Figure 1.
Organ distribution of leukemic clone and reactive CARTs. (A) IGH sequencing demonstrates dominance of the B-ALL clone (marked with a red dot) over all other B-cell clones (blue dots) in PB at autopsy (PB day 5 [d5]), bone marrow (BM), and several other tissues, including the lymph nodes (LN). The frequency of unique clonotypes as a proportion of all immunoglobulin H reads is plotted for the baseline blood sample (all x-axes) vs the day 5 autopsy tissues (y-axis). (B) The leukemic clone represents the largest fraction of B-cell clones in all tissues examined. (C) Quantitative analysis of the IGH sequencing data identifies the B-ALL clone predominantly in the BM and PB. Much lower concentrations of the leukemic clone were seen in the remaining examined tissues, including the LN and liver. (D) The T-cell clones that dominate the repertoires within the LN, liver, and BM (green triangles, blue circles, and red squares, respectively) originate predominantly from the CD8+ fraction of the infused CARTs, rather than the CD8– (E) fraction. (F) The most dominant clones and their frequencies in the LN, BM, and liver. The sharing among these organs of dominant clones indicates the presence of the same immune reaction, almost certainly being carried out by CARTs stimulated by CD19 expressed by B-ALL cells. (G) ISH identifies frequent CAR cells among the T-cell infiltrate in the LN and liver. MC, mononuclear cell; PB, peripheral blood.