Incidence of persistent/late chronic anemia in newly diagnosed patients with chronic myeloid leukemia responsive to imatinib

Abstract

In patients with chronic myeloid leukemia (CML) responsive to imatinib, it is still unknown whether the longlasting treatment could induce the appearance of a persistent/late chronic anemia. To highlight this issue, we revised 128 patients with CML (M/F 64/64, median age at diagnosis 56.9 years, interquartile range 43.0-69.3) treated at our Institution with 1st line imatinib for at least 36 months and in stable complete cytogenetic response. At the 36th month of imatinib, a chronic anemia (Hb < 12 g/dl for > 6 months) was present in 38/128 patients (29.6%): the anemia was moderate (Hb > 8 10 g/dl) in 12 patients (9.3%) and mild (Hb > 10 < 12 g/dl) in 26 patients (20.3%). All patients with persistent/late chronic anemia had a low reticulocyte count and 8/38 a condition of iron deficiency without clinical and instrumental signs of chronic blood loss. Four out of 38 patients (10.5%) needed red cell transfusions during the follow-up. At a landmark analysis from the 36th month of imatinib treatment, cumulative 4-year overall survival (OS) for patients with chronic anemia was 94.4% (CI 95% 83.8-100) compared to 93.5% (CI 95% 87.2-99.8) for patients without chronic anemia (P 5 0.617). In conclusion, the occurrence of a late chronic anemia during long-lasting treatment with imatinib has been observed in about 30% of our responsive patients: its occurrence does not seem to affect OS, but its real impact should be evaluated on a larger cohort of patients. Am. J.

ULK1 inhibition promotes oxidative stress–induced differentiation and sensitizes leukemic stem cells to targeted therapy

“…Hence, only 10 to 15% of patients with CML achieve sustained treatment-free remission (TFR) ( 24 ). In addition, the vast majority of the patients require life-long TKI treatment, associated with chronic side effects, including chronic anemia, which in turn has been linked to less favorable treatment responses ( 25 , 26 ). Furthermore, 20 to 30% of patients with CML develop resistance to TKIs or progress to lethal blast phase (BP) with very limited therapeutic options ( 24 ).…”

Erythropoietin treatment in chronic phase chronic myeloid leukemia patients treated with frontline imatinib who developed late anemia

“…In a previous study, the occurrence of late chronic anemia was reported in about 30% of patients treated frontline with imatinib at a single Center, with a higher incidence in elderly patients, in female and in patients with high Sokal risk at diagnosis [5]. This complication is often associated with patient discomfort and a reduced QoL, particularly in aged subjects due to their baseline frailty and the usual presence of concomitant severe diseases: in addition, a reduced event-free survival was recently reported in elderly CML patients with untreated late chronic anemia compared to elderly without chronic anemia [11].…”

“…Among other specific chronic toxicities related to the drug, late occurrence of moderate/severe anemia during long-lasting treatment with imatinib has been reported in a moderate rate of patients and seems to be more common in elderly [5]. It has been recently shown that bone marrow fibrosis is very common in CML patients at diagnosis (65% have grade 1 and 27% grade 2) [6], and that patients with two or more chromosomal abnormalities in Ph'-negative cells (including those that are related to clonal hematopoiesis or myelodysplasia) showed sometimes worse response to TKIs [7].…”

Autoimmune Hemolytic Anemia in Chronic Myeloid Leukemia

“…New onset severe anemia due to imatinib is very unusual [33]. It was hypothesized that the mechanism behind it is either due to the effect of imatinib on hematopoietic stem cells or through an interaction with iron absorption or metabolism, although iron replacement did not improve the outcome [34].…”