Bosutinib as a fourth-line therapy for a patient with T315I-positive lymphoid blastic phase chronic myeloid leukemia: A case report

Komeno,Yukiko; Uchida,Naoyuki; Satoh,Yumiko; Uryu,Hideki; Iwata,Yuko; Masuda,Akiko; Iihara,Kuniko; Yatomi,Yutaka; Taniguchi,Shuichi; Ryu,Tomiko

doi:10.3892/ol.2017.5989

Bosutinib as a fourth-line therapy for a patient with T315I-positive lymphoid blastic phase chronic myeloid leukemia: A case report

Authors:
- Yukiko Komeno
- Naoyuki Uchida
- Yumiko Satoh
- Hideki Uryu
- Yuko Iwata
- Akiko Masuda
- Kuniko Iihara
- Yutaka Yatomi
- Shuichi Taniguchi
- Tomiko Ryu
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Affiliations: Department of Hematology, Japan Community Healthcare Organization (JCHO) Tokyo Yamate Medical Center, Hyakunin‑cho, Shinjuku, Tokyo 169‑0073, Japan, Department of Hematology, Toranomon Hospital, Toranomon, Minato, Tokyo 105‑8470, Japan, Department of Clinical Laboratory, The University of Tokyo Hospital, Hongo, Bunkyo, Tokyo 113‑8655, Japan, Department of Pathology, JCHO Tokyo Yamate Medical Center, Hyakunin‑cho, Shinjuku, Tokyo 169‑0073, Japan
Published online on: April 5, 2017 https://doi.org/10.3892/ol.2017.5989
Pages: 4285-4289
Copyright: © Komeno et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

A 35-year-old male was diagnosed with chronic myeloid leukemia in the chronic phase and was prescribed 100 mg daily dasatinib. However, dasatinib was discontinued due to thrombocytopenia, and within six months, the disease progressed to the lymphoid blastic phase. Hyper‑cyclophosphamide, vincristine, adriamycin and dexamethasone chemotherapy combined with 140 mg dasatinib or 600 mg imatinib was prescribed. The two inhibitors were soon discontinued due to severe thrombocytopenia and jaundice, respectively. Myelosuppression persisted subsequent to the nadir. Bone marrow (BM) aspiration and biopsy revealed hypercellular marrow filled with blasts. Sequencing of the leukemia cells revealed overlapping peaks for the wild‑type sequence and the T315I mutant sequence. The patient was treated with 500 mg bosutinib (which was later reduced to 300 mg) for pretransplant cytoreduction. After 5 months, the patient's spleen exhibited a reduction in volume and the percentage of blasts in the BM decreased from 96.1 to 17.5%. The patient successfully underwent cord blood transplantation. The patient has been disease‑free for 5 months subsequent to transplantation. This case suggests that bosutinib may be effective for cytoreduction prior to stem cell transplantation, unless the leukemia cells consistently harbor the T315I mutation.

