Valganciclovir as CMV reactivation prophylaxis in patients receiving alemtuzumab for marrow failure syndromes

Abstract

Dear Editor, Elter et al. recently published in your journal a comprehensive report on the management of infectious risk during treatment by alemtuzumab [1]. Their paper referred exclusively to chronic lymphocytic leukemia patients. Marrow failure syndromes are a group of hematological disorders sharing an immune pathophysiology and may benefit from intense immunosuppressive treatment including antilymphocyte antibodies, such as heterologous antithymocyte globulin (ATG), and cyclosporine A (CyA) [2]. However, given its potent lympholytic effect, alemtuzumab may also be appropriate for patients requiring intense immunosuppression. We recently developed an alemtuzumab-based immunosuppressive treatment for patients suffering from aplastic anemia or singlelineage bone marrow failure disorders [3], with the aim of inducing a more potent and prolonged immunosuppression and allowing retreatment in case of relapse (retreatment is difficult to attempt when using heterologous antisera). We wish to add our own experience in this particular setting, with specific attention to prophylaxis of cytomegalovirus (CMV) reactivation, which remains a major problem limiting a broader use of alemtuzumab. A cohort of consecutive patients suffering from either severe aplastic anemia (SAA), pure red cell aplasia (PRCA) or pure white cell aplasia (PWCA) were enrolled in a prospective phase II clinical trial with alemtuzumabbased immunosuppression (EUDRACT number 2008001151-22). The drug was administered subcutaneously as a single course, at 3–10–30–30–(30) mg doses on four (five) consecutive days (non-SAA patients received the 4day dose), followed by low-dose (1 mg/kg) cyclosporine A starting from day 7; retreatment by alemtuzumab (as complete courses or single shoots) was allowed in case of relapse. Anti-CMV prophylaxis was administered per protocol to all seropositive patients starting day 7, using oral valganciclovir at the dose of 450 mg, bidaily. Initially, anti-CMV prophylaxis was scheduled until CD4+ T cells reached 250 per microliter; however, since after assessment of immune reconstitution performed in the first patients CD4+count sometimes remained below the planned cutoff for many months, the protocol was amended to withdraw valganciclovir at CD4+ levels above 100 per microliter, and in any case 3 months after treatment. All patients received also anti-Pneumocystisjiroveci prophylaxis by low-dose oral trimethoprimsulfamethoxazole (bidaily three times per week), as well as standard antibacterial and antifungal prophylaxis in case of severe (<500 per microliter) neutropenia. Twentythree consecutive patients were enrolled in the study (ten SAA, ten PRCA, and three PWCA) and received a total of 45 courses of alemtuzumab; additional courses were given in five SAA, four PRCA, and one PWCA patients who relapsed after responding to the initial treatment. All patients received prophylactic valganciclovir because they were CMV IgG seropositive. All patients showed complete lymphoablation within 2–3 days, which lasted several months. CMV antigenemia was monitored weekly by polymerase chain reaction (PCR), to be ready for preemptive therapy; CMV reactivation was defined as a positive PCR (detection limit 1,000 copies per milliliter) in two consecutive samples. After a cumulative follow-up Ann Hematol (2009) 88:1261–1262 DOI 10.1007/s00277-009-0749-z