Impact of an Additional Chromosome on the Clinical Outcomes of Hematopoietic Stem Cell Transplantation in Philadelphia Chromosome–Positive Acute Myeloid Leukemia in Adults

Abstract

The incidence of Philadelphia chromosome positivity (Ph) in adults with acute myeloid leukemia (AML) is very low. Ph AML is considered to be high risk for failure to attain remission or for early relapse after standard chemotherapy. Because of the low incidence of the disease, it has been difficult to determine the best treatment, including the effects of tyrosine kinase inhibitors. We retrospectively analyzed 29 patients with Ph AML (median age, 45 years; range, 18 to 80) managed at our center between 2002 and 2016. Two patients were not treated at all, 3 received repeated low-dose cytarabine, and 24 were treated with 3 + 7 standard induction chemotherapy. All 27 treated patients also received interim imatinib 400 mg orally until the day of the next chemotherapy cycle began or as conditioning for allogeneic hematopoietic cell transplantation (HCT), which was performed in 17 patients. Of the 29 patients with Ph AML, 7 (24.1%) had additional inv(16), 3 of whom had therapy-related AML. In the 7 with inv(16), the median age was younger (31 versus 44 years, P = .083) and the complete remission (CR) rate was relatively higher (85.7% versus 54.5%, P = .214) than in those without inv(16). Among the 27 treated patients, 20 (74.1%) achieved CR after standard chemotherapy with interim imatinib and 2 (7.4%) achieved CR after low-dose cytarabine with interim imatinib. After a median follow-up of 65.5 months (range, 13.4 to 156.6), the 5-year overall survival (OS) among all 27 treated patients was 43.1%. For the 17 patients who underwent HCT the 5-year OS of 17 patients (10 in subgroup without inv(16) and 7 in subgroup with inv(16)) treated with allogeneic HCT was 69.3%. All 7 with inv(16) were still alive at the end of the study. In contrast, all patients not treated with HCT died within a median of 6.25 months (range, .2 to 18.2). Interim imatinib combined with chemotherapy yielded an acceptable remission rate in adult patients with Ph AML. Allogeneic HCT as a postremission therapy provided long-term disease control in two-thirds of those who underwent the transplant. We also demonstrated that inv(16) was related to a favorable outcome in Ph AML, including therapy-related AML.

Allogeneic hematopoietic cell transplantation for acute myeloid leukemia with BCR::ABL1 fusion

“…However, our study evaluated a small TA B L E 2 Univariable analyses of overall survival, relapse, and non-relapse mortality rates after 3 years in acute myeloid leukemia (AML) with BCR::ABL1 group. and 44.4% in the MRD-negative and MRD-positive groups, respectively, before allo-HCT [21]. In addition, MRD-negative status before allo-HCT was reported to be associated with improved GVHD-free relapse-free survival [8].…”

Imatinib with intensive chemotherapy in AML with t(9;22)(q34.1;q11.2)/BCR::ABL1. A DATAML registry study.

“…4,7,14 In a retrospective study from Korea on 29 patients with Ph + AML including 7 with additional inv(16), the CR rate was 81.5% following imatinib added to intensive chemotherapy. 17 Two recent studies from transplantation registries showed a better outcome in de novo patients who received an allogeneic stem cell transplantation. 18,19 In our study, the proportion of allografted patients (67%) may have contributed to the good outcome although the few non-transplanted patients did well too.…”

Flumatinib plus venetoclax as an effective therapy for Philadelphia chromosome‐positive acute myeloid leukemia: A case report

“…The five‐year OS rate was 69.3%. 10 Furthermore, Yılmaz summarized the ongoing trials recruiting CML‐MBP patients. The management of Ph + AML can refer to CML‐MBP because of the similar clinical characteristics.…”

“…Min reported that 10 patients were treated with traditional chemotherapy combined with imatinib, and the median OS time was 6.5 months. 10 To the best of our knowledge, the combination of flumatinib and venetoclax has not been reported in clinical application.…”

“…Another report showed that 17 patients were treated with imatinib combined with traditional chemotherapy and then bridged to HSCT. The five‐year OS rate was 69.3% 10 . Furthermore, Yılmaz summarized the ongoing trials recruiting CML‐MBP patients.…”