Oral ganciclovir versus valganciclovir for cytomegalovirus prophylaxis in high-risk liver transplant recipients

Abstract: This retrospective review compared oral valganciclovir (VGCV) 450 mg daily for 6 months versus oral ganciclovir (GCV) 1000 mg 3 times daily for 3 months in preventing cytomegalovirus (CMV) disease in high-risk liver transplant recipients. We evaluated all CMV donor positive–recipient negative liver transplant recipients managed at University Health System in San Antonio, Texas from August 1996 to September 2006. CMV disease was confirmed by polymerase chain-reaction or antigenemia assay, and CMV invasive disease by tissue biopsy. Patient demographics, laboratory results, complications, and therapies were collected via retrospective chart review. Patients <18 years of age or those who died during transplant admission were excluded. Primary endpoints included incidence, onset, and severity of CMV disease up to 1 year post transplant. Data collection also included patient demographics, immunosuppression, CMV treatment regimens, and relevant lab results. A total of 64 patients (43 VGCV and 21 GCV) were identified. Four patients developed CMV disease: VGCV (3/43, 7%) versus GCV (1/21, 5%) ( P =1.0), with 1 VGCV patient experiencing tissue-invasive CMV. In all cases, onset of CMV disease occurred after prophylaxis was discontinued. Onset occurred at 24, 27, and 45 weeks post transplant in the VGCV group, and at 26 weeks in the 1 patient on GCV. Four patients received rabbit anti-thymocyte globulin (rATG) induction; 1 patient received rATG and developed CMV disease, with no statistical difference compared with the 3 remaining patients who received rATG but did not develop CMV disease ( P =0.09). No difference was found in incidence of CMV disease between patients who received GCV and those who received VGCV at our institution.     

Extended antigenemia surveillance and late cytomegalovirus infection after allogeneic BMT.

Late CMV disease remains a major concern in allogeneic BMT recipients. Few surveillance data are available on the occurrence of CMV infection and recurrences after day +100. We evaluated the occurrence of antigenemia (AG) recurrences until day +365 in 76 patients who received pre-emptive ganciclovir (GCV) therapy prompted by AG > or = 2 positive cells. Sixty-two episodes of AG recurrences were detected in 33 of the 52 patients who had positive AG. Survival analysis showed a 45.4% probability of AG recurrence on day +100, 64.8% on day +180 and 71.2% on day +365. The median time for AG recurrences was 113 (35 to 343) days. Thirty-five of the 62 episodes (56.4%) occurred after day +100. More than 70% of the patients responded to a 2-week course of GCV and no CMV disease was observed shortly after discontinuation of GCV. The Cox proportional model showed a significant effect of AG recurrences on patient's follow-up only when the patient developed chronic GVHD (P = 0.012). Extended surveillance favored early introduction of GCV and late CMV pneumonia occurred in only one of the 76 patients (1.3%). AG recurrences are frequent after day +100 and extended surveillance until day +365 is recommended for patients who develop chronic GvHD.     

Preemptive therapy with ganciclovir 5 mg/kg once daily for cytomegalovirus infection after unrelated cord blood transplantation

The efficacy and safety of preemptive therapy using ganciclovir (GCV) 5 mg/kg once daily for CMV infection after unrelated cord blood transplantation (CBT) were studied. The initial preemptive therapy with GCV 5 mg/kg once daily led to resolution of CMV antigenemia in 25 of 34 patients (74%). In the remaining 9 patients (26%), antigenemia resolved after dose-escalation of GCV or change to foscarnet therapy. Recurrence of antigenemia was seen in 18 patients (53%). A total of 12 patients received the second preemptive therapy with GCV 5 mg/kg once daily, which led to resolution of antigenemia in 11 of 12 patients (92%). The remaining 1 patient (8%) required change to foscarnet therapy. None of 34 patients developed CMV disease. Neutropenia with an absolute neutrophil number of less than 1 and 0.5 x 10(9) per liter after GCV therapy occurred in 12 (35%) and 1 (3%) patients, respectively, after the initial therapy, and in 2 (17%) and 0 (0%) patients, respectively, after the second therapy. No patients developed neutropenic fever or secondary graft failure after GCV therapy. There were no deaths directly attributable to GCV therapy. The present study suggests that antigenemia-based preemptive strategy using GCV 5 mg/kg once daily is feasible and effective for CBT recipients.     

