Risk factors of Ganciclovir-related neutropenia after allogeneic stem cell transplantation: a retrospective monocentre study on 547 patients

Abstract

Cytomegalovirus (CMV) infection is a serious complication that may occur in the weeks or months following bone marrow transplantation. However, both Ganciclovir and the CMV infection itself can cause marrow toxicity, notably neutropenia, that may consequently expose these immunosuppressed patients to life-threatening bacterial and/or fungal infections. The aim of this retrospective study was to identify factors associated with the occurrence of grade III-IV neutropenia among patients receiving pre-emptive Ganciclovir therapy after allogeneic stem cell transplantation at our Institution. We identified 547 consecutive patients transplanted from January 2005 to June 2011 at our Institution. In all, 190 patients (35%) presented with CMV reactivation of whom 30 patients (5%) were excluded from the analysis because they already had neutropenia at the time of reactivation. Finally, 160 (29%) patients were analysed. According to multivariate analysis, at the time of treatment initiation, the risk factors significantly associated with a grade III-IV Ganciclovir-related neutropenia included a high viral load (hazard ratio (HR) = 2.68, 95% CI 1.25-5.737, p 0.01); an absolute neutrophil count >3000 was a protective factor (HR = 0.26, 95% CI 0.125-0.545, p <0001) whereas serum creatinine >2 mg/dL was associated with higher Ganciclovir-related neutropenia (HR = 2.4, 95% CI 1.11-5.17, p 0.002). This large analysis revealed three risk factors for Ganciclovir-related neutropenia among patients with CMV reactivation after allogeneic stem cell transplantation; prompt identification of patients at risk when antiviral therapy is started may allow clinicians to adopt adequate preventive measures, so reducing the morbidity and mortality associated with CMV reactivation.

CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia

“…CMV-associated neutropenia (absolute neutrophil count , 500 per mm 3 within 60 days after CMV reactivation) was also evaluated as a timedependent risk factor compared with patients who had CMV reactivation without subsequent neutropenia. 15 Peak acute GVHD (grades 0-1, 2, or 3-4) was graded according to standard definitions and analyzed in a timedependent manner. 16 Multivariable regression models were constructed in a stepwise manner.…”

Risk Factors for Ganciclovir-Induced Thrombocytopenia and Leukopenia

“…[8][9][10] Ganciclovir is principally excreted via the kidneys. Reduced renal function has been shown to prolong the halflife of ganciclovir.…”

“…Our results regarding a low WBC count as a risk factor for ganciclovirinduced leukopenia are consistent with the findings of previous studies. [8][9][10] Therefore, special attention should be paid to patients with low WBC counts (<6000 cells/mm 3 ) receiving a high ganciclovir dose (≥12 mg/kg/d).…”

“…9) Multivariate analysis revealed that the risk factors that correlated with ganciclovir-induced neutropenia at the time of treatment initiation included a high viral load; an absolute neutrophil count >3000 was a protective factor whereas serum creatinine >2 mg/dL was associated with more severe ganciclovir-induced neutropenia. 10) However, risk factors have not yet been determined for thrombocytopenia. Identifying the risk factors for hematotoxicity in ganciclovir recipients is useful for lowering the incidence of hematotoxicity and designing alternative strategies for highrisk patients.…”

The immune response to cytomegalovirus in allogeneic hematopoietic stem cell transplant recipients

“…Although these drugs are considered effective strategies for preventing CMV disease early after transplantation, they are associated with drug-related toxicities (myelosuppressive and immunosuppressive effects) [78] and they have been found to impair and delay the development of CMV-specific CTLs [50, 79]. Lilleri et al have shown that patients treated pre-emptively developed protection against CMV at a median time of 139 days compared to those that resolved CMV infection or did not have infection (median time 70 days) [52,80].…”