Figure 1.
Figure 1. Association between HHV-6 viral load, WBC, and host chimerism at various time points before and after HSCT. (A) Pre- and early posttransplant until donor engraftment (when all circulating cells were of host origin), the HHV-6 viral load (copies per mL) was approximately equal to WBC (count per mL), except for the initial episode of HHV-6 viremia (day −15) after reinduction with a vorinostat (V)–containing regimen. Presence of ciHHV-6 in the host was confirmed with a ratio-based PCR on 2 separated time points (days −9 and −1), with an HHV-6 viral copies per cell genome ratio of ∼1, indicating that the source of HHV-6 viremia was circulating host cells with ciHHV-6. The only exception was day −15 when HHV-6 viral load (copies per mL) >> WBC (count per mL) in combination with fever and rash, suggesting presence of HHV-6 reactivation from ciHHV-6 state, possibly induced by exposure to a histone deacetylase (HDAC) inhibitor. (Results of ratio-based PCR assay for the detection of ciHHV-6: *1.12, **0.9.) (B) After donor engraftment and before full donor chimerism was achieved, the HHV-6 viral load (copies per mL) was much lower than WBC (count per mL). We reasoned that the donor did not have ciHHV-6 and that circulating nucleated cells of host origin with ciHHV-6 were the source of ongoing HHV-6 viremia during this time. Indeed, we observed that host WBC count (count per mL), which was calculated by multiplying PB host chimerism as measured by interphase FISH by the total WBC count obtained from same-day hemograms, approximated the HHV-6 viral load (copies per mL). (C) The calculated HHV-6 viral load to total WBC ratio can be used to estimate persistent host chimerism when the HSCT recipient, but not donor, has ciHHV-6. In the late posttransplant period, the HHV-6 viral load to WBC count ratio had greater sensitivity for the detection of host microchimerism compared with interphase FISH. Specifically, because the sensitivity of the FISH chimerism assay depends on the number of cells analyzed, 1 to 2 log more cells would have been needed to detect host microchimerism at that time. (The horizontal interrupted line represents the detection limit of 200-cell interphase FISH assay.)

Association between HHV-6 viral load, WBC, and host chimerism at various time points before and after HSCT. (A) Pre- and early posttransplant until donor engraftment (when all circulating cells were of host origin), the HHV-6 viral load (copies per mL) was approximately equal to WBC (count per mL), except for the initial episode of HHV-6 viremia (day −15) after reinduction with a vorinostat (V)–containing regimen. Presence of ciHHV-6 in the host was confirmed with a ratio-based PCR on 2 separated time points (days −9 and −1), with an HHV-6 viral copies per cell genome ratio of ∼1, indicating that the source of HHV-6 viremia was circulating host cells with ciHHV-6. The only exception was day −15 when HHV-6 viral load (copies per mL) >> WBC (count per mL) in combination with fever and rash, suggesting presence of HHV-6 reactivation from ciHHV-6 state, possibly induced by exposure to a histone deacetylase (HDAC) inhibitor. (Results of ratio-based PCR assay for the detection of ciHHV-6: *1.12, **0.9.) (B) After donor engraftment and before full donor chimerism was achieved, the HHV-6 viral load (copies per mL) was much lower than WBC (count per mL). We reasoned that the donor did not have ciHHV-6 and that circulating nucleated cells of host origin with ciHHV-6 were the source of ongoing HHV-6 viremia during this time. Indeed, we observed that host WBC count (count per mL), which was calculated by multiplying PB host chimerism as measured by interphase FISH by the total WBC count obtained from same-day hemograms, approximated the HHV-6 viral load (copies per mL). (C) The calculated HHV-6 viral load to total WBC ratio can be used to estimate persistent host chimerism when the HSCT recipient, but not donor, has ciHHV-6. In the late posttransplant period, the HHV-6 viral load to WBC count ratio had greater sensitivity for the detection of host microchimerism compared with interphase FISH. Specifically, because the sensitivity of the FISH chimerism assay depends on the number of cells analyzed, 1 to 2 log more cells would have been needed to detect host microchimerism at that time. (The horizontal interrupted line represents the detection limit of 200-cell interphase FISH assay.)

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