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Journal of Clinical Oncology, Vol 24, No 4 (February 1), 2006: pp. e6-e7 © 2006 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.03.8083
First Case of an AIDS Patient With Systemic Mast Cell Disease Associated With Eosinophilia FIP1-Positive Treated With Imatinib Mesylate TherapyInstitute of Hematology, Istituto di Ricerca e Cura a Carattere Scientifico Policlinico San Matteo, University of Pavia, Italy
Department of Infectious Diseases, Istituto di Ricerca e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy
Department of Pathology, Istituto di Ricerca e Cura a Carattere Scientifico Policlinico San Matteo, University of Pavia, Italy
Department of Clinical and Biological Science, University of Turin, Hospital San Luigi Gonzaga-Orbassano, Turin, Italy
Institute of Hematology and Medical Oncology "L. e A. Seragnoli", Bologna, Italy
Department of Clinical and Biological Science, University of Turin, Hospital San Luigi Gonzaga-Orbassano, Turin, Italy
Institute of Hematology and Medical Oncology "L. e A. Seragnoli", Bologna, Italy To the Editor: Hypereosinophilia is a frequent finding in HIV-infected patients.1,2 It is often associated with dermatologic diseases, and less frequently associated with parasitic infections, allergies, or malignancies. The mechanism is probably linked to T-lymphocyte disorders,3,4 but the real cause in most patients remains unknown. Recent reports show that immunocompetent patients affected by hypereosinophilic syndrome (HES)5 and systemic mast cell disease associated with eosinophilia (SMCD-eos) FIPL1- positive6,7 who present a FIP1L1-PDGFR alpha fusion gene are responsive to imatinib mesylate (IM), a tyrosine kinase receptor inhibitor. No data are available in HIV patients regarding FIP1L1 positive HES and systemic mast-cells diseases. We report the first case of HIV-related systemic mast cell disease associated with SMCD-eos FIP1-positive responsive to IM therapy. A 32-year-old, HIV-1-infected patient (risk factor: Men who have sex with men, Centers for Disease Control 1993: C1) was admitted to Department of Infectious Diseases referring severe asthma, cough, leukocytosis (28 x 109/L), and hypereosinophilia (14 x 109/L) for 1 year. Recurrent episodes of papular eruption were reported. Hemoglobin level and platelet count were within normal range. The patient was on antiretroviral therapy with lamivudine (3TC), abacarvi (ABC), and stavudine (d4T), HIV RNA was persistently undetectable, and the CD4+ count was 614 cells/µL (12.5%). He had chronic liver disease HBV-related. The patient denied opioid, cocaine, and other illicit substances use. He denied any journey in foreign countries. The physical examination showed expiratory wheezes in both lungs. A small number of pruritic follicular papules were present on his abdomen and legs. A computed tomography scan of the chest showed a lymph node above diafragmatic region, probably of inflammatory origin. Infectious causes of hypereosinophilia were excluded. A bone marrow biopsy and bone marrow aspirate with a complete cytogenetic and molecular analysis had been done. The presence of FIP1L1-platelet derived growth factor receptor (PDGFR) alpha fusion transcript was searched. A reverse transcriptase polymerase chain reaction coupled with restriction fragment length polymorphism (PCR-RFLP) assay was performed to study c-kit (D816V) gene mutation. The serum triptase and IgE level had been assessed. The bone marrow biopsy and the PCR assays showed the presence of a systemic mast cell disease associated with SMCD-eos FIP1- positive. The patient, after a written consent, received imatinib mesylate therapy (an excalating dose from 100 mg/die to 400 mg/die) according to the protocol for HES disease ongoing in our institution.
The patient obtained a complete hematologic response (defined as a normal value of WBCs and a normal value of absolute eosinophilic count) and the resolution of symptoms after the first week of imatinib therapy (at 100 mg/die dose). He obtained a complete molecular remission, defined as PCR negativity of FIP1L1-PDGFR-alpha rearrangement, after 8 weeks of IM therapy. We observed also a reduction in triptase dosage that ranged normal value (11.3 microgr/L). The IM therapy has been well tolerated and no toxic effects have been reported. The patient is currently on therapy; at the last follow-up visit after 6 months he was still in complete hematologic and molecular response. This AIDS-patient with systemic mast cell disease associated with SMCD-eos FIPL1- positive shows hematologic, morphofunctional, and molecular features overlapping with those reported in immunocompetent populations.8,9 In immunocompetent patients, the FIP1L1-PDGFR Acknowledgment Associazione Italiana Ricerca contro il Cancero, Ministero Universita Ricerca Scientifica Tecnologica, Cofin 2003, and Fondazione del Monte di Bologna e Ravenna. We thank Patricia Zucchi, MD, and Angela Di Matteo, MD, for their support in the writing of this letter. REFERENCES 1. Colebunders R, Van Den Eynde C, Tolo A, et al: Eosinophilia in patients infected with human immunodeficiency virus. J Infect Dis 175:1283, 1997[Medline] 2. Skiest DJ, Keiser P: Clinical significance of eosinophilia in HIV-infected individuals. Am J Med 102:449-453, 1997[CrossRef][Medline] 3. Simon HU, Yousefi S, Dommann-Scherrer CC, et al: Expansion of cytokine-producing CD4-CD8-T cell associated with abnormal fas expression and hypereosinophilia. J Exp Med 183:1071-1082, 1996 4. Becker Y: The changes in the helper 1 (Th1) and T helper 2 (Th2) cytokine balance during HIV-1 infection are indicative of an allergic response to viral proteins that may be reversed by Th2 cytokine inhibitors and immune response modifiers: A review and hypothesis. Virus Genes 28:5-18, 2004[CrossRef][Medline] 5. Cools J, DeAngelo DJ, Gotlib J, et al: A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 348:1201-1214, 2003 6. Pardanani A, Ketterling RP, Brockman SR, et al: CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy. Blood 102:3093-3096, 2003 7. Klion AD, Noel P, Akin C, et al: Elevated serum tryptase levels identify a subset of patients with a myeloproliferative variant of idiopathic hypereosinophilic syndrome associated with tissue fibrosis, poor prognosis and imatinib responsiveness. Blood 101:4660-4666, 2003 8. Tefferi A, Lasho TL, Brockman SR, et al: FIP1L1-PDGFRA and c-kit D816V mutation-based clonality studies in systemic mast cell disease associated with eosinophilia. Haematologica 89:871-873, 2004 9. Pardanani A, Tefferi A: Imatinib therapy for hypereosinophilic syndrome and eosinophilia-associated myeloproliferative disorders. Leuk Res 28:S47-52, 2004 (suppl 1)[Medline] 10. Koon HB, Bubley GJ, Pantanowitz L, et al: Imitinib-induced regression of AIDS-related Kaposi's sarcoma. J Clin Oncol 23:982-989, 2005 11. Krause DS, Van Etten RA: Tyrosine kinases as targets for cancer therapy. N Engl J Med 353:172-187, 2005
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Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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rearrangement arises in approximately 30% of the HES. HIV infection could play a role in delaying the correct diagnosis because other causes of hypereosinophilia may be present in immunocompromised patients. HIV-1 is a retrovirus, and it has been recently reported that there is some evidence for a relationship between the virus and tyrosine kinase activity.
