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Multipl Miyelom ve Lenfoma Hastalarında Düşük Doz Etoposid Kemomobilizasyonunun Etkinliği ve Güvenilirliği

Yıl 2024, Cilt: 50 Sayı: 3, 367 - 373, 12.01.2025
https://doi.org/10.32708/uutfd.1518837

Öz

Çalışmalarda yüksek doz etoposid ile tedaviye bağlı lösemi ve miyelodisplastik sendrom riskinin keşfedilmesi, daha düşük dozların etkinliğine daha yakından bakılmasına neden olmuştur. Bu çalışmada, multiple miyelom (MM) ve lenfoma hastalarında düşük doz etoposidin etkinliğini göstermeyi amaçladık. Bursa Uludağ Üniversitesi Tıp Fakültesi Hematoloji Bölümü Kök Hücre Nakli Ünitesi’nde düşük doz etoposid (1. ve 2. günler, 375 mg/m²) ve granulocyte colony-stimulating factor (G-CSF, 3. günden sonra 10-15 μg/kg) ile kök hücre mobilizasyonu yapılan MM ve refrakter lenfomalı 48 hasta retrospektif olarak analiz edildi. Başarılı mobilizasyon (> 2x106/kg CD34+ hücre toplanması) oranı %95 olup en az 1, en fazla 3 aferezde gerçekleştirildi. Toplanan median CD34+ hücre sayısı 9,165 × 10⁶/kg idi (good mobilizerlerde 11,7 vs poor mobilizerde 3,98× 10⁶/kg, p<0,001). İlk gün periferik CD34+ hücre sayısının düşük olmasının (Hazard ratio (HR); 0.00, %95 confidence interval (CI) 0.00-0.660; p=0,040) ve önceki otolog hematopoietik kök hücre naklinin (HR; 1.206, %95 CI 1.009-1.442; p=0,043) kötü mobilizasyon için bağımsız risk faktörleri olduğu belirlendi. Hastaların %18,8'inde febril nötropeni saptandı (good mobilizerlerde %11,4 vs poor mobilizerlerde %38,5, p=0,048) ve %16,7'sinde eritrosit transfüzyonu ihtiyacı oldu (good mobilizerlerde %14,3 vs poor mobilizerlerde %23,1, p=0,664). Median 35,5 aylık takip süresinde hastaların hiçbirinde tedaviye bağlı ikincil malignite saptanmadı. Çalışmamızın sonuçları düşük doz etoposid ve G-CSF'nin MM ve refrakter lenfoma hastalarında tolere edilebilir toksisite ile etkili mobilizasyon ajanları olduğunu ortaya koydu.

