Hematopoietic Stem Cell Transplantation (HSCT)
Hematopoietic refers to the blood; therefore, HSCT is a blood stem cell transplant. Possible sources of blood stem cells include bone marrow, peripheral blood, and umbilical cord blood
To date, HSCT represents one of the few therapies with proven, long-term benefit for some, but not all, MPS disorders. The MPS disorders benefiting most significantly from HSCT include severe MPS I (Hurler syndrome), MPS VI (Maroteaux-Lamy syndrome), and MPS VII (Sly syndrome). Unfortunately, benefit from HSCT for the nervous system and/or the skeletal system has not been shown for MPS II (Hunter syndrome), MPS III (Sanfilippo syndrome) and MPS VI (Morquio syndrome).
MPS Disorders for which HSCT Is Effective
MPS I (Hurler syndrome): Successful HSCT has been performed for children with Hurler syndrome since 1980. The immediate benefits include correction of the enzyme deficiency and clearance of glycosaminoglycans (GAGs). Long-term benefits include the possibility of long-term survival by protecting the heart, lungs, and brain from the effects of progression of the MPS disorder. Other organs and tissues can also show benefits from the HSCT; these include the eyes and ears, liver, spleen, joints, airway, etc. However, it should be noted that many children are still requiring a variety of orthopedic surgeries despite a successful transplant. While the term “cure” should not be used, HSCT has the longest track record of any effective therapy for Hurler syndrome, including the ability to preserve cognitive function and development in the normal range.
MPS VI (Maroteaux-Lamy syndrome): The principal clinical features of children with MPS VI are bone abnormalities, severe short stature, corneal clouding, lung problems, liver and spleen enlargement, and heart valve abnormalities. Intelligence is felt to be preserved in most individuals. For over twenty years, HSCT has been used successfully to treat MPS VI with resolution of liver and spleen enlargement, airway obstruction and sleep apnea, and improved joint mobility. There has also been prevention of further heart and lung deterioration. Visual acuity has improved in some individuals although corneal haze does not necessarily resolve. As in other MPS disorders, HSCT has not been able to treat effectively the skeletal abnormalities. Consequently, successfully transplanted children have still required orthopedic surgical interventions on the knees and hips.
MPS VII (Sly syndrome): Use of HSCT for MPS VII is limited by the rarity of the disorder and tendency toward stillbirths, although there are also milder adult forms of this disease. In certain circumstances, MPS VII can be effectively treated by HSCT provided that the developmental and clinical status of the individual is good at the time of HSCT.
ML II (I-cell disease): To date, HSCT represents a therapy with a relatively short but effective track record for ML II (I-cell disease) as was published in the medical journal Bone Marrow Transplantation in 2003 by the group from the University of Minnesota. Over the past 5 years, three patients (0.3-1.7 year of age at HCT) have been transplanted at the University of Minnesota. The early follow-up has shown good cardiopulmonary function in two patients while one has developed pulmonary hypertension. All children remain mildly to moderately neurodevelopmentally delayed and are receiving appropriate additional educational resources.
HSCT should be performed at centers with experience in offering comprehensive, multi-specialty care for MPS individuals whose underlying diseases can be appropriately treated by transplant. Contact the National MPS Society for additional information, firstname.lastname@example.org.