442. Infectious Complications in Patients Treated with Dasatinib
Session: Poster Session: Hospital-acquired and Transplant Infections
Friday, October 30, 2009: 12:00 AM
Room: Poster Hall A
Background: Tyrosine kinase inhibitors (TKI) interrupt T-cell receptor mediated T-cell proliferation, activation and selective inhibition of memory CTL responses without affecting primary T or B cell responses. Few cases of Cytomegalovirus, Varicella-zoster virus and Parvovirus B19 infections have been reported during dasatinib therapy. However, the true spectrum of infections in patients receiving this TKI remains unknown.
Methods: This retrospective analysis from April 2005 to December 2007 included 69 patients who received dasatinib alone or in combination with other antineoplastic regimens.
Results: Fifty-seven episodes of infection (table 1) were identified in 35 patients (51%) including 29 episodes during neutropenia. Duration of chemotherapy was 143±199 days in patients who developed infection [Group 1(G1)] vs. 155±335 days in whom no infection occurred [Group 2(G2)]. Patient in G1 were older (52±15 vs 48±15; p=0.05) and more females (22 vs 13; p=0.05). There were no significant differences in co-morbid conditions and prior hematopoietic stem cell transplantation in both groups. Patients in G1 had more Ph+ acute lymphocytic leukemia (51% vs 17%; P=0.005) and had received high-dose steroids (51% vs 26%; P=0.05). Although more patients in G1 received dasatinib with another antineoplastic agent but the data was not significant (57% vs 35%; P=0.09). Dasatinib was discontinued due to adverse events in 26% of patients in G1 vs. 9% in G2. Overall mortality was higher in G1 (57%) compared with 29% in G2 (P=0.18). In only two patients infection was considered as the cause of death.
Conclusions: Infections were common in patients treated with dasatinib and were significantly more frequently seen in patients with ALL and those who received steroids.
TABLE 1.
TYPE OF INFECTION EPISODES57 (100%)
CLINICALLY DOCUMENTED INFECTIONS32 (56)
Clinical Pneumonia13 (23)
Possible Fungal Pneumonia5 (9)
Soft Tissue Infection*3 (5)
Gastroenteritis/Mucositis**4 (7)
Febrile Neutropenia3 (5)
Urinary Tract Infection2 (4)
Upper Respiratory Tract Infection2 (4)
MICROBIOLOGICALLY DOCUMENTED INFECTIONS
Gram-positive Bacteria13 (23)
C. diff Colitis6 (11)
CoNS CRBSI1 (2)
Enterococcus CRBSI2 (4)
MRSA CRBSI2 (4)
MRSA Soft Tissue Infection***1 (2)
Streptococcal CRBSI1 (2)
Gram-negative Bacteria7 (12)
E.Coli CRBSI1 (2)
Klebsiella spp. Enterocolitis2 (4)
Pseudomonas spp. CRBSI2 (4)
Pseudomonas spp. Perirectal Abscess1 (2)
Pseudomonas spp / Klebsiella spp. Urinary Tract Infection1 (2)
Viral4 (7)
RSA Pneumonia2 (4)
Oral-labial HSV1 (2)
CMV Colitis1 (2)
Fungal
Candida Krusei CRBSI1 (2)

*2 Cellulitis, 1 Perirectal abscess
** Neutropenic Enterocolitis
***External Otitis

CRBSI: Catheter Related Blood Stream Infection

Saud Ahmed, MD1, Fadi Al Akhrass, MD1, Vijayashri Rallapalli, MD1, Gilhen Rodriguez, MD, Amar Safdar, MD3 and  S. I. Ahmed, None..
G. H. Rodriguez, None..
F. Al Akhrass, None..
V. Rallapalli, None..
A. Safdar, None., (1)University of Texas, Houston / M.D. Anderson Center, Houston, TX, (2)MD Anderson Cancer Center, Houston, TX