A 22-year-old male with Ph-positive chronic myelogenous leukemia (CML) was started on treatment with imatinib. After 12 months of therapy, he achieved a complete cytogenetic response (CCyR). Although the CCyR persisted in his bone marrow, he developed an isolated CML blast crisis in his central nervous system (CNS) after 29 months of therapy. He underwent allogeneic hematopoietic stem cell transplantation (HSCT) following combination therapy with dasatinib, intrathecal chemotherapy and cranial irradiation. Subsequently, 168 days after allogeneic HSCT, he was started on dasatinib maintenance therapy to prevent a CNS relapse. Thirty-eight months after allogeneic HSCT, he has sustained a complete molecular response in both bone marrow and CNS. We believe dasatinib has the potential to prevent CNS relapse if used for maintenance therapy after allogeneic HSCT.

1.
Bornhauser M, Jenke A, Freiberg-Richter J, Radke J, Schuler US, Mohr B, Ehninger G, Schleyer E: CNS blast crisis of chronic myelogenous leukemia in a patient with a major cytogenetic response in bone marrow associated with low levels of imatinib mesylate and its N-desmethylated metabolite in cerebral spinal fluid. Ann Hematol 2004;83:401-402.
2.
Johnson NA, Fetni R, Caplan SN: Isolated central nervous system relapse in patients with chronic myeloid leukemia on imatinib mesylate. Leuk Lymphoma 2005;46:629-630.
3.
Matsuda M, Morita Y, Shimada T, Miyatake J, Hirase C, Tanaka M, Tatsumi Y, Maeda Y, Kanamaru A: Extramedullary blast crisis derived from 2 different clones in the central nervous system and neck during complete cytogenetic remission of chronic myelogenous leukemia treated with imatinib mesylate. Int J Hematol 2005;81:307-309.
4.
Barlow A, Robertson M, Doig A, Stewart W, Drummond MW: Isolated central nervous system lymphoid blast crisis in chronic myeloid leukaemia in major molecular remission. Br J Haematol 2008;142:327.
5.
Petzer AL, Gunsilius E, Hayes M, Stockhammer G, Duba HC, Schneller F, Grunewald K, Poewe W, Gastl G: Low concentrations of STI571 in the cerebrospinal fluid: a case report. Br J Haematol 2002;117:623-625.
6.
Bujassoum S, Rifkind J, Lipton JH: Isolated central nervous system relapse in lymphoid blast crisis chronic myeloid leukemia and acute lymphoblastic leukemia in patients on imatinib therapy. Leuk Lymphoma 2004;45:401-403.
7.
Leis JF, Stepan DE, Curtin PT, Ford JM, Peng B, Schubach S, Druker BJ, Maziarz RT: Central nervous system failure in patients with chronic myelogenous leukemia lymphoid blast crisis and Philadelphia chromosome positive acute lymphoblastic leukemia treated with imatinib (STI-571). Leuk Lymphoma 2004;45:695-698.
8.
Altintas A, Cil T, Kilinc I, Kaplan MA, Ayyildiz O: Central nervous system blastic crisis in chronic myeloid leukemia on imatinib mesylate therapy: a case report. J Neurooncol 2007;84:103-105.
9.
Aichberger KJ, Herndlhofer S, Agis H, Sperr WR, Esterbauer H, Rabitsch W, Knobl P, Haas OA, Thalhammer R, Schwarzinger I, Sillaber C, Jager U, Valent P: Liposomal cytarabine for treatment of myeloid central nervous system relapse in chronic myeloid leukaemia occurring during imatinib therapy. Eur J Clin Invest 2007;37:808-813.
10.
Alimena G, Breccia M, Latagliata R, Grammatico S, Matturro A, Capria S, De Propris MS, Diverio D, Meloni G: Dasatinib in the management of lymphoid blast crisis of Philadelphia-positive chronic myeloid leukemia with multiple extra-medullary and intracranial localizations. Leuk Res 2009;33:e134-136.
11.
Abdelhalim A, Barcos M, Block AW, Sait SNJ, Starostik P, Wetzler M, Wang ES: Remission of Philadelphia chromosome-positive central nervous system leukemia after dasatinib therapy. Leuk Lymphoma 2007;48:1053-1056.
12.
Gutiérrez-Aguirre H, García-Rodríguez F, Cantú-Rodríguez O, González-Llano O, Jaime-Pérez J, Gómez-Almaguer D: Effectiveness of dasatinib in relapsed CNS, Ph+ ALL that is refractory to radiochemotherapy plus imatinib: a case report. Clin Adv Hematol Oncol 2011;9:875-878.
13.
Porkka K, Koskenvesa P, Lundan T, Rimpilaeinen J, Mustjoki S, Smykla R, Wild R, Luo R, Arnan M, Brethon B, Eccersley L, Hjorth-Hansen H, Hoeglund M, Klamova H, Knutsen H, Parikh S, Raffoux E, Gruber F, Brito-Babapulle F, Dombret H, Duarte RF, Elonen E, Paquette R, Zwaan CM, Lee FYF: Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia. Blood 2008;112:1005-1012.
14.
Takayama N, Sato N, O'Brien SG, Ikeda Y, Okamoto S: Imatinib mesylate has limited activity against the central nervous system involvement of Philadelphia chromosome-positive acute lymphoblastic leukaemia due to poor penetration into cerebrospinal fluid. Br J Haematol 2002;119:106-108.
15.
Sumi M, Tauchi T, Sashida G, Shoji N, Gotoh A, Itoh Y, Miyazawa K, Kimura Y, Ohyashiki JH, Ohyashiki K: Clinical usefulness of transcription-mediated amplification and hybridization protection assay in imatinib-treated chronic myelogenous leukemia patients. Clin Lab Haematol 2005;27:416-417.
16.
Marin D, Milojkovic D, Olavarria E, Khorashad JS, de Lavallade H, Reid AG, Foroni L, Rezvani K, Bua M, Dazzi F, Pavlu J, Klammer M, Kaeda JS, Goldman JM, Apperley JF: European LeukemiaNet criteria for failure or suboptimal response reliably identify patients with CML in early chronic phase treated with imatinib whose eventual outcome is poor. Blood 2008;112:4437-4444.
17.
Cortes J: Central nervous system involvement in adult acute lymphocytic leukemia. Hematol Oncol Clin North Am 2001;15:145-162.
18.
Isobe Y, Sugimoto K, Masuda A, Hamano Y, Oshimi K: Central nervous system is a sanctuary site for chronic myelogenous leukaemia treated with imatinib mesylate. Int Med J 2009;39:560-560.
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