Monitoring for cytomegalovirus and Epstein-Barr virus infection in chronic lymphocytic leukemia patients receiving i.v. fludarabine-cyclophosphamide combination and alemtuzumab as consolidation therapy

September 13, 2008

Published Ahead of Print on September 11, 2008, as doi:10.3324/haematol.13265.

Monitoring for cytomegalovirus and Epstein-Barr virus infection in chronic

lymphocytic leukemia patients receiving i.v. fludarabine-cyclophosphamide

combination and alemtuzumab as consolidation therapy

The combination of fludarabine and cyclophosphamide (FC) has become the standard

of care in chronic lymphocytic leukemia (CLL) patients. Due to the

wellrecognized F-related immunosuppression,1 a higher risk of opportunistic

infections could be expected by adding another immunosuppressive agent.

Randomized trials2-4 do not report a significantly higher rate of infections in

patients receiving FC combination versus F alone as firstline therapy, although

they do not focus on reactivation of latent viral infections. However, the

combination of FC and dexamethasone has been associated with Epstein- Barr virus

(EBV) infection in heavily pre-treated patients with lymphoproliferative

diseases5 and with EBV-related histological transformation of CLL.6

In addition, sporadic cases of cytomegalovirus (CMV) infection on F-based

therapy have been reported.7 The susceptibility to opportunistic infections

related to defective cell-mediatedimmunity is even higher with alemtuzumab

(AL),8 with particular concern for CMV infection. We report results from our

surveillance program for CMV and EBV infections in patients treated with FC and

AL as consolidation of response.

Sixty-seven CLL patients ² 65 years old ( median age 54 yrs) received FC

combination for progressive disease defined according to NCIWG criteria (as

first-line therapy in 53 and second-line in 14). All patients had signed an

informed consent before inclusion in treatment and monitoring programs. Median

time to treatment was 36 months (range: 1-79 mos) for first-line patients, while

median interval from previous therapy to FC administration was 15 months (range

5-32 mos).

FC consisted of F 25 mg/m2/d i.v. and C 250 mg/m2/d i.v. for three days every

four weeks for 4-6 courses. Corticosteroids were not routinely administered. All

patients received anti- Pneumocyctis Carinii (PC) prophylaxis and oral acyclovir

or valacyclovir.

According to institutional treatment protocol, 17 responding patients (CR and PR

according to NCIWG) with residual disease at 4-color flow cytometry underwent AL

consolidation 3-4 months after completion of FC, at the dose of 30-60mg/wk for

3-10 weeks (median: 6 wks). AL was administered i.v. in 5 patients and s.c. in

12. The median cumulative dose of AL was 360 mg(range: 90-540). In these

patients anti-infectious prophylaxis was maintained.

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