High-grade cytomegalovirus antigenemia after hematopoietic stem cell transplantation

Clinical impact of high-grade (HG) cytomegalovirus (CMV) antigenemia after hematopoietic stem cell transplantation has not been clarified. Therefore, in order to investigate the risk factors and outcome for HG-CMV antigenemia, we retrospectively analyzed the records of 154 Japanese adult patients who underwent allogeneic hematopoietic stem cell transplantation for the first time from 1995 to 2002 at the University of Tokyo Hospital. Among 107 patients who developed positive CMV antigenemia at any level, 74 received risk-adapted preemptive therapy with ganciclovir (GCV), and 17 of these developed HG-antigenemia defined as > or = 50 positive cells per two slides. The use of systemic corticosteroids at > or = 0.5 mg/kg/day at the initiation of GCV was identified as an independent significant risk factor for HG-antigenemia. Seven of the 17 HG-antigenemia patients developed CMV disease, with a cumulative incidence of 49.5%, which was significantly higher than that in the low-grade antigenemia patients (4%, P<0.001). However, overall survival was almost equivalent in the two groups. In conclusion, the development of HG-antigenemia appeared to depend on the profound immune suppression of the recipient. Although CMV disease frequently developed in HG-antigenemia patients, antiviral therapy could prevent a fatal outcome.     

Cytomegalovirus ventriculoencephalitis in a reduced‐ intensity conditioning cord blood transplant recipient

T. Ando, N. Mitani, K. Yamashita, T. Takahashi, E. Ohama, H. Miyata, T. Yujiri, Y. Tanizawa. Cytomegalovirus ventriculoencephalitis in a reduced‐intensity conditioning cord blood transplant recipient.
Transpl Infect Dis 2010: 12: 441–445. All rights reserved Abstract: Cytomegalovirus (CMV) encephalitis most commonly occurs in patients with advanced human immunodeficiency virus infection and profound CD4 cell depletion and is rare in transplant recipients. We describe a patient with pathologically proven CMV ventriculoencephalitis that occurred after human herpesvirus‐6 limbic encephalitis, following reduced‐intensity conditioning cord blood transplantation (CBT). At approximately day 150 after CBT, the patient became acutely confused after steroid therapy for grade III acute graft‐versus‐host disease. Fluid‐attenuated inversion recovery magnetic resonance imaging of the brain revealed a communicating hydrocephalus with abnormal periventricular hyperintensity. Neuropathologic examination of the brain at autopsy revealed necrotizing CMV ventriculoencephalitis, limbic encephalitis, and multifocal necrotizing leukoencephalopathy. This case represents the first report of CMV encephalitis following CBT and serves to highlight the interrelationship between viruses in transplant recipients.     

Cytomegalovirus infection with perineal pain after living donor liver transplantation: report of four cases

We report on 4 adult cases of presumptive cytomegalovirus (CMV) disease with perineal pain after living donor liver transplantation. Patients presented with severe perineal pain without any other symptoms related to CMV infection, except pyrexia. All patients had an episode of acute cellular rejection (ACR) before the onset of perineal pain, and 1 patient needed OKT3 therapy. The severe perineal pain was not well controlled with medication, and 1 patient needed epidural anesthesia. In the first 3 patients, pp65 CMV antigenemia (pp65CMV-Ag) test results were positive and intravenous administration of ganciclovir (GCV) therapy was initiated. In the last patient, GCV therapy was preemptively administered before a positive pp65CMV-Ag test result was confirmed. After administration of GCV, the pain gradually disappeared and all patients had negative pp65CMV-Ag test results. In conclusion, unusual perineal pain can be a symptom related to CMV infection. CMV infection needs to be kept in mind when a liver transplant recipient has severe perineal pain, especially after receiving treatment for ACR.     

