Prevalence and Patterns of Cytomegalovirus (CMV) Reactivation In Adult Acute Lymphoblastic Leukemia Patients on Chemotherapy: Single Center Experience

Management of acute lymphoblastic leukemia (ALL) requires use of immunosuppressive agents like high-dose steroids and antimetabolites for prolonged periods which can predispose these patients for CMV reactivation and disease. As opposed to hematopoietic stem cell transplant there has been a real paucity of literature regarding clinical manifestations and management of CMV reactivation in ALL. In countries like India with a background of high CMV seropositivity (>90%), reactivation is a serious concern in ALL patients while receiving chemotherapy. Timely recognition and treatment can avoid the morbidity and mortality as well as help maintaining dose intensity which is the key to achieve cure in ALL patients.

This retrospective case series included adult ALL patients (>14 years) who were being treated with chemotherapy between July 2009 to July 2011 at a tertiary care centre and detected to have CMV viraemia (Real time quantitative PCR with Roche CMV DNA QuantKit). PCR was done in patients with possibility of CMV infection based on clinical suspicion. Case records were analyzed for demography, chemotherapy details, clinical features, laboratory parameters, viral load, antiviral therapy and response.

Among 203 adult ALL patients, 23 (males-18, females-5) were detected to have CMV viremia. Median age was 23 years (range, 16–44 years). Occurrence of CMV reactivation was most common during later part of induction or re-induction phase of therapy which includes high dose of steroids (14/23) followed by maintenance therapy with 6-mercaptopurine and methotrexate (5/23) and high dose cytarabine based treatment (4/23). Presenting features were: fever (19/23), fever alone (2/23) respiratory symptoms (9/23), anorexia (10/23), loose stools (8/23), abdominal pain (7/23) and splenomegaly (1/23). Abnormal laboratory parameters were: leukopenia or thrombocytopenia (14/23), deranged liver function tests (12/23). CT thorax was abnormal in 3 patients. Bacterial and fungal co-infection was seen in 5/23 patients. Median CMV viral load was 3.0 ×103 copy numbers (range, 708–1.38×10⁶). Eighteen of these patients were treated with intravenous gancyclovir for a period of 14 days. In remaining 5 patients abnormal clinical and lab parameters improved either with antibiotic therapy or spontaneously. Median time to fever defervescence was 4 days (range, 2–5 days). Blood counts recovered after median period of 5 days (range 3–9 days). Gancyclovir related neutropenia and transaminitis developed in 1 patient. CMV titre became undetectable after a period of 2–4 weeks.

Awareness of diverse clinical manifestations of CMV infection and high index of suspicion is important for timely diagnosis. Early diagnosis and treatment with gancyclovir reduces the morbidity, empirical use of other antimicrobials and avoids delays in administration of chemotherapy.

No relevant conflicts of interest to declare.