Study endpoints and definitions
The objective of this study was to clarify the impact of conditioning
interruptions on clinical outcomes after HCT. Clinical endpoints
included OS, EFS, non-relapse mortality (NRM), relapse rate (RR),
engraftment, and acute or chronic GVHD incidence. The incidences of
veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS),
thrombotic microangiopathy (TMA), and interstitial pneumonia were
evaluated as transplantation-associated complications. EFS was defined
as survival without death due to any cause, or survival without
recurrence of the primary disease. NRM was defined as death for any
reason other than primary disease relapse or progression, and RR was
estimated by considering death without prior relapse as a competing
event. The engraftment definition was attainment of >
0.5×109/L absolute neutrophil count for three
consecutive days. The diagnosis and grading of acute graft-versus-host
disease (aGVHD) were implemented based on the manifestation of skin,
intestine, and liver symptoms arising within 100 days after HCT. Other
causes for the symptoms were excluded. The aGVHD grading was conducted
according to the consensus conference on aGVHD grading in 1994 [14].
The diagnosis of chronic graft-versus-host disease (cGVHD) was also made
using the signs and symptoms of cGVHD occurring beyond 100 days after
HCT. The distinctive symptoms of cGVHD employed were similar to those
specified in the National Institute of Health criteria for cGVHD in 2005
[15].
Interruption of conditioning was defined as a regimen in which one or
two vacant days (no chemotherapy drug administration or TBI) were added
to the initially scheduled regimen. Examples of interrupted conditioning
are shown in Figure 1.