中 華 民 國 血 液 病 學 會中華民國血液及骨髓移植學會

時間：93年 7月 31日(星期六)下午 13:00-18:00

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地點：台中榮民總醫院研究大樓一樓第二會場

中 華 民 國 血 液 病 學 會第 127次聯合學術研討會中華民國血液及骨髓移植學會時間：93 年 7 月 31 日（星期六）下午 13:00-18:00地點：台中榮民總醫院研究大樓一樓第二會場會長：楊吉雄主任13:00 起 PM 報到13:10-13:15 PM 會長楊吉雄主任致歡迎詞13:15-13:20 PM 中華民國血液病學會林勝豐理事長致開幕詞13:20-13:50 PM 專題演講 主持人：楊吉雄主任

講 題：Thrombotic Thrombocytopenic Purpura(TTP) 主講人：Dr. William Bell

The John Hopkins Univ. Hospital

會員演講（Ⅰ） 主持人： 柯麗鏞 張正雄13:50-14:00 PM Management of myelofibrosis-related marked splenomegaly by partial splenic

embolization – a case report楊陽生 楊吉雄 黃文豊 林增熙 滕傑林台中榮民總醫院 內科部 血液腫瘤科

14:00-14:10 PM Primary CNS lymphoma: Taichung VGH experience洪伯斌 林增熙 陽楊生 黃文豊 楊吉雄

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台中榮民總醫院內科部血液腫瘤科14:10-14:20 PM A fulminant Langerhans cell histiocytosis in adult: A case report

滕傑林, 林增熙, 楊吉雄台中榮民總醫院血液腫瘤科

14:20-14:30 PM Pseudo-Gaucher cells in mycobacterial infection: a report of two cases洪玉馨 鄧波 郭明宗 長庚紀念醫院 血液腫瘤科

14:30-14:40 PM The Mitochondrial Pathway of As2O3-induced Apoptosis in Human T-cell Lymphoma 林增熙 1,4 陳亞雯 2 呂鋒洲 3 周芬碧 4 徐士蘭 2 楊吉雄 1

1 台中榮民總醫院 血液腫瘤科 2 教學研究部 3 中山醫學大學 應用化學系 4 生化暨生物科技研究所會員演講（Ⅱ） 主持人：沈銘鏡 張建國

14:40-14:50 PM Imatinib induced tumor lysis syndrome : Report of a case and review of literature張鴻 裴松南長庚紀念醫院 血液腫瘤科

14:50-15:00 PM Effective treatment of refractory immune thrombocytopenic purpura using Rituximab：A Case Report歐偉仁 萬祥麟 戴明燊 莊岳泉 姚乃舜 陳宇欽 謝安台 趙祖怡 高偉堯國防醫學院 三軍總醫院 血液腫瘤科

15:00-15:10 PM Severe Hemophilia B Patients with Inhibitors in Taiwan: Report of Two Cases郭政諭 1 林炫聿 1 張正雄 1 鍾智淵 1 王明倫 1 林正純 1 沈銘鏡 1,2 林正修 3

1 彰化基督教醫院 內科部 血液腫瘤科2 國立臺灣大學附設醫院 檢驗醫學部 3 彰化基督教醫院 檢驗醫學部

15:10-15:20 PM A Taiwanese Family of Type 2A von Willebrand Disease with S1506L Mutation林炫聿 1 林博淂 1 張正雄 1 鍾智淵 1 王明倫 1 林正純 1 沈銘鏡 1,2 林正修 3

1 彰化基督教醫院 內科部 血液腫瘤科2 國立臺灣大學附設醫院 檢驗醫學部 3 彰化基督教醫院 檢驗醫學部

15:20-15:30 PM A Pharmacokinetic Study of Recombinant Human Factor IX (BeneFIX®) in Previously Treated Patients with Hemophilia B in Taiwan 張修豪 1 楊永立 1,3 沈銘鏡 2,3 1 台大醫院小兒部 2 內科部 3 檢驗醫學部

15:30-15:50 PM COFFEE BREAK 休息會員演講（Ⅲ） 主持人：張德高 彭慶添

15:50-16:00 PM The UGT1A1 genotypes and gallbladder diseases in patients with transfusion-dependent -thalassemia in northern Taiwan

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陳鵬升 林凱信 蘇怡寧 盧孟佑 周獻堂 林東燦 林國信衛生署桃園醫院內科臺大醫院小兒部臺大醫院基因醫學部

16:00-16:10 PM Treatment-related leukoencephalopathy in a girl with recurrent acute lymphoblastic leukemia黃芳亮, 張德高,李秀芬*, 遲景上*台中榮民總醫院兒童醫學部 兒童血液腫瘤科,兒童神經科*

