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1
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Primary Mediastinal and Testicular Germ Cell Tumors in Adolescents and Adults: A Comparison of Genomic Alterations and Clinical Implications. Cancers (Basel) 2021; 13:cancers13205223. [PMID: 34680371 PMCID: PMC8533956 DOI: 10.3390/cancers13205223] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 10/11/2021] [Accepted: 10/14/2021] [Indexed: 11/28/2022] Open
Abstract
Simple Summary The germ cell tumors (GCTs) family is a heterogeneous group of neoplasms that includes tumors affecting testis (TGCTs) and rarer cases occurring in extragonadal sites. Mediastinal germ cell tumors (MGCTs) are more aggressive and have poorer prognosis. Due to their rarity of MGCTs, few molecular and clinical studies are reported. MGCTs share biological similarities with TGCT, and international guidelines recommend use of the same therapies validated for TGCT. However, while high response rate is achieved in TGCT, MGCT tend to be resistant to therapy. This review resumes all molecular findings reported in MGCTs, summarizing molecular characteristics common with TGCT and highlighting the different molecular alterations that characterize mediastinal tumors. A deeper understanding of the MGCT biology will help in clinical management of these patients. Abstract Mediastinal germ cell tumors (MGCTs) share histologic, molecular and biomarkers features with testicular GCTs; however, nonseminomatous MGCTs are usually more aggressive and have poorer prognosis than nonseminomatous TGCTs. Most nonseminomatous MGCT cases show early resistance to platinum-based therapies and seldom have been associated with the onset of one or more concomitant somatic malignancies, in particular myeloid neoplasms with recent findings supporting a common, shared genetic precursor with the primary MGCT. Genomic, transcriptomic and epigenetic features of testicular GCTs have been extensively studied, allowing for the understanding of GCT development and transformation of seminomatous and nonseminomatous histologies. However, MGCTs are still lacking proper multi-omics analysis and only few data are reported in the literature. Understanding of the mechanism involved in the development, in the progression and in their higher resistance to common therapies is still poorly understood. With this review, we aim to collect all molecular findings reported in this rare disease, resuming the similarities and disparities with the gonadal counterparts.
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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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3
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Expression and one step intein-mediated purification of biologically active human G-CSF in Escherichia coli. Mol Biol Rep 2020; 47:2861-2869. [DOI: 10.1007/s11033-020-05404-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Accepted: 03/25/2020] [Indexed: 01/15/2023]
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4
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Construction of a Pichia pastoris strain efficiently producing recombinant human granulocyte-colony stimulating factor (rhG-CSF) and study of its biological activity on bone marrow cells. Mol Biol Rep 2019; 47:607-620. [PMID: 31713007 DOI: 10.1007/s11033-019-05169-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Accepted: 10/30/2019] [Indexed: 10/25/2022]
Abstract
Non-glycosylated, recombinant human granulocyte colony-stimulating factor (rhG-CSF), produced by Escherichia coli (filgrastim, leukostim) is widely used to treat a number of serious human diseases and aids in the recovery post bone marrow transplantation. Although glycosylation is not required for the manifestation of the biological activity of G-CSF, a number of studies have shown that the carbohydrate residue significantly increases the physicochemical stability of the G-CSF molecule. Therefore, the aim of the present study was to design a Pichia pastoris strain capable of producing glycosylated rhG-CSF, and to study its effects on rat bone marrow cells. The nucleotide sequence of the rhG-CSF gene has been optimized for expression in P. pastoris, synthesized, cloned into the pPICZαA vector and expressed under the control of the AOX promoter in P. pastoris X33. One of the selected clones secreting rhG-CSF, produced 100-120 mg/l of rhG-CSF three days post-induction with methanol. The recombinant cytokine was purified using two-step, ion-exchange chromatography. The final yield of purified G-CSF was 35 mg/L of culture medium. The biological activity of rhG-CSF was examined in rat bone marrow cells. The P. pastoris strain was designed to produce relatively high levels of rhG-CSF. The rhG-CSF protein had a strong stimulating effect on the growth of rat bone marrow cells, which was comparable to that of the commercial drug leukostim, but showed a more persistent effect on granulocyte cells and monocyte sprouts, enabling the enhanced maintenance of the viability of the cells into the 4th day of incubation.
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Hematopoietic Progenitor Cell Mobilization for Autologous Stem Cell Transplantation in Multiple Myeloma in Contemporary Era. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2019; 19:200-205. [DOI: 10.1016/j.clml.2018.12.010] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 12/10/2018] [Accepted: 12/12/2018] [Indexed: 11/21/2022]
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6
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Innocenti R, Rigacci L, Restelli U, Scappini B, Gianfaldoni G, Fanci R, Mannelli F, Scolari F, Croce D, Bonizzoni E, Perrone T, Bosi A. Lenograstim and filgrastim in the febrile neutropenia prophylaxis of hospitalized patients: efficacy and cost of the prophylaxis in a retrospective survey. J Blood Med 2018; 10:21-27. [PMID: 30643475 PMCID: PMC6312059 DOI: 10.2147/jbm.s186786] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Purpose We conducted a retrospective study to evaluate the efficacy and related costs of using two different molecules of granulocyte-colony stimulating factor (G-CSF) (lenograstim - LENO or filgrastim - FIL) as primary prophylaxis of chemotherapy-induced neutropenia in a hematological inpatient setting. Methods The primary endpoints of the analysis were the efficacy of the two G-CSFs in terms of the level of white blood cells, hemoglobin and platelets at the end of the treatment and the per capita direct medical costs related to G-CSF prophylaxis. Results Two hundred twelve patients (96 LENO, 116 FIL) have been evaluated. The following statistically significant differences have been observed between FIL and LENO: the use of a higher number of vials (11 vs 7; P<0.03) to fully recover bone marrow, a higher grade 3-4 neutropenia at the time of G-CSF discontinuation (29.3% vs 16.7%; P=0.031) and an increased number of days of hospitalization (8 vs 5; P<0.005). A longer hospital stay before discharge was necessary (12 vs 10), which reflects the higher final costs per patient (median treatment cost per cycle 10.706 € for LENO, compared to 12.623 € for FIL). Conclusion The use of LENO has been associated with a lower number of days of hospitalization, number of vials and less incidence of grade 3-4 neutropenia at the time of G-CSF discontinuation. LENO seems to be cost-saving when compared with FIL (-15.2%).
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Affiliation(s)
- Rolando Innocenti
- Hematology Department, University of Florence and AOU Careggi, Florence, Italy,
| | - Luigi Rigacci
- Hematology Department, University of Florence and AOU Careggi, Florence, Italy, .,Hematology Unit and Bone Marrow Transplant Unit, San Camillo Forlanini Hospital, Rome, Italy,
| | - Umberto Restelli
- Center for Health Economics, Social and Health Care Management, LIUC - Università Cattaneo, Castellanza (VA), Italy.,School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Barbara Scappini
- Hematology Department, University of Florence and AOU Careggi, Florence, Italy,
| | - Giacomo Gianfaldoni
- Hematology Department, University of Florence and AOU Careggi, Florence, Italy,
| | - Rosa Fanci
- Hematology Department, University of Florence and AOU Careggi, Florence, Italy,
| | - Francesco Mannelli
- Hematology Department, University of Florence and AOU Careggi, Florence, Italy,
| | - Francesca Scolari
- Center for Health Economics, Social and Health Care Management, LIUC - Università Cattaneo, Castellanza (VA), Italy
| | - Davide Croce
- Center for Health Economics, Social and Health Care Management, LIUC - Università Cattaneo, Castellanza (VA), Italy.,School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Erminio Bonizzoni
- Section of Medical Statistics and Biometry "GA Maccacaro", Department of Clinical Science and Community, University of Milan, Milan, Italy
| | - Tania Perrone
- Medical Affairs Department, Italfarmaco SpA, Milan, Italy
| | - Alberto Bosi
- Hematology Department, University of Florence and AOU Careggi, Florence, Italy,
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Yu WL, Hua ZC. Evaluation of effectiveness of granulocyte-macrophage colony-stimulating factor therapy to cancer patients after chemotherapy: a meta-analysis. Oncotarget 2018; 9:28226-28239. [PMID: 29963274 PMCID: PMC6021338 DOI: 10.18632/oncotarget.24890] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Accepted: 02/28/2018] [Indexed: 12/24/2022] Open
Abstract
The impact of granulocyte-macrophage colony stimulating factor (GM-CSF) on hematologic indexes and complications remains existing contradictory evidence in cancer patients after treatment of chemotherapy. Eligible studies up to March 2017 were searched and reviewed from PubMed and Wanfang databases. Totally 1043 cancer patients from 15 studies were included in our research. The result indicated that GM-CSF could significantly improve white blood cells count (SMD = 1.16, 95% CI: 0.71 – 1.61, Z = 5.03, P < 0.00001) and reduce the time to leukopenia recovery (SMD = -0.85, 95% CI: -1.16 – -0.54, Z = 5.38, P < 0.00001) in cancer patients after treatment of chemotherapy. It also could improve absolute neutrophil count (SMD = 1.11, 95% CI: 0.39 – 1.82, Z = 3.04, P = 0.002) and significantly shorten the time to neutropenia recovery (SMD = -1.47, 95% CI: -2.20 – -1.75, Z = 3.99, P < 0.0001). However, GM-CSF could not improve blood platelet (SMD = 0.46, 95% CI: -0.37 – -1.29, Z = 1.10, P = 0.27). And GM-CSF had significant connection with fever (RR = 3.44, 95% CI: 1.43 – 8.28, Z = 2.76, P = 0.006). The publication bias existed in the data of the impact of GM-CSF on blood platelet and complication. In conclusions, GM-CSF had an intimate association with some hematologic indexes and complications. Our study suggested that more hematological indexes and even more other indexes need to be observed in future studies.
