Approximately two thirds of patients with CML BP exhibit a myeloid phenotype, and one third a lymphoid phenotype. In rare occasions, patients exhibit a mixed phenotype. Biphenotypic blast phase (Bi-BP) are rare and generally portend a very unfavorable prognosis. To evaluate the incidence and outcome of Bi-BP, we reviewed 1143 patients with CML BP diagnosed and treated at M.D. Anderson Cancer Center between November 1973 and February 2012. Only Bi-BP with both myeloid and B-lymphoid differentiation was included in this analysis. Twelve (1%) patients had Bi-BP. At presentation, the median age was 62 years (range, 29–81), WBC count 12×109/L (range, 6–214), hemoglobin 10 g/dL (range, 7–14), platelet count 94×109/L (range, 41–531), peripheral blood blasts 30% (range, 0–83), and bone marrow blasts 66% (range, 0–91). Five (42%) patients had extramedullary disease involving the central nervous system (CNS; n=2), lymph nodes (n=2), and CNS, orbit and skin without bone marrow disease (n=1) (Table 1). The median time from diagnosis to transformation was 15 months (range, 0–58). Six patients expressed a b2a2 BCR-ABL1 transcript (p210), whereas 4 patients expressed b3a2 (p210) and in 2 patients such information was not available. Three patients presented initially with BP and 9 evolved to BP from chronic phase (CP). Out those 9, 6 had failed imatinib, 3 interferon, 1 dasatinib, 1 ara-C and 1 hydroxyurea prior to transformation. Median number of treatments prior to BP was 1 (range, 1 to 3). Initial therapy for Bi-BP was hyper-CVAD in 2 patients, one of them achieving complete cytogenetic remission (CCyR); hyper-CVAD and dasatinib in 1 patient, achieving a marrow CR; idarubicin, ara-C, and imatinib followed by allogeneic stem cell transplantation in 1 patient, with no response; idarubicin, ara-C, vincristine and dexamethasone in 1 patient, achieving CCyR; troxicitabine in 1 patient, achieving CCyR; combination of decitabine and imatinib in 1 patient, achieving CCyR; azacitidine and valproic acid in 1 patient with no response; and imatinib with homoharrangtonine in 1 patient with no response. Overall, 5 patients responded, to a variety of chemotherapy regimens that included a tyrosine kinase inhibitor in 2 of them. Median duration of response was 7 months (range, 1–55). One patient died during induction chemotherapy. A total of 5 patients received subsequent therapy: TKI in 3 patients and allogeneic SCT in 2 patients. Three patients developed BCR-ABL1 gene mutations: Y253H (n=1), T315I (n=1), and F317L & V299L (n=1). At last follow up, 10 patients were dead (5 due to progression) and 2 were lost to follow up. In conclusion, Bi-BP is a rare entity, which frequently exhibits an aggressive course, extramedullary disease, and high resistance to conventional chemotherapy. Therapy requires the use of chemotherapy in combination with a TKI. Nevertheless, responses are short-lived and patients should be offered allogeneic SCT or novel investigational approaches.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.