İnci YILDIZ, Sait ALBAYRAM, Traje CELKAN, Barış EKİCİ, Hilmi APAK, Alp ÖZKAN, Ethem ERGİNÖZ, Gül Nihal ÖZDEMİR

Akut lenfoblastik lösemi tedavisinde düşük dozda metotreksatın beyin komplikasyonlarına etkisi

Amaç: Çocukluk çağı lösemilerinde koruyucu tedavinin olası yan etkilerinin kraniyal görüntüleme teknikleriyle incelenmesi amaçlanmıştır. Gereç ve Yöntem: Çalışmaya Ocak 1991 ile Aralık 2004 tarihleri arasında akut lenfoblastik lösemi (ALL) tanısı ile izlenen ve sistemik metotreksat dozu azaltılmış BFM 90 ve TR-ALL 2000 tedavi protokolü uygulanan hastalar alındı. Hastaların cinsiyeti, tanı yaşı, ALL tiplendirmesi, risk grubu, uygulanan tedavi protokolü, kraniyal ışınlama dozu, ek intratekal tedavi şekli, tedavi sırasında saptanan merkezi sinir sistemi bulguları, elektroansefalografi değerlendirmeleri, görüntüleme yöntemi ve tarihi değerlendirildi. Hastalar, görüntülemelerinde saptanan lezyonlara göre gruplanarak yukarıdaki değişkenlerle aralarındaki ilişki araştırıldı. Tanı anında merkezi sinir sistemi tutulumu saptanan veya B-ALL tanısı alanlar çalışma dışı bırakıldı.Bulgular: Çalışma grubunu 90 hasta oluşturdu. Hastaların 63’üne radyoterapi uygulanmıştı. İntratekal tedavi 77 hastaya sadece metotreksatla 11 doz, diğerlerine daha yoğun olarak yapılmıştı. Hastalarda kortikal atrofi ve kraniyal kalsifikasyon saptanmadı. Demiyelinizasyona bağlı değişik yoğunlukta lezyonlar ise dokuz hastada saptandı. Olguların sekizinde hafif derecede lezyon saptanırken, birinde orta derecede lezyon saptandı. Lezyon saptanan olguların sekizine radyoterapi uygulanmış olmakla beraber anlamlı ilişki saptanmadı (p>0,05). Değişik yoğunluktaki lezyonların cinsiyet, tanı yaşı, tedavi protokolü, risk grubu, intratekal tedavi yöntemi, nörolojik bulgu, elektroansefalografide bozulma ve görüntüleme yöntemleri ile anlamlı ilişkileri bulunmadı (p>0,05).Çıkarımlar: Bu bulgular, kortikal atrofinin intratekal tedaviyle ilişkili olmadığını ve beyaz madde lezyonlarından sorumlu tutulan sistemik metotreksatın dozunun belirleyici olmadığını göstermektedir. Lezyon saptanan hastaların çoğuna ışın tedavisi uygulanmış olması nedeniyle, radyoterapinin metotreksata bağlı beyaz madde lezyonlarının oluşmasına katkı sağlayabileceğini düşünüyoruz. Çalışmamızda radyoterapinin geç etkilerini saptamamamız tedavi ile görüntülemeler arasındaki sürenin kısa olmasına bağlı olabilir. Radyoterapi alan hastalarımıza, görüntülemelerin geç dönemde planlandığı bir çalışma bu durumu açıklamak için uygun olacaktır.

The impact of low dose methotrexate on cerebral complications in acute lymphoblastic leukemia treatment

Aim: The aim of this study is to determine the possible side effects of central nervous system (CNS) prophylactic treatment in childhood leukemia by using cranial imaging techniques.Material and Method: Data collected from records of 90 patients diagnosed as acute lymphoblastic leukemia (ALL) and treated according to BFM-90 or TR-ALL 2000 protocols which used lowered dose of methotrexate , between January 1991 and December 2004. Gender, age at diagnosis, immunophenotype, cranial radiation doses, risk groups, intrathecal treatment modalities, neurological and electroencephalography (EEG) findings, imaging interval and techniques were recorded. These variables were analyzed for their role in cranial lesions. Patiens with CNS leukemia and mature B-cell phenotype were excluded.Results: Ninety patients were enrolled in the study. Sixty three patients had up to 18 Gy cranial radiation, whereas in 27 patients radiation was not utilized. Eleven doses of Intrathecal methotrexate were administered to 77 patients and 13 patients had more intensive regimen. No patients demonstrated cortical atrophy or calcifications. Mild white matter changes (WMC) were observed in eight patients. Only one patient had moderate changes. Eight of the nine patients with WMC had radiotherapy but no significant correlation was found (p>0.05). There were also no significant relation of WMA with gender, age at diagnosis, treatment protocol, risk groups, intrathecal therapy, neurologic symptoms, EEG finding and imaging techniques (p>0.05).Conclusions: Intrathecal treatment does not cause cortical atrophy. White matter changes are not influenced by systemic methotrexate dose but radiotherapy may have an additive effect. Short interval between CNS prophylaxis and imaging can be responsible for the limitation of our study at detecting the late effects of radiotherapy. A new study aiming at investigating the late effects of radiotherapy by performing late imaging studies may be more informative.

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