Background.
Granulocyte-colony stimulating factor (G-CSF) has been shown to attenuate coronary disease in non-transplant population and decrease the incidence of acute rejections in experimental models of heart transplantation.
Hypothesis.
We hypothesized that G-CSF may decrease the incidence of allograft vasculopathy and rejection in heart transplant recipients.
Methods.
Of 247 patients who underwent heart transplantation at Stanford University Medical Center from 2000 to 2007 we enrolled 52 (21%) patients who presented with leukopenia (WBC < 2.5 x 10
9
cells/L) in the absence of active infection, rejection or malignancy. In 24 (46%) patients leukopenia was treated with G-CSF (mean dose 348 ± 78 mcg daily; G-CSF Group), and 28 (54%) patients received no G-CSF therapy (non-GCSF group). All patients were followed for 1 year after leukopenia occurence for the development of allograft vasculopathy (any new stenotic lesion on annual coronary angiography) and rejection incidence (ISHLT grade ≥3A or higher, or severe non-cellular rejection).
Results.
At baseline, G-CSF Group and non-G-CSF Group did not differ in age (54 ± 16 vs. 47 ± 14 years, respectively,
P
= 0.1), gender (male: 17% vs. 35%,
P
= 0.12), race (Caucasian: 79%, vs. 78%,
P
= 0.96), heart failure etiology (ischemic: 26% vs. 45%,
P
= 0.12), creatinine (1.6 ± 1.1 mg/dl vs. 1.5 ± 0.6 mg/dl,
P
= 0.6), LVEF (64 ± 8% vs. 64 ± 7%,
P
= 0.81), immunosupressive regimen (CyA/MMF/Prednisone: 42% vs. 54%,
P
= 0.4), or post-transplant time of leukopenia occurence (284 ± 396 days in the G-CSF Group vs. 347 ± 365 days in Controls,
P
= 0.57). During 1-year follow-up there were no events in the G-CSF Group, and 1 death in the non-G-CSF Group (
P
= 0.34). Rejection incidence was significantly lower in the G-CSF Group (8% vs. 36% in Controls,
P
= 0.019), as was cardiac allograft vasculopathy (4% vs. 29%,
P
= 0.02).
Conclusions.
G-CSF therapy appears to be associated with decreased incidence of acute rejections and allograft vasculopathy in heart transplant recipients, suggesting that G-CSF may have immunomodulatory effects.
Leukocytoclastic Vasculitis as a Complication of Recombinant Granulocyte Colony-Stimulating Factor Therapy in a Heart Transplant Patient