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Affiliation(s)
- Wen-Liang Yu
- The State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macao, China
| | - Zi-Chun Hua
- The State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macao, China.,The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.,Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou, China
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8
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Marchesi F, Vacca M, Giannarelli D, Ipsevich F, Pandolfi A, Gumenyuk S, Renzi D, Palombi F, Pisani F, Romano A, Spadea A, Papa E, Canfora M, Pierelli L, Mengarelli A. Lenograstim 5 µg/kg is not superior to biosimilar filgrastim 10 µg/kg in lymphoma patients undergoing peripheral blood stem cell mobilization after chemotherapy: preliminary results from a prospective randomized study. Transfusion 2018; 58:1143-1148. [PMID: 29446445 DOI: 10.1111/trf.14533] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Revised: 01/12/2018] [Accepted: 01/14/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Randomized trials comparing chemomobilization efficiency between lenograstim and biosimilar filgrastim are lacking. Our previous retrospective study suggested that lenograstim could be more effective than biosimilar filgrastim when used at the same conventional dosage (5 µg/kg) only in lymphoma patients undergoing peripheral blood stem cell mobilization. We planned a prospective randomized study comparing lenograstim 5 µg/kg with biosimilar filgrastim 10 µg/kg to verify the hypothesis of lenograstim superiority even at half the dosage (stress test). Herein we report data after enrolling 60% of planned patients. STUDY DESIGN AND METHODS From October 2014 to November 2017, a total of 42 of 70 planned patients with lymphoma were randomly assigned to receive lenograstim 5 µg/kg (21) or biosimilar filgrastim 10 µg/kg (21). Patients were stratified according to treatment line at the time of mobilization (1 or ≥2). Primary endpoint was the rate of achievement of the CD34+ cell collection target dose (≥ 4 × 106 /kg). An improvement by 23% was expected to validate the hypothesis of lenograstim superiority. RESULTS The two cohorts were balanced for all the baseline features. We observed an identical rate of patients able to reach the targeted CD34+ cell dose and of mobilization failures (90.4 and 4.8% in both cohorts) and a perfect equivalence in any of the secondary collection outcomes. The hypothesis of lenograstim superiority was not corroborated at interim analysis. CONCLUSION Lenograstim at conventional dosage has failed to demonstrate its superiority over biosimilar filgrastim at double the dosage at interim analysis in their first head-to-head trial.
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Affiliation(s)
| | - Michele Vacca
- Immuno-Transfusional Medicine, Leukapheresis and Cellular Therapy Unit, S. Camillo-Forlanini Hospital, Rome, Italy
| | - Diana Giannarelli
- Biostatistics Unit, Scientific Direction, IRCCS Regina Elena National Cancer Institute, Regina Elena National Cancer Institute
| | - Francesco Ipsevich
- Immuno-Transfusional Medicine, Leukapheresis and Cellular Therapy Unit, S. Camillo-Forlanini Hospital, Rome, Italy
| | - Annino Pandolfi
- Immuno-Transfusional Medicine, Leukapheresis and Cellular Therapy Unit, S. Camillo-Forlanini Hospital, Rome, Italy
| | | | | | | | | | | | | | - Elena Papa
- Hematology and Stem Cell Transplant Unit
| | - Marco Canfora
- Biostatistics Unit, Scientific Direction, IRCCS Regina Elena National Cancer Institute, Regina Elena National Cancer Institute
| | - Luca Pierelli
- Immuno-Transfusional Medicine, Leukapheresis and Cellular Therapy Unit, S. Camillo-Forlanini Hospital, Rome, Italy
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9
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Abstract
Peripheral blood stem cell collection is an effective approach to obtain a hematopoietic graft for stem cell transplantation. Developing hematopoietic stem/progenitor cell (HSPC) mobilization methods and collection algorithms have improved efficiency, clinical outcomes, and cost effectiveness. Differences in mobilization mechanisms may change the HSPC content harvested and result in different engraftment kinetics and complications. Patient-specific factors can affect mobilization. Incorporating these factors in collection algorithms and improving assays for evaluating mobilization further extend the ability to obtain sufficient HSPCs for hematopoietic repopulation. Technological advance and innovations in leukapheresis have improved collection efficiency and reduced adverse effects.
