Hematopoietic Recovery using Multi-Cytokine Therapy in 8 Patients Presenting Radiation-Induced Myelosuppression after Radiological Accidents

Abstract

Treatment of accidental radiation-induced myelosuppression is primarily based on supportive care and requires specific treatment based on hematopoietic growth factors injection or hematopoietic cell transplantation for the most severe cases. The cytokines used consisted of pegylated erythropoietin (darbepoetin alfa) 500 IU once per week, pegylated G-CSF (pegfilgrastim) 6 mg × 2 once, stem cell factor 20 μg.kg–1 for five days, and romiplostim (TPO analog) 10 μg.kg−1 once per week, with different combinations depending on the accidents. As the stem cell factor did not have regulatory approval for clinical use in France, the French regulatory authorities (ANSM, formerly, AFSSAPS) approved their compassionate use as an investigational drug “on a case-by-case basis”. According to the evolution and clinical characteristics, each patient's treatment was adopted on an individual basis. Daily blood count allows initiating G-CSF and SCF delivery when granulocyte <1,000/mm3, TPO delivery when platelets <50,000/mm3, and EPO when Hb<80 g/L. The length of each treatment was based on blood cell recovery criteria. The concept of “stimulation strategy” is linked to each patient's residual hematopoiesis, which varies among them, depending on the radiation exposure's characteristics and heterogeneity. This paper reports the medical management of 8 overexposed patients to ionizing radiation. The recovery of bone marrow function after myelosuppression was accelerated using growth factors, optimized by multiple-line combinations. Particularly in the event of prolonged exposure to ionizing radiation in dose ranges inducing severe myelosuppression (in the order of 5 to 8 Gy), with no indication of hematopoietic stem cell transplantation.

Novel Combination of Erythropoietin and Romiplostim to Treat Chemotherapy-Induced Anemia and Thrombocytopenia via Pharmacodynamic Interaction on Hematopoietic Stem and Progenitor Cells

“…In this study, we investigated a novel combination therapy of rHuEPO and romiplostim for treating CIAT simultaneously in cancer rats. The rationale for testing this innovative treatment strategy was based on our recent findings showing that romiplostim could synergize with rHuEPO to promote RBC production while EPO inhibited platelet production in a dose-dependent manner to reduce the risk of thrombocytosis., Recent reports also demonstrated the safety and efficacy of EPO-RA darbepoetin alfa and romiplostim for CIAT and radiation-induced myelosuppression in patients, which could achieve remission in the absence of blood product transfusions. − In one case report, a patient with myelodysplastic syndrome received darbepoetin and concomitant usage of romiplostim . The results were consistent with our hypothesis that romiplostim was suggested to stimulate the erythroid response in addition to the effect of darbepoetin and the reduced darbepoetin dosage.…”

Myelosuppression Alleviation and Hematopoietic Regeneration by Tetrahedral‐Framework Nucleic‐Acid Nanostructures Functionalized with Osteogenic Growth Peptide

“…[ 8 ] A single type of growth factor cannot produce a balanced response in multiple blood cell lines, but must be combined with other factors to reconstruct hematopoietic function. [ 9 ] Furthermore, growth factor receptors can also be expressed on tumor cells, so their application might lead to malignant growth, tumor progression, or recurrence. [ 10 ] Therefore, it is important to develop new types of drugs that protect the hematopoietic microenvironment and promote effective hematopoietic reconstitution.…”

The effect of chronoradiotherapy on cervical cancer patients: A multicenter randomized controlled study

“…Therefore, the occurrence of toxic reactions, such as diarrhea and mucositis, is more serious in the morning than in the evening ( 13 ). Myelosuppression and hematological toxicity are more serious in the evening after radiotherapy, which may be because proliferation and apoptosis of bone marrow cells exhibit circadian rhythm changes; indeed, apoptosis in the evening group was significantly higher than that in the morning group ( 28 , 29 ).…”