|
|
 Previous Article | Table of Contents | Next Article 
Outcome of unrelated donor bone marrow transplantation in 40 children with
Hurler syndrome
C Peters, M Balthazor, EG Shapiro, RJ King, C Kollman, JD Hegland, J Henslee- Downey, ME Trigg, MJ Cowan, J Sanders, N Bunin, H Weinstein, C Lenarsky, P Falk, R Harris, T Bowen, TE Williams, GH Grayson, P Warkentin, L Sender, VA Cool, M Crittenden, S Packman, P Kaplan and LA Lockman
Department of Pediatrics University of Iowa, Iowa City 52242, USA.
Long-term survival and improved neuropsychological function have occurred
in selected children with Hurler syndrome (MPS I H) after successful
engraftment with genotypically matched sibling bons marrow transplantation
(BMT). However, because few children have HLA-identical siblings, the
feasibility of unrelated donor (URD) BMT as a vehicle for adoptive enzyme
therapy was evaluated in this retrospective study. Forty consecutive
children (median, 1.7 years; range, 0.9 to 3.2 years) with MPS I H received
high-dose chemotherapy with or without radiation followed by BMT between
January 27, 1989 and May 13, 1994. Twenty-five of the 40 patients initially
engrafted. An estimated 49% of patients are alive at 2 years, 63%
alloengrafted and 37% autoengrafted. The probability of grade II to IV
acute graft-versus-host disease (GVHD) was 30%, and the probability of
extensive chronic GVHD was 18%. Eleven patients received a second URD BMT
because of graft rejection or failure. Of the 20 survivors, 13 children
have complete donor engraftment, two children have mixed chimeric grafts,
and five children have autologous marrow recovery. The BM cell dose was
correlated with both donor engraftment and survival. Thirteen of 27
evaluable patients were engrafted at 1 year following URD BMT. Neither
T-lymphocyte depletion (TLD) of the bone marrow nor irradiation appeared to
influence the likelihood of engraftment. Ten of 16 patients alive at 1 year
who received a BM cell dose greater than or equal to 3.5 x 10(8) cells/kg
engrafted, and 62% are estimated to be alive at 3 years. In contrast, only
3 of 11 patients receiving less than 3.5 x 10(8) cells/kg engrafted, and
24% are estimated to be alive at 3 years (P = .05). The mental
developmental index (MDI) was assessed before BMT. Both baseline and
post-BMT neuropsychological data were available for 11 engrafted survivors.
Eight children with a baseline MDI greater than 70 have undergone URD BMT
(median age, 1.5 years; range, 1.0 to 2.4 years). Of these, two children
have had BMT too recently for developmental follow-up. Of the remaining
six, none has shown any decline in age equivalent scores. Four children are
acquiring skills at a pace equal to or slightly below their same age peers;
two children have shown a plateau in learning or extreme slowing in their
learning process. For children with a baseline MDI less than 70 (median
age, 2.5 years; range, 0.9 to 2.9 years), post-BMT follow-up indicated that
two children have shown deterioration in their developmental skills. The
remaining three children are maintaining their skills and are adding to
them at a highly variable rate. We conclude that MPS I H patients with a
baseline MDI greater than 70 who are engrafted survivors following URD BMT
can achieve a favorable long-term outcome and improved cognitive function.
Future protocols must address the high risk of graft rejection or failure
and the impact of GVHD in this patient population.
Volume 87,
Issue 11,
pp. 4894-4902,
06/01/1996
Copyright © 1996 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
D. Wang, W. Zhang, T. A. Kalfa, G. Grabowski, S. Davies, P. Malik, and D. Pan
Reprogramming erythroid cells for lysosomal enzyme production leads to visceral and CNS cross-correction in mice with Hurler syndrome
PNAS,
November 24, 2009;
106(47):
19958 - 19963.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. H. Yeung, M. J. Cowan, B. Horn, and K. W. Rosbe
Airway Management in Children With Mucopolysaccharidoses
Arch Otolaryngol Head Neck Surg,
January 1, 2009;
135(1):
73 - 79.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. K. Prasad, A. Mendizabal, S. H. Parikh, P. Szabolcs, T. A. Driscoll, K. Page, S. Lakshminarayanan, J. Allison, S. Wood, D. Semmel, et al.
Unrelated donor umbilical cord blood transplantation for inherited metabolic disorders in 159 pediatric patients from a single center: influence of cellular composition of the graft on transplantation outcomes
Blood,
October 1, 2008;
112(7):
2979 - 2989.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. K Ormerod, T. D Palmer, and M. A Caldwell
Neurodegeneration and cell replacement
Phil Trans R Soc B,
January 12, 2008;
363(1489):
153 - 170.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. R. Adams, J. Kwon, F. J. Marshall, E. A. de Blieck, D. A. Pearce, and J. W. Mink
Neuropsychological Symptoms of Juvenile-Onset Batten Disease: Experiences From 2 Studies
J Child Neurol,
May 1, 2007;
22(5):
621 - 627.