Cytomegalovirus antigenemia and outcome of patients treated with pre-emptive ganciclovir: retrospective analysis of 241 consecutive patients undergoing allogeneic hematopoietic stem cell transplantation

CMV disease remains a major infectious complication after allogeneic hematopoietic stem cell transplantation (HSCT). To investigate the relationship between CMV antigenemia, treatment with ganciclovir (GCV), and outcome, we retrospectively analyzed 241 consecutive patients at risk for CMV infection who underwent allogeneic HSCT. Antigenemia-guided pre-emptive strategy with GCV was used for all patients. CMV antigenemia developed in 169 patients (70.1%), and CMV disease in 18 patients (7.5%). Multivariate analysis showed that acute GVHD (grades II-IV) was the only risk factor for developing antigenemia, and acute GVHD and advanced age for CMV disease. GCV use, as well as acute GVHD and advanced age, significantly increased the risk for bacterial and fungal infection after engraftment. Those who developed CMV antigenemia had a poorer outcome than those who did not (log-rank, P=0.0269), although the development of CMV disease worsened the outcome with only borderline significance (log-rank, P=0.0526). In conclusion, detection of antigenemia proved to be a poor prognostic factor for HSCT patients, which may be attributed to a combination of factors, including CMV disease itself, the effect of treatment, and a host status that allows for reactivation of CMV. Optimal pre-emptive strategy needs to be determined.     

CMV pneumonia in allogeneic BMT recipients undergoing early treatment of pre-emptive ganciclovir therapy

The incidence, treatment and outcome of CMV interstitial pneumonia (CMV-IP) were reviewed in 139 consecutive allogeneic BMT patients undergoing extended CMV antigenemia surveillance and two different ganciclovir (GCV) strategies to control CMV infection. Nineteen cases of CMV-IP were reviewed, 16 of 63 patients (25.4%) who received early GCV treatment (ET) and three of 76 patients (3.9%) who received preemptive (PE) GCV therapy. In the ET group, the median time for occurrence of CMV-IP was 55 (range 36 to 311) days. Two patients had three episodes of CMV-IP recurrences after day +100. CMV-IP-related death occurred in two patients (15.4%). In the PE group, 41 patients received pre-emptive GCV therapy prompted by the appearance of positive antigenemia > or =2 cells. The median time for the occurrence of CMV-IP was 92 (range 48 to 197) days. Response to therapy was observed when GCV was introduced within 6 days of antigenemia positivity. The use of IVIg in association with GCV did not play a major role in response to therapy. The median time for occurrence of CMV-IP was delayed during PE strategy and the cost-effectiveness of CMV surveillance after day +100 should be investigated in this population.     

Cytomegalovirus ventriculoencephalitis in a bone marrow transplant recipient receiving antiviral maintenance: clinical and molecular evidence of drug resistance.

We describe a case of CMV ventriculoencephalitis in a severely immunocompromised bone marrow transplant recipient who was receiving combination therapy with ganciclovir and foscarnet for treatment of viremia and retinitis. Analysis of sequential viral isolates recovered from the patient's cerebrospinal fluid suggested that disease developed because of the presence of viral resistance and, possibly, low tissue penetration of antiviral agents.     

