Hindawi Publishing Corporation Case Reports in Hematology Volume 2011, Article ID 263725, 4 pages doi:10.1155/2011/263725 Case Report Allografting for Bosutinib, Imatinib, Nilotinib, Dasatinib, and Interferon Resistant Chronic Myeloid Leukemia without ABL Kinase Mutation B. Uz,1 O. Bektas,1 E. Eliacık,1 H. Goker,1 Y. Erbilgin,2 M. Sayitoglu,2 N. Sayinalp,1 S. Aksu,1 Y. Buyukasik,1 O. Ozcebe,1 and I. C. Haznedaroglu1 1 Department of Hematology, Hacettepe University Medical School, 06100 Ankara, Turkey 2 Department of Genetics, Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey Correspondence should be addressed to B. Uz, burakuz78@gmail.com Received 2 August 2011; Accepted 18 September 2011 Academic Editors: D. J. Allsup, S. Aref, E. Arellano-Rodrigo, and M.-C. Kyrtsonis Copyright © 2011 B. Uz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The current treatment of chronic phase chronic myeloid leukemia (CML) consists of oral tyrosine kinase inhibitors (TKIs). However, high-risk CML may present with an aggressive course which may result in blastic crisis or a “diﬃcult-to-manage” state with available treatments. The aim of this paper is to report a patient with complicated CML resistant to treatment and progressed despite the administration of bosutinib, imatinib mesylate, nilotinib, dasatinib, interferon alpha 2a, cytotoxic chemotherapy, and allogeneic hematopoietic stem cell transplantation. The striking point of this case story is that no Abl kinase domain mutation against TKIs has been detected during this very complicated disease course of CML. Meanwhile, challenging cases will always be present despite the hope and progress in CML in the TKI era. 1. Introduction CML is a clonal myeloproliferative disorder with bone mar- row myeloid cell expansion [1] and peripheral leukocytosis [2]. CML is generated with the reciprocal balanced translo- cation of genetic material between the long arms of chromo- somes 9 and 22 (t(9; 22)) [3]. The resulting gene product is BCR-ABL, and the deregulated tyrosine kinase activity of this oncoprotein is responsible for leukemogenesis. The short- ened chromosome 22 can be visualized by standard cyto- genetic techniques and was termed as Philadelphia Chro- mosome (t(9; 22)(q34; q11)). Fibrosis and biological abnor- malities of cytokine network may be evident during the disease course [4–7]. The clinical course of CML consists of three stages; chronic phase (CP), accelerated phase (AP), and blastic crisis (BP). The historical treatment agenda for CML includes cytotoxic chemotherapy, a-interferon (aIFN), allogeneic hematopoietic stem cell transplantation (allo-HSCT) [8], imatinib mesylate, and second-generation tyrosine kinase inhibitors (dasatinib and nilotinib) [1, 3, 8– 10]. With the advent of TKIs to treatment of CML, the natural history of the disease changed dramatically in the last ten years and extremely longer survivals are expected for the CML patients. The annual resistance rate to imatinib has been about 4% in the ﬁrst 4 years [11]. Therefore, alternative drugs are needed for the patients with imatinib-resistant CML or intol- erant to imatinib and second-generation TKIs. Bosutinib (SKI-606) is a dual Src/Abl TKI with potent preclinical BCR- ABL inhibitory activity in imatinib-resistant CML cell lines [12, 13]. Unlike other second-generation TKIs, bosutinib exhibits a safer toxicity proﬁle [12, 14]. The progression of CML may result in blastic crisis, which can be “diﬃcult-to-manage” with only combination chemotherapy and dasatinib [1, 15, 16]. The aim of this paper is to report a complicated CML patient which is resis- tant to treatment and progressed despite the administration of bosutinib, imatinib mesylate, nilotinib, dasatinib, aIFN, cytotoxic chemotherapy, and ﬁnally allo-HSCT (Table 1).