Kaynakça

  • 1. Moreau P, San Miguel J, Sonneveld P, Mateos MV, ZamagniE, Avet-Loiseau H, et al. Multiple myeloma: ESMO ClinicalPractice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl_4):iv52-iv61.
  • 2. Milpied N, Deconinck E, Gaillard F, Delwail V, Foussard C,Berthou C, et al. Initial treatment of aggressive lymphoma withhigh-dose chemotherapy and autologous stem-cell support. N Engl J Med. 2004;350(13):1287-95.
  • 3. Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM,Haenel M, et al. Aggressive conventional chemotherapycompared with high-dose chemotherapy with autologoushaemopoietic stem-cell transplantation for relapsedchemosensitive Hodgkin's disease: a randomised trial. Lancet.2002;359(9323):2065-71.
  • 4. Bensinger W, DiPersio JF, McCarty JM. Improving stem cellmobilization strategies: future directions. Bone MarrowTransplant. 2009;43(3):181-95.
  • 5. DiPersio JF, Micallef IN, Stiff PJ, Bolwell BJ, Maziarz RT,Jacobsen E, et al. Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocytecolony-stimulating factor compared with placebo plusgranulocyte colony-stimulating factor for autologous stem-cellmobilization and transplantation for patients with non-Hodgkin's lymphoma. J Clin Oncol. 2009;27(28):4767-73.
  • 6. Gertz MA, Kumar SK, Lacy MQ, Dispenzieri A, Hayman SR, Buadi FK, et al. Comparison of high-dose CY and growthfactor with growth factor alone for mobilization of stem cellsfor transplantation in patients with multiple myeloma. BoneMarrow Transplant. 2009;43(8):619-25.
  • 7. Albini A, Pennesi G, Donatelli F, Cammarota R, De Flora S,Noonan DM. Cardiotoxicity of anticancer drugs: the need forcardio-oncology and cardio-oncological prevention. J NatlCancer Inst. 2010;102(1):14-25.
  • 8. Park Y, Kim DS, Jeon MJ, Lee BH, Yu ES, Kang KW, et al.Single-dose etoposide is an effective and safe protocol for stemcell mobilization in patients with multiple myeloma. J ClinApher. 2019;34(5):579-88.
  • 9. Ozkan HA, Bal C, Gulbas Z. Chemomobilization with high-dose etoposide and G-CSF results in effective and safe stemcell collection in heavily pretreated lymphoma patients: reportfrom a single institution study and review. Eur J Haematol.2014;92(5):390-7.
  • 10. Guner SI, Yanmaz MT, Selvi A, Usul C. The High Effect ofChemomobilization with High-Dose Etopside + Granulocyte-Colony Stimulating Factor in Autologous HematopoieticPeripheral Blood Stem Cell Transplantation: A Single CenterExperience. Hematol Rep. 2016;8(1):6319.
  • 11. Mahindra A, Bolwell BJ, Rybicki L, Elder P, Kalaycio M, Dean R, et al. Etoposide plus G-CSF priming compared with G-CSF alone in patients with lymphoma improves mobilizationwithout an increased risk of secondary myelodysplasia andleukemia. Bone Marrow Transplant. 2012;47(2):231-5.
  • 12. Duarte RF, Shaw BE, Marin P, Kottaridis P, Ortiz M, Morante C, et al. Plerixafor plus granulocyte CSF can mobilizehematopoietic stem cells from multiple myeloma andlymphoma patients failing previous mobilization attempts: EUcompassionate use data. Bone Marrow Transplant.2011;46(1):52-8.
  • 13. Li B, Yang JL, Shi YK, He XH, Han XH, Zhou SY, et al.Etoposide 1.0 g/m2 or 1.5 g/m2 combined with granulocytecolony-stimulating factor for mobilization of peripheral bloodstem cells in patients with malignancy: efficacy and toxicity.Cytotherapy. 2009;11(3):362-71.
  • 14. Song GY, Jung SH, Ahn SY, Jung SY, Yang DH, Ahn JS, et al.Optimal chemo-mobilization for the collection of peripheral blood stem cells in patients with multiple myeloma. BMCCancer. 2019;19(1):59.
  • 15. Hopman RK, DiPersio JF. Advances in stem cell mobilization. Blood Rev. 2014;28(1):31-40.
  • 16. Hyun SY, Cheong JW, Kim SJ, Min YH, Yang DH, Ahn JS, etal. High-dose etoposide plus granulocyte colony-stimulating factor as an effective chemomobilization regimen forautologous stem cell transplantation in patients with non-Hodgkin Lymphoma previously treated with CHOP-based chemotherapy: a study from the Consortium for Improving Survival of Lymphoma. Biol Blood Marrow Transplant. 2014;20(1):73-9.
  • 17. Cai Y, Wan L, Yang J, Zhu J, Jiang J, Li S, et al. High-dose etoposide could discriminate the benefit from autologousperipheral blood stem cell transplantation in the patients withrefractory diffuse large B cell lymphoma. Ann Hematol.2019;98(4):823-31.
  • 18. Zucenka A, Peceliunas V, Maciutaite E, Chaleckaite J,Jakimaviciute R, Griskevicius L. Etoposide + GranulocyteColony-Stimulating Factor and Optional Plerixafor in PatientsWho Failed Chemomobilization with or without Plerixafor.Biol Blood Marrow Transplant. 2019;25(7):1304-11.
  • 19. Krishnan A, Bhatia S, Slovak ML, Arber DA, Niland JC, Nademanee A, et al. Predictors of therapy-related leukemia andmyelodysplasia following autologous transplantation forlymphoma: an assessment of risk factors. Blood.2000;95(5):1588-93.
  • 20. Ameen RM, Alshemmari SH, Alqallaf D. Factors associated with successful mobilization of progenitor hematopoietic stemcells among patients with lymphoid malignancies. ClinLymphoma Myeloma. 2008;8(2):106-10.
  • 21. Demirer T, Ayli M, Ozcan M, Gunel N, Haznedar R, Dagli M,et al. Mobilization of peripheral blood stem cells withchemotherapy and recombinant human granulocyte colony-stimulating factor (rhG-CSF): a randomized evaluation ofdifferent doses of rhG-CSF. Br J Haematol. 2002;116(2):468-74.
  • 22. Mollee P, Pereira D, Nagy T, Song K, Saragosa R, Keating A,et al. Cyclophosphamide, etoposide and G-CSF to mobilizeperipheral blood stem cells for autologous stem celltransplantation in patients with lymphoma. Bone MarrowTransplant. 2002;30(5):273-8.
  • 23. Wood WA, Whitley J, Moore D, Sharf A, Irons R, Rao K, et al. Chemomobilization with Etoposide is Highly Effective inPatients with Multiple Myeloma and Overcomes the Effects ofAge and Prior Therapy. Biol Blood Marrow Transplant.2011;17(1):141-6.
  • 24. Wood WA, Whitley J, Goyal R, Brown PM, Sharf A, Irons R,et al. Effectiveness of etoposide chemomobilization inlymphoma patients undergoing auto-SCT. Bone MarrowTransplant. 2013;48(6):771-6.
  • 25. Hsu YM, Cushing MM. Autologous Stem Cell Mobilizationand Collection. Hematol Oncol Clin North Am.2016;30(3):573-89.