16:10-16:20 PM Cytogenetics and Outcome in Childhood Acute Lymphoblastic Leukemia in Taiwan: An Institutional Experience張修豪 1 盧孟佑 1,3 周獻堂 1 林凱信 1 田蕙芬 2 林東燦 1

1 台大醫院小兒部 2 內科部 3 中華民國兒童癌症基金會16:20-16:30 PM PIG-A gene analysis for PNH

汪天祥 楊吉雄 林增熙 楊陽生 台中榮民總醫院 血液腫瘤科

16:30-16:40 PM Retinoblastoma—the Experience of a Single Medical Center In Northern Taiwan張家堯、洪君儀、謝玉林*、黃碧桃台北榮民總醫院 兒童醫學部

16:40-16:50 PM Successful treatment of a steroid-refractory Kasabach-Merritt syndrome using anti-platelet agents吳孟哲 黃芳亮 陳靜鈺 張德高臺中榮民總醫院兒童醫學部 兒童血液腫瘤科會員演講（Ⅳ） 主持人：邱昌芳 黃文豊

16:50-17:00 PM Topic: Successful adult dual unit Cord Blood Transplantation complicated with fatalEBV-associated Post Transplant Lymphoproliferative Disease (PTLD) 傅雪美 蕭樑材 林鵬展 趙大中 陳博明 台北榮民總醫院 內科部腫瘤科

17:00-17:10 PM Two units umbilical cord blood transplant to chronic myelogenous leukemia: a case report邱宗傑 洪君儀 1 張家堯 1 鄧豪偉 陳博明 黃碧桃 1

台北榮民總醫院內科部腫瘤科 兒童醫學部 1

17:10-17:20 PM Prevention of transmission of hepatitis C virus in allogeneic peripheral blood stem cell transplantation by treating seropositive donor with peginterferon alfa-2b and ribavirin曾士賓 余明隆* 蔡慧珍 劉益昌 蕭惠樺 劉大智 張肇松 陳田柏 林勝豐高雄醫學大學 血液腫瘤內科、肝膽胰內科*

17:20-17:30 PM Cord Blood Transplantation譚傳德 陳博文 高國彰 黃達夫辜公亮基金會和信治癌中心醫院 血液腫瘤科 小兒血液腫瘤科 血庫

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17:30-17:40 PM Thromboembolic Thrombocytopenic Purpura Induced By Cyclosporin-A After Allogeneic Peripheral Blood Stem Cell Transplantation: A Case Report黃馨慧 林振源 葉士芃 廖裕民 沈盈君 邱昌芳 中國醫藥大學血液腫瘤科

17:40-17:50 PM Pure red cell aplasia due to parvovirus B19 infection in a renal transplantation recipient ; patient report蕭培靜 1 威廉貝爾 2連榮達 3

中山醫學大學附設醫院內科部血液科 1腎臟科 3

美國霍普金斯大學醫學院內科部 2

17:50-17:55 PM 中華民國血液及骨髓移植學會邱昌芳理事長致閉幕詞18:30- PM 晚宴備註：會員演講每題 10分鐘，討論 2分鐘，7分鐘鈴響一聲，8分鐘鈴響兩聲，請結束演講。

主辦單位：中華民國血液病學會、中華民國血液及骨髓移植學會協辦單位：台中榮民總醫院贊助單位：麒麟藥品股份有限公司教育積分：中華民國血液病學會 5分、中華民國癌症醫學會 3 分、

台灣兒科醫學會 2 分 、中華民國內科醫學會 5 分、台灣家庭醫學醫學會乙類 5分

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Management of myelofibrosis-related marked splenomegaly by partial splenic embolization – a case report

利用脾臟栓塞術處理骨髓纖維化導致之脾臟腫大－一病例報告楊陽生　楊吉雄　黃文豊　林增熙　滕傑林

台中榮民總醫院 內科部　血液腫瘤科Marked splenomegaly causing abdominal symptoms is a complication of

myeloproliferative disorders. However, timing of management of splenomegaly and how to reduce splenomegaly are constroversial. We present a case management experience here.

A 49-year-old female searched medical help to TCVGH due to dizziness and fatigue in 1997. Her peripheral blood cell count showed leukocytosis and thrombocytosis. Serial studies including bone marrow biopsy revealed myeloproliferative disorder with myelofibrosis. In later one year, several episodes of splenic infarction developed. Partial splenic embolization was performed after consideration. Splenic abscess followed. The abscess improved after treatment and splenic size reduced.

