Routine Prophylactic Granulocyte Colony-Stimulating Factor Use Post Autologous Peripheral Blood Stem Cell Transplantation for Hodgkin's Disease, Non-Hodgkin's Lymphoma and Germ Cell Tumors Shortens Duration of Hospital Stay and Reduces Mortality: A Retrospective Single Center Experience

Background: High-dose chemotherapy followed by autologous stem cell transplant (HDC/AutoSCT) is an effective therapy for various chemo-sensitive malignancies. Post-transplant complications often occur during the cytopenic period, which synthetic Granulocyte Colony Stimulating Factor (G-CSF) can shorten. G-CSF use is linked to faster engraftment and shorter hospital stays, though it hasn't shown benefits for overall survival (OS). At Vancouver General Hospital, we shifted from therapeutic G-CSF (TGCSF) to prophylactic G-CSF (PGCSF) for HDC/AutoSCT in 2019. This single-centre experience compares patient outcomes between routine PGCSF use and a historical group with TGCSF.

Methods: This single-centre experience includes 581 patients who received HDC/AutoSCT from June 2015 to June 2023. Patients from June 2015 to May 2019 (285) received TGCSF, which meant patients only received G-CSF when there were concerns of delayed engraftment, febrile neutropenia, or infections. Patients from June 2019 to June 2023 (296) received PGCSF starting on day +7 post stem cell re-infusion. Data was collected by reviewing electronic charts and our BMT electronic database for 581 transplants performed at the L/BMT program of British Columbia, Canada during this specified period. Baseline demographics, patients' characteristics, primary disease, disease status prior to HDC/AutoSCT, conditioning HDC, stem cell dose, complications, length of stay (LOS) in hospital, number of infections, presence of mucositis, mucositis severity, days to engraftment, transfusions required, cell dose, presence of engraftment syndrome, number of re-admissions, mortality at three months and at six months were all collected. Comparison of continuous variables between the groups were performed using two-sample t-test with unequal variance and that of dichotomous variables using Chi-square test. The statistical program used was STATA version 18.0 (Texas, 2023).

Results: Baseline characteristics included median ages of 54 years (18-72) in the TGCSF group and 57.5 years (18-72) in the PGCSF group (p=0.06). The TGCSF group had higher proportions of males (70.6% vs. 63.9% (p=0.083)). The primary diseases treated were non-Hodgkin's lymphoma, Hodgkin's lymphoma, and germ cell tumors representing 74%, 21%, and 2% in the TGCSF group respectively compared to 69%, 17%, and 11% in the PGCSF group. Other disease indications encompassed 3% in both groups. The most common conditioning regimen was BEAM, used in 74% of TGCSF and 68% of PGCSF transplants. The TGCSF group had a higher median cell dose (9.66 x 10^8 cells/Kg vs. 7.96 x 10^8 cells/Kg) and a greater proportion of patients in a partial or complete response prior to HDC/AutoSCT (52% vs. 44%).

Despite higher cell doses and better disease control in the TGCSF group, the PGCSF group showed faster neutrophil engraftment (11.4 vs. 10.4 days (p<0.001)) but no difference in platelet engraftment (10.1 vs 9.5 days (p=0.2679)). The PGCSF group also utilized less red cell units (1.78 vs. 1.28 (p< 0.001)) but equivalent adult platelet doses (3.6 vs. 3.1 (p=0.1223)). There was a three-day shorter hospital stay for the PGCSF group (23.3 vs 20.4 days (p<0.001)). Both groups had similar mucositis rates, but higher-grade mucositis was more common in the TGCSF group (33% vs. 23%). Mortality at 6 months and incidence of engraftment syndrome favored the PGCSF group (11% vs. 6% (p=0.055) and 4% vs. 5%). Mortality at 3 months was equivalent between the two groups. There were similarities between the two groups in number of infections, engraftment syndrome and number of readmissions.

Discussion: In this large retrospective single-centre study, routine G-CSF (PGCSF) use in HDC/AutoSCT showed better outcomes with faster engraftment, less red cell transfusions, less severe mucositis and shorter hospital stay. Mortality at 6 months favored the routine use of G-CSF. Our retrospective review supports routine G-CSF use and shows an association with reduction in mortality with this strategy.

Cherniawsky:Astellas: Honoraria; KITE: Honoraria. Sanford:Pfizer: Research Funding; Astellas: Consultancy, Research Funding, Speakers Bureau; AbbVie: Consultancy, Research Funding, Speakers Bureau. Song:GSK: Research Funding; BMS: Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Current holder of stock options in a privately-held company, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Stubbins:Kite/Gilead: Speakers Bureau; Pfizer: Honoraria; Astellas: Honoraria; Takeda: Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria. Toze:Abbvia: Research Funding; Janssen, BeiGene: Honoraria. Abou Mourad:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Alexion: Consultancy; Paladin: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau.