myeloperoxidase MPO FCM CD.,CD.,CD., CD.,CD., HLA-DR., MPO. CD, CD, CD, CD, CD, CD, CD, CD, CD, CD b, CD, CDa, CD, TdT CD +CD +,XY,addition q/ French-

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1 症例報告岡智子 1,2), 室井一男 1,2), 森政樹 1,2), 松山智洋 1,2), 藤原慎一郎 1), 翁家国 1), 佐藤一也 1), 上田真寿 1), 鈴木隆浩 1), 尾崎勝俊 1), 永井正 1) 1,2), 小澤敬也要約 acute myeloblastic leukemia: AML minimal residual disease MRD AML AML CD +CD +CD + flow cytometry MRD MRD Key words: flow cytometry Ⅰ はじめに acute myeloblastic leukemia: AML minimal residual diseasemrd AML MRD MRD AML graft-versusleukemiagvl AML MRD AML flow cytomteyr FCM bone marrow transplantationbmtaml MRDMRD AML Ⅱ 症例症例主訴既往歴現病歴入院時検査所見 x / L Hb. g/dl. x / L

myeloperoxidase MPO FCM CD.,CD.,CD., CD.,CD., HLA-DR., MPO.

+,XY,addition q/ French- American-British FAB AML-M 入院後経過 CD45-PerCP

CD7-PE 図 1 3 重染色 flow cytometry a, CD side scatter b, CD +CD + c, CD

2 myeloperoxidase MPO FCM CD.,CD.,CD., CD.,CD., HLA-DR., MPO. CD, CD, CD, CD, CD, CD, CD, CD, CD, CD b, CD, CDa, CD, TdT CD +CD +,XY,addition q/ French- American-British FAB AML-M 入院後経過 CD45-PerCP a CD34-FITC b Side Scatter CD7-PE CD34-FITC c CD34-FITC d CD7-PE CD7-PE 図 1 3 重染色 flow cytometry a, CD side scatter b, CD +CD + c, CD +CD + d, CD +CD +. FCM CD +CD + FCM CD +CD + d CR FCMCD +CD + MRD BMT CR FCM MRD x / L HLA

3 day 20 day 60 day 90 a b c d 0.07% e f g h 0.07% i j k l 図 2 4 重染色 flow cytometry(1) R a, e, i b, f, j c, g, k d, h, l CD +CD +CD + HLA/ BMT cyclophosphamide mg/kg mg/kg Gy Gy graft-versus-host diseasegvhd methotrexate tacrolimus - FCM CD +CD +CD + MRD day short tandem repeat-polymerase chain reaction FCM day GVHD stage,grade prednisolone PSL mg/kg PSL day PSL day FCM MRD day day FCM CD +CD +CD + day, XY; / day tacrolimus day FCM MRD

MRD (x10-2 %) 0 0 0 7 0 9 0 15 7 8 ( 10 4 /µl) 10.7 3.3 4.8 4.2 6.6 4.3 6.6 18.6 12.9 6.6 8.6 9.7 96 0 0 0 0 0 0 0 0 0 0 62.

4 MRD (x10-2 %) ( 10 4 /µl) (%) x10 2 /µ 300 BMT : : PSL GVHD 図 3 臨床経過 BMT, bone marrow transplantation PSL prednisolone; GVHD, graft-versus-host disease. tacrolimus day tacrolimusday FCM MRD day CR BMT Ⅲ 考察 MRD fluorescence in situ hybridization FISH FCM polymerase-chain reaction FCM MRD FISH AML asynchronous expression FCM AML MRD AML CD, CD, CD, CD CD + CD CD CD +CD +CD + AML MRD CD +CD +CD + MRD CD CD FCM AML FCM MRD AMLMRD

5 Day 120 day 180 day 240 day 360 a b c d 0.09% 0.15% 0.07% 0.08% e f g h 0.09% 0.15% 0.07% 0.08% i j k l 図 4 4 重染色 flow cytometry (2) R a, e, f b, f, j c, g, k d, h, l CD +CD +CD + FCMNegler BMT BMT - MRD BMT MRD BMT BMT MRD Venditti EORTC/GIMEMA AML- AMLMRD AML x - MRD Laane AML MRD MRD Díez-Campelo AML MDS MRD MRD - - p=. MRD FCM MRD AML CD,CDCDCD CD CDCD FCM MRD MRD

6 CD CD CDBMT MRD MRD MRD MRD MRD FCMMRD MRD MRD AML MRD FCM MRD MRD MRD GVL MRD bcr/abl PML/RARA GVL MRD Ⅳ 結語 FCM AML MRD BMT BMT FCM MRD Ⅴ 参考文献 Chung NG, Buxhofer-Ausch V and Radich JP: The detection and significance of minimal residual disease in acute and chronic leukemia. Tissue Antigens : -, Cilloni D, Renneville A, Hermitte F et al : Real-time quantitative polymerase chain reaction detection of minimal residual disease by standardized WT assay to enhance risk stratification in acute myeloid leukemia: a European LeukemiaNet study. J Clin Oncol : -, Bacher U, Badbaran A, Fehse B et al.: Quantitative monitoring of NPM mutations provides a valid minimal residual disease parameter following allogeneic stem cell transplantation. Exp Hematol : -, Candoni A, Tiribelli M, Toffoletti E et al.: Quantitative assessment of WT gene expression after allogeneic stem cell transplantation is a useful tool for monitoring minimal residual disease in acute myeloid leukemia. Eur J Haematol : -, Oka S, Muroi K, Matsuyama T et al. : Correlation between flow cytometric identification of CD -positive cells and morphological evaluation of myeloblasts in bone marrow of patients with acute myeloblastic leukemia. Hematology : -, Flow cytometry :-, Reichle A, Rothe G, Krause S et al.: Transplant characteristics: minimal residual disease and impaired megakaryocytic colony growth as sensitive parameters for predicting relapse in acute myeloid leukemia. Leukemia : -, Sievers EL, Lange BJ, Alonzo TA et al. : Immunophenotypic evidence of leukemia after induction therapy predicts relapse: results from a prospective Children s Cancer Group study of patients with acute myeloid leukemia. Blood : -, MRD-AML-BFM Study Group, Langebrake C, Creutzig U et al.: Residual disease monitoring in childhood acute myeloid leukemia by multiparameter flow cytometry: the MRD-AML-BFM Study Group. J Clin Oncol : -, San Miguel JF, Vidriales MB, López-Berges C et al.: Early immunophenotypical evaluation of minimal residual disease in acute myeloid

7 leukemia identifies different patient risk groups and may contribute to postinduction treatment stratification. Blood : -,, pp. -. Macedo A, Orfao A, Ciudad J, et al.: Phenotypic analysis of CD subpopulations in normal human bone marrow and its application for the detection of minimal residual disease. Leukemia : -, Kosugi N, Ebihara Y, Nakahata T, et al.: CD +CD + leukemic progenitor cells may be involved in maintenance and clonal evolution of chronic myeloid leukemia. Clin Cancer Res Pt : -, Nagler A, Condiotti R, Rabinowitz R et al.: Detection of minimal residual disease MRD after bone marrow transplantation BMT by multi-parameter flow cytometry MPFC. Med Oncol : -, Venditti A, Maurillo L, Buccisano F et al.: Pretransplant minimal residual disease level predicts clinical outcome in patients with acute myeloid leukemia receiving high-dose chemotherapy and autologous stem cell transplantation. Leukemia : -, Laane E, Derolf AR, Björklund E et al.: The effect of allogeneic stem cell transplantation on outcome in younger acute myeloid leukemia patients with minimal residual disease detected by flow cytometry at the end of post-remission chemotherapy. Haematologica : -, Díez-Campelo M, Pérez-Simón JA, Pérez J et al.: Minimal residual disease monitoring after allogeneic transplantation may help to individualize post-transplant therapeutic strategies in acute myeloid malignancies. Am J Hematol : -, Baer MR, Stewart CC, Dodge PK et al.: High frequency of immunophenotype changes in acute myeloid leukemia at relapse: implications for residual disease detection Cancer and Leukemia Group B Study Blood : -, Langebrake C, Brinkmann I, Teigler-Schlegel A, et al.: Immunophenotypic differences between diagnois and relapse on childhood AML:Implications for MRD monitoring. CYtometry B Clin Cytom : -, Sánchez J, Serrano J, Gómez P et al.: Clinical value of immunological monitoring of minimal residual disease in acute lymphoblastic leukaemia after allogeneic transplantation. Br J Haematol : -, Björklund E, Mazur J, Söderhäll S et al.: Flow cytometric follow-up of minimal residual disease in bone marrow gives prognostic information in children with acute lymphoblastic leukemia. Leukemia : -, Maurillo L, Buccisano F, Spagnoli A et al.: Monitoring of minimal residual disease in adult acute myeloid leukemia using peripheral blood as an alternative source to bone marrow. Haematologica : -, Ikeda A, Shankar DB, Watanabe M, et al.: Molecular targets and the treatment of myeloid leukemia. Mol Genet Metab : -,

8 Jichi Medical University Journal Flow cytometry to detect minimal residual disease after bone marrow transplantation in a patient with acute myeloblastic leukemia Satoko Oka, Kazuo Muroi, Masaki Mori, Tomohiro Matsuyama, Iekuni Oh, Shin-ichiro Fujiwara, Kazuya Sato, Masuzu Ueda, Takahiro Suzuki, Katsutoshi Ozaki, Tadashi Nagai, Keiya Ozawa Abstract Detection of minimal residual disease MRD in acute myeloblastic leukemia AML after bone marrow transplantation is important to predict relapse. It is well known that AML cells show various abnormal antigen expressions. MRD was detected in an AML patient after BMT by flow cytometry measurements of CD +CD +CD + cells. Subsequently, the patient s AML relapsed. Divison of Hematology, Department of Medicine, Jichi Medical University Hospital Division of Cell Transplantation and Transfusion, Jichi Medical University Hospital

m x:daycpa mg/m x:day-vcr.mg/ m x:daydxr mg/m x:daydex mg/ m x:day-ittx mg+dex mg/body TX mg/m x:daycpa mg/ m x:day-vcr.mg/m x:dayetp mg/m x:day-dex m

m x:daycpa mg/m x:day-vcr.mg/ m x:daydxr mg/m x:daydex mg/ m x:day-ittx mg+dex mg/body TX mg/m x:daycpa mg/ m x:day-vcr.mg/m x:dayetp mg/m x:day-dex m 原著論文笹崎美幸, 森政樹, 上澤光世, 藤原慎一郎, 菊池裕二, 佐藤一也, 松山智洋, 大嶺謙, 上田真寿, 鈴木隆浩, 尾崎勝俊, 永井正, 室井一男, 小澤敬也 Ⅰ 要約 / Burkitt lymphoma/leukemia;bl c-myc Ig B Hyper-CVAD/HD-TX/ Ara-C+Rituximab c-myc Hyper-CVAD/HD-TX/ Ara-C+Rituximab