There are several resports mentioning management of marked splenomegaly of myeloproliferative disorders. The benefit and complications of these intervention will be reviewed.

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原發性中樞神經淋巴瘤: 台中榮總的經驗Primary CNS lymphoma: Taichung VGH experience

洪伯斌 林增熙 陽楊生 黃文豊 楊吉雄台中榮民總醫院內科部血液腫瘤科

In primary central nervous system lymphoma (1 percent or less of all primary brain tumors), unlike other brain tumors, resection does not have a therapeutic role, and the diagnosis is usually established by stereotactic biopsy. Chemotherapy should be the first treatment for all patients with the disease. The best regimens include high-dose methotrexate, which can penetrate the blood-brain barrier and is associated with complete-response rates of 50 to 80 percent. Standard regimens of combination chemotherapy, useful for systemic lymphomas, are ineffective in the treatment of cerebral lymphoma. In the past, radiotherapy was the mainstay of treatment, resulting in a median survival of 12 to 18 months. When methotrexate-based regimens are used in addition to cranial irradiation, the median survival is increased to at least 40 months. Regimens that rely on disruption of the blood–brain barrier, followed by intraarterial chemotherapy, have resulted in a median survival of 40months without the use of radiotherapy; however, high-dose systemic regimens can achieve similar results without the morbidity associated with this procedure.

We collected nine patients, who hospitalized between August, 1995 and April, 2004. The gender distribution was roughly balanced (5 female vs 4 male); but age distribution was not adjusted due to small patient number. Three patients were lost clinical follow-up, and 2 patients expired. Four survivaled patients, Two is in disease-free state and the rest are under ongoing standard R-CHOP regimen. Compare the treatment strategy between them, and the results showed that the overall prognosis of spinal lymphoma (all 4 survialed patients) was superior than brain lymphoma. In addition, surgical resection with or without cranial radiotherapy showed inadequate treatment and high relasping rate in one patient.

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A fulminant Langerhans cell histiocytosis in adult: A case report

滕傑林, 林增熙, 楊吉雄台中榮民總醫院血液腫瘤科

IntroductionLangerhans cell histiocytosis (LCH), previous termed as histiocytosis X, is a systemic

disorder of unknown etiology, characterized by an abnormal proliferation of cells of a dendritic cell lineage, which phenotypically resemble normal activated Langerhans cell. LCH is a rare disorder, which can occur at any age, with peak between 1 and 3 years. The estimated pediatric incidence is approximately 3-4 per million. The incidence in adult is uncertain, but much lower than that in children. Most of the LCH is single system disease. The multisystem LCH, especially in adults is extremely rare. We present a case of a fulminant adult Langerhans cell histiocytosis with multiple systems involvement.

Case Presentation A 28-year-old male was referred with presentation of persistent fever up to 39 degree,

chills and progressive petechiae and ecchymosis for 2 weeks. He was a previous smoker with 1 PPD for 2 years, and has quitted for 2 years. Besides, he was relatively well in the past without any other systemic disease.

About 2 weeks prior current admission, he started to suffer from persistent fever up to 39 degree and dry cough. He went to LMD for help, but in vain. Three days before referring, progressive petechiae, and ecchymosis, especially over lower limbs and nose happened. He was referred then.

In our hospital, initial hemogram was as below: DATE WBC RBC HGB HCT MCV PLT BLS PRO MY BAND NEUT LYM MON EOS BAS921116 400 2.39 7.4 22.0 92.1 70 1 3 1

Pancytopenia was noted. Due to persistent fever, empirical antibiotics were given. And bone marrow biopsy was performed, which showed 10-15% marrow cellularity. Langerhans histiocytosis and hemosiderin-laden macrophages predominated. Trilineage hematopoietic elements markedly decreased in number. Blasts and reticulum fibers were within normal limit. Skin biopsy showed the same diagnosis. Special stain revealed negative PAS stain. Immunohistochemistry (IHC) stains for MPO, L26, and OPD4 were all negative. S-100 protein and CD 68 were positive however. Besides, no apparent eosinophilic infiltration was seen.

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Respiratory failure occurred 3 days after admission. He was intubated. CT of chest was performed, which revealed disseminated alveolar densities with various sizes and some consolidations in right lower lung filed. Bronchoscopic larvage revealed 14x10000 cells with composition of 83% histiocyte, 9% lymphocyte, and 8% neutrophil. Besides, no bacteria, no malignant cells could be found. The whole bronchial trees were erythematous and edematous. Sonography of abdomen showed splenomegaly. CT of brain revealed no active lesion.

