Efficacy of Artesunate for Treatment of Cytomegalovirus Reactivations in Allogeneic Haematopoietic Stem Cell Transplant Recipients Who Are Intolerant/Unsuitable for Ganciclovir Therapy

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.4506-4506
• Main Authors: Shenoy, Ramnath K, Gokarn, Anant, Toshniwal, Anup, Kalantri, Siddhesh Arun, Chichra, Akanksha, Punatar, Sachin, Bonda, Avinash, Nayak, Lingaraj, Mathew, Libin J, Bhat, Vivek, Biswas, Sanjay, Kelkar, Rohini, Khattry, Navin
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-128766

Background: Cytomegalovirus (CMV) reactivations are common post allogeneic stem cell transplant (ASCT) especially in developing countries like India, where most of the patients as well as donors are CMV seropositive. Ganciclovir is the drug of choice for preemptive therapy. However, myelosuppression which is a prominent side effect of ganciclovir, precludes its use in many post ASCT patients who are already cytopenic. Unavailability of second line agents like foscarnet and cidofovir in India leaves few therapeutic options for such patients. Artesunate is an inexpensive antimalarial agent and has been sporadically reported in literature to be effective in CMV reactivation in patients who are intolerant or resistant to ganciclovir. Here we report utility of artesunate in ASCT patients who could not be given or continued on ganciclovir due to cytopenias. This is the largest report of artesunate use in CMV reactivation to the best of our knowledge. Methods: All patients who underwent ASCT between April 2015 and October 2018 were included in this retrospective analysis. CMV IgG serology was tested at baseline for patients and donors. Conditioning regimen used was either myeloablative (CyTBI/BuCy) or reduced intensity with fludarabine in combination with either melphalan or treosulphan + 2 Gy TBI. Graft versus host disease (GVHD) prophylaxis used was calcineurin inhibitor (CNI), with methotrexate or mycofenolate mofetil (MMF) for matched sibling (MSD) and matched unrelated donor (MUD) transplants. MUD transplant recipients additionally received rabbit ATG (2.5-5 mg/kg). Post transplant cyclophosphamide (PTCy) with CNI and MMF was used for haploidentical transplants (HIT). CMV was monitored twice a week with quantitative polymerase chain reaction (QPCR) from start of conditioning till at least D+100 post ASCT or longer if patient was on immunosuppression. Those with a QPCR >500 copies/mL at 2 consecutive time points were started on preemptive therapy. Ganciclovir was preferred as first line agent, however in case of cytopenia, artesunate was used. In case cytopenia developed while patient was on ganciclovir, artesunate was started as second line. Artesunate dose was 2.4 mg/kg (upto 120 mg) twice daily. Artesunate was given till clearance of CMV (unquantifiable CMV DNA on QPCR at 2 consecutive time points) or intolerance. Artesunate failure was defined as > 1 log increase in CMV copies after 2 weeks of therapy or development of CMV end organ involvement while on t