小動物の骨髄異形成症候群(MDS)における診断および治療法の検討

骨髄異形成症候群(MDS)は,白血球,赤血球および血小板の血球減少が認められ,さらに高頻度に急性白血病への進行が認められる前白血病段階の疾患である。しかしながら,犬のMDSにおける診断および治療法についてはまだ明らかとなっていないことが多い。そこで我々はMDSと診断されたイヌ9例について血液異常について検討を行ない,さらに近年白血病細胞の分化誘導薬として期待されているビタミンK2の治療効果を血液学的に評価した。血液異常は,汎血球減少が2例,2系統の減少が3例,1系統の減少が4例であった。赤血球系細胞の異形成所見として核の断片化,巨赤芽球様変化,核型不整といったものが認められ,さらに顆粒球系細胞では,輪状核好中球,左右非対称性の核分裂像,好中球の低分葉化,血小板系では,微小巨核球や小型巨核球が比較的高頻度に認められた。これらの所見は,人および猫の所見と一致するものであった。また,治療については,ビタミンK2単独で治療を行った症例は5例で,残りの4例は治療経過中にプレドニゾロン,シクロスポリンA,ヒト胎盤製剤等を用いた。血液学的治療効果はWHOが報告したヒトの治療効果の判定基準に準じ,赤血球,好中球,血小板,それぞれの治療反応ついて評価を行なった。その結果,MDSの犬9例に対し5例(約63%)において血球減少の改善が認められた。また反応のあった5例中4例はビタミンK2単独での効果が確認された。また治療中,全ての症例においてビタミンK2による副作用と考えられる症状は認められなかった。以上の結果から,イヌのMDSの血液異常および異形成所見は,人および猫のMDSと極めて類似するものであった。また,今回の調査でビタミンK2がMDSの犬に対しMDSの新規の治療薬としての可能性が見出された。Myelodysplastic Syndromes (MDS) is a pre-leukemic disorder characterized by cytopenia including myeloid, erythroid and platelet cell lineage, and the progression of acute myeloid leukemia were often seen. Recently, the reports describe about canine MDS are increasing, and the disease is thought as one of the important cause in canine hematological disorders, however the appropriate diagnosis and effective therapeutic protocol have been unclear. In the present study, we analyzed the hematological abnormalities of 9 canine MDS cases and estimated the therapeutic response of vitamin K2, which was capable to induce the differentiation of leukemic cells. Hematological abnormalties, including pancytopenia (2 cases), bi-cytopenia (3 cases), and a cytopenia (4 case) were indicated. In the erythroid cell lineage, megaroblastic changes and abnormal shape of nuclei were seen, and myeloid cell showed the dysplastic feature including ring shaped nuclei, unequal division of nuclei, hyposegmentation, and the dysplasia of platelet was including micromegakaryocyte and dwarf megakaryocyte. The therapy of these MDS dogs was carried out by vitamin K2, predonisolone cyclosporine A, human placenta extract, and antibiotics, 4 of 9 dogs were treated by vitamin K2 and other 5 dogs were treated by vitamin K2 plus other medicine. The response of therapy was estimated by using standard human criteria of MDS therapy response described by World Health Organization. Five of 9 dogs (63%) showed obvious hematological improvement, and 4 of 5 dogs with therapeutic response were treated by only vitamin K2. There was no symptom due to side effect of vitamin K2 in these dogs during therapy. These results of hematological feature indicated that the hematological abnormalities and dysplasia of canine MDS were similar to that of human and cat, and that vitamin K2 might be one of the new effective agent to treat canine MDS