Haploidentical stem cell transplantation in two children with mucopolysaccharidosis VI: clinical and biochemical outcome

Research output: Contribution to journalArticle

Standard

Haploidentical stem cell transplantation in two children with mucopolysaccharidosis VI: clinical and biochemical outcome. / Jester, Sandra; Larsson, Julia; Eklund, Erik; Papadopoulou, Domniki; Mansson, Jan-Eric; Békássy, Albert; Turkiewicz, Dominik; Toporski, Jacek; Øra, Ingrid.

In: Orphanet Journal of Rare Diseases, Vol. 8, No. 134, 2013.

Research output: Contribution to journalArticle

Harvard

Jester, S, Larsson, J, Eklund, E, Papadopoulou, D, Mansson, J-E, Békássy, A, Turkiewicz, D, Toporski, J & Øra, I 2013, 'Haploidentical stem cell transplantation in two children with mucopolysaccharidosis VI: clinical and biochemical outcome', Orphanet Journal of Rare Diseases, vol. 8, no. 134. https://doi.org/10.1186/1750-1172-8-134

APA

CBE

MLA

Vancouver

Author

Jester, Sandra ; Larsson, Julia ; Eklund, Erik ; Papadopoulou, Domniki ; Mansson, Jan-Eric ; Békássy, Albert ; Turkiewicz, Dominik ; Toporski, Jacek ; Øra, Ingrid. / Haploidentical stem cell transplantation in two children with mucopolysaccharidosis VI: clinical and biochemical outcome. In: Orphanet Journal of Rare Diseases. 2013 ; Vol. 8, No. 134.

RIS

TY - JOUR

T1 - Haploidentical stem cell transplantation in two children with mucopolysaccharidosis VI: clinical and biochemical outcome

AU - Jester, Sandra

AU - Larsson, Julia

AU - Eklund, Erik

AU - Papadopoulou, Domniki

AU - Mansson, Jan-Eric

AU - Békássy, Albert

AU - Turkiewicz, Dominik

AU - Toporski, Jacek

AU - Øra, Ingrid

PY - 2013

Y1 - 2013

N2 - Background: Mucopolysaccharidosis VI (MPS VI) is an autosomal recessive progressive multiorgan disorder due to mutation in the gene encoding the enzyme Arylsulfatase B (ARSB). Dysfunctional ARSB causes lysosomal accumulation of glycosaminoglycans (GAG). Currently, enzyme replacement therapy (ERT) is preferred to hematopoietic stem cell transplantation (SCT) due to the treatment-related risks of the latter. However, ERT constitutes an expensive life-long treatment. Increased experience and safety of SCT-procedures in recent years suggest that SCT should be further explored as a treatment option. This is the first report on haploidentical SCT in patients with MPS VI. The primary objective was to assess the treatment safety and clinical and biochemical outcome. Patients and methods: Two siblings diagnosed with MPS VI at 10 months of age and at birth with genotype p. C192R, reported as mild to intermediate phenotype, underwent unrelated umbilical cord blood transplantation pre-symptomatic. Due to graft failure, both patients were urgently re-transplantated with haploidentical SCT with the father as donor. Continuous clinical and biochemical status was monitored and concluded 3.8 and 4.6 years after the haploidentical SCT. Results: Haploidentical SCT resulted in prompt and sustained engraftment. Complete donor chimerism was achieved in both patients, apart from mixed B cells chimerism in patient 2. ARSB activity in leukocytes post transplant increased from 0.0 to 19.0 mu kat/kg protein (patient 1) and from 3.6 to 17.9 mu kat/kg protein (patient 2) (ref. 17-40). Total urinary GAG normalized in both patients, although patient 2's values slightly exceed normal range since 6 months. However, dermatan sulfaturia was substantially normalized since 16 months and 12 months post-SCT, respectively. Height was -1.85 SD and -1.27 SD at follow-up. Patient 1 had impaired visual acuity and discrete hepatomegaly. Patient 2 had elevated intraocular pressure and X-ray revealed steep acetabular angles and slightly flattened lumbar vertebrae. Conclusion: This study demonstrates that young children with MPS VI tolerate haploidentical SCT. Normalization of enzyme production and dermatan sulfaturia indicates correction of the inborn error of metabolism and coincide with no obvious symptoms of progressive MPS VI up to 4.6 years post-SCT.

AB - Background: Mucopolysaccharidosis VI (MPS VI) is an autosomal recessive progressive multiorgan disorder due to mutation in the gene encoding the enzyme Arylsulfatase B (ARSB). Dysfunctional ARSB causes lysosomal accumulation of glycosaminoglycans (GAG). Currently, enzyme replacement therapy (ERT) is preferred to hematopoietic stem cell transplantation (SCT) due to the treatment-related risks of the latter. However, ERT constitutes an expensive life-long treatment. Increased experience and safety of SCT-procedures in recent years suggest that SCT should be further explored as a treatment option. This is the first report on haploidentical SCT in patients with MPS VI. The primary objective was to assess the treatment safety and clinical and biochemical outcome. Patients and methods: Two siblings diagnosed with MPS VI at 10 months of age and at birth with genotype p. C192R, reported as mild to intermediate phenotype, underwent unrelated umbilical cord blood transplantation pre-symptomatic. Due to graft failure, both patients were urgently re-transplantated with haploidentical SCT with the father as donor. Continuous clinical and biochemical status was monitored and concluded 3.8 and 4.6 years after the haploidentical SCT. Results: Haploidentical SCT resulted in prompt and sustained engraftment. Complete donor chimerism was achieved in both patients, apart from mixed B cells chimerism in patient 2. ARSB activity in leukocytes post transplant increased from 0.0 to 19.0 mu kat/kg protein (patient 1) and from 3.6 to 17.9 mu kat/kg protein (patient 2) (ref. 17-40). Total urinary GAG normalized in both patients, although patient 2's values slightly exceed normal range since 6 months. However, dermatan sulfaturia was substantially normalized since 16 months and 12 months post-SCT, respectively. Height was -1.85 SD and -1.27 SD at follow-up. Patient 1 had impaired visual acuity and discrete hepatomegaly. Patient 2 had elevated intraocular pressure and X-ray revealed steep acetabular angles and slightly flattened lumbar vertebrae. Conclusion: This study demonstrates that young children with MPS VI tolerate haploidentical SCT. Normalization of enzyme production and dermatan sulfaturia indicates correction of the inborn error of metabolism and coincide with no obvious symptoms of progressive MPS VI up to 4.6 years post-SCT.

KW - Mucopolysaccharidosis VI

KW - Haploidentical stem cell transplantation

KW - Clinical outcome

U2 - 10.1186/1750-1172-8-134

DO - 10.1186/1750-1172-8-134

M3 - Article

VL - 8

JO - Orphanet Journal of Rare Diseases

T2 - Orphanet Journal of Rare Diseases

JF - Orphanet Journal of Rare Diseases

SN - 1750-1172

IS - 134

ER -