Effectiveness and Safety of Low-Dose Etoposide Chemomobilization in Patients with Multiple Myeloma and Lymphoma

Yıl 2024, Cilt: 50 Sayı: 3, 367 - 373, 12.01.2025
https://doi.org/10.32708/uutfd.1518837

Öz

Studies have discovered a risk of treatment-related leukemia and myelodysplastic syndromes with high doses of etoposide prompting a closer look, at the effectiveness of lower doses. In this study, we aimed to demonstrate the efficacy of low-dose etoposide in patients with MM and lymphoma. Forty-eight patients with MM and refractory lymphoma who underwent stem cell mobilization with low-dose etoposide (days 1 and 2, 375 mg/m²) and granulocyte colony-stimulating factor (G-CSF, 10-15 μg/kg after the 3rd day) in Bursa Uludağ University Faculty of Medicine Hematology Department Stem Cell Transplantation Unit were analyzed retrospectively. The rate of successful mobilization (> 2x106/kg CD34+ cell collection) was 95% and was performed in a minimum of 1 and a maximum of 3 apheresis. The median collected CD34+ cell count was 9.165 × 10⁶/kg (11.7 in good vs 3.98 in poor mobilizers, p<0.001). It was determined that a low number of peripheral CD34+ cells on the first day (Hazard ratio (HR); 0.00, 95% Confidence interval (CI) 0.00-0.660; p=0.040) and prior autologous hematopoietic stem cell transplantation (HR; 1.206, 95% CI 1.009-1.442; p=0.043) were independent risk factors for poor mobilization. Febrile neutropenia occurred in 18.8% (11.4% in good vs 38.5% in poor mobilizers, p=0.048), and 16.7% required erythrocyte transfusions (14.3% in good vs 23.1% in poor mobilizers, p=0.664). In the median follow-up of 35.5 months, no treatment-related secondary malignancy was detected in any patients. Our results show that low-dose etoposide and G-CSF are effective mobilization agents with tolerable toxicity in patients with MM and refractory lymphoma.

