Risk factors for outcome after allogeneic stem cell transplantation in patients with advanced phase CML

Abstract

Allogeneic hematopoietic stem-cell transplantation (HSCT) remains the only curative option for patients with advanced chronic myeloid leukemia (CML). However, outcome is dismal and of short follow-up. The objective of the study was to determine long-term outcome and risk factors in patients with a history of CML Blast Crisis (BC; n = 96) or accelerated phase (n = 51) transplanted between 1990 and 2018. At transplant, patients had a median age of 39 (range 7–76) years and were in ≥CP2 (n = 70), in AP (n = 40) or in BC (n = 37) with a diagnosis-HSCT interval of median 1.9 (range 0.3–24.4) years. Overall survival (OS) amounted 34% (95% CI 22–46) and progression-free survival (PFS) 26% (95% CI 16-36) at 15 years. Adverse risk factors for OS and PFS were low CD34+ count in the graft, donor age (>36 years) and BC. Cumulative incidence of Non-Relapse Mortality (NRM) was 28% (95% CI 18–38) and of relapse (RI) 43% (95% CI 33–53) at 15 years. PB-HSCT and HSCT after 2008 were favorable prognostic factors for NRM, while family donor and patient age >39 years were independently associated with higher RI. HSCT resulted in long-term OS in patients with advanced CML. OS was improved in non-BC patients, with donors ≤36 years and with higher CD34+ dose in the graft.

Treatment of blast phase chronic myeloid leukaemia: A rare and challenging entity

“…Other adverse prognostic factors include a high EBMT risk score (≥5), 63,65 reduced performance status, 64 low CD34 + cell count in graft, and donor age. 62 Radujkovic et al 64 also reported transplant prior to 2010 was associated with increased non-relapse mortality.…”

“…Peripheral-blood stem cells are preferred over bone marrow as the stem cell source, with lower non-relapse mortality. 62 Patients who achieve a CP2 or better have a superior outcome compared to those transplanted in frank BP. 63,64 Khoury et al and Radujkovic et al reported a three-year OS of 35%-40% and 51.1%, respectively, for BP-CML in remission compared to 8%-11% and 23.3%, respectively, for patients transplanted with active BP-CML, likely due to a higher rate of relapse in the active BP-CML cohorts.…”

“…However, limited data are available reporting on transplant outcomes in the TKI era; available studies are presented in Table 5. Peripheral‐blood stem cells are preferred over bone marrow as the stem cell source, with lower non‐relapse mortality 62 . Patients who achieve a CP2 or better have a superior outcome compared to those transplanted in frank BP 63,64 .…”

“…Khoury et al and Radujkovic et al reported a three‐year OS of 35%–40% and 51.1%, respectively, for BP‐CML in remission compared to 8%–11% and 23.3%, respectively, for patients transplanted with active BP‐CML, likely due to a higher rate of relapse in the active BP‐CML cohorts. Other adverse prognostic factors include a high EBMT risk score (≥5), 63,65 reduced performance status, 64 low CD34 + cell count in graft, and donor age 62 . Radujkovic et al 64 also reported transplant prior to 2010 was associated with increased non‐relapse mortality.…”

Outcomes of Allogeneic Stem Cell Transplant in Chronic Myeloid Leukemia - Blast Phase: A Single-center Experience from South India

“…17 In the most recent report by Neiderweiser et al, donor age >36 years, BP at AlloSCT, and low CD34þ count were shown to be risk factors for inferior OS. 18 ►Table 2 summarizes the contemporary data on transplant outcomes in CML advanced phase. For patients with CML-BP, the data show definitively that AlloSCT represents the best chance of long-term remission or cure.…”