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

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.

Anahtar Kelimeler

• low-dose etoposide
• stem cell mobilization
• multiple myeloma
• lymphoma
• autologous hematopoietic stem cell transplantation

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

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.

Anahtar Kelimeler

• düşük doz etoposid
• kök hücre mobilizasyonu
• multiple miyelom
• lenfoma
• otolog hematopoetik kök hücre transplantasyonu

Kaynakça

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