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1	Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J and Vardiman JW: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th Edition. International Agency for Research on Cancer; Lyon: pp. 130–139. 2008
2	Wilson MB, Schreiner SJ, Choi HJ, Kamens J and Smithgall TE: Selective pyrrolo-pyrimidine inhibitors reveal a necessary role for Src family kinases in Bcr-Abl signal transduction and oncogenesis. Oncogene. 21:8075–8088. 2002. View Article : Google Scholar : PubMed/NCBI
3	Lionberger JM, Wilson MB and Smithgall TE: Transformation of myeloid leukemia cells to cytokine independence by Bcr-Abl is suppressed by kinase-defective Hck. J Biol Chem. 275:18581–18585. 2000. View Article : Google Scholar : PubMed/NCBI
4	Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, Cervantes F, Clark RE, Cortes JE, Guilhot F, et al: European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 122:872–884. 2013. View Article : Google Scholar : PubMed/NCBI
5	O'Hare T, Zabriskie MS, Eiring AM and Deininger MW: Pushing the limits of targeted therapy in chronic myeloid leukaemia. Nat Rev Cancer. 12:513–526. 2012. View Article : Google Scholar : PubMed/NCBI
6	Eide CA and O'Hare T: Chronic myeloid leukemia: Advances in understanding disease biology and mechanisms of resistance to tyrosine kinase inhibitors. Curr Hematol Malig Rep. 10:158–166. 2015. View Article : Google Scholar : PubMed/NCBI
7	Azam M, Seeliger MA, Gray NS, Kuriyan J and Daley GQ: Activation of tyrosine kinases by mutation of the gatekeeper threonine. Nat Struct Mol Biol. 15:1109–1118. 2008. View Article : Google Scholar : PubMed/NCBI
8	Cortes JE, Kantarjian H, Shah NP, Bixby D, Mauro MJ, Flinn I, O'Hare T, Hu S, Narasimhan NI, Rivera VM, et al: Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 367:2075–2088. 2012. View Article : Google Scholar : PubMed/NCBI
9	Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre P, Paquette R, Chuah C, Nicolini FE, Apperley JF, Khoury HJ, Talpaz M, et al: A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 369:1783–1796. 2013. View Article : Google Scholar : PubMed/NCBI
10	Redaelli S, Piazza R, Rostagno R, Magistroni V, Perini P, Marega M, Gambacorti-Passerini C and Boschelli F: Activity of bosutinib, dasatinib, and nilotinib against 18 imatinib-resistant BCR/ABL mutants. J Clin Oncol. 27:469–471. 2009. View Article : Google Scholar : PubMed/NCBI
11	Redaelli S, Mologni L, Rostagno R, Piazza R, Magistroni V, Ceccon M, Viltadi M, Flynn D and Gambacorti-Passerini C: Three novel patient-derived BCR/ABL mutants show different sensitivity to second and third generation tyrosine kinase inhibitors. Am J Hematol. 87:E125–E128. 2012. View Article : Google Scholar : PubMed/NCBI
12	Barrett AJ and Ito S: The role of stem cell transplantation for chronic myelogenous leukemia in the 21st century. Blood. 125:3230–3235. 2015. View Article : Google Scholar : PubMed/NCBI
13	Saussele S and Silver RT: Management of chronic myeloid leukemia in blast crisis. Ann Hematol. 94 Suppl 2:S159–S165. 2015. View Article : Google Scholar : PubMed/NCBI
14	Rix LL Remsing, Rix U, Colinge J, Hantschel O, Bennett KL, Stranzl T, Müller A, Baumgartner C, Valent P, Augustin M, et al: Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells. Leukemia. 23:477–485. 2009. View Article : Google Scholar : PubMed/NCBI
15	Cortes JE, Kantarjian HM, Brummendorf TH, Kim DW, Turkina AG, Shen ZX, Pasquini R, Khoury HJ, Arkin S, Volkert A, et al: Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib. Blood. 118:4567–4576. 2011. View Article : Google Scholar : PubMed/NCBI
16	Gambacorti-Passerini C, Brümmendorf TH, Kim DW, Turkina AG, Masszi T, Assouline S, Durrant S, Kantarjian HM, Khoury HJ, Zaritskey A, et al: Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance: Minimum 24-month follow-up. Am J Hematol. 89:732–742. 2014. View Article : Google Scholar : PubMed/NCBI