Risk factors for late cytomegalovirus infection after allogeneic stem cell transplantation using HLA-matched sibling donor: donor lymphocyte infusion and previous history of early CMV infection

An increased incidence of late cytomegalovirus (CMV) infection has been reported during the last decade since the introduction of ganciclovir (GCV) prophylaxis or GCV pre-emptive therapy. Given that a donor lymphocyte infusion (DLI) can induce more severe GVHD, this may predispose a patient to late CMV infection. In all, 64 patients (median age 36, M/F 38/26) underwent allogeneic stem cell transplantation (SCT) using a matched sibling donor with bone marrow (n=9) or peripheral blood stem cells (n=55). The overall incidence of CMV infection, early and late CMV infection was 46.9 (30/64), 42.2 (27/64), and 16.4% (9/55), respectively. Early CMV infection was treated with GCV pre-emptive therapy that produced a 92.6% success rate. Among the 20 patients who received 35 DLIs, late CMV infection developed in eight (42.1%) of 19 evaluable cases with a median onset at 127 days post transplant. Risk factors for late CMV infection in a logistic regression analysis included DLIs (P=0.001) and a previous history of CMV infection (P=0.006). In conclusion, late CMV infection was strongly associated with DLIs and a previous history of early CMV infection. Accordingly, extended surveillance of CMV antigenemia is recommended for patients receiving DLIs or who have a previous history of CMV infection.     

Clinical features of late cytomegalovirus infection after hematopoietic stem cell transplantation

Late cytomegalovirus (CMV) disease beyond day 100 after hematopoietic stem cell transplantation (HSCT) has become an increasing problem after the introduction of preemptive ganciclovir (GCV) administration. To clarify the risk factors and outcome for late CMV reactivation and disease, we retrospectively analyzed the records of 101 Japanese adult patients who underwent allogeneic HSCT between 1998 and 2005 at our hospital. Fifty-one developed late positive CMV antigenemia, with a cumulative incidence of 53%. Recipient CMV seropositivity, the use of alemtuzumab, chronic GVHD, and high-dose steroids were significantly associated with late positive antigenemia. Eight patients developed late CMV disease, with a cumulative incidence of 8%, including retinitis and gastrointestinal disease. None progressed to a fatal disease. The use of alemtuzumab was identified as an independent significant risk factor for late CMV disease, although it was not associated with increased non-relapse mortality. Among the 51 patients with late positive antigenemia, 28 had consistently less than three positive cells, 25 of whom showed negative conversion without antiviral agents. In conclusion, late CMV antigenemia appeared to develop frequently, especially in patients with profound immune suppression; however, a fatal outcome could be prevented by optimal preemptive therapy. Low-level antigenemia may not require antiviral treatments.     

Tetramer-based quantification of cytomegalovirus (CMV)-specific CD8+ T lymphocytes in T-cell-depleted stem cell grafts and after transplantation may identify patients at risk for progressive CMV infection

Recovery of cytomegalovirus (CMV)-specific T-cell-mediated immunity after allogeneic hematopoietic stem cell transplantation (SCT) is critical for protection against CMV disease. The study used fluorochrome-conjugated tetrameric complexes of HLA-A2 molecules loaded with the immunodominant NLVPMVATV (NLV) peptide derived from the CMV protein pp65 to quantify A2-NLV-specific CD8+ T cells in partially T-cell-depleted grafts administered to 27 HLA-A*0201+ patients and to monitor recovery of these T cells during the first 12 months after SCT. None of the 9 CMV-seronegative patients became infected with CMV, whereas 14 of 18 CMV-seropositive patients developed CMV antigenemia after SCT. CMV-seropositive recipients of grafts from CMV-seronegative donors required more preemptive treatment with ganciclovir (GCV) than those of grafts from CMV-seropositive donors (3 [1-6] versus 1 [0-3] courses, respectively; P =.009). The number of A2-NLV-specific CD8+ T cells in the grafts correlated inversely with the number of preemptive GCV courses administered (r = -0.61; P =.01). None of the 9 CMV-seronegative patients mounted a CMV-specific immune response as measured by monitoring A2-NLV-specific CD8+ T cells after SCT. Thirteen of 14 CMV-seropositive patients without CMV disease recovered these T cells. In spite of preemptive GCV treatment, CMV disease developed in 4 patients, who all failed to recover A2-NLV-specific CD8+ T cells after SCT (P =.002). Thus, enumeration of HLA-restricted, CMV-specific CD8+ T cells in the grafts and monitoring of these T cells after SCT may constitute a rapid and sensitive tool to identify SCT recipients at risk for developing CMV disease.     