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Affiliation(s)
- Yen-Michael S Hsu
- Pathology and Laboratory Medicine, Transfusion Medicine and Cellular Therapy, Weill Cornell Medical College, 525 East 68th Street, Box 251, New York, NY 10065, USA.
| | - Melissa M Cushing
- Transfusion Medicine and Cellular Therapy, Weill Cornell Medical College, 525 East 68th Street, Box 251, M09, New York, NY 10065, USA.
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10
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Sivgin S, Karakus E, Keklik M, Zararsiz G, Solmaz M, Kaynar L, Eser B, Cetin M, Unal A. Evaluation of the efficacy and safety of original filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) in CD34(+) peripheral hematopoietic stem cell mobilization procedures for allogeneic hematopoietic stem cell transplant donors. Transfus Apher Sci 2016; 54:410-415. [PMID: 27052362 DOI: 10.1016/j.transci.2016.03.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Revised: 02/14/2016] [Accepted: 03/20/2016] [Indexed: 02/08/2023]
Abstract
OBJECTIVES AND AIM In this study, we aimed to compare the potency of different G-CSF agents including original filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) on CD34(+) cell mobilization in patients that underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). PATIENTS AND METHODS The data of 243 donors for alloHSCT recipients diagnosed with mostly acute leukemia and myelodsyplastic syndromes (MDS) were analyzed, retrospectively. Data for stem cell mobilization have been recorded from patients' files. Donors who received Filgrastim (Neupogen®, Group I), biosimilar Filgrastim (Leucostim®, Group II) and Lenograstim (Granocyte®, Group III) were analyzed for total CD34(+) cell count at the end of mobilization procedures. RESULTS A total of 243 donors and patients for alloHSCT were analyzed retrospectively. The diagnosis of the patients were; acute myeloid leukemia (AML) (110 patients, 45.2%), acute lymphoid leukemia (ALL) (61 patients, 25.1%), aplastic anemia (AA) (38 patients, 15.6%), lymphomas (14 patients, 5.7%) and others (20 patients, 8.4%). The median number of total collected PB CD34(+) cells (×10(6)/kg) was 7.12 (min-max: 5.38-7.90) in the Neupogen® group, 7.27 (min-max: 6.79-7.55) in the Leucostim® group and 7.15 (min-max: 5.34-7.58) in the Granocyte® group. There was no statistically significant difference among groups in terms of total collected PB CD34(+) cells (p = 0.919). The median doses of G-CSF agents (µg/kg/day) in PBSC collection in Neupogen® group was; 11.00 (10.00-12.00) in Leucostim® group10.35 (min-max: 10.00-11.10) and in Granocyte® group11.00 (min-max: 10.00-11.00). There was no statistical significance among groups (p = 0.215). CONCLUSION Biosimilar filgrastim (Leucostim®) was found comparable to original Filgrastim (Neupogen®) and Lenograstim (Granocyte®) for PBSC mobilization in donors of the patients that underwent alloHSCT.
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Affiliation(s)
- Serdar Sivgin
- Department of Hematology, Erciyes Stem Cell Transplantation Hospital, Kayseri, Turkey.
| | - Esen Karakus
- Department of Hematology, Erciyes Stem Cell Transplantation Hospital, Kayseri, Turkey
| | - Muzaffer Keklik
- Department of Hematology, Erciyes Stem Cell Transplantation Hospital, Kayseri, Turkey
| | - Gokmen Zararsiz
- Department of Medical Statistics, Erciyes University, Kayseri, Turkey
| | - Musa Solmaz
- Apheresis Unit, Erciyes Stem Cell Transplantation Hospital, Department of Hematology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - Leylagul Kaynar
- Department of Hematology, Erciyes Stem Cell Transplantation Hospital, Kayseri, Turkey
| | - Bulent Eser
- Department of Hematology, Erciyes Stem Cell Transplantation Hospital, Kayseri, Turkey
| | - Mustafa Cetin
- Department of Hematology, Erciyes Stem Cell Transplantation Hospital, Kayseri, Turkey
| | - Ali Unal
- Department of Hematology, Erciyes Stem Cell Transplantation Hospital, Kayseri, Turkey
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Rossi L, Martignano F, Gallà V, Maugeri A, Schepisi G. Impact of Non-Pulmonary Visceral Metastases in the Prognosis and Practice of Metastatic Testicular Germ Cell Tumors. Oncol Rev 2016; 10:292. [PMID: 27471579 PMCID: PMC4943091 DOI: 10.4081/oncol.2016.292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Accepted: 04/07/2016] [Indexed: 12/03/2022] Open
Abstract
Non-pulmonary visceral metastases, in bones, brain and liver, represent nearly the 10% of metastatic sites of advanced germ cell tumors and are associated with poor prognosis. This review article summarizes major evidences on the impact of different visceral sites on the prognosis, treatment and clinical outcome of patients with germ cell tumors. The clinic-biological mechanisms by which these metastatic sites are associated with poor clinical outcome remain unclear. The multimodality treatment showed a potential better survival, in particular in patients with relapsed disease. Patients with advanced germ cell tumors with visceral metastases should be referred to centers with high expertise in the clinical management of such disease.
