Leucopenia in the First Year After Renal Transplantation During Valganciclovir Prophylaxis

Leucopenia is a well-known side effect of Valganciclovir (Vgc) prophylaxis but also of mycophenolate (MPA) and CMV infection. In this retrospective analysis we investigated incidence, impact of immunosuppressants and outcome of leucopenia during Vgc prophylaxis in the first year post-transplant (Tx). Between 08/2003 - 08/2011 637 renal Tx patients (pts) received Vgc prophylaxis. Pts with mild (<3500/μl) + severe leucopenia (<2000/μl) occurring only during Vgc prophylaxis were analyzed and compared to pts without leucopenia. Vgc exposure (≙ as daily dose given in relation to the prescribing information), MPA + steroid doses, tacrolimus (Tac) + cyclosporine (CsA) trough levels were investigated at time of leukopenia + on day (d) 30, 60, 90 post Tx. In total, 268/637pts (42.1%) had leucopenia within the first year post-Tx, 166/637 (26.1%) during prophylaxis. 4/166 pts (2.4%) died; 5/166 pts (3.1%) experienced graft loss, which was comparable to the control group (9/368 (2.4%) death, 6/368 (1.6%) graft loss). 58 (9.1%) developed severe leucopenia. Median time to leucopenia was 70d (4-270). Median leucopenia period was 4d (1-104). At time of leucopenia 75 (45.2%) pts were underexposed, 48 (28.9%) received recommended Vgc dosing, 43 (25.9%) were overexposed. Vgc doses + exposure on d30 + d60 were significantly higher in pts experiencing leucopenia (d30: 43/166, 25.9%) than in controls (d30: 48/349, 13.0%) (p=0.007). No significant difference in leucopenia occurrence was found between pts on Tac (73/166; 44.0%) or CsA (93/166; 56.0%) (p=0.898) nor were there any differences in trough levels on d30- d90 post-tx (Tac, p=0.629; Cya, p=0.626). At time of leucopenia most patients (106/166; 64.6%) received steroid doses of <12mg. Almost all pts (159/166, 95.2%) received MPA. Mean MPA dose at time to leucopenia was 1446±534mg. MPA doses were significantly (day 30: p<0.05) higher in pts with leucopenia (1703±572mg) than in controls (1554±606mg) on d30- d90. In 8 (4.8%) pts leucopenia was associated with mild CMV infection during prophylaxis. Only 2/166 (1.2%) received G-CSF. Vgc dose was reduced in 25/166pts (15.1%), Vgc prophylaxis was terminated prematurely in 28/166 (16.9%) after a median time of 97d (68-147). MPA dose adjustments were preferred (81/159; 50.9%). Leucopenia is frequent (26%) under Vgc prophylaxis in combination with MPA, occurring mostly during steroid taper between month 2 + 3 post Tx. With our strategy of timely MPA + VGC dose reductions excellent outcomes were achieved. DISCLOSURES:Rissling, O.: Grant/Research Support, Roche. Neumayer, H.: Grant/Research Support, Roche, Speaker's Bureau, Roche. Budde, K.: Grant/Research Support, Roche, Speaker's Bureau, Roche.