Figure 6.
Pharmacokinetics of 4HCY correlate with IBW PTCy dosing and the apparent clinical benefits of reduced-dose PTCy. (A-B) The area-under-the-curve (AUC) of cyclophosphamide (CY) and its active metabolite 4HCY were measured for patients in all DLs although 2 DL2 patients had missing samples precluding AUC calculations. ∗P < .05; ∗∗P < .01. (C-D) For each patient, the relationship between PTCy weight-based dose and 4HCY AUC were compared using either the (C) ABW or (D) IBW for the PTCy dose calculation. Spearman correlation coefficients (ρ) and associated P values are shown. Colors reflect the race/ethnicity of individual patients. Green = White/Hispanic; red = White/Non-Hispanic; yellow = African-American; orange = Asian; light blue = American Indian/Alaskan Native; dark blue = multiracial. (E-H) Measured 4HCY exposures significantly correlated with clinical outcomes that appeared superior for ID-PTCy compared with HD-PTCy, including (E) time to neutrophil engraftment, (F) duration of mucositis (oral, pharyngeal, and/or rectal), and (G) absolute number of CD4+ T cells in the blood on day +14. Patients with graft failure, mixed T-cell chimerism, or those receiving tocilizumab (n = 1) were excluded from panels E-G. (H) No difference was seen in 4HCY exposure among evaluable ID-PTCy–treated patients with regard to the development of cGVHD.

Pharmacokinetics of 4HCY correlate with IBW PTCy dosing and the apparent clinical benefits of reduced-dose PTCy. (A-B) The area-under-the-curve (AUC) of cyclophosphamide (CY) and its active metabolite 4HCY were measured for patients in all DLs although 2 DL2 patients had missing samples precluding AUC calculations. ∗P < .05; ∗∗P < .01. (C-D) For each patient, the relationship between PTCy weight-based dose and 4HCY AUC were compared using either the (C) ABW or (D) IBW for the PTCy dose calculation. Spearman correlation coefficients (ρ) and associated P values are shown. Colors reflect the race/ethnicity of individual patients. Green = White/Hispanic; red = White/Non-Hispanic; yellow = African-American; orange = Asian; light blue = American Indian/Alaskan Native; dark blue = multiracial. (E-H) Measured 4HCY exposures significantly correlated with clinical outcomes that appeared superior for ID-PTCy compared with HD-PTCy, including (E) time to neutrophil engraftment, (F) duration of mucositis (oral, pharyngeal, and/or rectal), and (G) absolute number of CD4+ T cells in the blood on day +14. Patients with graft failure, mixed T-cell chimerism, or those receiving tocilizumab (n = 1) were excluded from panels E-G. (H) No difference was seen in 4HCY exposure among evaluable ID-PTCy–treated patients with regard to the development of cGVHD.

This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal