Philadelphia (Ph) Chromosome (BCR-ABL1 fusion) As a Recurrent Genetic Abnormality Among Therapy-Related Acute Leukemia

• Published in: Blood 2016-12, Vol.128 (22), p.3974-3974
• Main Authors: Aldoss, Ibrahim, Stiller, Tracey, Song, Joo Y., al Malki, Monzr M, Ali, Haris, Salhotra, Amandeep, Khaled, Samer K, Aribi, Ahmed, Gaytan, Popsie, Murata-Collins, Joyce L., Snyder, David S., Stein, Anthony S., O'Donnell, Margaret, Nakamura, Ryotaro, Palmer, Joycelynne M., Forman, Stephen J., Marcucci, Guido, Pullarkat, Vinod
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.3974.3974

Philadelphia (Ph) chromosome [t(9;22)] was reported as a rare recurrent balanced translocation among therapy-related acute leukemia (N=10, 2%) [Gene Chromosomes Cancer. 2002]. Here, we conducted a retrospective analysis of therapy-related acute leukemia with Ph chromosome (Ph+ t-AL) to better understand this entity. We included cases diagnosed at our institution between 2000 and 2016, excluding patients with CML in blastic phase. We defined Ph+ t-AL as acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) harboring Ph chromosome that developed after prior exposure to cytotoxic therapy (chemotherapy, radiation or both). Of the 330 patients with Ph+ AL, 28 cases (8.4%) met our definition of Ph+ t-AL, including 25 (89%) B-cell ALL, 1 case of T-cell ALL, and 2 cases of AML. The median age at diagnosis was 56 years (range: 29-79), and 64% (N=18) of them were female. Breast cancer was the most common prior malignancy [N=8, 29%], followed by lymphoma [N=6, 21%] and sarcoma [N=4, 14%]. Prior cytotoxic therapy consisted of chemotherapy (32%), radiotherapy (29%) and chemoradiation (39%). Among 20 patients who had prior chemotherapy, 70% had received alkylating agents (i.e., cyclophosphamide, temozolomide), 70% had received topoisomerase II inhibitors (i.e., etoposide, anthracycline), 40% had received antimetabolites, (i.e., methotrexate) and 50% both alkylators and topoisomeraseII inhibitor. The median interval between prior malignancy and Ph+ t-AL diagnosis was 6.8 years (range: 2.5-19.6) and was not different according to prior cytotoxic therapy modality [chemotherapy/radiotherapy vs. either chemotherapy or radiotherapy alone (P = 0.66)]. The median white blood cells count at presentation was 20 x103/µL (range: 1.4-230). Myelodysplastic syndrome preceded one case of AML. Among 22 patients with available standard cytogenetics, 7 (32%) had Ph chromosome as the sole abnormality, while 15 (68%) had an additional cytogenetic abnormality (ACA). Complex (≥ 3 abnormalities) or monosomal karyotypes were observed respectively in 12 and 9 cases. Chromosome 7 abnormality was observed in 6 (27%) cases, including 5 of them with monosomy 7. In 18 patients (ALL = 17; AML = 1) with available molecular study for BCR/ABL1, all were positive for p190 fusion transcript, including 3 patients who carried both p210 and p190 (ALL =2; AML =1). The median time from prior diagnosis to AL onset was not different according to cytogenetics (isolated Ph chromosome vs. complex/monoso