Pb2424: oral versus intravenous anti-cmv preemptive therapy in allogeneic stem cell transplant patients with cmv reactivation: experience from national center of bone marrow transplantation, tunisia.

Topic: 22. Stem cell transplantation - Clinical Background: Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality in allogeneic stem cell transplant recipients (ASCT). Since the introduction of prophylactic and preemptive therapies, the incidence of CMV disease has been significantly reduced. Aims: We compared the efficacy and safety of oral and intravenous anti-CMV preemptive therapy in ASCT recipients. Methods: Retrospective study including patients who received their first ASCT between January 2018 and June 2022 at the National Bone Marrow Transplant Center in Tunisia. Viral load was assessed weekly from day+15 to day+100. Monitoring of CMV infection was performed by real time PCR in EDTA plasma (Cobas AmpliPrep/ COBAS TaqMan), with 56 IU/mL as limit of detection and 137 UI/mL as limit of quantification. Reactivation was considered positive if qPCR is higher than 150 copies/mL. Response was defined by undetectable qPCR. Preemptive therapy is started if qPCR ≥150 cps/mL in patients on steroid or qPCR ≥150 cps/mL with increasing load in two consecutive tests and stopped in patients with undetectable qPCR in two consecutive tests. Anti-viral prophylaxis consisted of high dose Aciclovir given from day+1 until preemptive therapy. Results: Fifty-five patients were included developing 72 CMV reactivations. Patients’ median age was 29 years (range, 6-50). Underlying diseases were aplastic anemia (n=10), acute leukemia (n=38), myelodysplastic syndrome (n=3), chronic myeloid leukemia (n=2), lymphoma (n=1) and myelofibrosis (n=1). All patients are at high risk of CMV reactivation. Stem cell sources were bone marrow and peripheral blood stem cell in 32 (58%) and 23 (42%) patients, respectively. CMV reactivations are observed at a median of 43 days (range, 16-270) post ASCT with 58 (80%) of episodes occurring before day+100. The median viral load at diagnosis was 248 copies/mL (range, 150-4800). Thirty-six (65%) of patients had acute GVHD grade II-IV and were on steroid prior to CMV infection. The first-line preemptive treatment was oral in 51 (71%) of episodes (valganciclovir, n=40; leflunomide, n=11) and intravenous in 21 (29%) of episodes (foscarnet, n=16; ganciclovir, n= 5). All patients responded to anti-CMV therapy, 69% and 76% responded to first line therapy at a median time of 27 and 21 days with oral and intravenous therapies, respectively. Sixteen (31%) and 4 (19%) episodes needed second line therapy, in oral and intravenous group, respectively. Hematological toxicity was significantly higher in the oral group (61% vs 29%, p=0.013). Neutropenia and thrombocytopenia grad ≥2 were observed in 17(33%) vs 3 (14%) and 20 (39%) vs 2 (9%) in oral and intravenous groups, respectively. With the median follow up in the entire cohort of 18 months (range, 2-55), the 2-years overall survival (OS) and event-free survival (EFS) was 85% and 75%, respectively. Cumulative incidences of relapse and non-relapse mortality were 29% and 6%, respectively with no significant differences between oral and intravenous therapy. Summary/Conclusion: Our results showed that oral preemptive therapy for CMV reactivations after ASCT is as effective as intravenous formulations, but it is associated with more hematological toxicity. Keywords: Clinical outcome, Bone marrow transplant, CMV, Therapy