Outcomes after related and unrelated umbilical cord blood transplantation for hereditary bone marrow failure syndromes other than Fanconi anemia

Abstract

BackgroundAllogeneic stem cell transplantation is the only curative option for patients with hereditary bone marrow failure syndromes. Umbilical cord blood is an alternative source of stem cells for allogeneic transplantation. Design and MethodsThis multicenter, retrospective study is based on data reported to the Eurocord Registry about patients with hereditary bone marrow failure syndrome who underwent umbilical cord blood transplantation. ResultsSixty-four patients with hereditary bone marrow failure syndromes were transplanted from related (n=20) or unrelated donors (n=44). Diagnoses were Diamond-Blackfan anemia (21 patients), congenital amegakaryocytic thrombocytopenia (16 patients), dyskeratosis congenita (8 patients), Shwachman-Diamond syndrome (2 patients), severe congenital neutropenia (16 patients) and unclassified (1 patient). In the group of patients who received grafts from related donors, all patients but one received an HLA-matched sibling transplant. The median number of total nucleated cells infused was 5¥10 7 /kg. The cumulative incidence of neutrophil recovery at 60 days was 95%. Two patients had grade II-IV acute graft-versus-host disease, while the 2-year cumulative incidence of chronic graft-versus-host disease was 11%. The 3-year overall survival rate was 95%. In the group of patients who received grafts from unrelated donors, 86% had HLA-mismatched grafts and three received two umbilical cord blood units. The median number of total nucleated cells infused was 6.1¥10 7 /kg. The cumulative incidence of neutrophil recovery at day 60 in this group was 55%. The 100-day cumulative incidence of grade II-IV acute graft-versus-host disease was 24%, while the 2-year cumulative incidence of chronic graft-versus-host disease was 53%. The 3-year overall survival rate was 61%; better overall survival was associated with age less than 5 years (P=0.01) and 6.1¥10 7 /kg or more total nucleated cells infused (P=0.05). ConclusionsIn patients with hereditary bone marrow failure syndromes, related umbilical cord blood transplantation is associated with excellent outcomes while increasing cell dose and better HLA matching might provide better results in unrelated umbilical cord blood transplantation.Key words: cord blood transplantation, hereditary bone marrow failure syndromes, engraftment, HLA compatibility.Citation: Bizzetto R, Bonfim C, Rocha V, Socié G, Locatelli F, Chan K, Ramirez O, Stein J, Nabhan S, Miranda E, Passweg J, de Souza CA, Gluckman E, on

Reduced intensity conditioning is effective for hematopoietic SCT in dyskeratosis congenita-related BM failure

“…The most common ones include sepsis, GVHD and early death. 24 Various factors contribute to endothelial damage in DKC patients after allografting. These factors include the cytokine storm, especially after myeloablative conditioning regimen, CsA, infectious diseases and GVHD.…”

Umbilical cord blood banking: an update

“…To address issues related to cord blood banking, the Eurocord registry was established in 1999 in Europe with the responsibility for collecting and analyzing clinical outcomes on cord blood transplantation. The American registry CIBMTR reports information regarding cord blood banking and transplantation clinical outcomes [9,10,12].…”

“…For siblings, there is a 25% chance of a six for six haploidentical HLA match, which is ideal for transplantation, and a 75% chance of at least a three for six haplo-identical HLA match. The three for six HLA match is considered at the threshold for an acceptable transplant [9][10][11]36]. Families are also more likely to find an equivalent or preferable HLA match within extended family members than in a public bank of unrelated donors.…”

“…Lastly, Bizzetto et al [9] reported in 2011 on 64 patients with hereditary bone marrow failure syndromes receiving cord blood transplants from related and unrelated donors.…”

“…Cord blood is considered a treatment option in pediatric and adult patients with hematologic malignancies and disorders (leukemia, thalassemia, sickle cell disease, etc. ), bone marrow failures, inherited metabolic disorders, immunological defects and other genetic diseases [1][2][3][4][5][6][7][8][9][10][11][12]. Double umbilical cord blood grafts, that use cord blood units from two donors, mitigate cell dose limitations for larger children and adults with malignant disorders [12][13][14].…”