Optimal Use of Granulocyte Colony Stimulating Factor (G-CSF) after Autologous Hematopoietic Stem Cell Transplantation
Authors: Al Sabty Firas , Mistrik Martin , Hrubiko Mikulá , Bojtárová Eva , Martinka Ján , Batorova Angelika 
Published: November 2019

Abstract
Introduction:high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (autoHSCT) is widely used in the treatment of patients with haematological and non-haematological malignancies. One of the most common causes of mortality after HSCT is infection during the time of prolonged neutropenia. Prolonged neutropenia more than 7 days increase the risk of fungal infections and it is an indication for the use of antifungal prophylaxis. After hematopoietic SCT, G-CSF is commonly used to enhance stem cell engraftment to minimize the morbidity and mortality associated with prolonged neutropenia. However, there is no consensus on the optimal use of G-CSF after autoHSCT, most studies have been conducted on small numbers of patients and have varied significantly in patient’s demographics, G-CSF dosage regimen and other factors affecting outcomes.
Objective:restrospective study to evaluate the efficacy of early vs. delayed initiation of G-CSF after autoHSCT in patients with lymphoid malignancies.
Methods: between January 2009 and July 2014, 117 patients with lymphoid malignancies who underwent autoHSCT in the Department of Hematology and Transfusion medicine in Bratislava were included. The patients were divided into two groups; in the first group (43 patients), G-CSF (filgrastim, 5μg/kg s.c.) was applied late (on day 6.-8.) after autoHSCT. In the second group (74 patients), G-CSF (filgrastim, 5μg/kg s.c.) was applied early (on day 3.-4.) after autoHSCT. All patients received standard conditioning regimen for the underlying disease, and standard supportive treatment, including treatment of febrile neutropenia. Patient’s demographics are shown in table 1. Statistical analysis was performed using SPSS statistical software v. 20, with significant Pvalue of 0.05 (two-tailed).
Results: sever neutropenia (ANC < 0.5 x 109) and very severe neutropenia (ANC < 0.1 x 109) for more than 7 days were recorded as following: in the first group (delayed G-CSF), 34/42 (81%) and 25/41 (61%) patients respectively. In the second group (early G-CSF), 11/66 (17%) and 2/52 (4%) patients respectively (RR = 4.8, 95% CI = 2.7 to 8.4 and RR = 15, 95% CI = 3.9 to 63). Median time to engraftment of leukocytes above 1, granulocytes above 0.5, and 0.1 x 109/l was 6, 5, and 4 days for patients who received G-CSF early and 7, 7 and 5 days for patients who received G-CSF late (P <0001). The median duration of hospitalization was 19 (15-28) days in the first group and 16 (11-23) days in the second group (P = 0.001, 95% CI =2.02-4.17). There was no significant difference in the rate of febrile neutropenia in both groups (P = 0.53), but the rate of fungal infection and the use of HRCT scan of the lung was higher in the group of patients who received delayed G-CSF than early G-CSF (19% vs. 3%, P=0.005) and (23% vs. 6%, P=0.007) respectively.
Conclusion:early application of G-CSF (3rd-4th day) after autologous HSCT accelerates engraftment, shorten the duration of neutropenia, reduce the risk of infectious complications (especially fungal infections), reduce the use of antimicrobial drugs, shorten the hospital stay and overall costs.
Table.1 Delayed application of G-CSF Early application of G-CSF Patient N. 43 74 Age, m edian(range) 60 (39-67) years 59 (33-68) years P = 0.694 Sex P = 0.079 Male, N (%) 16 (37%) 40 (54%) Female, N (%) 27 (63%) 34 (46%) CD34+cells x106/kg, m edian(range) 2.5 (1.3-5.6) 2.3 (1.3-4.5) P = 0.138 Diagnosis P = 0.855 Multiple myeloma, N (%) 41 (95%) 72 (97%) NHL, N (%) 2 (5%) 2 (3%) ECOG performance status P = 0.221 0 35 (82%) 53 (72%) 1 7 (16%) 18 (24%) 2 1 (2%) 2 (3%) 3 0 0 4 0 1 (1%) Engraftment , median(range) Leu. > 1 x 109/l 7 (4-12) days 6 (3-9) days P ≤ 0,0001 Neut.> 0.5 x 109/l 7 (5-9) days 5 (3-7) days P ≤ 0,0001 Neut. > 0.1 x 109/l 5 (3-6) days 4 (2-6) days P ≤ 0,0001 Hospitalization, median(range) 19 (15-28) days 16 (11-23) days P= 0,001 Sever neutropenia ≥ 7 days, N (%) 34/42 (81%) 11/66 (17%) RR = 4.8, 95% CI = 2.7 to 8.4 Very sever neutropenia ≥ 7 days, N (%) 25/41 (61%) 2/52(4%) RR = 15, 95% CI = 3.9 to 63 Febrile neutropenia, N (%) 40 (93%) 64 (88%) P = 0.531 Invasive fungal infection, N (%) 8/43 (19%) 2/73 (3%) P = 0,005 HRCT scan use, N (%) 10 (23%) 4 (6%) P = 0.007 Cost 3582 (787-18187) Eur. 1408 (263-2143) Eur. P=0,041

Disclosures
No relevant conflicts of interest to declare.