title: Outcomes of mismatched and unrelated donor hematopoietic stem cell transplantation in Fanconi anemia conditioned with chemotherapy only.
abstract: Fanconi anemia (FA) is a genomic instability syndrome associated with bone marrow failure, myelodysplastic syndrome (MDS), and/or acute myeloid leukemia (AML) requiring hematopoietic stem cell transplantation (HSCT) to restore normal hematopoiesis. Although low-intensity fludarabine-based preparative regimens without radiation confer excellent outcomes in FA HSCTs with HLA-matched sibling donors, outcomes for FA patients with alternative donors are less encouraging, albeit improving. We present our experience with 17 FA patients who completed mismatched related or unrelated donor HSCT using a non-radiation fludarabine-based preparative regimen at Charité University Medicine Berlin. All patients engrafted; however, one patient had unstable chimerism in the setting of multi-viral infections that necessitated a stem cell boost to revert to full donor chimerism. Forty-seven percent of patients developed grade I acute graft-verus-host disease (aGVHD). No grade II-IV aGVHD or chronic graft-versus-host disease of any severity occurred. At a median follow-up of 30 months, 88 % of patients are alive with normal hematopoiesis. Two patients died of infections 4 months post-transplantation. These results demonstrate that short-term outcomes for FA patients with mismatched and unrelated donor HSCTs can be excellent using chemotherapy only conditioning. Viral reactivation, however, was a major treatment-related complication.
authors: Department of Pediatric Hematology Oncology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625, Hannover, Germany, chao.mwe@mh-hannover.de.
authors: M M
authors: MM
authors: Chao
authors: J S
authors: JS
authors: Kuehl
authors: G
authors: G
authors: Strauss
authors: H
authors: H
authors: Hanenberg
authors: D
authors: D
authors: Schindler
authors: H
authors: H
authors: Neitzel
authors: C
authors: C
authors: Niemeyer
authors: I
authors: I
authors: Baumann
authors: H
authors: H
authors: von Bernuth
authors: J
authors: J
authors: Rascon
authors: M
authors: M
authors: Nagy
authors: M
authors: M
authors: Zimmermann
authors: C P
authors: CP
authors: Kratz
authors: W
authors: W
authors: Ebell
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D005199:Fanconi Anemia / Q000175:diagnosis* / Q000628:therapy*; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000639:trends; D006801:Humans; D008297:Male; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents