Do We Need the Chelation Therapy during Intensive Treatment of Acute Lymphoblastic Leukemia (ALL) in Children?

Introduction

Children with ALL during the intensive chemotherapy receive multiple transfusions of packed red blood cell (pRBC) that may lead to iron overload. With each transfusion of pRBC the body is supplied with an about 200-250 mg of iron, which excessive accumulation in tissues, due to the lack of mechanism for its active excretion, may cause toxic organ damage.

Methods

The aim of the study was to evaluate the serum ferritin concentration in children with ALL, depending on the amount of transfused pRBCs and to determine the group of patients with a risk of iron overload. The study patients included 54 children with newly diagnosed ALL treated at the Department of Pediatrics, Hematology and Oncology between 2008 and 2011, according to the ALL IC BFM 2002 therapy protocol. Prior to initiation the treatment and during the intensive chemotherapy, serum ferritin concentration and the number of pRBC transfusions (ml/kg) were assessed separately for each of the three ALL risk groups-standard risk (SR), intermediate risk (IR) and high risk (HR).

Results

After the intensive chemotherapy the mean ± standard deviation (SD) of serum ferritin concentration in group HR (2770 ± 1175 ng/ml) was significantly higher compared to the median in group SR 844.4 ng/ml (452.5; 1316) (p = 0.0007) and the mean ± SD in group IR-1270 ± 673.1 ng/ml (p = 0.0040).

Throughout the intensive chemotherapy children in HR group received the largest volume of pRBC transfusions (ml/kg) (156.2 ± 68.31 ml/kg). In IR and SR groups the amounts of transfused pRBCs were comparable, respectively 113.5 ± 39.86 and 113.8 ± 29.56 ml/kg.

Significant positive correlation was found between the serum ferritin concentration and the total amount of transfused pRBCs (ml/kg) after intensive chemotherapy (p <0.0001).

After intensive treatment the concentration of serum ferritin exceeding 1000 ng/ml, that has traditionally been used as a trigger for chelation therapy, was found in 30 of 54 patients, for a prevalence in the entire cohort of 55,6% including 6 out of 6 patients in HR group (100%), 14 out of 22 patients in IR group (63,6%) and 10 out of 24 patients in SR group (41,7%).

The group of patients with post-treatment serum ferritin concentration exceeding 1000 ng/mL, received significantly more pRBC transfusions (ml/kg) (139.8 ± 44.92) than the groups with serum ferritin levels between 500-1000 ng/mL (103.6 ± 18.96) (p <0.001) and <500 ng/mL-83.52 ± 17.66 (p <0.05).

Conclusions

These observations indicate a need of monitoring the cumulative volumes of pRBC transfusions, especially in children with ALL HR group. There is a need of routine screening for iron overload using serum ferritin in patients during intensive chemotherapy, in order to identify patients with indications for early iron chelation therapy. This is particularly important because some of them will be candidates to a hematopoietic stem cell transplantation, whereas iron overload adversely affects outcome of transplantation.