İlknur Girişgen, Selçuk Yüksel, Yücel Pekal

Nefrotik sendromlu çocuklarda rituximab deneyimi, farklı ne gözlemledik?

Amaç: Amacımız nefrotik sendromlu çocuklarda rituksimab tedavisinin etkinliğini değerlendirmek ve kendi deneyimlerimizi paylaşmaktır. Gereç ve Yöntemler: Rituksimab tedavisi verilen 12 nefrotik sendromlu (dördü steroid bağımlı, sekizi steroid dirençli nefrotik sendrom) çocuğun klinik, laboratuvar sonuçları ve CD19-CD20 seviyeleri geriye dönük olarak değerlendirildi. Tüm hastalara dört hafta süre ile haftada bir rituximab 375mg/m2tedavisi uygulandı. Hastalara rituximab tedavisi vermek için steroid tedavisi ile proteinürisiz döneme girmeleri beklenmedi. Bulgular: Remisyon oranları; steroid bağımlı ve steroid dirençli nefrotik sendromlu hastalarda sırası ile %100 ve %27 idi. Fokal segmental glomeruloskleroz tanılı 6 hastanın %33’ünde remisyon gözlendi. CD19 deplesyonu 12 hastanın 10’unda gözlendi. Bu 10 hastanın yedisinde parsiyel ya da komplet remisyon gözlenirken, üç hastada CD19 deplesyonuna rağmen nefrotik proteinüri sebat etti. CD 19 deplesyonu sağlanmayan iki hasta remisyona girmedi. İzlemde yedi hastanın üçünde görülen relaps CD19 artışı ile birlikte idi. Çıkarımlar: Rituksimab tedavisinin, hastaların steroid ile proteinürisiz döneme girmelerini beklemeden verilebileceğini gözlemledik. Nefrotik proteinürili çocukların idrarında kaybedilen ilaç miktarı göz önüne alındığında, haftada dört doz rituximab uygulamasının remisyon olasılığını artırdığına inanıyoruz. Bununla birlikte, bulgularımız daha büyük popülasyonlarla yapılan doz karşılaştırmalı ve uzun vadeli yan etkilerin değerlendirildiği çalışmalar ile doğrulanmalıdır. Bazı hastalarda B hücre deplesyonuna rağmen remisyon sağlanmadığını saptamak, B hücre deplesyonunun remisyon için gerekli ancak yetersiz olduğunu düşündürdü.

Rituximab experience in children with nephrotic syndrome: what have we observed differently

Aim: We aimed to evaluate the efficacy of rituximab therapy in childrenwith nephrotic syndromes and to share our experiences.Material and Methods: Twelve children with nephrotic syndrome (fourwith steroid-dependent, eight with steroid-resistant nephrotic syndrome) who were treated with rituximab were retrospectively evaluatedin terms of clinical and laboratory data and CD19-20 levels. All patientsreceived rituximab (375 mg/m2) once weekly for 4 weeks. A proteinuria-free period under steroid therapy was not sought prior to initiatingrituximab therapy.Results: The overall remission rates in patients with steroid-dependent and steroid-resistant nephrotic syndrome were 100% and 27%.Focal segmental glomerulosclerosis was diagnosed in six patients andthe remission rate was 33% in this population. CD19 cell depletion wasobserved in 10 of the 12 children. Seven of the 10 patients with CD19depletion achieved remission, whereas the other three had persistentnephrotic proteinuria despite CD19 depletion. Two patients withoutCD19 depletion never achieved remission. Relapse occurred in three ofthe seven patients associated with increased CD19.Conclusion: We observed that rituximab could be given without waitingfor a proteinuria-free period under steroid therapy. Our result suggestthat administering four weekly doses of rituximab increases the likelihood of remission, considering the amount of drug lost in the urineof children with nephrotic proteinuria. However, our findings must beconfirmed with dose-comparison studies conducted with larger populations and an evaluation of long-term adverse effects. Some patientsdid not achieve remission despite B cell depletion, which suggests thatB cell depletion is necessary but insufficient for remission in nephroticsyndromes.

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