Heterogeneous Clearance of Antithymocyte Globulin after CD34+-Selected Allogeneic Hematopoietic Progenitor Cell Transplantation Irina Kakhniashvili,

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Presentation transcript:

Heterogeneous Clearance of Antithymocyte Globulin after CD34+-Selected Allogeneic Hematopoietic Progenitor Cell Transplantation Irina Kakhniashvili, Joanne Filicko, Walter K. Kraft, Neal Flomenberg Biology of Blood and Marrow Transplantation Volume 11, Issue 8, Pages 609-618 (August 2005) DOI: 10.1016/j.bbmt.2005.05.001 Copyright © 2005 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 ATG titration. A, Mean log fluorescence progressively declines as rabbit ATG concentration is diluted, reflecting the fact that these ATG concentrations are not saturating. B, A sample ATG titration is shown, depicting the association between mean log fluorescence (x-axis) and standard dilutions of ATG (y-axis). Mean log fluorescence from patient samples from the same experiment are used in the equation y = 0.0251x − 0.7147, where y is the mean fluorescence and x is the result that corresponds to the patient’s ATG level. Biology of Blood and Marrow Transplantation 2005 11, 609-618DOI: (10.1016/j.bbmt.2005.05.001) Copyright © 2005 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 ATG disappearance: the gradual loss of ATG from the serum of a sample patient is illustrated. A, An overlay of histograms from a sample patient shows the mean log fluorescence of samples from each time point, with a gradual decline of fluorescence over time. B, The same data with corresponding ATG levels plotted against time after HPCT. In most cases, pharmacokinetic parameters were best described by a biexponential model. Biology of Blood and Marrow Transplantation 2005 11, 609-618DOI: (10.1016/j.bbmt.2005.05.001) Copyright © 2005 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 ATG levels. A, Observed peak ATG levels for all 30 patients. In most patients, this level was obtained on day 7 after HPCT and reflects a total of 4 or 5 doses of ATG; the final dose was given on day +4 or +6. Levels ranged from 8.07 to 40.74 μg/mL (median, 21.69 μg/mL). Patient identification numbers are shown along the x-axis and indicate that there was no difference between patients treated earlier in the study (who received a 20 mg/kg ATG total dose) and those treated later in the study (who received a 16 mg/kg total dose). B, Lack of correlation between observed peak ATG levels and time to disappearance to an ATG level <1 μg/mL. Similarly, there was no correlation between these levels and the time to an ATG level <2.5, 2.0, or 1.5 μg/mL (data not shown for all levels). Biology of Blood and Marrow Transplantation 2005 11, 609-618DOI: (10.1016/j.bbmt.2005.05.001) Copyright © 2005 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 Two-color flow assay: by using single-color flow (A), 2 FITC+ populations of cells can be seen. In this example, the brighter population is the larger one, although in other cases (data not shown) it is the smaller population. With the 2-color flow-based assay and the addition of CD3 PE (B and C), it becomes clear that the brighter population is the clinically relevant CD3+ population. Biology of Blood and Marrow Transplantation 2005 11, 609-618DOI: (10.1016/j.bbmt.2005.05.001) Copyright © 2005 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 5 ATG binding to white cell subsets: the disappearance of antibody capable of binding to CD3 (T cells), CD13 (myeloid cells), and CD56 (NK cells) is illustrated. Biology of Blood and Marrow Transplantation 2005 11, 609-618DOI: (10.1016/j.bbmt.2005.05.001) Copyright © 2005 American Society for Blood and Marrow Transplantation Terms and Conditions