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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; 12:746-766. [PMID: 34631440 PMCID: PMC8479351 DOI: 10.5306/wjco.v12.i9.746] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 06/19/2021] [Accepted: 07/30/2021] [Indexed: 02/06/2023] Open
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.
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Affiliation(s)
- Eleni Porfyriou
- Department of Medical Oncology and Hematopoietic Cell Transplant Unit, “Metaxa” Cancer Hospital, Piraeus 18537, Greece
| | - Sylvia Letsa
- Department of Medical Oncology and Hematopoietic Cell Transplant Unit, “Metaxa” Cancer Hospital, Piraeus 18537, Greece
| | - Christos Kosmas
- Department of Medical Oncology and Hematopoietic Cell Transplant Unit, “Metaxa” Cancer Hospital, Piraeus 18537, Greece
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Wu CY, Chiou TJ, Liu CY, Lin FC, Lin JS, Hung MH, Hsiao LT, Yen CC, Gau JP, Yen HJ, Hung GY, Hsu HC, Tzeng CH, Liu JH, Yu YB. Decision-tree algorithm for optimized hematopoietic progenitor cell-based predictions in peripheral blood stem cell mobilization. Transfusion 2016; 56:2042-51. [PMID: 27232662 DOI: 10.1111/trf.13666] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2015] [Revised: 04/02/2016] [Accepted: 04/07/2016] [Indexed: 11/28/2022]
Abstract
BACKGROUND Enumerating hematopoietic progenitor cells (HPCs) by using an automated hematology analyzer is a rapid, inexpensive, and simple method for predicting a successful harvest compared with enumerating circulating CD34+ cells. However, the optimal HPC cutoff count and the indicating factors to be considered for improved predicting have not yet been determined. STUDY DESIGN AND METHODS Between 2007 and 2012, a total of 189 consecutive patients who proceeded to peripheral blood stem cell (PBSC) harvesting were retrospectively recruited. Baseline characteristics were analyzed to identify the risk factors for a failed harvest, which were defined as less than 2 × 10(6) CD34+ cells/kg. Variables identified by multivariate logistic regression and correlation analysis for predicting a successful harvest were subjected to classification and regression tree (CART) analysis. RESULTS PBSCs were successfully harvested in 154 (81.5%) patients. An age of at least 60 years, a diagnosis of a solid tumor, at least five prior chemotherapy cycles, prior radiotherapy, and mobilization with granulocyte-colony-stimulating factor alone or high-dose cyclophosphamide were independent baseline predictors of poor mobilization. In CART analysis, patients with zero to two host risk factors and either higher HPC (≥28 × 10(6) /L) or mononuclear cell (MNC; ≥3.5 × 10(9) /L) counts were categorized as good mobilizers and their harvest success rate was 92.3%. By contrast, 30.3% of harvests were adequate in the patients with three to five host risk factors and lower HPC and MNC counts. CONCLUSION A CART algorithm incorporating host predictors and HPC and MNC counts improves predictions in a successful harvest and might reduce the necessity of monitoring peripheral CD34+ cells.
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Affiliation(s)
- Chia-Yun Wu
- Division of Hematology, Department of Medicine.,Division of Medical Oncology, Department of Oncology.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Tzeon-Jye Chiou
- Division of Hematology, Department of Medicine.,Division of Transfusion Medicine, Department of Medicine.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chun-Yu Liu
- Division of Medical Oncology, Department of Oncology.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Feng-Chang Lin
- Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Jeong-Shi Lin
- Division of Hematology, Department of Medicine.,Division of Transfusion Medicine, Department of Medicine.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Man-Hsin Hung
- Division of Medical Oncology, Department of Oncology.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Liang-Tsai Hsiao
- Division of Hematology, Department of Medicine.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chueh-Chuan Yen
- Division of Medical Oncology, Department of Oncology.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Jyh-Pyng Gau
- Division of Hematology, Department of Medicine.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Hsiu-Ju Yen
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Giun-Yi Hung
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Hui-Chi Hsu
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Medicine, Saint Mary's Hospital Luodong, Yilan, Taiwan
| | - Cheng-Hwai Tzeng
- Division of Hematology, Department of Medicine.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Jing-Hwang Liu
- Division of Hematology, Department of Medicine.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Yuan-Bin Yu
- Division of Hematology, Department of Medicine.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
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Delamain MT, Marques JFC, de Souza CA, Lorand-Metze I, Metze K. An algorithm based on peripheral CD34+ cells and hemoglobin concentration provides a better optimization of apheresis than the application of a fixed CD34 threshold. Transfusion 2008; 48:1133-7. [PMID: 18422851 DOI: 10.1111/j.1537-2995.2008.01687.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND Optimization of peripheral blood stem cell (PBSC) collection for autologous bone marrow transplantation is necessary for a good standard of care and cost-effectiveness. An algorithm was validated for prediction of the day of maximum peripheral CD34+ cell concentration after mobilization chemotherapy (Day(CD34peak)). STUDY DESIGN AND METHODS This study compared mobilization and collection variables of a cohort of patients where apheresis was started at the Day(CD34peak) predicted by the algorithm with a patient group where PBSCs were collected when PB CD34+ cell concentration reached 10 per microL per day (Day(CD34threshold)). Day(CD34peak) was calculated according to the equation Day(CD34peak) = -0.41 x Hb(D0) + 0.99 x Day(CD34threshold) + 7.8 (with Hb(D0) representing the hemoglobin value on Day 0). RESULTS The mean number of apheresis procedures per patient based on the Day(CD34threshold) was 1.74, but decreased to 1.35 when applying the new method (Day(CD34peak)). For lymphomas, the mean number of apheresis procedures decreased from 1.98 to 1.47 (p = 0.03), while in patients with multiple myeloma it did not change significantly (1.23 and 1.26, respectively). Age and primary disease influenced the number of apheresis procedures needed to achieve the collection target. CONCLUSION The application of our algorithm can lower the number of apheresis procedures by improving the timing, especially in patients suffering from malignant lymphomas with a poor marrow potential after several chemotherapy lines.
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Affiliation(s)
- Márcia T Delamain
- Center of Hematology and Hemotherapy, Department of Internal Medicine, Faculty of Medicine, State University of Campinas, Campinas-SP, Brazil
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