For febrile neutropenia, empirical antibiotics were used as below:

Fever surveys, including blood culture, urine routine and culture were all negative, except one set sputum culture, which revealed Candida albicans. Thalidomide started on the 12 th day of admission with initial dose of 400g per day and added to 600mg per day 3 days later. Renal function deteriorated progressively. He expired on the 22nd day of admission with diagnosis of Langerhans cell histiocytosis, complicated with septic shock and multiple organ failure.

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AdmissionTazocin+amikinFungizone

11/15 11/18

DC Tazocin+AikinAdd Cefepime

On ETT

11/19

DC Cefepime+Funizone+VancoAdd Tazocin+Amikin+Fluconazole

11/21

Thalidomide

11/26

Bronchoscope

11/20

Expired

12/6

Pseudo-Gaucher cells in mycobacterial infection: a report of two cases

洪玉馨 Δ 鄧波 郭明宗長庚紀念醫院 血液腫瘤科

Pseudo-Gaucher cells are reticuloendothelial cells with abundant cytoplasm containing linear striations, resembling the storage cells found in Gaucher’s disease. These pseudo-Gaucher cells have been described in hematologic diseases such as chronic myelgenous leukemia, thalassemia, multiple myeloma and myelodysplastic syndrome. The occurrences of pseudo-Gaucher cells in mycobacterial infection have been report in 3 incidences. Two were associated with mycobacterium avium intracellulare infections and the third was in a patient with pulmonary tuberculosis. Here we present two patients with mycobacterial infection, pseudo-Gaucher cells were found in lymph nodes and bone marrow, respectively.Case 1:This 61-year-old male is an alcoholic. He suffered from cough and afternoon fever in May 2002. Chest X-ray showed tuberculosis lesion over Rt upper lung and pleural effusion. Sputum culture grew mycobacterium kansassi. He was treated with isoniazid, refampicin, pyrazinamide, ethambutol and streptomycin. The latter 2 drugs were omitted 5 weeks later. Two months after starting treatment, cough and fever subsided. Five months later, he was admitted because of jaundice for 2 weeks. Multiple lymphadenopathy over bilateral neck, supraclavicular and inguinal areas were noted. Aspiration from cervical lymph node showed infiltration of Gaucher-like cells. AFB stains of lymph nodes (cervical, axillary and inguinal lymph nodes) were positive. Culture of sputum and lymph node aspirates still grew M. kanasasii. Anti-HIV test was negative. He died of disseminated mycobacterial infection one month later. Case 2: This 28-year-old male is a homosexual. He presented with general weakness, progressive shortness breath since one month ago. Body weight loss about 6 kg was noted. On physical examination, marked pale and splenomegaly (6fb below LCM) were found. Hemogram showed Hb 3.9gm/dl, RBC 1.56 x 106/ul, Ret 10%, WBC count 4.8 x 109/L with metamyelocyte 1.5%, band 0.5%, seg 91%, monocyte 3.5%, lymphocytes 3.5%, platelet count 2.4 x 109/L. Bone marrow aspiration showed histiocytes contained many crystalline inclusions or cell debris. Acid fast stain of bone marrow aspirates demonstrated positive AFB in histiocytes. Bone marrow biopsies revealed aggregates of histiocytes forming granulomatous lesions. Antibody to HIV was positive. Chest X-ray showed peribronchial infiltration on bilateral lower lung field. AFB stain of sputum was positive. Culture of sputum and bone marrow grew Mycobacterium avim intracellulare, 1 and 2 months later, respectively. A diagnosis of AIDS with MAI infections in lung and BM was made, he was treated with clarithromycin, ethambutol and rifabutin and anti-retroviral regimens (lopinavir, ritonavir, stavudine, lamivudine). Two month later, he achieved complete recovery from disseminated MAI infection.

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The Mitochondrial Pathway of As2O3-induced Apoptosis in Human T-cell Lymphoma

林增熙 1,4 陳亞雯 2 呂鋒洲 3 周芬碧 4 徐士蘭 2 楊吉雄 1

1 台中榮民總醫院 血液腫瘤科 2 教學研究部 3 中山醫學大學 應用化學系4 生化暨生物科技研究所

近年來三氧化二砷在治療復發的急性前骨髓性白血病有確定的效果，但是在其它腫瘤之抗癌機轉尚未完全清楚．因此，我們利用三氧化二砷研究在人類 T細胞淋巴瘤細胞株之抗癌機轉．以不同濃度之三氧化二砷處理(1, 5, 10 μM)．利用 trypan blue染色進行細胞存活率之測定．使用 TUNEL assay及流式細胞分析儀測定細胞凋亡，與細胞週期之變化．以西方轉漬法測定 Bcl-2，death receptor，caspases 家族及 cytochrome c蛋白之表現量之變化及 caspases之活性．結果發現以 As2O3連續處理二天，細胞的生長明顯被抑制，且呈現劑量及時間依存性的效果，而超過二天後細胞則進行死亡，且也呈現劑量及時間的依存性．由細胞形態的改變，DAPI、TUNEL螢光染色及流式細胞分析儀之結果得知 As2O3 明顯誘導細胞凋亡，但是處理 As2O3細胞之 Bcl-2，death receptor 家族之蛋白質表現量沒有變化，但粒腺體 cytochrome c 有釋放出來。由caspases活性測定之結果得知，caspase-2, -3, -6, -8, -9之活性皆有上升，且西方轉漬法之結果也明顯看出有被切下來的片斷，此凋亡反應可以被 p53抑制劑所阻斷。此外，利用共軛焦顯微鏡亦可見 bcl-2蛋白和 p53蛋白有相互結合現象。由以上的結果,我們推論As2O3造成 T細胞淋巴瘤 SUP-T1凋亡主要路徑可能是透過粒腺體凋亡路徑，而 p53誘導細胞凋亡可以經由 p53蛋白轉位，並非轉錄依賴之訊息。

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Imatinib induced tumor lysis syndrome : Report of a case and review of literature

張鴻 裴松南

長庚紀念醫院 血液腫瘤科Imatinib is a specific tyrosine kinase inhibitor which acts on bcr/abl positive leukemias including CML, ALL and a minority of AML. The impact of imatinib on the treatment of such diseases is enormous. The best target of imatinib is CML. For ALL, Philadelphia chromosomes bcr/abl transcripts can be found in up to 20% of adult ALL cases. Imatinib can be used in the treatment of such patients, although with less durable effects. Only about 20% of such patients may achieve complete remission. In case of imatinib monotherapy, ALL invariable relapses in a median of 2 months. Other treatment, including stem cell transplantation, should always be considered concomitantly or sequentially.

In clinical observations, imatinib was found to induce rapid apoptosis of cells. It could cause tumor lysis syndrome in patients with high tumor burden. We reported a 30 year-old male patient with positive bcr/abl transcript ALL, which was refractory to conventional chemotherapy. After 10 days' treatment with imatinib, he developed tumor lysis syndrome. It improved after hydration, urine alkalinization and allopurinol treatment. Imatinib was resumed after a short withdrawl. We reviewed the literature and found only 3 such cases reported, one briefly mentioned in the pilot dose escalation study, one with CML and another with ALL. These reports revealed the likelihood of imatinib to induce tumor lysis syndrome. Clinicians should be alert to such side effects. Preventive measures including allopurinol and hydration should be taken in case of high tumor burden. Parameters of tumor lysis such as LDH, uric acid, creatinine, calcium, potassium and phosphate levels should be monitored on a routine basis.

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Effective treatment of refractory immune thrombocytopenic purpura using Rituximab：

A Case Report

歐偉仁 萬祥麟 戴明燊 莊岳泉 姚乃舜 陳宇欽 謝安台 趙祖怡 高偉堯Wei-Jen Ou, Hsiang-Lin Wan, Ming-Shen Dai, Yoke-Chun Chung, Nai-Shun Yao,

Yeu-Chin Chen, An-Tai Hsieh, Tsu-Yi Chao, Woei-Yau Kao國防醫學院 三軍總醫院 血液腫瘤科

Division of Hematology/Oncology, Tri-Service General Hospital,National Defense Medical Center

Treatment of chronic refractory idiopathic thrombocytopenic purpura is a dilemma because many patients have minimal symptoms, response to treatment is uncertain, and treatments may have serious side effects.

Rituximab is a chimeric monoclonal antibody directed against normal and malignant B-lymphocytes expressing CD20 antigen. Recently, rituximab has been successfully used to treat several autoimmune disorders including immune thrombocytopenic purpura (ITP) through its B-cell depletion effect.

We report our experience in treating a woman with chronic ITP refractory to steroids and splenectomy complicated with subdural hematoma and upper gastrointestinal bleeding. The ITP achieved a partial response to intravenous Rituximab 600 mg (375 mg/m2; body surface 1.6 square meter) once weekly for 4 consecutive doses in June 2003. Platelet count reached 80,000 to 100,000/uL 17 days after the last dose of Rituximab infusion.

In our experience, Rituximab is worthy to try in patients with refractory ITP complicated with bleeding diathesis and life threatening bleeding and its toxicity is mild.

