Outcome of patients with Fanconi anemia developing myelodysplasia and acute leukemia who received allogeneic hematopoietic stem cell transplantation: A retrospective analysis on behalf of EBMT group

TY - JOUR

T1 - Outcome of patients with Fanconi anemia developing myelodysplasia and acute leukemia who received allogeneic hematopoietic stem cell transplantation: A retrospective analysis on behalf of EBMT group

AU - Giardino, Stefano

AU - de Latour, Regis P

AU - Aljurf, Mahmoud

AU - Eikema, Dirk-Jan

AU - Bosman, Paul

AU - Bertrand, Yves

AU - Tbakhi, Abdelghani

AU - Holter, Wolfgang

AU - Bornhäuser, Martin

AU - Rössig, Claudia

AU - Burkhardt, Birgit

AU - Zecca, Marco

AU - Afanasyev, Boris

AU - Michel, Gerard

AU - Ganser, Arnold

AU - Alseraihy, Amal

AU - Ayas, Mouhab

AU - Uckan-Cetinkaya, Duygu

AU - Bruno, Benedicte

AU - Patrick, Katharine

AU - Bader, Peter

AU - Itälä-Remes, Maija

AU - Rocha, Vanderson

AU - Jubert, Charlotte

AU - Diaz, Miguel A

AU - Shaw, Peter J

AU - Junior, Luiz G D

AU - Locatelli, Franco

AU - Kröger, Nicolaus

AU - Faraci, Maura

AU - Pierri, Filomena

AU - Lanino, Edoardo

AU - Miano, Maurizio

AU - Risitano, Antonio

AU - Robin, Marie

AU - Dufour, Carlo

AU - Severe Aplastic Anemia and Chronic Malignancies Working Parties of the European Group for Blood and Marrow Transplantation

N1 - © 2020 Wiley Periodicals, Inc.

PY - 2020/7

Y1 - 2020/7

N2 - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is curative for bone marrow failure in patients with Fanconi anemia (FA), but the presence of a malignant transformation is associated with a poor prognosis and the management of these patients is still challenging. We analyzed outcome of 74 FA patients with a diagnosis of myelodysplastic syndrome (n = 35), acute leukemia (n = 35) or with cytogenetic abnormalities (n = 4), who underwent allo-HSCT from 1999 to 2016 in EBMT network. Type of diagnosis, pre-HSCT cytoreductive therapies and related toxicities, disease status pre-HSCT, donor type, and conditioning regimen were considered as main variables potentially influencing outcome. The 5-year OS and EFS were 42% (30-53%) and 39% (27-51%), respectively. Patients transplanted in CR showed better OS compared with those transplanted in presence of an active malignant disease (OS:71%[48-95] vs 37% [24-50],P = .04), while none of the other variables considered had an impact. Twenty-two patients received pre-HSCT cytoreduction and 9/22 showed a grade 3-4 toxicity, without any lethal event or negative influence on survival after HSCT(OS:toxicity pre-HSCT 48% [20-75%] vs no-toxicity 51% [25-78%],P = .98). The cumulative incidence of day-100 grade II-IV a-GvHD and of 5-year c-GvHD were 38% (26-50%) and 40% (28-52%). Non-relapse-related mortality and incidence of relapse at 5-years were 40% (29-52%) and 21% (11-30%) respectively, without any significant impact of the tested variables. Causes of death were transplant-related events in most patients (34 out of the 42 deaths, 81%). This analysis confirms the poor outcome of transformed FA patients and identifies the importance of achieving CR pre-HSCT, suggesting that, in a newly diagnosed transformed FA patient, a cytoreductive approach pre-HSCT should be considered if a donor have been secured.

AB - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is curative for bone marrow failure in patients with Fanconi anemia (FA), but the presence of a malignant transformation is associated with a poor prognosis and the management of these patients is still challenging. We analyzed outcome of 74 FA patients with a diagnosis of myelodysplastic syndrome (n = 35), acute leukemia (n = 35) or with cytogenetic abnormalities (n = 4), who underwent allo-HSCT from 1999 to 2016 in EBMT network. Type of diagnosis, pre-HSCT cytoreductive therapies and related toxicities, disease status pre-HSCT, donor type, and conditioning regimen were considered as main variables potentially influencing outcome. The 5-year OS and EFS were 42% (30-53%) and 39% (27-51%), respectively. Patients transplanted in CR showed better OS compared with those transplanted in presence of an active malignant disease (OS:71%[48-95] vs 37% [24-50],P = .04), while none of the other variables considered had an impact. Twenty-two patients received pre-HSCT cytoreduction and 9/22 showed a grade 3-4 toxicity, without any lethal event or negative influence on survival after HSCT(OS:toxicity pre-HSCT 48% [20-75%] vs no-toxicity 51% [25-78%],P = .98). The cumulative incidence of day-100 grade II-IV a-GvHD and of 5-year c-GvHD were 38% (26-50%) and 40% (28-52%). Non-relapse-related mortality and incidence of relapse at 5-years were 40% (29-52%) and 21% (11-30%) respectively, without any significant impact of the tested variables. Causes of death were transplant-related events in most patients (34 out of the 42 deaths, 81%). This analysis confirms the poor outcome of transformed FA patients and identifies the importance of achieving CR pre-HSCT, suggesting that, in a newly diagnosed transformed FA patient, a cytoreductive approach pre-HSCT should be considered if a donor have been secured.

KW - Acute Disease

KW - Allografts

KW - Disease-Free Survival

KW - Fanconi Anemia/complications

KW - Female

KW - Follow-Up Studies

KW - Hematopoietic Stem Cell Transplantation

KW - Humans

KW - Leukemia/etiology

KW - Male

KW - Myelodysplastic Syndromes/etiology

KW - Retrospective Studies

KW - Survival Rate

U2 - 10.1002/ajh.25810

DO - 10.1002/ajh.25810

M3 - SCORING: Journal article

C2 - 32267023

VL - 95

SP - 809

EP - 816

JO - AM J HEMATOL

JF - AM J HEMATOL

SN - 0361-8609

IS - 7

ER -