Analysis of factors influencing the efficiency of autologous hematopoietic stem cell mobilization before apheresis in pediatric patients with malignant tumors

Introduction. Autologous hematopoietic stem cell transplantation (auto-HSCT) is an effective method of treatment a number of malignant neoplasms and severe non-malignant diseases in addition to standard treatment protocols. Auto-HSCT requires previous successful collection of autologous hematopoietic stem cells (HSC) by apheresis with preliminary mobilization. Standard mobilization schemes include the use of granulocyte colony-stimulating factor (G-CSF), however, some patients have insufficient mobilization (IM) of HSC, which creates significant obstacles to the collection of HSC. Timely detection of predictors of IM can allow to adjust its protocol, as well as individualize the HSC apheresis regimen. Aim of the study – based on the results of the analysis of mobilization and apheresis modes of autologous HSC in patients with various malignant neoplasms to identify the most significant factors causing IM of HSC for the further development of methods for optimizing the mobilization and collection modes of HSC.

Materials and methods. The study included 257 patients aged from 3 to 215 months (median age – 84 [36.0; 144.0] months) with various malignant neoplasms who received treatment at the Research Institute of Pediatric Oncology and Hematology named after Academician of the Russian Academy of Medical Sciences L.A. Durnov at N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia from 2019 to 2023. According to the treatment protocol of malignant neoplasms, all patients received high-dose polychemotherapy followed by auto-HSCT as a consolidation phase of treatment. HSC mobilization was performed in advance in order to successfully perform apheresis of autologous HSCs. The main group (the group IM, n = 64) of patients included persons who did not achieve a CD34⁺ cells in peripheral blood of 20 cells/μl by the day of apheresis, despite full compliance with the established mobilization protocol. The comparison group (the “sufficient mobilization” (SM) group, n = 193) consisted of patients who achieved a CD34⁺ cells in peripheral blood of 20 cells/μl or more by the day of apheresis. Mobilization regimens included various chemotherapeutic agents (G-CSF, cyclophosphamide in the previous chemotherapy scheme, plerixafor and its combinations), the dose of which, the duration of the regimen, as well as the dose escalation depended on the initial characteristics of both the main treatment protocol and the somatic and infectious status of the patient. In the studied patient groups, the frequency of factors potentially capable of influencing the quality of mobilization before HSC apheresis was analyzed: the tumor type and stage, the number of previous courses of polychemotherapy, the presence and amount of myelotoxic agents in polychemotherapy, recovery of hematopoiesis before the start of mobilization, pretreatment, response to therapy, history of radiation therapy and surgery, the need for escalation of the G-CSF dose in the mobilization mode.

Results. Significant differences (p < 0.05) between the comparison groups were obtained for such factors influencing the success of mobilization as the main diagnosis (the worst mobilization results were in patients with Ewingʼs sarcoma), tumor stage and response to previous treatment (mobilization was more successful in patients with disease stabilization). A significant negative impact on the efficiency of mobilization was also demonstrated by such factors as the lack of hematopoiesis recovery before mobilization, pretreatment (4 or more courses of chemotherapy preceding mobilization), the presence of radiation therapy, a combination of radiation and surgical treatment in the therapy protocol preceding mobilization, the presence of carboplatin and temozolomide in the chemotherapy course, as well as three myelotoxic agents simultaneously, and escalation of the G-CSF dose during mobilization. Despite the worse characteristics of the graft, as well as the technically more difficult procedure for collecting HSCs in the IM group of patients, the average number of CD34⁺ cells per kg was 1.5 × 10⁶ /kg [0.7–2.7], which demonstrates the possibility of achieving a suboptimal number of stem cells in one apheresis procedure even in patients with poor mobilization. However, in the group of IM, not only escalation of doses of stimulant agents, but also prolongation of the apheresis procedure itself with an increase a number of processed blood volume and the volume of the graft. This not only increases the resources spent on the procedure, but also increases the risks for patients and creates additional difficulties for specialists performing the procedure. To optimize the mobilization and collection modes of the HSC, it is necessary to take into account the presence of risk factors for poor mobilization and plan in advance for such patients an individual regimen of both escalation and monitoring of the mobilization, as well as preparation for a special regimen of HSC collection.

Conclusion. According to the results of our study, significant predictors of IM are the characteristics of the main diagnosis, not an achievement of tumor regress, lack of hematopoiesis recovery before the start of mobilization, pretreatment, the presence of radiation therapy in the treatment protocol preceding mobilization, a combination of radiation and surgical treatment, the presence of carboplatin and temozolomide in the chemotherapy scheme, as well as three myelotoxic agents simultaneously, and escalation of the G-CSF dose in the mobilization mode. It is the patients who may require optimization of the mobilization and collection of HSCs.

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