Hemofagositoz

Hemofagositik lenfohistiyositoz (HLH) makrofajların anormal çoğalması ve sitokin artışı ile belirgin olan bir hastalıktır. Klinik olarak ateş, karaciğer-dalak büyüklüğü ve sitopeni ile kendini gösterir. Tedavi edilmediğinde apopitozun hatalı tetiklenmesi ve sitotoksik etkinin azalması sonucunda T lenfosit ve etkinleşmiş makrofaj birikimi ile sonuçlanır. Birbirinden ayırımı çoğu zaman çok zor olan birincil ve ikincil HLH olarak ikiye ayrılarak incelenir. Birincil hemafagositozda tanı seyir için önemli bir etmendir. Hastalığa bağlı ölümün en önemli nedeni doğru tanı konulmaması ve bunun sonucunda doğru tedavi verilmemesidir. Kök hücre nakli öncesinde yapılan kemoterapiye ilk 2 ay içinde yanıt veren olgulann seyrinin daha iyi olduğu tam olarak kanıtlanmamış olsa da bilinen bir gerçektir. Hastalıkta kesin iyileşme kök hücre nakli ile olduğu için tam uyumlu kemik iliği vericisinin bulunması hastalık seyrini etkileyen diğer bir etmendir. Hastalığın kabul edilmiş tedavisinde başlangıç (endüksiyon) tedavisi olarak VP-16 (etoposid) ve kortikosteroidlere ek olarak gerektiğinde intratekal tedavi verilmektedir. İkincil HLH'de ise altta yatan hastalığın (enfeksiyon, malinite) tedavisi öncelikli tedavi seçeneğidir. Dikkat edilmesi gereken birincil hemafagositozun da enfeksiyonun tetiklemesi ile başlayabildiği ve hastalığın ağır ve uzun sürdüğü ve tekrarlamalar gösterdiği durumda altta yatan hemafagositozun birincil olabileceğidir. Yeni tandı malin hastalıkla ilişkili hemafagositozlarda, genellikle malin hastalık kontrol altına alındığında hemafagositik sendrom da düzelir. Kemoterapi alan malin hastalıklı olgularda gelişen hemafagositoza yaklaşım ise daha zordur, çünkü olayın malin hastalığın nüksüne mi yoksa kemoterapinin oluşturduğu immün yetersizliğe mi bağlı olarak geliştiğini ayırt etmek her zaman kolay olmamaktadır. İmmün düşkün konaklarda önerilen, immün hastalanmaya neden olan ilaçların kesilmesidir. Bu tedaviye yanıt alınmadığında ise birincil hemafagositoz tedavisi denenmelidir. Hemafagositik sendromun kanser grubu hastalıklar değil de bir kalıtımsal hastalık olduğu artık iyice bilinmektedir.

Hemophagocytosis

Hemophagocytic lymphohistiocytosis (HLH) is a disorder characterized by abnormal proliferation of macrophages associated with hypercytokinemia. This entity can be separated into two categories that can be difficult to distinguish, namely primary and secondary HLH, both clinically characterized by fever, hepatosplenomegaly, and cytopenia. Hemophagocytic lymphohistiocytosis, an autosomal recessive disease invariably fatal when untreated, is associated with defective triggering of apoptosis and reduced cytotoxic activity, resulting in a widespread accumulation of T lymphocytes and activated macrophages. In primary hemophagocytic lymphohistiocytosis, an important prognostic factor is the diagnosis. A common cause of death is still the failure to make a correct diagnosis, with subsequent lack of appropriate treatment. With regards to pre-BMT chemotherapy, it has been suggested but not yet proven, that the response to the first 2 months of therapy is associated with a better survival. Since successful BMT is a prerequisite for cure, the availability of a suitable bone marrow donor is a positive prognostic factor. Initial induction treatment with VP-16 (etoposide) and steroids, with or without intrathecal therapy, is standard treatment. In patients with secondary hemophagocytic lymphohistiocytosis, definitive treatment of the underlying disease process (infection, malignancy) is standard option. In patients with infection-associated hemophagocytic lymphohistiocytosis, treatment of the associated infection is recommended. But the possibility of a primary hemophagocytic lymphohistiocytosis, elicited by the infection, has to be considered, and if the disease is severe, prolonged or recurrent, HLH-specific therapy is also recommended. In newly diagnosed malignancy-associated hemophagocytic lymphohistiocytosis, the syndrome may resolve if the malignancy is controlled. In patients with ongoing cancer chemotherapy the situation is more difficult and one has to consider whether the 'Hemophagocytic Syndrome' is due to reactivation of the malignancy or is secondary to the immunosuppression caused by the chemotherapy itself. In immunocompromised hosts, withdrawal of immunosuppressive therapy is recommended. In patients with disease progression despite the steps outlined above, treatment with VP-16 and steroids with or without intrathecal therapy is suitable. Hemophagocytic lymphohistiocytosis has now been shown to be a genetic disorder, not a cancer.

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