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Affiliation(s)
- Lorena Rossi
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)-IRCCS , Meldola (FC), Italy
| | - Filippo Martignano
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)-IRCCS , Meldola (FC), Italy
| | - Valentina Gallà
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)-IRCCS , Meldola (FC), Italy
| | - Antonio Maugeri
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)-IRCCS , Meldola (FC), Italy
| | - Giuseppe Schepisi
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)-IRCCS , Meldola (FC), Italy
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12
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Kuan JW, Su AT, Leong CF, Tharyan P. Pegylated granulocyte colony stimulating factor versus non-pegylated granulocyte colony stimulating factor for peripheral stem cell mobilization. Hippokratia 2016. [DOI: 10.1002/14651858.cd010103.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Affiliation(s)
- Jew-Win Kuan
- Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak; Department of Medicine; 94300 Kota Samarahan Sarawak Malaysia
| | - Anselm Ting Su
- Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak; Department of Community Medicine and Public Health; 94300 Kota Samarahan Sarawak Malaysia
| | - Chooi-Fun Leong
- University Kebangsaan Malaysia Medical Center; Department of Pathology; Jalan Yaakob Latif Kuala Lumpur Wilayah Persekutuan Malaysia 56000
| | - Prathap Tharyan
- Christian Medical College; Cochrane South Asia, Prof. BV Moses Center for Evidence-Informed Health Care and Health Policy; Carman Block II Floor CMC Campus, Bagayam Vellore Tamil Nadu India 632002
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13
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Bozdag SC, Ilhan O. Peripheral blood stem cell mobilization and collection from elderly patients and elderly healthy donor. Transfus Apher Sci 2015; 53:8-12. [DOI: 10.1016/j.transci.2015.05.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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14
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Marchesi F, Vacca M, Gumenyuk S, Pandolfi A, Renzi D, Palombi F, Pisani F, Romano A, Spadea A, Ipsevich F, Santinelli S, De Rienzo M, Papa E, Canfora M, Laurenzi L, Foddai ML, Pierelli L, Mengarelli A. Biosimilar filgrastim (Zarzio®) vs. lenograstim (Myelostim®) for peripheral blood stem cell mobilization in adult patients with lymphoma and myeloma: a single center experience. Leuk Lymphoma 2015; 57:489-492. [DOI: 10.3109/10428194.2015.1063147] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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15
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Martino M, Recchia AG, Moscato T, Fedele R, Neri S, Gentile M, Alati C, Vincelli ID, Piro E, Penna G, Musolino C, Ronco F, Molica S, Morabito F. Efficacy of biosimilar granulocyte colony-stimulating factor versus originator granulocyte colony-stimulating factor in peripheral blood stem cell mobilization in de novo multiple myeloma patients. Cytotherapy 2015; 17:1485-93. [PMID: 26188967 DOI: 10.1016/j.jcyt.2015.05.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2015] [Revised: 04/08/2015] [Accepted: 05/14/2015] [Indexed: 11/28/2022]
Abstract
BACKGROUND AIMS Filgrastim and lenograstim are the standard granulocyte colony-stimulating factor (G-CSF) agents for peripheral blood stem cell mobilization (PBSC) in patients who undergo autologous stem cell transplantation. METHODS To assess whether biosimilars are effective, we conducted a single-center, prospective study that included 40 consecutive de novo multiple myeloma patients who received cyclophosphamide 4 g/m(2) per day plus biosimilar filgrastim G-CSF to mobilize PBSC. These patients were compared with a group of 37 patients matched for age, diagnosis, previous chemotherapy and mobilization who had been treated with originator G-CSF. The mean number of CD34+ cells/μL in the peripheral blood was 199.6 ± 207.4 in the biosimilar and 192.8 ± 154.7 in the originator group (P = 0.87). The median number of CD34+ cells/kg recipient collected was 11.5 ± 5.8 and 12.3 ± 5.3 in the biosimilar and originator groups, respectively (P = 0.51). The mobilization failure rate was 2.5% and 2.7% in the biosimilar filgrastim and originator filgrastim cohorts (P = NS), respectively. RESULTS Twenty-nine patients in the biosimilar group and 28 patients in the originator group underwent autologous transplantation. There were no statistically significant differences between the biosimilar and originator G-CSF cohorts in terms of hematopoietic recovery parameters and transplant-related toxicities. CONCLUSIONS The efficacy of biosimilar G-CSF appears to be equivalent to the reference G-CSF.
