PB2321 OUTCOMES AFTER ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION FOR INHERITED BONE MARROW FAILURE SYNDROMES
Authors: C. Lopes Pedrosa, A. Barbosa Ribeiro, F. Campilho, C. Pinho Vaz, R. Branca, L. Leite, G. Brás, S. Roncon, A. Campos
Journal: HemaSphere (2019)

Background: Inherited Bone Marrow Failure Syndromes (IBMFS) are rare, heterogeneous disorders characterized by multiorgan disease, congenital malformations, high risk of solid tumors and hematopoietic impairment with predisposition to clonal evolution to secondary Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML). The four most frequent syndromes are Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond Blackfan anemia (DBA) and Shwachman Diamond syndrome (SDS). Allogeneic hematopoietic cell transplantation (AlloHCT) is the only potentially curative treatment despite only correcting the hematopoietic defect. Aims: Our aim was to analyze the results of patients (pts) transplanted for IBMFS at our center. Methods: We performed a retrospective study of all pts submitted to AloHCT for IBMFS, in a single Portuguese transplant center, between 1989 and 2018. We analyzed the outcomes in terms of incidence of graft‐ versus ‐host disease, transplant related mortality and overall survival (OS). Results: We identified a total of 36 AlloHCT, in 30 pts in this time period, with a median age at transplant of 8 years (range 6 months – 37 years). Diagnoses were Fanconi anemia (n = 23), Diamond Blackfan anemia (n = 4), dyskeratosis congenita (n = 2) and Shwachman Diamond Syndrome (n = 1). One patient (pt) presented with MDS and two pts with AML, all associated with FA. At the time of 1 st transplant the donor was an HLA matched sibling in 13 pts, an HLA mismatched sibling in 1 (graft source: 2 peripheral blood [PB], 11 bone marrow [BM] and 1 cord blood [CB]), an unrelated HLA matched donor in 5 pts, an unrelated mismatched donor in 11 (graft source: 5 PB, 8 BM, 3 CB). Three patients (13%) developed acute graft‐ versus ‐host disease (GvHD) and 6 (26,1%) developed chronic GvHD. We found no differences when comparing the incidence of GvHD according to the source of stem cells, donor type or HLA typing. The median follow‐up of alive pts was 8 years (range 4 months – 17,5 years). Median time to neutrophil recovery (&gt; 500/μL) was 14 days (d) and to platelet recovery was 16d (&gt;20 G/L), without statistically significant difference regarding the conditioning regimen or donor type. The stem cell source appears to influence the time to hematologic recovery, particularly a delay in platelet recovery in CB grafts (19d for PB vs 30d for BM, 72d for CB; p&lt;0,05) and longer neutrophil recovery time without statistically significant difference (19d for PB vs 20d for BM, 44d for CB). Matched donor grafts were associated with faster neutrophil recovery (15d vs. 33d; p&lt;0,05). The 100‐day mortality risk was 10,3% (± 5,7%). In FA pts there were 4 graft failures (3 primary, 1 secondary) and, interestingly, primary graft failures occurred only in pts with unrelated donors. The overall survival (OS) at 1 year was 75,4% (±8,1%) and at 3, 5 and 10 years was 67,9% (±8,9%). One patient died due to a secondary solid neoplasia, 16 years after AlloHCT. Summary/Conclusion: It is currently accepted that AlloHCT is curative of the BM failure in IBMFS. However, there is no clear evidence on the best approach to the transplant. There are still many unanswered questions, especially those concerning the conditioning regimen, the choice of donor, the graft source and the prophylaxis of GVHD. We present the results of a cohort of patients with IBMFS, 6 of them surviving more than 10 years and with a relatively low incidence of transplant related complications. The first two authors contributed equally to this work.