Cytomegalovirus antigenemia and outcomes of patients undergoing allogeneic peripheral blood stem cell transplantation: effects of long-term high-dose acyclovir prophylaxis and preemptive ganciclovir treatment

Cytomegalovirus (CMV) disease is a frequent cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. In order to investigate the relationships between antigenemia, high-dose acyclovir (HDACV) prophylaxis, preemptive ganciclovir (GCV) therapy, and outcomes, we analyzed the records of 105 patients, including both pediatric and adult populations, who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) and who were at risk for CMV reactivation and disease (both recipient and donor seropositive). All received HDACV until neutrophil engraftment, but prophylaxis was continued till post-transplant day 180 only in pediatric patients in conjunction with weekly CMV pp65 antigenemia monitoring. Antigenemia-guided preemptive strategy with GCV was used for all patients. CMV antigenemia developed in 45 patients (42.9%) and CMV disease in 13 (12.4%). The frequencies for antigenemia were 31.3 and 63.2% in pediatric and adult groups (P = 0.002). All CMV diseases were in the adult group (P<0.001). Age at transplantation, underlying disease, long-term HDACV prophylaxis and acute graft versus host disease (aGVHD) were all found to be a significant risk factors for antigenemia. All of these factors other than aGVHD and conditioning regimen were also the significant risk factors for CMV disease. However, when we analyzed the pediatric and adult patients separately, dropping "long-term HDACV prophylaxis," none of these parameters were significant risk factors for CMV disease. In conclusion, we hypothesize that long-term HDACV prophylaxis in the GCV era results in a low incidence of CMV reactivation and disease in patients undergoing PBSCT.     

Cytomegalovirus infection: the point in 2001

The incidence of cytomegalovirus (CMV) disease, one of the most prevalent opportunistic infections in HIV‐infected persons in the early 1990s, has decreased by more than 80% since the introduction of highly active antiretroviral therapy (HAART). The rare cases of CMV disease still observed in Western countries occur mainly in profoundly immunosuppressed patients who have failed to respond to HAART. A new finding is the occasional occurrence of inflammatory retinitis in some patients on HAART with a history of healed retinitis. New tools for CMV detection have become available recently, including use of polymerase chain reaction (PCR) to detect CMV DNA from plasma. It has been possible to redefine, in the HAART period, patients at risk for CMV disease as those who have a low CD4 cell count as well as a blood marker of CMV blood dissemination (plasma CMV DNAaemia or high pp65 antigenaemia). Besides the classical therapeutic approach using ganciclovir (GCV), foscarnet and cidofovir, development of valganciclovir (VGCV), an orally administered prodrug of GCV, appears promising. There is evidence to suggest that it is as effective as intravenous GCV for the treatment of CMV retinitis, and it is currently being studied as a pre‐emptive therapy in patients at high risk for CMV disease. Finally, patients with inactive CMV retinitis receiving HAART and with stable immune reconstitution may be able to discontinue maintenance therapy provided a regular ophthalmological and virological surveillance is maintained.     

Increased transplant-related morbidity and mortality in CMV-seropositive patients despite highly effective prevention of CMV disease after allogeneic T-cell-depleted stem cell transplantation

