title: Impact of velaglucerase alfa on bone marrow burden score in adult patients with type 1 Gaucher disease: 7-year follow-up.
abstract: BACKGROUND
  Bone marrow infiltration by substrate-engorged "Gaucher" cells manifests early in Gaucher disease (GD). The impact of velaglucerase alfa on bone marrow burden (BMB) was evaluated as an exploratory assessment.
  
  
  METHODS
  BMB scores were assessed using T1- and T2-weighted magnetic resonance images of the lumbar spine (LS) and femora among symptomatic GD patients who participated in the 9-month Phase I/II trial and long-term extension study for velaglucerase alfa. A post-hoc assessment of marrow involvement was performed. BMB scores per site are 0-8 (0/1=normal; 8=severe infiltration).
  
  
  RESULTS
  The median LS-BMB score at baseline was 6 (n=12; range 3-8); at 9 months, compared with baseline, there was a median change of -2 (n=11; two-sided p-value=0.0078). LS-BMB scores continued to decrease through 5 years (n=8; median change from baseline -5 [p=0.0078], median score 1 [range 1-4]) and were subsequently sustained through 7 years (n=8). LS-BMB decreases of ≥2 points occurred in 6/11 patients at 9 months, and in all assessable patients (8/8) by 5 years. Long-term femoral BMB (F-BMB) assessment was possible for three patients; all experienced reductions of ≥2 points at 5 years with a total score (LS-BMB+F-BMB) decrease ≥4.
  
  
  CONCLUSIONS
  This post hoc analysis suggests improvement in BMB scores through 5 years that was sustained through 7 years, despite dose reduction from 15 months. Prospective studies in a large cohort are needed to validate these findings.
authors.affiliation: Gaucher Clinic, Shaare Zedek Medical Center, The Hebrew University-Hadassah School of Medicine, Jerusalem, Israel. Electronic address: elstein@szmc.org.il.
authors.forename: Deborah
authors.initials: D
authors.lastname: Elstein
authors.affiliation: Department of Radiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Haims
authors.affiliation: Shire, Lexington, MA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Zahrieh
authors.affiliation: Shire, Lexington, MA, USA.
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Cohn
authors.affiliation: Gaucher Clinic, Shaare Zedek Medical Center, The Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.
authors.forename: Ari
authors.initials: A
authors.lastname: Zimran
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D056947:Enzyme Replacement Therapy; D005260:Female; D005500:Follow-Up Studies; D005776:Gaucher Disease / Q000188:drug therapy*; D005962:Glucosylceramidase / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008159:Lumbar Vertebrae / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005962:Glucosylceramidase; C550184:Velaglucerase alfa, human
keywords: Bone marrow burden; Bone mineral density; Enzyme replacement therapy; Gaucher disease; MRI; Velaglucerase alfa