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Severe Hemophilia B Patients with Inhibitors in Taiwan:Report of Two Cases

郭政諭 1 林炫聿 1 張正雄 1 鍾智淵 1 王明倫 1 林正純 1 林正修 2 沈銘鏡 1,3

1 彰化基督教醫院 內科部 血液腫瘤科2 彰化基督教醫院 檢驗醫學部3 國立臺灣大學附設醫院 檢驗醫學部

The incidence of factor IX (FIX) inhibitors in hemophilia B is far less common than that of factor VIII inhibitors in hemophilia A (1~5% v.s. 10~30%). In National Taiwan University Hospital, 26 out of 195 hemophilia A patients (13.3%) and 2 out of 41 hemophilia B (4.9%) have been found to have inhibitors respectively during the year 2000 to 2002. Therapeutic strategies have become more complex in FIX inhibitors because of the unique features of simultaneous occurrence of anaphylaxis to FIX at the time of inhibitor development and the possible complication of inducing nephrotic syndrome. Here we report two patients who suffered from severe hemophilia B with inhibitors and briefly review the literature. The first patient is a nine year-old boy who got anaphylaxis reaction at one year of age while receiving FIX and was detected to have inhibitors two months later. Recent data showed FIX activities of less than 1% and FIX inhibitors of 42.5 Bethesda units. The other patient is a twenty-five year-old young man with FIX inhibitor of high responder, who developed gastrointestinal bleeding recently and received initial treatment of recombinant activated factor VII without satisfactory effect, and he was then successfully treated with high dose FIX when FIX inhibitor was found to be only 5.0 Bethesda units. The gastrointestinal bleeding stopped eventually after twice administration of high dose FIX.

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A Taiwanese Family of Type 2A von Willebrand Disease with S1506L Mutation

林炫聿 1 林博淂 2 張正雄 1 鍾智淵 1 王明倫 1 林正純 1 林正修 3 沈銘鏡 1,4

1 彰化基督教醫院 內科部 血液腫瘤科2 彰化基督教醫院 教學研究部3 彰化基督教醫院 檢驗醫學部

4 國立臺灣大學附設醫院 內科部 檢驗醫學部 Clinical, laboratory and genetic defect of a Taiwanese family with type 2A von Willebrand disease (VWD) were studied. The proband was a 69-year-old woman who gave birth to two sons and four daughters. She came to Changhua Christian Hospital in May, 2004 because of vaginal bleeding for one day. She had had frequent prolonged nasal bleeding since she was young. She also had easy bruising with development of ecchymoses, and got prolonged bleeding from the gum as well as after a minor injury. Tooth extraction which was performed once during her childhood was uneventful and she had not received any operation. She had not experienced hypermenorrhea, postpartum hemorrhage, hematuria, blackish stool nor joint bleeding. Her three daughters and one son had similar abnormal mucocutaneous bleedings since their childhood.

Her prothrombin time, activated partial thromboplastin time and platelet count were all within normal limits. The template bleeding time was 18 minutes, factor VIII activities was 39%, von Willebrand antigen (vWF:Ag) was 28%, von Willebrand factor ristocetin-cofactor (vWF:RCo) was 0%, and ristocetin-induced platelet aggregation (RIPA) at 0.6mg/mL, 1.2mg/mL and 1.5mg/mL of ristocetin was 1%, 2% and 0%, respectively. Analysis of von Willebrand factor (vWF) multimer of her plasma revealed complete absence of high-molecular weight (HMW) multimer. Four of her children mentioned above all had similar laboratory findings.

Exon 28 of vWF gene was amplified using polymerase chain reaction (PCR) and sequenced. The prohand and her two daughters were all found to be heterozygous for C to T transition at nucleotide 4517 resulting in Ser1506Leu (S1506L) substitution, which has been reported to cause impaired transport of vWF multimer between the endoplasmic reticulum and the Golgi complex with more profound effects on the secretion of HMW multimers than lower molecular weight multimers.

In conclusion, we firstly report a Taiwanese family of type 2A von Willebrand disease with the S1506L mutation on vWF gene.

