title: Chronic myeloid leukemia (CML) with P190 BCR-ABL: analysis of characteristics, outcomes, and prognostic significance.
abstract: The most common BCR-ABL transcripts in chronic myeloid leukemia (CML) are e13a2(b2a2) and e14a2(b3a2). Other transcripts such as e1a2 are rare and their outcome with tyrosine kinase inhibitors (TKI) therapy is undefined. We analyzed 1292 CML patients and identified 14 with only e1a2 transcripts, 9 in chronic phase (CP), 1 in accelerated phase (AP), and 4 in blast phase (BP). Of the CP, 4 achieved complete hematologic response (CHR); 2, complete cytogenetic response (CCyR); 2, partial cytogenetic response (PCyR), and 1 did not respond to imatinib. Five patients progressed to myeloid BP (3), lymphoid BP (1), or AP (1). The AP patient received various TKIs sequentially and achieved only CHR. BP patients received hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, adriamycin, dexamethasone) plus imatinib/dasatinib or idarubicin plus cytarabine (Ara-C); 2 did not respond, 1 had CCyR, and 1 short-lasting complete molecular response (CMR). Overall, cytogenetic responses lasted 3 to 18 months; only 2 achieved major molecular response (MMR) on TKI. P190(BCR-ABL) CML is rare and is associated with an inferior outcome to therapy with TKI. These patients need to be identified as high-risk patients.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Dushyant
authors.initials: D
authors.lastname: Verma
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Rios
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001549:Benzamides; D001752:Blast Crisis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D000069439:Dasatinib; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D012189:Retrospective Studies; D015996:Survival Rate; D013844:Thiazoles / Q000008:administration & dosage; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D003561:Cytarabine; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D000068877:Imatinib Mesylate; D003520:Cyclophosphamide; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib; D015255:Idarubicin