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Mortality after hematopoietic stem cell transplantation for severe mucopolysaccharidosis type I: the 30-year University of Minnesota experience

Abstract

Background and aim

Mucopolysaccharidosis IH (MPS IH, Hurler syndrome) naturally leads to death within the first decade of life, primarily from cardiac and pulmonary causes. To determine how hematopoietic stem cell transplantation (HSCT) has altered mortality, we analyzed our institution’s 30-year experience of patients with MPS IH undergoing HSCT.

Methods

Using chart review and the National Death Index, we determined survival status of 134 patients (males = 69) with MPS IH transplanted between 9/16/1983 and 7/25/2013 on 12/31/2013. Analysis included descriptive statistics, Kaplan-Meier curves, and regression analysis by Cox proportional hazards model.

Results

Overall survival (95% CI) at one- and 25-years was 70% (62–78%) and 37% (19–55%), respectively. From 2004 onward, overall survival at one- and 8-years was 84% (73–96%) and 81% (69–94%), respectively, compared to 65% (55–74%) and 57% (47–67%) prior to 2004 (Log-rank p = 0.032). Regardless of era, male survival was significantly better than female (HR 0.40, [95% CI: 0.21–0.74], p = 0.004). The cumulative incidence of death (95% CI) at 25 years was 63% (45–81%); incidence of pulmonary-related death was the highest at 27% (10–41%) compared to 8% (0.3–16%) for cardiac, 12% (6–17%) for infectious disease, and 16% (3–27%) from other complications.

Conclusions

HSCT has increased survival in MPS IH beyond the third decade of life and decreased the incidence of cardiac mortality, but deaths after the third year post-HSCT occur in excess of expected US mortality. It is important to determine if improved transplant strategies since 2004 result in better long-term survival in the current patient population.

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Abbreviations

CDC:

Centers for Disease Control

ERT:

enzyme replacement therapy

GAG:

glycosaminoglycan

GvHD:

graft-versus-host disease

HSCT:

hematopoietic stem cell transplant

IDUA:

alpha-L-iduronidase

MPS IH:

mucopolysaccharidosis IH, Hurler syndrome

NDI:

National Death Index

TBI:

total body irradiation

TLI:

total lymphoid irradiation

TRM:

transplant-related mortality

UCB:

umbilical cord blood

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Authors

Corresponding author

Correspondence to Nathan J. Rodgers.

Ethics declarations

All procedures followed were in accordance with the ethical standards of the responsible committee on human studies (institutional) and with the Helsinki Declaration of 1975, as revised in 2000.

Disclosures

Dr. Rodgers wrote the first draft of the manuscript with the assistance of his mentor, Dr. Braunlin. This study had no study sponsor. Dr. Braunlin receives research funding and travel reimbursement from BioMarin Pharmaceuticals, a company which (in conjunction with Genzyme Pharmaceutical) produces the enzyme replacement therapy discussed in this manuscript. Dr. Orchard receives research funding and travel reimbursement from both BioMarin and Genzyme. Neither BioMarin nor Genzyme played a role in the study design, the collection, analysis and interpretation or the date, the writing of the report or the decision to submit the paper for publication. Drs. Braunlin and Orchard received no financial compensation (no honorarium, grant or other form of payment) for the manuscript from either BioMarin or Genzyme.

Sources of funding

Funding came from the University of Minnesota Department of Pediatrics. Statistical support was funded in part by NCATS award UL1TR000114.

Informed consent

Informed consent was obtained from all patients or their legal guardians prior to hematopoietic stem cell transplantation for use of their medical records in research.

Animal rights

This article does not contain animal subjects.

Conflict of interest

None.

Additional information

Communicated by: Frits Wijburg

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Rodgers, N.J., Kaizer, A.M., Miller, W.P. et al. Mortality after hematopoietic stem cell transplantation for severe mucopolysaccharidosis type I: the 30-year University of Minnesota experience. J Inherit Metab Dis 40, 271–280 (2017). https://doi.org/10.1007/s10545-016-0006-2

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Keywords

  • Hematopoietic Stem Cell Transplantation
  • Enzyme Replacement Therapy
  • Umbilical Cord Blood
  • National Death Index
  • Umbilical Cord Blood Transplant