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A Pharmacokinetic Study of Recombinant Human Factor IX (BeneFIX®) in Previously Treated Patients with Hemophilia B in Taiwan

針對已接受治療之 B型血友病病患使用賓凝適凍晶注射劑 (BeneFIX®第九凝血因子重組製劑) 的藥物動力學試驗

Hsiu-Hao Chang,1 M.D.; Yong-Li Yang,1, 3 M.D.; Ming-Ching Shen2, 3 , M.D.張修豪, 楊永立, 沈銘鏡

1. From Departments of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan2. From Departments of Internal Medicine, National Taiwan University Hospital, Taipei,

Taiwan3. From Departments of Laboratory Medicine, National Taiwan University Hospital, Taipei,

Taiwan台大醫院小兒部，內科部，檢驗醫學部

Background and Purpose: Benefix is a newly purified recombinant factor IX (rFIX) product for treatment of patients with hemophilia B, and free from the risk of transmitting plasma-derived human virus. The pharmacokinetic study of it in previously treated patients with hemophilia B had been performed in area other than Taiwan and found wide product- and patient-related variability in results . This study is conducted to determine the pharmacokinetics of rFIX in Taiwanese patients with hemophilia B, which should be taken into account in optimizing treatment regimens for individual patients with hemophilia B.Patients and Methods: This study included 10 male previously treated patients with nine severe and one moderate severe hemophilia B without inhibitor. All patients received rFIX at a dose of 75 IU/kg intravenously over 10 minutes. Blood samples were collected at prior to dosing, 0.25, 0.5, 1, 2, 3, 6, 12, 24, 48, 72 hours after rFIX administration for pharmacokinetic study. Any adverse events were recorded during the study. Results: The mean age of our patients is 24.6 years old (range, 15.5~47.0 years old). At baseline, rFIX infusion of 75 IU/kg resulted in a mean factor IX activity increase of 1.00% per IU/kg (range, 0.67~1.37%), corresponding to an in vivo recovery of 49.4% (range, 35.3~65.2%). The mean elimination half-life was 24.3 hours (range, 14.1~35.3 hours). These results are not different from those previously reported. There were three adverse events, including fever, hypertension, and dizziness, in three patients respectively. All of them resolved spontaneously without any sequences.Conclusions: The results of pharmacokinetic study of rFIX in previously treated Taiwanese patients with hemophilia B are similar to those reported by other populations.

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The UGT1A1 genotypes and gallbladder diseases in patients with transfusion-dependent -thalassemia in northern Taiwan

依賴輸血之-海洋性貧血病患其膽囊疾病及UGT1A1 基因型之調查研究陳鵬升 林凱信 蘇怡寧 盧孟佑 周獻堂 林東燦 林國信

衛生署桃園醫院內科臺大醫院小兒部

臺大醫院基因醫學部Jimmy P.S. Chern, MD, Kai-Hsin Lin, MD, Yi-Ning Su, MD, PhD, Meng-Yao Lu, MD,

Shiann-Tarng Jou, MD, Dong-Tsamn Lin, MD, Kuo-Sin Lin, MD, PhD

Objectives: Transfusion-dependent -thalassaemia is a cause for cholelithiasis in paediatric and adolescent population. The co-existence of Gilbert’s mutations has been reported to increase the incidence of cholelithiasis. The UTG1A1 genotypes and incidence of gallbladder diseases are unknown in patients with transfusion-dependent -thalassaemia in Taiwan. The purpose of this study is to estimate the prevalence and elucidate the risk factors of gallbladder diseases in patients with transfusion-dependent -thalassaemia in Taiwan, especially the correlation with promoter polymorphism and 211G>A mutation in UGT1A1 gene.Methods: Sixty-eight patients were recruited from the thalassaemia clinics of National Taiwan University Hospital and Tao-Yuan General Hospital. Abdominal ultrasosnography was performed. Serum bilirubin levels and the promoter polymorphism and 211G>A mutation of UTG1A1 gene were determined. Results: 7 patients (10.3%) had gallbladder sludge, and 5 patients (7.4%) had gallstones. Age (P = 0.011) and total bilirubin concentration (P = 0.013) were independent risk factors for gallbladder diseases. The UTG1A1 genotypes were not correlated significantly with serum bilirubin levels.Conclusions: The existence of UTG1A1 mutations is not a risk factor for development of gallbladder diseases in patients with transfusion-dependent -thalassaemia in Taiwan.

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Treatment-related leukoencephalopathy in a girl with recurrent acute lymphoblastic leukemia

黃芳亮, 張德高,李秀芬*, 遲景上*台中榮民總醫院兒童醫學部 兒童血液腫瘤科,兒童神經科*

The 13 years old girl was a victim of acute lymphoblastic leukemia (ALL). She had received TPOG ALL 93 HR protocol since Sep 1995 to Sep 1998. Isolated bone marrow relapse of ALL was noted in Aug 2000 and then she received TPOG ALL 97 VHR protocol. Chronic pancreatitis with hyperglycemia developed during the period of chemotherapy and she had received insulin treatment. Bone marrow examination showed remission after one month later. The 2nd relapse showed 77% blast over bone marrow examination in Sep2002.The treatment agents were shifted to MSKCC (Memorial Sloan Kettering Caner Center, New York) protocol. General condition was well and bone marrow 3rd remission noted in Oct 2002.

