Impact of Febrile Neutropenia on Mobilization Efficacy in Multiple Myeloma Patients and Post-Transplant Infection Risk in Lymphoma Patients: Insights from Real-World Multicenter Data
Authors: Qian Hu , Wang Xinwei , Yang Liping , Peng Juan , Zhao Jie , He Shaolong , Zhao Jin , Guo Jiaqi , Fang Yuekun , Meng Fankai , Cao Yang , Huang Lifang , Wei Junni , Ma Liangming , Su Li-Ping , Tian Weiwei , Zhang Yicheng , Wei Jia 
Published: December 2024

Background: High-dose chemotherapy combined with autologous stem cell transplantation (ASCT) remains pivotal in the treatment of multiple myeloma (MM) and lymphoma. The safety and efficacy of ASCT, as well as the quantity of stem cells harvested during apheresis, are heavily reliant on the efficacy of peripheral blood stem cell (PBSC) mobilization. In China, chemotherapy coupled with G-CSF mobilization is the predominant strategy. However, the influence of febrile neutropenia (FN) during chemomobilization on CD34+ PBSC collection and the risk of post-transplant infection in MM and lymphoma patients undergoing ASCT is still a matter of debate.

Methods: This multi-center, real-world, retrospective study was conducted at Tongji Hospital in Wuhan, Shanxi Bethune Hospital, and Shanxi Province Cancer Hospital from October 1st 2010 to January 31st 2024. We reviewed the records of 148 MM and 130 lymphoma patients, all aged 18 years or older, who underwent ASCT within this period. All participants received chemotherapy followed by G-CSF stimulation for stem cell mobilization. For MM patients, the mobilization regimens primarily involved the cyclophosphamide (CTX) protocol and the etoposide protocol. For lymphoma patients, the regimens mainly included the DHAP protocol, the CTX protocol, and the etoposide protocol. The study received ethics approval from the Ethics Committees of Tongji Hospital, Shanxi Bethune Hospital, and Shanxi Province Cancer Hospital, adhering to the ethical guidelines of the Declaration of Helsinki. The impact of FN during chemomobilization on stem cell collection and post-transplant infection was analyzed using GraphPad Prism 9, with significance set at P &lt; 0.05.

Results: Patients were categorized into FN and non-FN groups. MM patients in the FN group required more than 5 days of G-CSF stimulation (P &lt; 0.001) and more than 2 days of apheresis (P = 0.007) to achieve the target CD34+ cell count of 2 × 106/kg. The median CD34+ counts were significantly lower in the FN group (3.75 × 106/kg versus 6.22 × 106/kg, P &lt; 0.001). Additionally, these patients exhibited lower good-mobilization rates (P &lt; 0.001) and prolonged times to neutrophil (P = 0.006) and platelet engraftment (P = 0.03). In lymphoma patients, those in the FN group required more than 2 days of apheresis (P = 0.001) and experienced longer times to platelet engraftment (P = 0.02). FN was associated with an increased risk of pre-engraftment infection (P = 0.03) in lymphoma patients. Univariate analysis revealed that more than 5 days of G-CSF stimulation (P = 0.004), more than 2 days of apheresis (P = 0.01) and FN during mobilization (P &lt; 0.001) were significant risk factors impacting good mobilization in MM patients. FN during mobilization was identified as a risk factor for reduced good mobilization in MM patients (univariate P &lt; 0.001; multivariate OR = 3.06, 95% CI = 1.22-8.03, P = 0.02) and for pre-engraftment infection in lymphoma patients (OR = 0.29, 95% CI = 0.10-0.86, P = 0.03). Further scrutiny into the long-term survival implications revealed that FN during chemomobilization might impact the long-term survival of MM patients (P = 0.002). The 5-year overall survival in FN and non-FN subgroups of MM patients was 61.01% and 84.36%, respectively.

Conclusions: Febrile neutropenia during chemomobilization has a detrimental effect on stem cell mobilization in multiple myeloma patients and heightens the risk of pre-engraftment infections in lymphoma patients undergoing ASCT. These findings underscore the necessity for improved strategies to manage FN in these patient populations to enhance ASCT outcomes.