Predictors of CD34+ Cell Mobilization and Collection in Adult Men With Germ Cell Tumors: Implications for the Salvage Treatment Strategy |
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| Institution: | 1. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;2. Clinical Epidemiology and Trials Organization Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;3. Department of Oncology and Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;4. Immunohematology and Transfusion Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;5. Department of Surgery, Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;6. Department of Oncology and Hematology, Humanitas Cancer Center, Humanitas Clinical and Reseach Center, Rozzano, Italy;7. Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy;8. Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy;1. Department of Urology, University of Washington School of Medicine, Seattle, WA;2. Department of Medicine, Division of Oncology, University of Washington School of Medicine, Seattle, WA;3. Group Health, Seattle, WA;4. University of Utah, Salt Lake City, UT;5. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA;1. Department of Medical Oncology, Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy;2. Department of Medical Oncology, Oncologia Medica 2, IRCCS Ospedale Policlinico San Martino, Genova, Italy;3. Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy;4. Department of Internal Medicine and Medical Specialties, School of Medicine, University of Genova, Genova, Italy;5. Department of Clinical Medicine and Surgery, University of Naples Federico II, Napoli, Italy;6. Division of Breast Oncology, Istituto Nazionale Tumori, IRCCS, Fondazione G Pascale, Napoli, Italy;7. Clinical Trial Unit, Istituto Nazionale Tumori, IRCCS, Fondazione G Pascale, Napoli, Italy;8. Oncology Department, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy;9. Department of Oncology, ASST Mantova, AO Carlo Poma, Mantova, Italy;10. Breast Unit, ASL Citta'' di Torino, Torino, Italy;11. Medical Oncology Unit, ASL Frosinone, Frosinone, Italy;12. Division of Medical Oncology 1, Regina Elena National Cancer Institute, Roma, Italy;13. Unit of Precision Medicine in Breast Cancer, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Roma, Italy;14. Department of Oncology, Ospedale di Insegnamento S Croce e Carle, Cuneo, Italy;15. Medical Oncology, Fondazione IRCCS Ca'' Granda Ospedale Maggiore Policlinico Milano, Milan, Italy;p. Department of Oncology, UOC Oncologia, Azienda Ospedaliera Universitaria, Sassari, Italy;q. Department of Medical Oncology, Hospital Businco, Cagliari, Italy;r. Department of Oncology, ASUFC Santa Maria Della Misericordia, Udine, Italy;s. Department of Medical Oncology, Ospedale Papa Giovanni XXIII, Bergamo, Italy;t. Medical Oncology Unit, Grand Metropolitan Hospital “Bianchi-Melacrino-Morelli”, Reggio Calabria, Italy;u. Department of Medicine, University of Udine, Udine, Italy;v. Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano, Italy;w. Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy;x. Medical Oncology, Azienda Ospedaliera S Giuseppe Moscati, Avellino, Italy;1. Department for BioMedical Research, University of Bern, Murtenstrasse 24, Bern 3008, Switzerland;2. Department of Medical Oncology, Inselspital, University Hospital of Bern, Bern 3010, Switzerland;3. Department of Radiation Oncology, University of California, 1600 Divisadero Street, Suite H-1031, San Francisco, CA 94115, USA;4. Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific St Seattle, WA 98195-7110, USA;5. Bern Center for Precision Medicine, Inselspital, University Hospital of Bern, Bern, 3008, Switzerland;1. The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK;2. The Institute of Cancer Research, London, UK;3. University College Hospital, University College London Hospitals NHS Foundation Trust, London, UK;4. The Christie NHS Foundation Trust, Manchester, UK;5. University of Glasgow and Beatson West of Scotland Cancer Centre, Glasgow, UK;6. The Clatterbridge Cancer Centre, Wirral, UK;7. St James''s Institute of Oncology, University of Leeds, Leeds, UK;8. Queen''s University, Belfast, UK;9. Musgrove Park Hospital, Taunton, UK;10. Royal Blackburn Hospital, Blackburn, UK;11. University of Southampton, Southampton, UK;12. Royal Sussex County Hospital, Brighton, UK;13. Western General Hospital, Edinburgh, UK;14. Royal Lancaster Infirmary, Lancaster, UK;15. Velindre Cancer Centre, Cardiff, UK;p. Vall d''Hebron Institute of Oncology (VHIO), Barcelona, Spain;q. Peter McCallum Cancer Center, Melbourne, VIC, Australia;1. Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA;2. Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA;3. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA;4. Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA;5. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;6. Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA;7. Institute for Precision Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA;8. New York Presbyterian Hospital, New York, NY 10021, USA;9. Computational Biology Program, Public Health Sciences Division and Basic Science Division, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA 98109, USA;10. Department of Medicine and VAPSHCS, University of Washington, Seattle, WA 98109, USA;11. Cancer Biomarkers Team, Division of Clinical Studies, The Institute of Cancer Research, London SM2 5NG, UK;12. Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, London SM2 5NG, UK;13. Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA;14. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;15. Prostate Cancer Clinical Trials Consortium, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;16. Department of Internal Medicine, Division of Hematology Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA;17. Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109, USA;18. Department of Urology, University of Michigan Medical School, Ann Arbor, MI 48109, USA;19. Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109, USA;20. Genitourinary Oncology Service, Department of Medicine, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;21. Interventional Radiology, Department of Radiology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;22. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;23. Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02215, USA;24. Division of Hematology-Oncology, Department of Medicine, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA;25. Department of Musculoskeletal Radiology, Brigham and Women’s Hospital, Boston, MA 02115, USA;26. Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA;27. Department of Radiology, University of Washington, Seattle, WA 98109, USA;28. Department of Pathology, University of Washington Medical Center, Seattle, WA 98109, USA;29. Laboratory of Computational Oncology, CIBIO, Centre for Integrative Biology, University of Trento, 38123 Mattarello TN, Italy;30. Institute for Computational Biomedicine, Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, NY 10021, USA;31. Division of Interventional Radiology, Department of Radiology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10021, USA;32. Department of Physiology & Biophysics, Weill Medical College of Cornell University, New York, NY 10021, USA;33. Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA;34. Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA;35. The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA;36. Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA;37. Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA;38. Meyer Cancer, Weill Medical College of Cornell University, New York, NY 10021, USA;39. Department of Pathology, Brigham & Women’s Hospital, Boston, MA 02115, USA;40. Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;41. Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;42. Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109, USA |
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| Abstract: | BackgroundHigh-dose chemotherapy with tandem or triple carboplatin and etoposide course is currently the first curative choice for relapsing GCT. The collection of an adequate amount of hematopoietic (CD34+) stem cells is a priority.Patients and MethodsWe analyzed data of patients who underwent HDCT at 2 referral institutions. Chemotherapy followed by myeloid growth factors was applied in all cases. Uni- and multivariable models were used to evaluate the association between 2 prespecified variables and mobilization parameters. Analyses included only the first mobilizing course of chemotherapy and mobilization failures.ResultsA total of 116 consecutive patients underwent a mobilization attempt from December 1995 to November 2012. Mobilizing regimens included cyclophosphamide (CTX) 7 gr/m2 (n = 39), cisplatin, etoposide, and ifosfamide (PEI) (n = 42), paclitaxel, cisplatin, and gemcitabine (TPG) (n = 11), and mixed regimens (n = 24). Thirty-seven percent were treated in first-line, 50% (n = 58) in second-line, 9.5% (n = 11) and 3.4% (n = 4) in third- and fourth-line settings, respectively. Six patients did not undergo HDCT because they were poor mobilizers, 2 in first- and second-line (1.9%), and 4 beyond the second-line (26.7%). In the multivariable model, third-line or later setting was associated with a lower CD34+ cell peak/μL (P = .028) and a lower total CD34+/kg collected (P = .008). The latter was also influenced by the type of mobilizing regimen (P < .001).ConclusionA decline in significant mobilization parameters was found, primarily depending on the pretreatment load. Results lend support to the role of CD34+ cell mobilization in the therapeutic algorithm of relapsing GCT, for whom multiple HDCT courses are still an option, and potentially a cure. |
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| Keywords: | Hematopoietic stem cell transplantation High-dose chemotherapy Male germ cell tumor Testicular neoplasms |
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