Porfyriou E, Letsa S, Kosmas C. Hematopoietic stem cell mobilization strategies to support high-dose chemotherapy: A focus on relapsed/refractory germ cell tumors. World J Clin Oncol 2021; 12(9): 746-766 [PMID: 34631440 DOI: 10.5306/wjco.v12.i9.746]
Corresponding Author of This Article
Eleni Porfyriou, MD, Doctor, Department of Medical Oncology and Hematopoietic Cell Transplant Unit, “Metaxa” Cancer Hospital, 51 Botassi Street, Piraeus 18537, Greece. porfyriou7@gmail.com
Research Domain of This Article
Oncology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Sep 24, 2021; 12(9): 746-766 Published online Sep 24, 2021. doi: 10.5306/wjco.v12.i9.746
Hematopoietic stem cell mobilization strategies to support high-dose chemotherapy: A focus on relapsed/refractory germ cell tumors
Eleni Porfyriou, Sylvia Letsa, Christos Kosmas
Eleni Porfyriou, Sylvia Letsa, Christos Kosmas, Department of Medical Oncology and Hematopoietic Cell Transplant Unit, “Metaxa” Cancer Hospital, Piraeus 18537, Greece
Author contributions: Porfyriou E and Letsa S collected and analyzed data, wrote, and approved the article; Kosmas C wrote parts of the original and made additions in the revised article, critically evaluated collected data, supervised the study, and corrected and approved the article; All authors read, approved, and agreed on submission of the final version of the article.
Conflict-of-interest statement: The authors declare that they have no conflicting interests.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Eleni Porfyriou, MD, Doctor, Department of Medical Oncology and Hematopoietic Cell Transplant Unit, “Metaxa” Cancer Hospital, 51 Botassi Street, Piraeus 18537, Greece. porfyriou7@gmail.com
Received: May 3, 2021 Peer-review started: May 3, 2021 First decision: June 16, 2021 Revised: June 19, 2021 Accepted: July 30, 2021 Article in press: July 30, 2021 Published online: September 24, 2021 Processing time: 136 Days and 19 Hours
Abstract
High-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation has been explored and has played an important role in the management of patients with high-risk germ cell tumors (GCTs) who failed to be cured by conventional chemotherapy. Hematopoietic stem cells (HSCs) collected from the peripheral blood, after appropriate pharmacologic mobilization, have largely replaced bone marrow as the principal source of HSCs in transplants. As it is currently common practice to perform tandem or multiple sequential cycles of HDCT, it is anticipated that collection of large numbers of HSCs from the peripheral blood is a prerequisite for the success of the procedure. Moreover, the CD34+ cell dose/kg of body weight infused after HDCT has proven to be a major determinant of hematopoietic engraftment, with patients who receive > 2 × 106 CD34+ cells/kg having consistent, rapid, and sustained hematopoietic recovery. However, many patients with relapsed/refractory GCTs have been exposed to multiple cycles of myelosuppressive chemotherapy, which compromises the efficacy of HSC mobilization with granulocyte colony-stimulating factor with or without chemotherapy. Therefore, alternative strategies that use novel agents in combination with traditional mobilizing regimens are required. Herein, after an overview of the mechanisms of HSCs mobilization, we review the existing literature regarding studies reporting various HSC mobilization approaches in patients with relapsed/refractory GCTs, and finally report newer experimental mobilization strategies employing novel agents that have been applied in other hematologic or solid malignancies.
Core tip: High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is a curative treatment option for patients with relapsed/refractory germ cell tumors (GCTs). Mobilization of adequate numbers of hematopoietic stem cells (HSCs) is a prerequisite for successful ASCT. As the benefit of HDCT+ASCT is largely evident with > one HDCT cycle, it is anticipated that an appreciable percentage of patients will not mobilize adequate HSCs and require salvage strategies. Herein, we review the history of HSC transplantation, with emphasis in GCTs, pathophysiological mechanisms of HSC mobilization, initial and salvage mobilization strategies, and finally discuss novel mobilizing agents and approaches to overcome failures.