We evaluated the efficacy, toxicity, and outcome of preemptive ganciclovir (GCV) therapy in 80 cytomegalovirus (CMV)-seropositive patients allografted between 1991 and 1996 and compared their outcome to 35 seronegative patients allografted during the same period. Both cohorts were comparable with respect to diagnosis and distribution of high- versus standard-risk patients. All patients received a stem cell graft from an HLA-identical sibling donor, and grafts were partially depleted of T cells in 109 patients. Patients were monitored for CMV antigenemia by leukocyte expression of the CMV-pp65 antigen. Fifty-two periods of CMV reactivation occurring in 30 patients were treated preemptively with GCV. A favorable response was observed in 48 of 50 periods, and only 2 patients developed CMV disease: 1 with esophagitis and 1 with pneumonia. Ten of 30 treated patients developed GCV-related neutropenia (less than 0.5 x 10(9)/L), which was associated with a high bilirubin at the start of GCV therapy. Overall survival at 5 years was 64% in the CMV-seronegative cohort and 40% in the CMV-seropositive cohort (P =.01). Increased treatment-related mortality accounted for inferior survival. CMV seropositivity proved an independent risk factor for developing acute graft-versus-host disease, and acute graft-versus-host disease predicted for higher treatment-related mortality and worse overall survival in a time-dependent analysis. We conclude that, although CMV disease can effectively be prevented by preemptive GCV therapy, CMV seropositivity remains a strong adverse risk factor for survival following partial T-cell-depleted allogeneic stem cell transplantation.     

Sequential treatment of cytomegalovirus infection or disease with a short course of intravenous ganciclovir followed by oral valganciclovir: efficacy,safety, and pharmacokinetics

A. Caldés, S. Gil‐Vernet, Y. Armendariz, H. Colom, L. Pou, J. Niubó, L. Lladó, J. Torras, N. Manito, G. Rufí, J.M. Grinyó. Sequential treatment of cytomegalovirus infection or disease with a short course of intravenous ganciclovir followed by oral valganciclovir: efficacy, safety, and pharmacokinetics
Transpl Infect Dis 2010: 12: 204–212. All rights reserved Abstract: Oral (p.o.) or intravenous (IV) ganciclovir (GCV) has been the first‐line agent for prevention and treatment of cytomegalovirus (CMV) infection and disease in solid organ transplantation (SOT). The introduction of p.o. valganciclovir, with higher bioavailability than p.o. GCV, has proven to be a suitable approach toward outpatient p.o. therapy for CMV infection/disease. The present single‐arm, exploratory pilot trial performed with 21 patients investigates the efficacy and safety of a short therapeutic course (21 days) based on an initial IV treatment with GCV (5 mg/kg twice daily, for 5 days) followed by p.o. valganciclovir (900 mg twice daily, for 16 days) for CMV infection/disease in SOT patients. In all cases, doses were adjusted for renal function. Moreover, the study allowed comparison of exposure to GCV after p.o. valganciclovir with respect to IV GCV in the same patients. Response to treatment was monitored until day 180. Viral load eradication was achieved in 66.7% of patients, on day 21. Although not statistically significant, a trend was seen toward increased persistence of viral load on day 21 for patients with donor positive/recipient negative CMV serostatus or receiving either anti‐rejection therapy or polyclonal anti‐thymocyte globulin. CMV clinical infection recurred in 14.3% of patients, with higher recurrence rates in patients with risk factors for persistence of viremia. Exposures to GCV after using IV GCV or p.o. valganciclovir showed comparable values (P=0.054). This short course, combining initial IV GCV and subsequent p.o. valganciclovir, may provide effective exposure and therapeutic response in the treatment of CMV infection in SOT patients with adequate drug exposure and with the additional potential benefit of shortening the length of hospital stay, which may result in cost reduction and improved patient comfort.     

Cytomegalovirus as a cause of very late interstitial pneumonia after bone marrow transplantation

Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality after allogeneic transplant. Interstitial pneumonia (IP) is the most common manifestation of CMV in BMT patients, with a 30-48% mortality rate despite adequate treatment. Most CMV infection occurs in the first 100 days. However, prolonged ganciclovir (GCV) prophylaxis has favored the occurrence of late CMV IP, probably by inhibition of the development of CMV-specific T cell lymphocyte responses. We report the case of a patient treated with an allogeneic BMT who received pre-emptive GCV until day +100 because of CMV-positive antigenemia. He developed a CMV IP on day +811 post BMT, which responded to treatment. We intend to alert clinicians that even at long-term (>1 year) post-BMT, CMV is a possible cause of IP in high-risk patients.     

