMT survey and to establish suggested harmonised guidelines for such clinical situations, which are presented here.