To the editor:

Dasatinib is a novel oral multitargeted kinase inhibitor of Bcr-Abl and Src family widely used for the treatment of imatinib-resistant chronic myelogenous leukemia. Furthermore, preclinical studies by Shah et al1  indicate that dasatinib may also inhibit gastrointestinal stromal tumor (GIST)–related mutations that result in resistance to imatinib. We describe the case of a dasatinib-responsive chronic lymphocytic leukemia (CLL) in a 61-year-old woman with coexisting relapsed GIST.

The patient was diagnosed with CLL in August 2007 (Binet stage B with unmutated IgVH genes, del 17p13.1, and symptomatic disease). She was treated with fludarabine and rituximab and achieved a complete remission according to the International Workshop on Chronic Lymphocytic Leukemia criteria.2  In January 2008 she underwent emergency laparotomy due to gastrointestinal bleeding. A jejunal GIST (8 × 10 × 7 cm) was completely resected and the patient was initiated on imatinib mesylate 400 mg daily until March 2008, when she developed unresectable metastases on the left hepatic lobe. Sunitinib 50 mg/day was administered for 4 consecutive weeks. In April 2008, computed tomography (CT) and magnetic resonance imaging (MRI) scans showed further tumor hepatic progression and numerous 2-cm lymph nodes in the anterior and posterior cervical chains as well as the supraclavicular, inguinal, and axillary regions. Her white blood cell count was 70.1 × 109/L with 96% lymphocytes with ZAP-70 and high CD38 expression in more than 20% of B cells by flow cytometric analysis; β2 microglobulin was 4620 ng/mL (v.n. 1010-2150 ng/mL). Given the patient's poor performance status, no CLL therapy was initiated, she was prescribed oral dasatinib 140 mg daily after patient and institutional ethical board consensus.

After 3 months of dasatinib therapy the patient had normal complete blood counts. A new total body CT scan showed that all the lymph nodes had nearly completely resolved themselves. Bone marrow aspirate was free of CLL infiltration on cytologic and flow cytometric examinations, and hepatic MRI scans showed substantial tumor shrinkage. The most relevant aspect of our case is the powerful antineoplastic activity of dasatinib on CLL cells even if recent studies have revealed the in vitro capacity of dasatinib to induce apoptosis in CLL cells of patients with unmutated IgVH genes3  and the inhibition of antiapoptotic CD40 program in CLL cells with dysfunctional p53.4 

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Correspondence: Prof Vincenzo Pitini, Medical Oncology (Pad H 5°p), University of Messina, Via Consolare Valeria, 98125 Messina, Italy; e-mail: [email protected].

1
Shah
 
NP
Lee
 
FY
Luo
 
R
et al. 
Dasatinib (BMS-354825) inhibits KITD816V, and imatinib-resistant activating mutation that trigger neoplastic growth in most patients with systemic mastocytosis.
Blood
2006
, vol. 
108
 (pg. 
286
-
291
)
2
Hallek
 
M
Cheson
 
BD
Catovsky
 
D
et al. 
Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute–Working Group 1996 guidelines.
Blood
2008
, vol. 
111
 (pg. 
5446
-
5456
)
3
Veldurthy
 
A
Patz
 
M
Hagist
 
S
et al. 
The kinase inhibitor dasatinib induces apoptosis in chronic lymphocytic leukemia cells in vitro with preference for a subgroup of patients with unmutated IgVH genes.
Blood
2008
, vol. 
112
 (pg. 
1443
-
1452
)
4
Hallaert
 
DYH
Jaspers
 
A
van Noesel
 
CJ
et al. 
c-Abl kinase inhibitors overcome CD40-mediated drug resistance in CLL: implications for therapeutic targeting of chemoresistant niches.
Blood
2008
, vol. 
112
 (pg. 
5141
-
5149
)
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