Prophylaxis And Treatment Of Chemotherapy Induced Neutropenia And Associated Events

Purpose: To explore efficacy and safety of prophylactic use of half-dose(3mg)pegylated recombinant human granulocyte-colony stimulating factor(PEG-rhG-CSF),aspects related to the treatment of chemotherapy induced neutropenia(CIN)and febrile neutropenia(FN),which mainly focused on lung cancer,and find the facing problems and needs in clinical reality.To instruct and improve future clinical practice based on the data obtained from this retrospective study.Methods: This paper is divided into four parts.In the first part,patients who experienced a severe reduction or recovery delay of absolute neutrophil count(ANC)in the previous chemotherapy cycle and received half-dose(3mg)PEG-rhG-CSF prophylaxis in the next cycle were included in the study.The paired analysis was conducted between the two cycles to evaluate the safety and efficacy of prophylaxis of 3mg PEG-rhG-CSF,and to explore the problems that deserve attention in practical clinical use.The second part of this paper was conducted after clarifying the efficacy of half-dose(3mg)prevention in the first part.To analyze the non-inferiority of secondary prophylaxis between the half-dose(3mg)and the 6mg fixed-dose groups,the ratio of post-treatment grade ≥ 3 anemia or thrombocytopenia or grade ≥ 2thrombocytopenia between groups.In the third part,the chemotherapy cycles without prophylactic use of granulocyte-colony stimulating factor(G-CSF)were retrospectively analyzed.The frequency of receiving complete blood count tests,the occurrence of severe neutropenia,and the efficacy of grade ≥ 3 neutropenia treatment with various doses and duration of short-acting G-CSF administration based on different intervals following chemotherapy.To evaluate the clinical significance of G-CSF therapeutic use on the recovery of ANC and chemotherapy of the next cycle without delay.In the fourth part,we compared the chemotherapy cycles in which FN occurred and the cycles in which ANC recovered on time without management even though grade ≥ 3 neutropenia occurred.Both groups did not receive G-CSF prophylactic use.We evaluated the risk factors of FN,and analyzed the features of complete blood counts and the period when fever initially occurred to help recognize the possibility of FN occurrence.Results:In the first part,the occurrence of grade ≥ 3 neutropenia was significantly lower in the half-dose(3mg)PEG-rhG-CSF prophylactic cycles than the previous cycles without prophylaxis(16.5% vs 82.4%,P < 0.01).The rate of grade 4 neutropenia was also significantly lower in the prophylactic cycles than the previous cycles(9.4% vs48.2%,P < 0.01).Half-dose(3mg)PEG-rhG-CSF prophylactic use significantly elevated the nadir of white blood cell(WBC)and ANC.The ANC nadir of grade ≥ 3neutropenia in the three-week interval regimen subgroup appeared 2.5 days significantly earlier with half-dose(3mg)PEG-rhG-CSF support than without prophylactic support.Two-week interval regimen tended earlier appearance of ANC nadir with 3mg PEG-rhG-CSF support.Half-dose(3mg)PEG-rhG-CSF prophylaxis also significantly reduced FN occurrence,chemotherapy delay related to neutropenia but did not increase the rate of severe anemia and thrombocytopenia.Side effects of the 3mg PEG-rhG-CSF in our department were mild to moderate.The rate of bone pain was 5.9%.When PEG-rhG-CSF is used prophylactically,there is often no need to supplement short-acting G-CSF,and the Standardized application needs to be strengthened.The second part: There was no significant difference in the occurrence of grade≥ 3 neutropenia between the 3mg PEG-rhG-CSF prophylactic group and the 6mg dose group(16.5% vs 27.8%,P = 0.430).There was also no significant difference in the rate of grade 4 neutropenia between groups(9.4% vs 16.7%,P = 0.627).The two groups had no significant differences in the post-treatment nadir of ANC and WBC,the median time of ANC nadir appearance,the FN rate,and the chemotherapy dose reduction due to neutropenia.No chemotherapy delay related to neutropenia occurred in both groups.Thus this part reached the non-inferiority goal of half-dose PEG-rhG-CSF prevention.As for safety,there was no significant difference between groups in combining with grade ≥ 3 anemia and thrombocytopenia.But the rate of grade 2 thrombocytopenia in the 6mg dose group was significantly higher compared with the 3mg dose group.No severe adverse events correlating with PEG-rhG-CSF occurred in both groups.The third part: If grade ≥ 3neutropenia occurred in the second or third week of chemotherapy,G-CSF 150μg/d with a duration of three to four days was suggested.It was not easy to recover for grade ≥ 3 neutropenia in the first week of chemotherapy(d4-7)and grade 4 neutropenia in the entire chemotherapy interval.G-CSF 150μg/d starting with a three to four days duration,receiving a complete blood count test every three days,and monitor of the temperature were recommended.As for the three-week interval regimen subgroup,the proportion of ANC recovery on time for the first consecutive exposure to G-CSF was significantly higher than that of the first non-exposure to G-CSF group.The fourth part: The FN rate in our department was 1.44% for cycles without G-CSF prophylaxis.The mean values of WBC,ANC,lymphocyte(LYMPH)and PLT when fever began to appear in the FN group were significantly lower than the corresponding indicators when grade ≥ 3 neutropenia was initially found in the ANC self-recovery group.The median time for the onset of fever in the FN group was not statistically different from the control group’s median time when initial discovery of grade ≥ 3 was found.Both the median time was in the middle of the second week of chemotherapy.Conclusion: Half-dose(3mg)PEG-rhG-CSF prophylaxis was effective and safe and non-inferior to the 6mg fixed-dose.Therapeutic use of short-acting G-CSF in patients who did not receive G-CSF prophylaxis has its regularity and practical significance.However,future management of therapeutic use may change.Various factors could influence FN occurrence.The overall bone marrow function is inhibited when FN occurs.The blood routine test and temperature monitoring in the second week of chemotherapy are the most important.