Immunologic outcomes.
lymphopenia, neutropenia, μg/kg/d
LYMPHOPENIA, ADVERSE EVENT, NEUTROPENIA
All patients had severe baseline neutropenia and lymphopenia: the mean ± SEM ANC was 246 ± 42 (range, 50–740 cells/μL), and the mean ± SEM absolute lymphocyte count (ALC) was 597 ± 48 (range, 320–1,010 cells/μL) (Sixteen patients had the same predefined success outcome in maintaining at least 75% of planned measurements of the ANC above 500 cells/μL during both treatment phases (11 succeeded in both, and 5 failed in both), and 3 had success only on G-CSF, leading to a difference in proportion of success on G-CSF minus the proportion of success on plerixafor of 14/19 – 11/19 = 0.158 (95% CI, –0.081, 0.396), which is significantly less than the prespecified margin of 0.40 (Regarding reversal of lymphopenia, 4 patients failed on both drugs, 1 succeeded on both drugs, and 14 succeeded only on plerixafor, leading to a difference in success proportions of 1/19 to 15/19 = –0.737 (95% CI, –0.909, –0.341); thus, plerixafor was judged superior for maintaining the ALC above the prespecified threshold of 1,000 cells/μL for 1 year (The 4 patients who failed the ALC maintenance test during the treatment period for both drugs — M07, M09, M14, and M17 — all failed on plerixafor because they were study dropouts for that phase, as detailed previously. However, examination of data from the equilibration phase for all 4 patients and limited data from the treatment phase prior to dropout for patients M07 and M17 indicated that the ALC consistently exceeded 1,000 cells/μL on plerixafor for these patients (The only patients to fail the ANC maintenance test for both drugs were the 3 youngest children in the study, patients M07, M11, and M13, despite receiving the maximal allowable doses of both drugs (The 3 patients who were ANC successes on G-CSF but not on plerixafor (M04, M06, and M09) failed on plerixafor for different reasons. M09 had an adverse event during the equilibration phase that prevented entry into the plerixafor treatment phase. M04 and M06 both fell short of the prespecified 75% threshold for success (60% for M04 and 73% for M06). M04, M06, and M09 received a total actual daily dose of 92, 33, and 33 μg/kg/d of plerixafor, respectively, relative to the prespecified total target dose range for the protocol of 20–80 μg/kg/d.The baseline absolute monocyte counts were below the lower limit of normal for all but 1 patient and normalized on plerixafor for most patients but did not increase on G-CSF (Baseline serum IgG levels were below the lower limit of normal for 2 of 11 patients not receiving supplemental IgG, and baseline serum IgM and IgA levels were low in only 2 and 7 of the 19 patients, respectively (Neither drug affected patient hemoglobin levels, which were normal at baseline, nor the platelet count, which distributed below and at the lower limit of the normal range at baseline (