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Modeling Chemotherapy Resistant Leukemia In Vitro
Published on: February 9, 2016
THE PROLIFERATIVE-DIFFERENTIAL PROCESSES IN BONE MARROW UNDER CHEMOTHERAPY DELIVERY DEPENDING ON THE IRON METABOLISM
D A Bazyka1, V A Zhovnir1, K M Bruslova1
1State Institution «National Research Center for Radiation Medicine, Hematology and Oncology of the National Academy of Medical Sciences of Ukraine», 53 Yuriia Illienka Str., Kyiv, 04050, Ukraine.
Insights
Iron metabolism significantly influences hematopoietic recovery in children with acute lymphoid leukemia (ALL) undergoing chemotherapy. Excess iron negatively impacts prognosis, highlighting its critical role in treatment outcomes.
Area of Science:
- Pediatric Oncology
- Hematology
- Iron Metabolism
Background:
- Acute lymphoid leukemia (ALL) is a significant pediatric cancer.
- Chemotherapy (CT) is a primary treatment for ALL.
- Understanding factors influencing treatment response is crucial.
Purpose of the Study:
- To assess the role of iron metabolism in hematopoietic recovery during CT for pediatric ALL.
- To evaluate the impact of iron levels on treatment outcomes in ALL patients from radiologically contaminated territories (RCT).
Main Methods:
- Studied 61 children (3-15 years) with ALL receiving CT.
- Monitored hemogram, myelogram, serum iron, ferritin, and transferrin levels throughout treatment.
- Assessed bone marrow (BM) cellularity and recovery types (granulocytic, erythroid, monocytic).
Main Results:
- BM cellularity decreased during induction therapy and increased during consolidation.
- Granulocytic recovery was most common; erythroid and monocytic types were less frequent.
- Elevated serum iron and ferritin levels were observed in 37.7% and 24.6% of patients, respectively, post-CT.
- Higher iron levels correlated with poorer prognosis and were more pronounced in proB ALL.
- Radiation dose to BM did not affect recovery type or iron metabolism.
Conclusions:
- Hematopoietic recovery in ALL patients under CT is dependent on iron metabolism.
- Excess iron in the body is associated with a negative prognosis in pediatric ALL.
Objective:
assessment of the role of iron metabolism in proliferation, differentiation and hematopoietic recoverytypes under the chemotherapy (CT) delivery in children with acute lymphoid leukemia (ALL), living in radiologically contaminated territories (RCT) of Ukraine.
Materials And Methods:
The ALL patients (n = 61) aged 3 to 15 years, residing in RCT, were examined. The observation period was 20 years. There were preB (n = 7), «general» type (n = 50), and proB (n = 4) ALL variants amongthe study subjects. Patients had received CT according to the adapted protocols by the BerlinFrankfurtMunstergroup (BFM). Study schedule featured the Period «0» before the CT initiation with respective studied parameters,Period 1 and Period 2 corresponding to the remission induction therapy, and periods 3, 4 and 5 corresponding to theremission consolidation therapy. The hemogram and myelogram parameters were studied during all periods. Serumiron (SI), serum ferritin (SF) and transferrin levels were assayed. The results of treatment were taken into account.Radiation doses to the bone marrow (BM) were calculated.
Results:
There was the highest BM cellularity by the number of myelokaryocytes (MKC) ((202.0 ± 21.2) G/l) beforeCT initiation due to the tumor clone followed by a decrease during periods of remission induction therapy andincrease during periods of consolidation ((126.7 ± 11.5) G/l), not exceeding however the limits of normative values.More often the BM recovery during CT had occurred by the granulocytic type. The erythroid type was observed in athird of patients only at the beginning of CT. The monocytic type was specific to the patients in the first periods ofconsolidation. After the end of CT the content of iron in 62.3 % of children was within normal range with in 37.7 %of them being increased ((38.0 ± 2.1) μmol/l). Level of iron in 24.6 % of patients was high ((345.3 ± 16.4) ng/ml),indicating an excess of iron in the body. Level of iron after the CT completion was higher in proBALL type cases((485.0 ± 22.7) ng/ml) compared to preBHLL ((278.3 ± 19.6) ng/ml) and «general» type ones ((311.1 ± 21.3) ng/ml)(р < 0.05). An inverse correlation was established between the ALL prognosis and SI (r = 1.0; р < 0.001) and SF levels (r = 0.44; р < 0.05). The average radiation dose to the BM was (3.87 ± 1.12) mSv with no effect on the type ofBM recovery during CT and iron metabolism.
Conclusions:
Proliferation and differentiation of hematopoietic elements during the BM recovery in ALL patientsunder CT depend on the iron metabolism. Excess iron in the body negatively affects the disease prognosis in children.
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