Kaynakça

  • 1. Moreau P, San Miguel J, Sonneveld P, Mateos MV, ZamagniE, Avet-Loiseau H, et al. Multiple myeloma: ESMO ClinicalPractice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl_4):iv52-iv61.
  • 2. Milpied N, Deconinck E, Gaillard F, Delwail V, Foussard C,Berthou C, et al. Initial treatment of aggressive lymphoma withhigh-dose chemotherapy and autologous stem-cell support. N Engl J Med. 2004;350(13):1287-95.
  • 3. Schmitz N, Pfistner B, Sextro M, Sieber M, Carella AM,Haenel M, et al. Aggressive conventional chemotherapycompared with high-dose chemotherapy with autologoushaemopoietic stem-cell transplantation for relapsedchemosensitive Hodgkin's disease: a randomised trial. Lancet.2002;359(9323):2065-71.
  • 4. Bensinger W, DiPersio JF, McCarty JM. Improving stem cellmobilization strategies: future directions. Bone MarrowTransplant. 2009;43(3):181-95.
  • 5. DiPersio JF, Micallef IN, Stiff PJ, Bolwell BJ, Maziarz RT,Jacobsen E, et al. Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocytecolony-stimulating factor compared with placebo plusgranulocyte colony-stimulating factor for autologous stem-cellmobilization and transplantation for patients with non-Hodgkin's lymphoma. J Clin Oncol. 2009;27(28):4767-73.
  • 6. Gertz MA, Kumar SK, Lacy MQ, Dispenzieri A, Hayman SR, Buadi FK, et al. Comparison of high-dose CY and growthfactor with growth factor alone for mobilization of stem cellsfor transplantation in patients with multiple myeloma. BoneMarrow Transplant. 2009;43(8):619-25.
  • 7. Albini A, Pennesi G, Donatelli F, Cammarota R, De Flora S,Noonan DM. Cardiotoxicity of anticancer drugs: the need forcardio-oncology and cardio-oncological prevention. J NatlCancer Inst. 2010;102(1):14-25.
  • 8. Park Y, Kim DS, Jeon MJ, Lee BH, Yu ES, Kang KW, et al.Single-dose etoposide is an effective and safe protocol for stemcell mobilization in patients with multiple myeloma. J ClinApher. 2019;34(5):579-88.
  • 9. Ozkan HA, Bal C, Gulbas Z. Chemomobilization with high-dose etoposide and G-CSF results in effective and safe stemcell collection in heavily pretreated lymphoma patients: reportfrom a single institution study and review. Eur J Haematol.2014;92(5):390-7.
  • 10. Guner SI, Yanmaz MT, Selvi A, Usul C. The High Effect ofChemomobilization with High-Dose Etopside + Granulocyte-Colony Stimulating Factor in Autologous HematopoieticPeripheral Blood Stem Cell Transplantation: A Single CenterExperience. Hematol Rep. 2016;8(1):6319.
  • 11. Mahindra A, Bolwell BJ, Rybicki L, Elder P, Kalaycio M, Dean R, et al. Etoposide plus G-CSF priming compared with G-CSF alone in patients with lymphoma improves mobilizationwithout an increased risk of secondary myelodysplasia andleukemia. Bone Marrow Transplant. 2012;47(2):231-5.
  • 12. Duarte RF, Shaw BE, Marin P, Kottaridis P, Ortiz M, Morante C, et al. Plerixafor plus granulocyte CSF can mobilizehematopoietic stem cells from multiple myeloma andlymphoma patients failing previous mobilization attempts: EUcompassionate use data. Bone Marrow Transplant.2011;46(1):52-8.
