Malignant Gastrointestinal Stromal Tumor of the Small Intestine Complicated with Pulmonary Tuberculosis during Treatment with Imatinib Mesylate

Abstract

We describe a patient who had a metastatic gastrointestinal stromal tumor (GIST) after previous failed extensive therapy, including multiple surgeries and hepatic artery embolization. Within a few months of starting administration of imatinib mesylate, the patient exhibited a clinical response with grade 3 neutropenia, when pulmonary tuberculosis developed. A c-kit mutation in exon 11 was detected only in metastatic liver specimens. It is unclear whether or not pulmonary tuberculosis may be induced by imatinib mesylate treatment, but caution is warranted in immunocompromised GIST patients. This is the first report of tuberculosis associated with neutropenia during imatinib mesylate treatment.

Tuberculosis complicating imatinib treatment for chronic myeloid leukaemia

“…The fact that all three patients were treated with imatinib raises the question of whether this drug increases susceptibility to TB. To date, only one case has been reported where neutropenia and TB complicated treatment with imatinib for gastrointestinal stromal tumour [6]. However, there are several reports suggesting that imatinib might impair the immune system, leading to a variety of infections, including varicella zoster and hepatitis B [7][8][9].…”

Tuberculous and Non-Tuberculous Granulomatous Lymphadenitis in Patients Receiving ImatinibMesylate (Glivec) for Metastatic Gastrointestinal Stromal Tumor

“…The drug is usually well tolerated. Infectious and inflammatory complications have not been frequently reported except for rare cases of interstitial lung disease [11], and reactivation of hepatitis B virus [12] and herpes zoster [13]. However, the actual relationship of some of these diseases to IM therapy has not been proven and some might represent a mere coincidence or a complication of the underlying hematological disorder (CML).…”

“…To date, a total of 9 patients have been reported to have developed tuberculosis under or after IM treatmen; most of them had CML (n = 8) [7, 8, 9, 10] and only 1 patient had GIST [6]. The clinicopathological features of these patients are summarized in table 1.…”

“…It has been proposed that imatinib affects T-cell receptor signal transduction, thereby affecting the cellular immunity and the host susceptibility to reactivation of tuberculosis [8]. Furthermore, there are a few reports on reactivation of viral diseases (hepatitis B, varicella zoster) under IM treatment, suggesting that IM might impair the cellular immune system leading to infection reactivation [12, 13]. However, other researchers reported an intact control of primary viral infections in spite of the impaired cytotoxic T-cell response induced by IM [15].…”

“…Mycobacterial infection is not associated with IM treatment, since only 9 patients have been reported who developed tuberculosis during or after IM treatment for chronic myelogenous leukemia (CML, n = 8) and GIST (n = 1) [6, 7, 8, 9, 10]. In this report, we present our experience with 2 patients who developed lymphadenopathy under IM treatment for metastatic GIST.…”