Purpose Enzyme replacement therapy with rhGAA (Myozyme®) has lead to improved survival, which is largely attributable to improvements in cardiomyopathy and skeletal muscle function. However, crossreactive immunologic material-negative patients have a poor clinical response to enzyme replacement therapy secondary to high sustained antibody titers. Furthermore, although the majority of crossreactive immunologic material-positive patients tolerize or experience a downtrend in anti-rhGAA antibody titers, antibody response is variable with some crossreactive immunologic material-positive infants also mounting high sustained antibody titers. Methods We retrospectively analyzed 34 infants with Pompe disease: 11 crossreactive immunologic material-negative patients, nine high-titer crossreactive immunologic material-positive patients, and 14 low-titer crossreactive immunologic material-positive patients. Clinical outcome measures were overall survival, ventilator-free survival, left ventricular mass index, Alberta Infant Motor Scale score, and urine Glc4 levels. Results Clinical outcomes in the high-titer crossreactive immunologic material-positive group were poor across all areas evaluated relative to the low-titer crossreactive immunologic material-positive group. For the crossreactive immunologic material-negative and high-titer crossreactive immunologic material-positive groups, no statistically significant differences were observed for any outcome measures, and both patient groups did poorly. Conclusions Our data indicate that, irrespective of crossreactive immunologic material status, patients with infantile Pompe disease with high sustained antibody titer have an attenuated therapeutic response to enzyme replacement therapy. With the advent of immunomodulation therapies, identification of patients at risk for developing high sustained antibody titer is critical.

PURPOSE Following US military implementation of a cold-stored whole blood program, several US trauma centers have begun incorporating uncrossmatched, group O cold-stored whole blood into civilian trauma resuscitation. We set out to evaluate the safety profile, transfusion reactions events, and impact of low-titer group O whole blood (LTO-WB) at our center. METHODS In November 2017, we added LTO-WB to each of our helicopters and to our emergency department (ED) refrigerator, alongside that of existing red blood cells and plasma. We collected information on all patients with trauma receiving prehospital or ED transfusion of uncrossed, emergency release blood products between November 2017 and June 2018. Patients were divided into those receiving any LTO-WB and those receiving only red blood cell and or plasma (COMP). Serial hemolysis panels were obtained at 3 hours, 24 hours, and 48 hours. All data were run using STATA 12.1. Statistical significance was set at p < 0.05. RESULTS One hundred ninety-eight patients received LTO-WB and 152 patients received COMP. There were no differences in age, sex, or mechanism. The LTO-WB patients had higher chest Abbreviated Injury Scale scores (median, 3 vs. 2; p = 0.027), as well as worse arrival base excess (median, −7 vs. −5; p = 0.014) and lactate (5.1 vs. 3.5; p < 0.001). The LTO-WB patients received less post-ED blood products than the COMP patients (median, 0 vs. 3; p = 0.001). There was no difference in survival (LTO-WB, 73%; COMP, 74%; p = 0.805). There were only two suspected transfusion reactions, both in the COMP group (p = 0.061). There was no difference in hemolysis panel values. Controlling for age, severity of injury, and prehospital physiology, LTO-WB was associated with a 53% reduction in post-ED blood product transfusion (odds ratio, 0.47; 0.23–0.94 95% CI; p = 0.033) and two-fold increase in likelihood of survival (odds ratio, 2.19; 1.01–4.76 95% CI; p = 0.047). CONCLUSION Low-titer group O whole blood has similar evidence of laboratory hemolysis, similar transfusion reaction rates, and is associated with a reduction in post-ED transfusions and increase likelihood of survival. LEVEL OF EVIDENCE Therapeutic, Level II.