17	Khoury HJ, Cortes JE, Kantarjian HM, Gambacorti-Passerini C, Baccarani M, Kim DW, Zaritskey A, Countouriotis A, Besson N, Leip E, et al: Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. Blood. 119:3403–3412. 2012. View Article : Google Scholar : PubMed/NCBI
18	Kantarjian HM, Cortes JE, Kim DW, Khoury HJ, Brümmendorf TH, Porkka K, Martinelli G, Durrant S, Leip E, Kelly V, et al: Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors. Blood. 123:1309–1318. 2014. View Article : Google Scholar : PubMed/NCBI
19	Cortes JE, Kim DW, Kantarjian HM, Brümmendorf TH, Dyagil I, Griskevicius L, Malhotra H, Powell C, Gogat K, Countouriotis AM and Gambacorti-Passerini C: Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: Results from the BELA trial. J Clin Oncol. 30:3486–3492. 2012. View Article : Google Scholar : PubMed/NCBI
20	Brümmendorf TH, Cortes JE, de Souza CA, Guilhot F, Duvillié L, Pavlov D, Gogat K, Countouriotis AM and Gambacorti-Passerini C: Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukaemia: Results from the 24-month follow-up of the BELA trial. Br J Haematol. 168:69–81. 2015. View Article : Google Scholar : PubMed/NCBI
21	Nakaseko C, Takahashi N, Ishizawa K, Kobayashi Y, Ohashi K, Nakagawa Y, Yamamoto K, Miyamura K, Taniwaki M, Okada M, et al: A phase 1/2 study of bosutinib in Japanese adults with Philadelphia chromosome-positive chronic myeloid leukemia. Int J Hematol. 101:154–164. 2015. View Article : Google Scholar : PubMed/NCBI
22	Strati P, Kantarjian H, Thomas D, O'Brien S, Konoplev S, Jorgensen JL, Luthra R, Abruzzo L, Jabbour E, Quintas-Cardama A, et al: HCVAD plus imatinib or dasatinib in lymphoid blastic phase chronic myeloid leukemia. Cancer. 120:373–380. 2014. View Article : Google Scholar : PubMed/NCBI
23	Marin D, Bazeos A, Mahon FX, Eliasson L, Milojkovic D, Bua M, Apperley JF, Szydlo R, Desai R, Kozlowski K, et al: Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib. J Clin Oncol. 28:2381–2388. 2010. View Article : Google Scholar : PubMed/NCBI
24	Cortes J, Lipton JH, Rea D, Digumarti R, Chuah C, Nanda N, Benichou AC, Craig AR, Michallet M, Nicolini FE, et al: Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315I mutation. Blood. 120:2573–2580. 2012. View Article : Google Scholar : PubMed/NCBI
25	Pemovska T, Johnson E, Kontro M, Repasky GA, Chen J, Wells P, Cronin CN, McTigue M, Kallioniemi O, Porkka K, et al: Axitinib effectively inhibits BCR-ABL1(T315I) with a distinct binding conformation. Nature. 519:102–105. 2015. View Article : Google Scholar : PubMed/NCBI
26	Donato NJ, Wu JY, Stapley J, Gallick G, Lin H, Arlinghaus R and Talpaz M: BCR-ABL independence and LYN kinase overexpression in chronic myelogenous leukemia cells selected for resistance to STI571. Blood. 101:690–698. 2003. View Article : Google Scholar : PubMed/NCBI
27	Ptasznik A, Nakata Y, Kalota A, Emerson SG and Gewirtz AM: Short interfering RNA (siRNA) targeting the Lyn kinase induces apoptosis in primary, and drug-resistant, BCR-ABL1(+) leukemia cells. Nat Med. 10:1187–1189. 2004. View Article : Google Scholar : PubMed/NCBI
28	Hu Y, Liu Y, Pelletier S, Buchdunger E, Warmuth M, Fabbro D, Hallek M, Van Etten RA and Li S: Requirement of Src kinases Lyn, Hck and Fgr for BCR-ABL1-induced B-lymphoblastic leukemia but not chronic myeloid leukemia. Nat Genet. 36:453–461. 2004. View Article : Google Scholar : PubMed/NCBI
29	Hu Y, Swerdlow S, Duffy TM, Weinmann R, Lee FY and Li S: Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph+ leukemia in mice. Proc Natl Acad Sci USA. 103:16870–16875. 2006. View Article : Google Scholar : PubMed/NCBI
30	Larson RA: Is there a best TKI for chronic phase CML? Blood. 126:2370–2375. 2015. View Article : Google Scholar : PubMed/NCBI