Comparable Outcomes after HLA-Matched Sibling and Alternative Donor Hematopoietic Cell Transplantation for Children with Fanconi Anemia and Severe Aplastic Anemia

Abstract

Fanconi anemia (FA)-associated severe aplastic anemia (SAA) requires allogeneic hematopoietic cell transplantation (HCT) for cure. With the evolution of conditioning regimens over time, outcomes of alternative donor HCT (AD-HCT) have improved dramatically. We compared outcomes of HLA-matched sibling donor HCT (MSD-HCT; n = 17) and AD-HCT (n = 57) performed for FA-associated SAA at a single institution between 2001 and 2016. Overall survival at 5 years was 94% for MSD-HCT versus 86% for AD-HCT, neutrophil engraftment was 100% versus 95%, platelet recovery was 100% versus 89%, grade II-IV acute graft-versus-host disease (GVHD) was 6% versus 12%, grade III-IV acute GVHD was 6% versus 4%, and chronic GVHD was 0 versus 7%, with no statistically significant differences by type of transplant. The use of UCB was associated with decreased rates of neutrophil recovery in AD-HCT and platelet recovery in both MSD-HCT and AD-HCT. A trend toward a higher serious infection density before day +100 post-HCT was observed in AD-HCT compared with MSD-HCT (P = .02). These data demonstrate that AD-HCT should be considered at the same time as MSD-HCT for patients with FA-associated SAA.

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

“…Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) represents the only curative option for bone marrow failure 6,7 and the use of fludarabine‐based reduced intensity conditioning regimens (RIC) has improved the outcome over the last decades 8 . The diagnosis of transformation to myelodysplastic syndrome (MDS) or acute leukemia (AL) is associated with a poor outcome after HSCT 9 ‐ 11 …”

Considerations in Preparative Regimen Selection to Minimize Rejection in Pediatric Hematopoietic Transplantation in Non-Malignant Diseases

“…The barriers to engraftment are primarily immunologic, with its magnitude dictated by the patient's underlying disease and past treatment history (54,57,71). Certainly immunodeficiencies are presumed to be less capable of rejecting infused grafts, but there is wide variability in the immune competence between primary diagnoses and even for patients with the same disease.…”

“…Aplastic anemia, typically a disease of T cell mediated destruction of the hematopoietic system, is a condition where prior blood product exposure may sensitize the donor to an even greater risk of rejection (55). Alternatively, other conditions such as Fanconi's Anemia or Dyskeratosis Congenita, possess difficulties in DNA repair with intolerance to the even most modest doses of radiation or alkylating agents (57)(58)(59)(60)64). Thus, even conditions of poor marrow function present with a wide array of clinical challenges.…”

Current status of umbilical cord blood transplantation in children

“…Patients with FA are more susceptible to the toxicity of the preparative regimen due to the intrinsic chromosomal instability; therefore, conditioning should be reduced in intensity. Fludarabine has been proven safe and effective in this setting, normally combined with low dose cyclophosphamide and low dose TBI (Gluckman et al, 2007;Ebens et al, 2018).…”