Original ArticlesLow Incidence Rate of Opportunistic and Viral Infections During Imatinib Treatment in Chronic Myeloid Leukemia Patients in Early and Late Chronic Phase
Massimo Breccia, Corrado Girmenia, Roberto Latagliata, Giuseppina Loglisci, Michelina Santopietro, Vincenzo Federico, Luigi Petrucci, Alessandra Serrao, Adriano Salaroli and Giuliana Alimena
1Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome, Italy.
Correspondence to: Massimo Breccia, MD. Dept. of Human Biotechnologies and Hematology, University Sapienza, Via Benevento 6, 00161 Rome, Italy. Tel. +39 06 857951, Fax +39 06 44241984. e-mail: email@example.com
Published: May 16, 2011
Received: April 18, 2011
Accepted: May 9, 2011
Mediterr J Hematol Infect Dis 2011, 3: e2011021, DOI 10.4084/MJHID.2011.021
This article is available from: http://www.mjhid.org/article/view/8428
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Background: Imatinib has become first line therapy in chronic myeloid leukemia patients. Little is known about the infective consequences during the treatment with this drug in large series of chronic phase patients.
Material and methods: From January 2001 to September 2006 we treated with imatinib 250 patients in first line (early CP) or after interferon failure (late CP), out of clinical trials and recorded all the bacterial and viral infections occurred.
Results: We recorded a similar incidence of bacterial and viral infections both in first line and late CP patients (respectively, 16% and 13%) during 3.5 years of follow-up. Analysis of presenting features predisposing to infections revealed differences only in late CP patients, with elevated percentage of high Sokal risk patients and a more longer median time from diagnosis to start of imatinib.
Conclusions: Opportunistic infections and reactivation of Herpes Zoster are observed during imatinib therapy at very low incidence.
Targeted inhibition of BCR-ABL with imatinib mesylate has become the standard therapy for patients with chronic myeloid leukaemia (CML) where it induces a complete cytogenetic response in more than 80% of newly diagnosed patients. A recent 8-year follow-up of IRIS study showed an overall survival (OS) of 85% and event-free survival (EFS) of 81%. Several years after the introduction of imatinib in clinical practice no significant major incidence of infections was reported. However, different evidences that imatinib can impair several cellular functions involved in the immune response have been observed, in particular in cell-mediated immunity.[3-5] We refer here on the incidence of infectious episodes observed during imatinib treatment in our large series of early and late chronic phase CML patients.
Table 1. Characteristics of patients and of infective episodes.
In the series
of 100 CP patients who received imatinib as first line
therapy, with a median follow-up of 3.5 years, we recorded 17
infectious episodes in 16 patients (incidence 16%). They accounted for
0.02 infectious episodes per 1000 patient days. All the infective
episodes occurred at a median time of 13 weeks (range 9-26) from the
onset of imatinib treatment. No episode was associated to deep
neutropenia (absolute neutrophyl count < 500/cmm). Median
gammaglobulin dosage was 0.82 g/dl (range 0.7-2), with only 1 patient
presented with a slightly inferior dosage. Herpes zoster and pneumonia
represented the two more frequently observed infections occurring in 7%
and 4% of patients, respectively. In all patients who developed Herpes
zoster a reduction of lymphocyte count (median lymphocytes count 0.6 x
109/l, range 0.2-1.1, compared to 0.9 x 109/l of patients who did not
developed viral infections) was evidenced at the time of viral
infection (median time of development 11 weeks), in the absence of
induced leukopenia and serum Ig level (0.9 g/dl). One out of the 4
subjects who developed pneumonia presented two additional episodes of
fever with radiological evidence of pulmonary infiltrate diagnosed as
tuberculosis. This second infection occurred soon after underlying
hematologic disease progression to accelerated phase.
Table 2. Comparison of patients who developed infections and patients who did not