[Abstract]
[PDF]
|
|
|
|
|
|
|
K Ehlert, J Roth, M Frosch, N Fehse, N Zander, and J Vormoor
Farber's disease without central nervous system involvement: bone-marrow transplantation provides a promising new approach.
Ann Rheum Dis,
December 1, 2006;
65(12):
1665 - 1666.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Pan, M. S. Nelson, M. Reyes, L. Koodie, J. J. Brazil, E. J. Stephenson, R. C. Zhao, C. Peters, S. B. Selleck, S. E. Stringer, et al.
Functional abnormalities of heparan sulfate in mucopolysaccharidosis-I are associated with defective biologic activity of FGF-2 on human multipotent progenitor cells
Blood,
September 15, 2005;
106(6):
1956 - 1964.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.M. Sleeper, B. Fornasari, N.M. Ellinwood, M.A. Weil, J. Melniczek, T.M. O'Malley, C.D. Sammarco, L. Xu, K.P. Ponder, and M.E. Haskins
Gene Therapy Ameliorates Cardiovascular Disease in Dogs With Mucopolysaccharidosis VII
Circulation,
August 17, 2004;
110(7):
815 - 820.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Fujisaki, M. Kami, Y. Kishi, S. L. Staba, and J. Kurtzberg
Cord-Blood Transplants from Unrelated Donors in Hurler's Syndrome
N. Engl. J. Med.,
July 29, 2004;
351(5):
506 - 507.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. L. Staba, M. L. Escolar, M. Poe, Y. Kim, P. L. Martin, P. Szabolcs, J. Allison-Thacker, S. Wood, D. A. Wenger, P. Rubinstein, et al.
Cord-Blood Transplants from Unrelated Donors in Patients with Hurler's Syndrome
N. Engl. J. Med.,
May 6, 2004;
350(19):
1960 - 1969.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. S. Grewal, J. N. Barker, S. M. Davies, and J. E. Wagner
Unrelated donor hematopoietic cell transplantation: marrow or umbilical cord blood?
Blood,
June 1, 2003;
101(11):
4233 - 4244.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Leimig, L. Mann, M. d. P. Martin, E. Bonten, D. Persons, J. Knowles, J. A. Allay, J. Cunningham, A. W. Nienhuis, R. Smeyne, et al.
Functional amelioration of murine galactosialidosis by genetically modified bone marrow hematopoietic progenitor cells
Blood,
May 1, 2002;
99(9):
3169 - 3178.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Baxter, R. F. Wynn, J. A. Deakin, I. Bellantuono, K. G. Edington, A. Cooper, G. T. N. Besley, H. J. Church, J. E. Wraith, T. F. Carr, et al.
Retrovirally mediated correction of bone marrow-derived mesenchymal stem cells from patients with mucopolysaccharidosis type I
Blood,
March 1, 2002;
99(5):
1857 - 1859.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. W. Soper, M. D. Lessard, C. A. Vogler, B. Levy, W. G. Beamer, W. S. Sly, and J. E. Barker
Nonablative neonatal marrow transplantation attenuates functional and physical defects of {beta}-glucuronidase deficiency
Blood,
March 1, 2001;
97(5):
1498 - 1504.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. Keeling, D. A. Brooks, J. J. Hopwood, P. Li, J. N. Thompson, and D. M. Bedwell
Gentamicin-mediated suppression of Hurler syndrome stop mutations restores a low level of {{alpha}}-L-iduronidase activity and reduces lysosomal glycosaminoglycan accumulation
Hum. Mol. Genet.,
February 1, 2001;
10(3):
291 - 299.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Peters, E. G. Shapiro, J. Anderson, P. J. Henslee-Downey, M. R. Klemperer, M. J. Cowan, E. F. Saunders, P. A. deAlarcon, C. Twist, J. B. Nachman, et al.
Hurler Syndrome: II. Outcome of HLA-Genotypically Identical Sibling and HLA-Haploidentical Related Donor Bone Marrow Transplantation in Fifty-Four Children
Blood,
April 1, 1998;
91(7):
2601 - 2608.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Azizi, D. Stokes, B. J. Augelli, C. DiGirolamo, and D. J. Prockop
Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats---similarities to astrocyte grafts
PNAS,
March 31, 1998;
95(7):
3908 - 3913.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Phipps, R. Mulhern;, C. Peters, and E. G. Shapiro
Developmental Outcome of Unrelated Donor Bone Marrow Transplantation in Children With Hurler Syndrome
Blood,
January 15, 1997;
89(2):
732 - 734.
[Full Text]
[PDF]
|
|
|
|
|