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Affiliation(s)
- Massimo Martino
- Hematology and Stem Cell Transplant Unit, Azienda Ospedaliera BMM, Reggio Calabria, Italy.
| | - Anna Grazia Recchia
- Biotechnology Research Unit, Azienda Sanitaria Provinciale di Cosenza, Aprigliano (CS), Italy
| | - Tiziana Moscato
- Hematology and Stem Cell Transplant Unit, Azienda Ospedaliera BMM, Reggio Calabria, Italy
| | - Roberta Fedele
- Hematology and Stem Cell Transplant Unit, Azienda Ospedaliera BMM, Reggio Calabria, Italy
| | - Santo Neri
- Hematology Unit, Azienda Ospedaliera Papardo, Messina, Italy
| | | | - Caterina Alati
- Hematology Unit, Azienda Ospedaliera BMM, Reggio Calabria, Italy
| | | | - Eugenio Piro
- Hematology Unit, Azienda Ospedaliera Pugliese Ciaccio, Catanzaro, Italy
| | - Giuseppa Penna
- School and Division of Hematology, University Hospital "G. Martino", Messina, Italy
| | - Caterina Musolino
- School and Division of Hematology, University Hospital "G. Martino", Messina, Italy
| | - Francesca Ronco
- Hematology Unit, Azienda Ospedaliera BMM, Reggio Calabria, Italy
| | - Stefano Molica
- Hematology Unit, Azienda Ospedaliera Pugliese Ciaccio, Catanzaro, Italy
| | - Fortunato Morabito
- Biotechnology Research Unit, Azienda Sanitaria Provinciale di Cosenza, Aprigliano (CS), Italy; Haematology Unit, Azienda Ospedaliera Cosenza, Italy
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16
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Ria R, Reale A, Melaccio A, Racanelli V, Dammacco F, Vacca A. Filgrastim, lenograstim and pegfilgrastim in the mobilization of peripheral blood progenitor cells in patients with lymphoproliferative malignancies. Clin Exp Med 2014; 15:145-50. [PMID: 24722996 PMCID: PMC4412650 DOI: 10.1007/s10238-014-0282-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2014] [Accepted: 03/25/2014] [Indexed: 12/01/2022]
Abstract
Patients with lymphoproliferative disorders, candidate to autologous stem cell transplantation (ASCT), require mobilization with chemotherapy and granulocyte colony -stimulating factor (G-CSF). This study looked for differences in hematopoietic peripheral stem cells (HPSCs) mobilization in response to the three available G-CSFs, namely lenograstim, filgrastim, and pegfilgrastim. Between 2000 and 2012, 146 patients (66 M and 80 F) who underwent ASCT for multiple myeloma, non-Hodgkin's lymphoma or Hodgkin's lymphoma were studied. All patients received induction therapy and then a mobilization regimen with cyclophosphamide plus lenograstim, or filgrastim, or pegfilgrastim. From days 12 to 14, HPSCs were collected by two to three daily leukaphereses. Our results show that high-dose cyclophosphamide plus lenograstim achieved adequate mobilization and the collection target more quickly and with fewer leukaphereses as compared to filgrastim and pegfilgrastim. No differences between the three regimens were observed regarding toxicity and days to WBC and platelet recovery. Thus, lenograstim may represent the ideal G-CSF for PBSC mobilization in patients with lymphoproliferative diseases. Further studies are needed to confirm these results and better understand the biological bases of these differences.
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Affiliation(s)
- Roberto Ria
- Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy,
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17
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Martino M, Laszlo D, Lanza F. Long-active granulocyte colony-stimulating factor for peripheral blood hematopoietic progenitor cell mobilization. Expert Opin Biol Ther 2014; 14:757-72. [DOI: 10.1517/14712598.2014.895809] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Abstract
PURPOSE Chemotherapy-induced febrile neutropenia (FEN), which causes treatment delays or chemotherapy dose reductions, is a serious side effect of cancer treatment. In Turkey, recombinant G-CSF (rG-CSF) has been used since 2000 to control neutropenia. The purpose of this prospective randomized study is to compare the effectiveness, toxicities and the cost of these two drugs in children. METHODS Between April and December 2008, 29 patients were administered 40 courses of chemotherapy in each arm. A randomized crossover study was designed. All patients were administered rG-CSF 24 hours after the last day of chemotherapy as a secondary prophylaxis. Complete blood counts as well as peripheral blood progenitor (CD34+) cell levels were measured before G-CSF treatment and on the fifth and the seventh day of treatment. RESULTS The median duration of neutropenia, FEN, the length of hospitalization, the incidence of FEN, and documented infection was not different between the two rG-CSF treatment groups. Erythrocyte and platelet transfusion rates were also similar. After 7 days, the mean leukocyte (WBC [white blood cell]) and neutrophil count (ANC [absolute neutrophil count]), hemoglobin and platelet levels were not significantly different. However, the CD34+ cell level was significantly higher in the lenograstim group. Lenograstim was also more expensive than filgrastim. No serious side effects were reported for either rG-CSF treatment. CONCLUSIONS There is no difference following the administration of either lenograstim or filgrastim for the duration of neutropenia, FEN or hospitalization for pediatric cancer patients. For stem cell mobilization, lenograstim was superior to filgrastim.
