PMC3711263_01
Anti-rhGAA antibody titers, left ventricular mass index (LVMI), Alberta Infant Motor Scale (AIMS) score and time course of administration of immunomodulatory agents corresponding to weeks on enzyme replacement therapy (ERT). A 10-day extensive immunomodulation protocol using cyclophosphamide, intravenous immunoglobulin (IVIG), plasmapheresis, increased dose of rhGAA, and rituximab failed to diminish antibody titers. Of note, decrease in LVMI correlates with increased dose of rhGAA (cumulative dose of 100 mg/kg every other week as compared to recommended dose of 20 mg/kg every other week in Myozyme package insert), which was administered between weeks 56 and 112. Lowest LVMI value in this patient was 80.4 g/m2 at week 121 on ERT, which remained above the upper limit of normal LVMI for an infant of 64 g/m2. After an initial period of improvement, AIMS score declined and remained at <5% of normal age despite increased dose of rhGAA and extensive immunomodulation.
nihms484083f1.jpg
PMC3711263_02_nihms484083f1.jpg
F1
Details regarding the 10-day extensive immunomodulatory protocol consisting of cyclophosphamide, intravenous immunoglobulin (IVIG), plasmapheresis, and increased doses of rhGAA are described in Fig. 1. In addition to the repeating the 10-day extensive immunomodulatory protocols twice which included daily cyclophosphamide treatment, additional cyclophosphamide (2 mg/kg through G-tube) was continued between the immunomodulation attempts (week 42 through week 55; Fig. 1). With the increased dose of rhGAA, there was further improvement in cardiac status (LVMI 106 g/m2 at week 99) but LVMI did not normalize (Fig. 1). Moreover, there was no motor improvement (AIMS score 4 to 6; age equivalent of a 0.5-1 month old infant; weeks 38 through 99; Fig. 1).
PMC3711263_02
Anti-rhGAA antibody titers, left ventricular mass index (LVMI), Alberta Infant Motor Scale (AIMS) score and time course of administration of immunomodulatory agents corresponding to weeks on enzyme replacement therapy (ERT). A 10-day extensive immunomodulation protocol using cyclophosphamide, intravenous immunoglobulin (IVIG), plasmapheresis, increased dose of rhGAA, and rituximab failed to diminish antibody titers. Of note, decrease in LVMI correlates with increased dose of rhGAA (cumulative dose of 100 mg/kg every other week as compared to recommended dose of 20 mg/kg every other week in Myozyme package insert), which was administered between weeks 56 and 112. Lowest LVMI value in this patient was 80.4 g/m2 at week 121 on ERT, which remained above the upper limit of normal LVMI for an infant of 64 g/m2. After an initial period of improvement, AIMS score declined and remained at <5% of normal age despite increased dose of rhGAA and extensive immunomodulation.
nihms484083f1.jpg
PMC3711263_02_nihms484083f1.jpg
F1
Details regarding the 10-day extensive immunomodulatory protocol consisting of cyclophosphamide, intravenous immunoglobulin (IVIG), plasmapheresis, and increased doses of rhGAA are described in Fig. 1. In addition to the repeating the 10-day extensive immunomodulatory protocols twice which included daily cyclophosphamide treatment, additional cyclophosphamide (2 mg/kg through G-tube) was continued between the immunomodulation attempts (week 42 through week 55; Fig. 1). With the increased dose of rhGAA, there was further improvement in cardiac status (LVMI 106 g/m2 at week 99) but LVMI did not normalize (Fig. 1). Moreover, there was no motor improvement (AIMS score 4 to 6; age equivalent of a 0.5-1 month old infant; weeks 38 through 99; Fig. 1).