Hematopoietic Cell Transplantation for MPS Patients Is Safe and Effective: Results after Implementation of International Guidelines

Background: Allogeneic hematopoietic cell transplantation (HCT) is the only treatment option able to prevent progressive neurodegenerative disease in a selected group of mucopolysaccharidoses (MPS) disorders. However, its use was historically limited by the high risk of graft failure and HCT-related morbidity and mortality. Therefore in 2005, the European Blood and Marrow Transplantation group developed transplantation guidelines for HCT in MPS patients. We prospectively evaluated the outcomes of HCT in MPS patients, complying with these international guidelines in two centers performing the highest numbers of HCT in MPS patients in Europe.

Methods: Two consecutive conditioning regimens were used, either Busulfan/Cyclophosphamide (Bu/Cy) or Fludarabine/Busulfan (Flu/Bu)-based, both with exposure-targeted intravenous Busulfan. A non-carrier matched sibling donor (MSD), or an identical unrelated cord blood (UCB, 6/6 on intermediate resolution) or identical matched unrelated donor (MUD, 10/10 on high-resolution typing) were considered preferred donors. If not available, a mismatched UCB donor was used.

Results: 62 MPS patients were included (56 MPS type I – Hurler, 2 MPS type II, 2 MPS type III, and 2 MPS type VI); 29 receiving a BuCy, 33 a FluBu-based conditioning regimen. Median age at HCT was 13.5 (range 3-44) months. 41 patients received an UCB donor, 17 a MSD, and 4 a MUD. High overall survival (95.2%) and event-free survival (90.3%) were achieved (figure 1). All three patients with graft failure received a second HCT and are alive and with successful donor engraftment at latest follow-up. A mismatched donor predicted for lower event-free survival (p=0.04). The probability of aGVHD grade II-IV was 13.3%, while 14.8% of the patients were diagnosed with cGVHD (1.9% extensive). A higher age at HCT was a predictor for both aGVHD (p=0.001) and cGVHD (p=0.01). The use of a mismatched donor was a predictor for aGVHD (p=0.01). Full-donor chimerism and normal enzyme levels were found in 88.2% and 95.1% of the patients, respectively. Higher rates of full-donor chimerism were achieved in UCB recipients (p=0.002).

Conclusion: If complying with the international HCT guidelines, HCT in MPS patients results in high safety and efficacy. This allows extension of HCT to more attenuated MPS types such as MPS type I – Hurler-Scheie. As a younger age at HCT is associated with reduction of HCT-related toxicity, newborn screening may further increase safety.

Figure 1. Overall survival (OS) and event-free survival (EFS)