The Comparison of the Biosimilar Filgrastim (Tevagrastim) and the Original Filgrastim (Neupogen) in the Autologous Hematopoetic Stem Cell Mobilization: A Single Center Experience

INTRODUCTION: A sufficient dose of CD34+ stem cell mobilization is a prerequisite for successful autologous hematopoietic stem cell transplantation. We aimed to compare the original filgrastim (Neupogen) with the biosimilar filgrastim (Tevagrastimin) in terms of efficacy in peripheral blood stem cell mobilization.
METHODS: Ninety-five patients who underwent stem cell mobilization, were analyzed retrospectively. We used Cyclophosphamide (low dose: 2g / m2 or high dose: 3-4 g / m2), as a mobilization regimen, on the first day and G-CSF at a dose of 5 g / kg was started one day after chemotherapy.
RESULTS: Stem cell mobilization was performed with Neupogen in 50 patients and with Tevagrastim in 45 patients. While there was no statistically significant difference between the demographic characteristics of the patients out of cyclophosphamide dose. Higher dose cyclophosphamide was used more in the arm receiving Neupogen (p <0.05). No statistically significant difference was found between the use of original and biosimilar products in terms of achieving the target of 2 x 106 / kg, which is the minimum CD34+ cell dose required for adequate engraftment, and 4 x 106 / kg for double transplantation (p> 0.05). However, if the target level of CD34+ stem cell was above 6 x 106 / kg, a statistically significant difference was observed in favor of Neupogen arm (p = 0.021). Neutrophil engraftment was shorter in the Neupogen arm compared to the Tevagrastim arm (p = 0.015).
DISCUSSION AND CONCLUSION: The difference was observed in favor of the Neupogen arm, when stem cell collection was aimed at above 6 x 106 / kg. The reason for this difference was thought to be related to the higher dose of cyclophosphamide used in the original molecule arm. We need further studies that were included more cases which are used high-dose cyclophosphamide for comparing the biosimilar molecule with the original molecule.

Otolog Hematopoetik Kök Hücre Mobilizasyonunda Biobenzer Filgrastim (Tevagrastim) Ýle Orjinal Filgrastimin (Neupogen)Karþilaþtirilmasi (Tek Merkez Deneyimi)

GÝRÝÞ ve AMAÇ: Baþarýlý otolog hematopoetik kök hücre nakli için yeterli dozda CD34+ kök hücre mobilizasyonu ön koþuldur. Yapmýþ olduðumuz çalýþmada orjinal filgrastim (Neupogen) ile biyobenzer filgrastimin (Tevagrastimin) çevre kaný kök hücre mobilizasyonunda etkinlik açýsýndan karþýlaþtýrýlmasý amaçlanmýþtýr.
YÖNTEM ve GEREÇLER: Ankara Numune Eðitim ve Araþtýrma Hastanesi Kemik Ýliði Nakil servisinde Ocak 2015 ile Kasým 2018 tarihleri arasýnda kök hücre mobilizasyonu yapýlan 95 hasta retrospektif olarak analiz edildi. Tüm hastalara mobilizasyon rejimi olarak birinci gün siklofosfamid (düþük dozda: 2g/m2 veya yüksek dozda: 3-4 g/m2) ve kemoterapiden 1 gün sonra 5 g/kg dozunda G-CSF baþlanmýþtýr.
BULGULAR: Doksan beþ hastanýn 50’sine neupogen ile, 45’ine tevagrastim ile kök hücre mobilizasyonu yapýldý. Hastalarýn demografik özellikleri arasýnda yaþ, taný, radyoterapi alýp almamasý açýsýndan istatistiksel anlamlý farklýlýk yok iken (p> 0.05); alýnan siklofosfamid dozu (neupogen alan kolda daha çok yüksek doz siklofosfamid kullanýlmýþtýr.) ve cinsiyet (neupogen kolunda cinsiyet daðýlýmý eþit iken, tevagrastim kolunda daha çok erkek hastalar vardý.) açýsýndan farlýlýk tespit edildi (p<0.05). Yeterli engraftman için gereken minimum CD34 + hücre dozu olan 2 x 106/kg ve çift nakil için 4 x 106/kg lýk hedefe ulaþmak açýsýndan orjinal ve biyobenzer ürün kullanýmý arasýnda istatistiksel olarak anlamlý bir fark saptanmadý (p>0,05). Ancak 6 x 106/kg'ýn üzerinde kök hücre hedefine bakýldýðýnda neupogen lehine tevagrastim koluna göre istatistiksel olarak anlamlý bir fark izlenmiþtir (p=0,021). Otolog kök hücre nakli sonrasý nötrofil engraftman günleri karþýlaþtýrýldýðýnda, nötrofil engraftman zamanýnýn neupogen grubunda tevagrastim grubuna göre daha kýsa olduðu gözlenirken (yaklaþýk 1 gün) (p=0.015), trombosit engraftman zamaný neupogen ve tevagrastim gruplarýnda benzerdi (p=0.186).
TARTIÞMA ve SONUÇ: Calismamizda 6 x 106/kg'ýn üzerinde kök hücre toplanmasý hedeflendiðinde neupogen lehine farklýlýk gözlenmiþtir. Bu farklýlýðýn nedeni kullanýlmýþ olan siklofosfamid dozunun orjinal molekül (Neupogen) kolunda daha yüksek olmasý ile iliskili düþünülmüþtür. Daha çok vaka serileri içeren, yüksek doz siklofosfamidin kullanýldýðý, biyobenzer molekül (tevagrastim) ile orjinal molekülün (neupogen) kýyaslandýðý çalýþmalara ihtiyaç vardýr.