  • 13. Li B, Yang JL, Shi YK, He XH, Han XH, Zhou SY, et al.Etoposide 1.0 g/m2 or 1.5 g/m2 combined with granulocytecolony-stimulating factor for mobilization of peripheral bloodstem cells in patients with malignancy: efficacy and toxicity.Cytotherapy. 2009;11(3):362-71.
  • 14. Song GY, Jung SH, Ahn SY, Jung SY, Yang DH, Ahn JS, et al.Optimal chemo-mobilization for the collection of peripheral blood stem cells in patients with multiple myeloma. BMCCancer. 2019;19(1):59.
  • 15. Hopman RK, DiPersio JF. Advances in stem cell mobilization. Blood Rev. 2014;28(1):31-40.
  • 16. Hyun SY, Cheong JW, Kim SJ, Min YH, Yang DH, Ahn JS, etal. High-dose etoposide plus granulocyte colony-stimulating factor as an effective chemomobilization regimen forautologous stem cell transplantation in patients with non-Hodgkin Lymphoma previously treated with CHOP-based chemotherapy: a study from the Consortium for Improving Survival of Lymphoma. Biol Blood Marrow Transplant. 2014;20(1):73-9.
  • 17. Cai Y, Wan L, Yang J, Zhu J, Jiang J, Li S, et al. High-dose etoposide could discriminate the benefit from autologousperipheral blood stem cell transplantation in the patients withrefractory diffuse large B cell lymphoma. Ann Hematol.2019;98(4):823-31.
  • 18. Zucenka A, Peceliunas V, Maciutaite E, Chaleckaite J,Jakimaviciute R, Griskevicius L. Etoposide + GranulocyteColony-Stimulating Factor and Optional Plerixafor in PatientsWho Failed Chemomobilization with or without Plerixafor.Biol Blood Marrow Transplant. 2019;25(7):1304-11.
  • 19. Krishnan A, Bhatia S, Slovak ML, Arber DA, Niland JC, Nademanee A, et al. Predictors of therapy-related leukemia andmyelodysplasia following autologous transplantation forlymphoma: an assessment of risk factors. Blood.2000;95(5):1588-93.
  • 20. Ameen RM, Alshemmari SH, Alqallaf D. Factors associated with successful mobilization of progenitor hematopoietic stemcells among patients with lymphoid malignancies. ClinLymphoma Myeloma. 2008;8(2):106-10.
  • 21. Demirer T, Ayli M, Ozcan M, Gunel N, Haznedar R, Dagli M,et al. Mobilization of peripheral blood stem cells withchemotherapy and recombinant human granulocyte colony-stimulating factor (rhG-CSF): a randomized evaluation ofdifferent doses of rhG-CSF. Br J Haematol. 2002;116(2):468-74.
  • 22. Mollee P, Pereira D, Nagy T, Song K, Saragosa R, Keating A,et al. Cyclophosphamide, etoposide and G-CSF to mobilizeperipheral blood stem cells for autologous stem celltransplantation in patients with lymphoma. Bone MarrowTransplant. 2002;30(5):273-8.
  • 23. Wood WA, Whitley J, Moore D, Sharf A, Irons R, Rao K, et al. Chemomobilization with Etoposide is Highly Effective inPatients with Multiple Myeloma and Overcomes the Effects ofAge and Prior Therapy. Biol Blood Marrow Transplant.2011;17(1):141-6.
  • 24. Wood WA, Whitley J, Goyal R, Brown PM, Sharf A, Irons R,et al. Effectiveness of etoposide chemomobilization inlymphoma patients undergoing auto-SCT. Bone MarrowTransplant. 2013;48(6):771-6.
  • 25. Hsu YM, Cushing MM. Autologous Stem Cell Mobilizationand Collection. Hematol Oncol Clin North Am.2016;30(3):573-89.
Toplam 25 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Hematoloji, İç Hastalıkları
Bölüm Özgün Araştırma Makaleleri
Yazarlar

