Long-Term Follow-up on Adult Patients with Philadelphia-Chromosome Positive Acute Myeloid Leukemia Who Were Treated with Interim Imatinib Followed By Allogeneic Hematopoietic Cell Transplantation

Background: The incidence of Philadelphia chromosome (Ph)-positivity in adult patients with acute myeloid leukemia (AML) is very low ranging from only 1 to 2%. Ph-positive AML has been included in the high-risk group presenting lower complete remission (CR) rate and early relapse after standard chemotherapy. However, the treatment outcome in a large cohort is not well elucidated due to its low incidence and variable treatment strategies including the use of tyrosine kinase inhibitors. We attempted to unveil clinical outcomes of Ph-positive AML in association with concomitant chromosomal abnormalities.

Methods: We retrospectively analyzed 29 patients with Ph-positive AML (median age: 43 years old [range; 18-80]) from 2002 to 2016. Except for the 2 patients who did not get treated at all, 3 were treated repeatedly with low-dose cytarabine and 24 were treated with 3+7 standard induction chemotherapy, followed with the application of interim imatinib 400mg until the starting day of next chemotherapy or conditioning for hematopoietic cell transplantation (HCT). Among them, 17 underwent allogeneic HCT from sibling donors (n=6), unrelated donors (n=7), and haploidentical donors (n=4).

Results: In total of 29 patients, 7 (24.1%) had additional inv(16). There were 3 therapy-related AML in Ph-positive AML subgroup with inv(16), while none were observed in the subgroup without inv(16). In the Ph-positive AML subgroup with inv(16), median age was younger (31 vs. 44 years old, p= 0.083) and CR rate was higher (85.7% vs. 54.5%, p= 0.214) than the opposite. Among 27 treated patients, 20 (74.1%) patients achieved CR after standard chemotherapy with interim imatinib, and 2 achieved CR after low-dose cytarabine with interim imatinib. In the entire patients group, after a median follow-up duration of 41.5 months (range: 0.2 to 156.6), 5-year overall survival (OS) was 40.1%. However, 5-year OS of 17 patients (11 in subgroup without inv(16) and 6 in subgroup with inv(16)) treated with allogeneic HCT was 69.3%, and 6 patients among them with Ph-positive AML with inv(16) were all alive after allogeneic HCT. In contrast, all 12 patients who were not treated with allogeneic HCT expired within a median of 6.3 months [range: 0.2-18].

Conclusion: This study revealed that interim imatinib combined chemotherapy produced an acceptable CR rate, and allogeneic HCT as a post-remission therapy was a feasible choice for providing a long-term disease control in adult patients with Ph-positive AML. We also identified that inv(16) was related to favorable outcomes regardless of the coexisting t(9;22) and to therapy-related AML.