Risk factor analysis of outcomes after unrelated cord blood transplantation in patients with hurler syndrome.
Allogeneic stem cell transplantation (SCT) is considered effective in preventing disease progression in patients with Hurler syndrome (HS). Unrelated umbilical cord blood (UCB) grafts are suggested as an alternative to bone marrow (BM) or peripheral blood stem cells (PBSC). We studied 93 HS patients receiving an UCB graft to analyze risk factors for outcomes. The median time from diagnosis to transplant was 4.6 months, median follow-up was 29 months, and median number of nucleated CB cells infused was 7.6 x 10(7)/kg. Most of the patients received 1 or 2 HLA disparate grafts, and the most frequently used conditioning regimen was cyclophosphamide + busulfan (Bu/Cy). All patients received anti-T cell antibody. At post transplant day +60, the cumulative incidence of neutrophil engraftment was 85%. A younger age at transplant and a higher CD34(+) dose at infusion were favorably associated with engraftment. With the exception of 2 patients, all engrafted patients achieved full and sustained donor chimerism. The 3-year event-free survival (EFS) and 3-year overall survival (OS) rates were 70% and 77%, respectively. In a multivariate analyses, use of Bu/Cy and a shorter interval from diagnosis to transplant were predictors for improved EFS rate (82% for patients transplanted within 4.6 months after diagnosis compared to 57% for the rest). Improved outcomes from early transplantation and immediate availability of CB unit lead us to conclude that CB transplantation is a beneficial option, which should be considered expediently for children with HS.
Department of Immunology/Hematology and BMT, University Medical Center Utrecht, Utrecht, The Netherlands. j.j.boelens@umcutrecht.nl
Jaap Jan
JJ
Boelens
Vanderson
V
Rocha
Mieke
M
Aldenhoven
Robert
R
Wynn
Anne
A
O'Meara
Gerard
G
Michel
Irina
I
Ionescu
Suhag
S
Parikh
Vinod K
VK
Prasad
Paul
P
Szabolcs
Maria
M
Escolar
Eliane
E
Gluckman
Marina
M
Cavazzana-Calvo
Joanne
J
Kurtzberg
D000367:Age Factors; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D002066:Busulfan / Q000627:therapeutic use; D002452:Cell Count; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006085:Graft Survival; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008297:Male; D008059:Mucopolysaccharidosis I / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D014019:Tissue Donors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome
D000961:Antilymphocyte Serum; D003520:Cyclophosphamide; D002066:Busulfan