T Cell Blast Phase (T-BP) of Chronic Myelogenous Leuikemia (CML).
Authors: Quintás-Cardama Alfonso , Kantarjian Hagop , Cortes Jorge 
Published: October 2019

Abstract
Approximately 65% of patients with CMP BP exhibit a myeloid phenotype, 30% a lymphoid, and 5% of cases have and undifferentiated or mixed phenotype. Most cases of lymphoid BP are of B-cell origin. Only anecdotal cases of T-BP have been reported. To evaluate the incidence and outcome of T-BP, we reviewed 410 patients with CML who underwent transformation to BP at M.D. Anderson Cancer Center between January 1999 and April 2007. Six cases (4 female) were diagnosed as having T-BP (incidence 1.5%). Three patients presented initially with T-BP whereas 3 other cases evolved to T-BP from chronic phase. The median time from diagnosis to transformation was 8 months (range, 0–72). The median age was 50 years (range, 24–66), median white blood cell count at presentation 20.5x109/L (range, 2.6–104), hemoglobin 11.2 g/dL (range, 10.6–13.6), platelet count 139x109/L (range, 20–295), peripheral blood blasts 6% (range, 0–100), and bone marrow blasts 20% (range, 2–88). All but 1 presented with extramedullary disease: 2 with lymphadenopathy, 2 with lymphadenopathy and mediastinal mass (including 1 also with pericardial tamponade), and 1 with splenomegaly, lymphadenopathy, and granulocytic sarcoma of the breast. Four patients had an immunophenotype consistent with byphenotypic T-cell/myeloid leukemia and 2 exhibited an exclusive T-cell phenotype. Three patients expressed a b2a2 BCR-ABL1 transcript (p210), whereas 1 carried b2a2+b3a2 (p210), 1 e1a2 (p190), and 1 expressed an e13b2+e14a2 (p210) transcript at the time of transformation but this switched to e1a2 (p190) during the course of dasatinib therapy. Three patients had failed prior therapies, including interferon-alpha (n=3), high dose imatinib (n=1), and matched-unrelated stem cell transplantation (SCT; n=1) at the time of transformation. Initial therapy for T-BP consisted of chemotherapy: hyper-CVAD in 3 patients (in 1 case with imatinib 600 mg daily), VAD in 1 patient, and a combination of idarubicin and ara-C in 2 cases (1 of them with imatinib 600 mg daily and dexamethasone). Only the 2 patients treated with chemotherapy and imatinib responded, achieving a complete cytogenetic response (CCyR) that lasted 3 and 14 months, respectively. Subsequent therapy in the remainder 4 patients consisted of high-dose imatinib (600–800 mg daily; n=4), which was administered for a median of 27 months (range, 0.5–87), dasatinib (n=1), autologous SCT (n=1), allogeneic SCT (n=1), and other chemotherapeutic regimens (n=4). One of the patients treated with imatinib (600 mg daily) achieved a complete molecular response (CMR) that is ongoing after 87 months of therapy. The patient treated with dasatinib (70 mg twice daily) achieved a CCyR. This patient presented the previously unreported K271R ABL kinase domain mutation prior to the start of dasatinib therapy. At the time of dasatinib failure, DNA expansion of specific clones followed by DNA sequencing detected the dasatinib-resistant mutations V299L and F317L in 80% and 20% of clones, respectively. Currently, 4 patients are dead while 2 are still alive, 1 in CMR receiving imatinib and 1 in CCyR after allogeneic SCT. In conclusion, T-BP is a rare variety of BP CML, which frequently exhibits extramedullary disease and high resistance to conventional chemotherapeutic regimens. Long-term responses can be achieved with ABL kinase inhibitors and/or allogeneic SCT.