Rare Blast Phase (BP) Phenotypes of Chronic Myeloid Leukemia (CML)
Authors: Ghanem Hady , Kantarjian Hagop M. , Jabbour Elias J. , Cortes Jorge E. , Quintás-Cardama Alfonso 
Published: October 2019

Abstract
Abstract 4434
Approximately 65% of patients (pts) with CML BP exhibit a myeloid phenotype, 30% a lymphoid, and 5% of cases exhibit other phenotypes. The vast majority of lymphoid BP cases are of B-cell origin. Other phenotypes of CML BP are very infrequent and poorly characterized. To evaluate the incidence and outcome of unusual BP phenotypes, we reviewed 1143 pts with CML BP diagnosed and treated at M.D. Anderson Cancer Center between November 1973 and February 2012. Thirteen (1%) pts had non-B-cell/non-myeloid CML BP: 8 pts with T-cell differentiation (T-BP) (including 4 pts with biphenotypic T-cell/myeloid), 2 pts with basophilic (B-BP), and 3 pts with megakaryoblastic phenotype (M-BP) (Table 1). Five pts presented initially in BP, whereas 7 other cases evolved to BP from chronic phase (CP) and 1 pt from accelerated phase (AP). The median time from diagnosis to transformation was 15.2 months (mos) (range, 0–103). The median age was 50 years (range, 21–74), median WBC count at presentation 40.2×109/L (range, 2.6–236), hemoglobin 10.7 g/dL (range, 7.1–13.6), platelet count 171×109/L (range, 17–383), peripheral blood blasts 9% (range, 0–100), and bone marrow blasts 20% (range, 0–88). Nine (69%) pts developed extramedullary disease: 4 with lymphadenopathy (LAN), 1 with LAN and mediastinal mass, 1 with pericardial tamponade and mediastinal mass, 1 with central nervous system disease, 1 with facial muscle involvement and 1 with splenomegaly, LAN, and granulocytic sarcoma of the breast. Four pts expressed a b2a2 BCR-ABL1 transcript (p210), whereas 3 pts expressed b3a2 (p210), 3 expressed e1a2 (p190), 2 expressed b2a2+b3a2 (p210), and 1 expressed an e13b2+e14a2 (p210) transcript at transformation that switched to e1a2 (p190) during dasatinib (DAS) therapy. Median number of treatments received prior to BP was 2 (range, 1 to 12): 6 pts received interferon (IFN), 5 imatinib (IMA), 3 allogenetic stem cell transplant (ASCT), 3 Ara-C, 1 DAS and 1 hyper-CVAD (HCVAD). Initial therapy consisted of HCVAD (n=4, combined with IMA 600 mg/d in 1 pt and with DAS 70 mg/d in 1 pt), VAD (n=1), nilotinib 400 mg twice daily (n=1), DAS 50 mg twice daily (n=1), troxicitabine (n=1), gemtuzumab (n=1), idarubicin (IDA) and ara-C (n=3; 1 with IMA 600 mg/d and 1 with IMA 400 mg/d), and ara-C (n=1). Four pts responded: 3 with chemotherapy and IMA, achieving a complete cytogenetic response (CCyR) that lasted 22, 26 and 79 mos, respectively; 1 pt achieved a major molecular response (MMR) after receiving gemtuzumab followed by haploidenticial SCT, lasting for 24 mos. Median duration of response was 25 mos (range, 22–79). Subsequent therapy consisted of a tyrosine kinase inhibitor (TKI) in 6 out of 13 pts. Two pts treated with DAS at 140 mg/d and 70 mg twice daily achieved a CCyR and 1 pt achieved MMR on DAS 140 mg/d. Of the 7 pts treated with DAS, 2 had BCR-ABL1 mutations: 1 carried K271R, Y232C/K271R, and M343Y/K271R prior to DAS, then acquired V299L and F317I on DAS, while the other pt carried Y264S prior to DAS, then developed V299L on DAS. After a median follow up of 4.2 years (range, 0.2 to 14.4), 4/13 (30%) pts are alive: 1 in MMR on IMA 400 mg/d, 1 in complete molecular response (CMR) on DAS 100 mg/d, 1 not in remission (non-compliance to DAS 140 mg/d), and 1 currently receiving HCVAD and DAS. By phenotype, 5/8 pts with T-BP responded to TKIs: 1 CMR, 1 CCyR, 1 MMR, 1 partial cytogenetic response (PCyR) and 1 hematologic response (HR); 2/3 pts with M-BP responded: 1 CCyR and 1 CHR. None of the B-BP pts responded. In conclusion, non-B-cell/non-myeloid CML BP occurs in 1% of pts with CML, frequently infiltrates extramedullary sites, and exhibits high resistance to conventional chemotherapy. Long-term responses can be achieved with ABL1 TKIs (preferably in combination with chemotherapy), which can be used as a bridge to allogeneic SCT.
Table 1. Summary of pts clinical and molecular characteristics, response to treatments and outcomes by BP Phenotype

Disclosures:
No relevant conflicts of interest to declare.