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Affiliation(s)
- Neriman Sarı
- 1Department of Pediatric Hematology and Oncology, Dr Abdurrahman Yurtaslan Ankara Oncology Hospital, Ankara, Turkey
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19
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Abstract
The use of mobilized peripheral blood stem cells (PBSCs) has largely replaced the use of bone marrow as a source of stem cells for both allogeneic and autologous stem cell transplantation. G-CSF with or without chemotherapy is the most commonly used regimen for stem cell mobilization. Some donors or patients, especially the heavily pretreated patients, fail to mobilize the targeted number of stem cells with this regimen. A better understanding of the mechanisms involved in hematopoietic stem cell (HSC) trafficking could lead to the development of newer mobilizing agents and therapeutic approaches. This review will cover the current methods for stem cell mobilization and recent developments in the understanding of the biology of stem cells and the bone marrow microenvironment.
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Affiliation(s)
- Ibraheem H Motabi
- Siteman Cancer Center, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA.
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20
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Systematic Review of Randomized Controlled Trials of Hematopoietic Stem Cell Mobilization Strategies for Autologous Transplantation for Hematologic Malignancies. Biol Blood Marrow Transplant 2012; 18:1191-203. [DOI: 10.1016/j.bbmt.2012.01.008] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2011] [Accepted: 01/11/2012] [Indexed: 11/20/2022]
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21
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Pierelli L, Perseghin P, Marchetti M, Accorsi P, Fanin R, Messina C, Olivieri A, Risso M, Salvaneschi L, Bosi A. Best practice for peripheral blood progenitor cell mobilization and collection in adults and children: results of a Società Italiana Di Emaferesi e Manipolazione Cellulare (SIDEM) and Gruppo Italiano Trapianto Midollo Osseo (GITMO) consensus process. Transfusion 2011; 52:893-905. [DOI: 10.1111/j.1537-2995.2011.03385.x] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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22
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Novel agents and approaches for stem cell mobilization in normal donors and patients. Bone Marrow Transplant 2011; 47:1154-63. [DOI: 10.1038/bmt.2011.170] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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24
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Abstract
New advances in effective mobilization of peripheral blood stem cells have permitted a greater proportion of patients to benefit from autologous stem cell transplantation. In this review, the relative merits of peripheral blood and mobilized bone marrow are discussed. All available agents are reviewed. A critical assessment of the appropriate dosing and frequency of available growth factors is undertaken, and the most commonly used chemotherapy plus growth factor combinations are covered. Specific recommendations for patients who are poor mobilizers are dealt with including the role of plerixafor.
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Affiliation(s)
- Morie A Gertz
- Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
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25
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Gunzer K, Clarisse B, Lheureux S, Delcambre C, Joly F. Contribution of glycosylated recombinant human granulocyte colony-stimulating factor (lenograstim) use in current cancer treatment: review of clinical data. Expert Opin Biol Ther 2010; 10:615-30. [DOI: 10.1517/14712591003689964] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
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26
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Ria R, Gasparre T, Mangialardi G, Bruno A, Iodice G, Vacca A, Dammacco F. Comparison between filgrastim and lenograstim plus chemotherapy for mobilization of PBPCs. Bone Marrow Transplant 2009; 45:277-81. [DOI: 10.1038/bmt.2009.150] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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27
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Varki R, Pequignot E, Leavitt MC, Ferber A, Kraft WK. A glycosylated recombinant human granulocyte colony stimulating factor produced in a novel protein production system (AVI-014) in healthy subjects: a first-in human, single dose, controlled study. BMC CLINICAL PHARMACOLOGY 2009; 9:2. [PMID: 19175929 PMCID: PMC2639539 DOI: 10.1186/1472-6904-9-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/03/2008] [Accepted: 01/28/2009] [Indexed: 12/03/2022]
Abstract
Background AVI-014 is an egg white-derived, recombinant, human granulocyte colony-stimulating factor (G-CSF). This healthy volunteer study is the first human investigation of AVI-014. Methods 24 male and female subjects received a single subcutaneous injection of AVI-014 at 4 or 8 mcg/kg. 16 control subjects received 4 or 8 mcg/kg of filgrastim (Neupogen, Amgen) in a partially blinded, parallel fashion. Results The Geometric Mean Ratio (GMR) (90% CI) of 4 mcg/kg AVI-014/filgrastim AUC(0–72 hr) was 1.00 (0.76, 1.31) and Cmax was 0.86 (0.66, 1.13). At the 8 mcg/kg dose, the AUC(0–72) GMR was 0.89 (0.69, 1.14) and Cmax was 0.76 (0.58, 0.98). A priori pharmacokinetic bioequivalence was defined as the 90% CI of the GMR bounded by 0.8–1.25. Both the white blood cell and absolute neutrophil count area under the % increase curve AUC(0–9 days) and Cmax (maximal % increase from baseline)GMR at 4 and 8 mcg/kg fell within the 0.5–2.0 a priori bound set for pharmacodynamic bioequivalence. The CD 34+ % increase curve AUC(0–9 days) and Cmax GMR for both doses was ~1, but 90% confidence intervals were large due to inherent variance, and this measure did not meet pharmacodynamic bioequivalence. AVI-014 demonstrated a side effect profile similar to that of filgrastim. Conclusion AVI-014 has safety, pharmacokinetic, and pharmacodynamic properties comparable to filgrastim at an equal dose in healthy volunteers. These findings support further investigation in AVI-014.
