Abstract
Introduction
Chronic myeloid leukemia (CML) patients receive tyrosine kinase inhibitor (TKI) therapy
for long duration. In this study, we analyzed hematological changes and compared them
with hematological and cytogenetic response in 542 CML patients on TKI therapy with
a follow-up period of 84 months.
Objective
To study hematological changes in patients on TKI therapy.
Materials and Methods
CML patients on TKI therapy (imatinib, 400 mg) with a minimum follow-up of 6 months
were enrolled over a period of 8 years. Response was evaluated as per European Leukemia
Network guidelines.
Results
A total of 542 patients with CML were included in the study, with 507 (93.5%) being
in chronic phase disease, 21 (4%) in accelerated phase, and 14 (2.5%) in blast crisis.
The median age of patients was 38 years (range: 14–77 years), with male:female ratio = 1.4:1
(males = 317, 58.5% and females = 225, 41.5%).
At 3 months, 90% patients achieved complete hematological response (CHR). Normalization
of platelet count, total leucocyte count, marrow cellularity, and granulocytic hyperplasia
occurred by 3rd month of TKI therapy in majority of patients. Even though platelet
counts normalized by 3rd month, megakaryocytic hyperplasia in the marrow normalized
by 12th month of TKI therapy only.
Cytopenias were invariably seen in all follow-up time points, with anemia and thrombocytopenia
being most common. At 1 and 2 years, respectively, anemia was seen in 25 and 31% of
patients, leucopenia in 3 and 1% patients, and thrombocytopenia in 7 and 4% patients.
In addition, bicytopenia and pancytopenia, respectively, were seen in 14.5 and 3%
patients at 1 year and in 9 and 4% patients at 2 years.
Marrow hypocellularity and lymphoid nodules were seen in nearly 20% patients during
TKI therapy.
Marrow hypercellularity was seen in a higher proportion of patients who were in “not
in complete hematological response” (NCHR) than those who had achieved CHR (e.g.,
NCHR vs. CHR: at 6 months = 62 vs. 14%; at 12 months = 73 vs. 2%, at 18 months = 71
vs 9%, at 24 months = 57% vs. nil, at 36 months = 56 vs. 11%, at 42 months = 75 vs.
nil, and at 60 months = 50% vs. nil).
None of the peripheral blood and bone marrow parameters analyzed in our study were
consistently different between optimal and nonoptimal cytogenetic (warning and failure)
responders.
Conclusion
In this study, TKI-induced hematological changes were evaluated in CML patients.
The increased peripheral blood counts, marrow cellularity, and granulocytic hyperplasia
seen at diagnosis normalized in 90% patients by 3rd month of TKI therapy.
In patients who achieved CHR versus NCHR, a higher proportion of NCHR patients showed
bone marrow hypercellularity.
Between optimal and nonoptimal cytogenetic responders, none of the peripheral blood
and bone marrow parameter was found to be significantly different.
During follow-up, TKI-induced hematological changes observed included cytopenia, marrow
hypocellularity, and lymphoid nodules.
Keywords chronic myelogenous leukemia - tyrosine kinase inhibitors - hematological changes
- response
