Abstract
To evaluate the incidence of bone marrow suppression and consequences of MMF dose adjustment in patients within the first year after heart transplantation. Group I (n=47) was treated with a regimen currently used in patients after heart transplantation (mycophenolatemofetil - MMF, valganciclovir - VGC and trimethoprim/sulfamethoxazole - TMP-SMX). Group II (n=47) received only MMF of potentially myelotoxic medications. The myelotoxic effect and need for dose modification were assessed. The incidence of rejections and infectious episodes associated with MMF adjustment were analyzed during the first 12 months in Group I. There was a significantly greater proportion of patients with leukopenia (leukocyte count < 4 x 10^9/L) at 3 months after orthotopic heart transplantation in Group I compared with Group II (19.1% vs 2.1%; P = 0.02). The difference in lymphopenia (lymphocyte count < 0.8 x 10^9/L) at 3 months follow-up was highly significant (38.3 % vs 6.4 %; P = 0.0002). MMF was modified due to bone marrow suppression or severe infection in 63.8% patients in Group I and in only 8.5% of patients in Group II (P < 0.001). Reducing or stopping MMF was not associated with increased rejections. In Group I, at least 1 episode of higher degree cellular or humoral rejection occurred in 35% of patients with the standard MMF dosage compared with only 26% in patients with modified MMF (P = 0.0534). Addition of VGC+TMP-SMX to current immunosuppressive medication regimen in patients after heart transplantation is associated with significant lymphocytopenia and leukopenia. Importantly, modification of immunosuppressive prophylaxis (reducing or stopping MMF) leads to normalization of blood count without increased incidence of rejections.
Highlights
In the early period after orthotopic heart transplantation (HTx), patients are vulnerable to rejection[1] and infectious complications[2,3]
A significantly higher proportion of patients with leukopenia at three months after orthotopic heart transplantation was found in Group I compared to Group II (19.1% vs 2.1%; P = 0.02)
There were no major differences in number of other blood elements between the two groups in the reference periods (1 month, 3 months, 6 months and 12 months after heart transplantation)
Summary
In the early period after orthotopic heart transplantation (HTx), patients are vulnerable to rejection[1] and infectious complications[2,3]. Immunosuppressive and anti-infective drug prophylaxis consists of drugs with potentially myelotoxic effects. Current maintenance immunosuppression is achieved with a combination of different immunosuppressive agents. This generally comprises corticosteroids in combination with calcineurin inhibitors, tacrolimus or cyclosporin, and the antiproliferative agent mycophenolate mofetil (MMF). Current guidelines[4] recommend dual anti-infective prophylaxis composed of valganciclovir (VGC) and trimethoprim/sulfamethoxazole (TMP-SMX). One of most serious adverse reactions associated with immunosuppressive and anti-infective drug prophylaxis is bone marrow suppression. In this respect, leukopenia[5] and anemia[6] are the most frequent consequences
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