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Affiliation(s)
- Roslyn Varki
- Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, 132 South 10th Street, 1170 Main Building, Philadelphia, PA 19107, USA.
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Ataergin S, Arpaci F, Turan M, Solchaga L, Cetin T, Ozturk M, Ozet A, Komurcu S, Ozturk B. Reduced dose of lenograstim is as efficacious as standard dose of filgrastim for peripheral blood stem cell mobilization and transplantation: a randomized study in patients undergoing autologous peripheral stem cell transplantation. Am J Hematol 2008; 83:644-8. [PMID: 18508321 DOI: 10.1002/ajh.21206] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
In vitro studies have demonstrated a 27% increased efficacy of lenograstim over filgrastim. However, equal doses of 10 microg/kg/day of filgrastim and lenograstim have been recommended for mobilization of CD34+ cells without associated chemotherapy. In this study, we investigated whether a 25% reduced dose of lenograstim at 7.5 microg/kg/day is equavalent to 10 microg/kg/day filgrastim for autologous peripheral blood stem cell (PBSC) mobilization and transplantation. A total of 40 consecutive patients were randomized to either filgrastim (n = 20) or lenograstim (n = 20). The two cohorts were similar in regard to disease, sex, body weight, body surface area, conditioning regimens, previous chemotherapy cycles and radiotherapy. Each growth factor was administered for 4 consecutive days. The first PBSC apheresis was done on the 5th day. In the posttransplant period, the same G-CSF was given at 5 microg/kg/day until leukocyte engraftment. Successful mobilization was achieved in 95% of patients. Successful mobilization with the first apheresis, was achieved in 10/20 (50%) patients in the filgrastim group versus 9/20 (46%) patients in the lenograstim group. No significant difference was seen in the median number of CD34+cells mobilized, as well as the median number of apheresis, median volume of apheresis, percentage of CD34+ cells, and CD34+ cell number. Leukocyte and platelet engraftments, the number of days requiring G-CSF and parenteral antibiotics, the number of transfusions were similar in both groups in the posttransplant period. Lenograstim 7.5 microg/kg/day is as efficious as filgrastim 10 microg/kg/day for autologous PBSC mobilization and transplantation.
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Affiliation(s)
- Selmin Ataergin
- GATA (Gulhane) Faculty of Medicine, Department of Medical Oncology and Bone Marrow Transplantation Unit, 06018 Etlik, Ankara, Turkey.
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Thomas X. New emerging applications of molgramostim in acute myeloid leukaemia. Expert Opin Drug Metab Toxicol 2008; 4:795-806. [DOI: 10.1517/17425255.4.6.795] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Littlewood TJ, Collins GP. Granulocyte and erythropoietic stimulating proteins after high-dose chemotherapy for myeloma. Bone Marrow Transplant 2007; 40:1147-55. [PMID: 17846601 DOI: 10.1038/sj.bmt.1705845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
High-dose chemotherapy is an established treatment for patients with myeloma. In randomized trials it has been shown to prolong disease-free survival by around 1 year compared to patients receiving chemotherapy alone. Physically and psychologically high-dose therapy takes its toll on the patient who may be in hospital for around 3 weeks and take some weeks or months to convalesce after discharge. Granulocyte colony stimulating factors and erythropoietic stimulating agents will speed neutrophil and red cell recovery, respectively, when used at an appropriate time after the high-dose chemotherapy. The clinical value of these laboratory findings is uncertain and the role of these agents after high-dose chemotherapy remains a subject for debate.
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Affiliation(s)
- T J Littlewood
- Department of Haematology, John Radcliffe Hospital, Oxford, UK.
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