Filiz Mercan Sarıdaş 0000-0002-3135-9388

Vildan Ozkocaman 0000-0003-0014-7398

Fahir Özkalemkaş 0000-0001-9710-134X

Yayımlanma Tarihi 12 Ocak 2025
Gönderilme Tarihi 21 Temmuz 2024
Kabul Tarihi 9 Ekim 2024
Yayımlandığı Sayı Yıl 2024 Cilt: 50 Sayı: 3

Kaynak Göster

APA Mercan Sarıdaş, F., Ozkocaman, V., & Özkalemkaş, F. (2025). Effectiveness and Safety of Low-Dose Etoposide Chemomobilization in Patients with Multiple Myeloma and Lymphoma. Uludağ Üniversitesi Tıp Fakültesi Dergisi, 50(3), 367-373. https://doi.org/10.32708/uutfd.1518837
AMA Mercan Sarıdaş F, Ozkocaman V, Özkalemkaş F. Effectiveness and Safety of Low-Dose Etoposide Chemomobilization in Patients with Multiple Myeloma and Lymphoma. Uludağ Tıp Derg. Ocak 2025;50(3):367-373. doi:10.32708/uutfd.1518837
Chicago Mercan Sarıdaş, Filiz, Vildan Ozkocaman, ve Fahir Özkalemkaş. “Effectiveness and Safety of Low-Dose Etoposide Chemomobilization in Patients With Multiple Myeloma and Lymphoma”. Uludağ Üniversitesi Tıp Fakültesi Dergisi 50, sy. 3 (Ocak 2025): 367-73. https://doi.org/10.32708/uutfd.1518837.
EndNote Mercan Sarıdaş F, Ozkocaman V, Özkalemkaş F (01 Ocak 2025) Effectiveness and Safety of Low-Dose Etoposide Chemomobilization in Patients with Multiple Myeloma and Lymphoma. Uludağ Üniversitesi Tıp Fakültesi Dergisi 50 3 367–373.
IEEE F. Mercan Sarıdaş, V. Ozkocaman, ve F. Özkalemkaş, “Effectiveness and Safety of Low-Dose Etoposide Chemomobilization in Patients with Multiple Myeloma and Lymphoma”, Uludağ Tıp Derg, c. 50, sy. 3, ss. 367–373, 2025, doi: 10.32708/uutfd.1518837.
ISNAD Mercan Sarıdaş, Filiz vd. “Effectiveness and Safety of Low-Dose Etoposide Chemomobilization in Patients With Multiple Myeloma and Lymphoma”. Uludağ Üniversitesi Tıp Fakültesi Dergisi 50/3 (Ocak 2025), 367-373. https://doi.org/10.32708/uutfd.1518837.
JAMA Mercan Sarıdaş F, Ozkocaman V, Özkalemkaş F. Effectiveness and Safety of Low-Dose Etoposide Chemomobilization in Patients with Multiple Myeloma and Lymphoma. Uludağ Tıp Derg. 2025;50:367–373.
MLA Mercan Sarıdaş, Filiz vd. “Effectiveness and Safety of Low-Dose Etoposide Chemomobilization in Patients With Multiple Myeloma and Lymphoma”. Uludağ Üniversitesi Tıp Fakültesi Dergisi, c. 50, sy. 3, 2025, ss. 367-73, doi:10.32708/uutfd.1518837.
Vancouver Mercan Sarıdaş F, Ozkocaman V, Özkalemkaş F. Effectiveness and Safety of Low-Dose Etoposide Chemomobilization in Patients with Multiple Myeloma and Lymphoma. Uludağ Tıp Derg. 2025;50(3):367-73.

ISSN: 1300-414X, e-ISSN: 2645-9027

Uludağ Üniversitesi Tıp Fakültesi Dergisi "Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License" ile lisanslanmaktadır.


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Journal of Uludag University Medical Faculty is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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