Sequence analysis of UL54 and UL97 genes and evaluation of antiviral susceptibility of human cytomegalovirus isolates obtained from kidney allograft recipients before and after treatment

Abstract: The frequency of infections caused by drug-resistant cytomegalovirus (CMV) in solid-organ transplant recipients is not known. Only a few resistant strains have been described in transplant recipients. Antiviral susceptibility to ganciclovir (GCV) and foscarnet (PFA) of CMV isolates from 24 renal transplant patients with CMV viremia and CMV disease before and after therapy were investigated by a solid phase ELISA. The CMV DNA polymerase (UL54) and viral phosphotransferase (UL97) genes were also sequenced. Ten patients did not receive antiviral treatment; five and nine patients were treated with PFA and GCV, respectively. No appearance of drug-resistant viruses was observed in the present study, but one isolate showed a reduced sensitivity to PFA after treatment with GCV. This finding could not be explained by the presence or development of mutations that have been associated with drug resistance in UL54. We found no evidence that short-term treatment of CMV with PFA- or GCV-induced resistance.     

A comparison of prophylactic vs pre-emptive ganciclovir to prevent cytomegalovirus disease after T-depleted volunteer unrelated donor bone marrow transplantation

The prophylactic and pre-emptive use of ganciclovir (GCV) both reduce significantly the incidence of CMV disease after sibling BMT but it is unclear which of these strategies is best for volunteer unrelated donor (VUD) BMT patients. We reviewed 49 consecutive patients, who received a T-depleted VUD BMT (from March 1990 to March 1996) for the treatment of CML in chronic phase, and were CMV seropositive before transplant or had a CMV seropositive donor. Patients were conditioned with cyclophosphamide (120 mg/kg for 2 days) and total body irradiation (13.2-14.4 Gy). Prophylaxis for GVHD was cyclosporin A and methotrexate with ex vivo or in vivo T cell depletion. Twenty-seven patients received pre-emptive GCV if CMV infection was detected by short-term culture before day +120 post BMT. Twenty-two patients received prophylactic GCV from engraftment until day +120 post BMT. The probabilities of CMV infection and disease occurring by 1 year post-BMT were greater in the pre-emptive GCV group than in the prophylactic GCV group (73.8% and 64.0% vs 53.1% and 30.0%, respectively; P=0.04 and 0.07). The incidence of death from CMV disease was similar in both groups (3/12 (25%) vs 3/10 (30%), respectively) and there was no difference in 1 year survival (55.6% vs 54.2%, respectively). New strategies are urgently required for the prevention of CMV disease after T-depleted VUD BMT.     

Low-dose short-course intravenous ganciclovir as pre-emptive therapy for CMV viremia post allo-PBSC transplantation

In contrast to allogeneic bone marrow transplantation (allo-BMT), there is a paucity of data on cytomegalovirus (CMV) infection and preemptive therapy (PT) strategies following allogeneic peripheral blood stem cell (allo-PBSC) transplantation. We report here on the patterns of CMV infection in a cohort of 225 patients following sibling donor allo-PBSC transplantation. In an attempt to reduce neutropenia, we used intravenous low-dose short-course (LDSC) ganciclovir (GCV) 5 mg/kg once daily for 21 days as preemptive therapy. A total of 165 recipient-donor pairs were CMV seropositive. An initial episode of viremia (detected by shell vial/tube culture) occurred in 75/165 (45%) at a median of day +35 (17-445) post allo-PBSC. In all, 58 patients received PT with LDSC GCV. Among 58, 55 (94%) completed the 21-day course of PT. A second episode of viremia occurred in 19/58 (33%) at day+80 (50-174) and a third episode in 5/58 (9%) at day+134 (103-218). Among patients receiving LDSC GCV, 5/58(9%) developed disease (four pneumonia, one colitis) at day+211 (63-487). No patient on LDSC GCV exhibited a decline in their ANC below 500/microl and none required growth factors. LDSC GCV is extremely well tolerated and cost-effective as PT for CMV viremia following allo-PBSC transplantation.