Unfortunately, generalized tonic-clonic seizure lasting for 2-3 minutes attacked at Nov 22, 2002. Lumbar puncture (cytospin examination) showed no malignant cell in CSF. Brain CT and brain MRI were performed. Diffuse brain atrophy with ventricular system dilatation, without hemorrhage lesion was found over the image studies. EEG showed low voltage with slow background activity. CNS infection was ruled out after a series of examinations including cultures of bacteria, fungus and virus. Frequent seizure attacked with headache, dizziness, nausea, nystagmus were still preset, although anti-convulsion agents such as rivotril, tegretol had been administrated. Leukemia with CNS involved could not be ruled out, so she received intra-thecal chemotherapy (MTX, Ara-C and hydrocortisone) since then. Total 10 times of TIT were performed. No more seizure attacked during TIT period. 3 weeks later progressive lower legs weakness, behavior change and dysphagia were developed. Brian MRI was rechecked in Feb 2003 and showed generalized brain atrophy with diffuse hyperintensity in cerebral white matter on T2W1. Leukoencephalopathy was diagnosed by brain MRI and clinical presentation. High dose methylprednisolone had been given for the brain insult but poor response noted. Frequent seizure attacked and progressive behavior withdrew later. She died on Aug 2003 due to recurrent acute leukemia with pneumonia and sepsis.

Drugs such as high dose MTX, intra-theca MTX, cyclophosphomide induced leukoencephalopathy in the leukemia patient had been reported. In our case, the patient who had been received intrathecal C/T and craniospinal irradiation, presented neurologic symptoms and a series of CNS examinations showed all negative finding. Drugs induced CNS insult such as leukoencephalopathy should be highly considered.

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Cytogenetics and Outcome in Childhood Acute Lymphoblastic Leukemia in Taiwan: An Institutional Experience

急性淋巴性白血病兒童的染色體與預後 : 臺大醫院的經驗Hsiu-Hao Chang,1 M.D.; Meng-Yao Lu,1, 3 M.D.; Shiann-Tarng Jou,1 M.D.; Kai-Hsin Lin,1

M.D.; Hwei-Fang Tien,2 M.D.; Dong-Tsamn Lin1, M.D.張修豪, 盧孟佑, 周獻堂, 林凱信, 田蕙芬, 林東燦

4. From Departments of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan

5. From Departments of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan

6. Consultant of Childhood Cancer Foundation of ROC, Taipei, Taiwan台大醫院小兒部, 內科部; 中華民國兒童癌症基金會

Background and Purpose: Cytogenetic studies of leukemic cells have significant prognostic value in childhood acute lymphoblastic leukemia (ALL) and the karyotype pattern are various between different populations. The aim of present study was to define the frequency and types of acquired chromosomal aberrations in a group of Taiwanese children with ALL, compare these data with those reported in the literature, and assess the outcome of children in various cytogenetic groups and with defined cytogenetic abnormalities.Patients and Methods: The study included patients younger than 18 years of age with newly diagnosed ALL who underwent cytogenetic studies and had adequate metaphase chromosomes for analysis at our hospital from 1993 to 2001. Metaphase chromosomes were banded by the conventional trypsin-Giemsa banding technique and karyotyped according to the International System for Human Cytogenetic Nomenclature.Results: Ninety-six patients were enrolled in our study. Among them, 34 (35.4%) patients had normal karyotypes, and the remaining 62 (64.6%) patients had abnormal karyotypes with structural abnormalities in 49 (79%) patients and numerical only abnormalities in 13 (21%) patients. Analysis of ploidy indicated that 34 (35.4%) patients with normal diploidy, 28 (29.2%) with pseudodiploidy, 25 (26%) with hyperdiploidy, and 9 (9.4%) with hypodiploidy in our ALL patients. Among patients with abnormal karyotypes, recurrent structural abnormalities were found in 30 (48.4%) cases, and the most frequent was t(9;22), followed by t(8;14). Chromosomal aberrations involving band 11q23 were found in six of our patients. Prognostic evaluation of cytogenetics indicated that translocation is a high-risk indicator in our patients. Patients with hyperdiploidy more than 50 chromosomes without recurrent abnormalities had better outcome and patients with t(9;22) had very poor prognosis.Conclusions: The frequency and types of acquired chromosomal aberrations found in our Taiwanese children with ALL were similar to those reported in the literature by other pediatric populations. Translocation is a significant independent risk factor in our patients.

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PIG-A gene analysis for PNH

汪天祥 楊吉雄 林增熙 楊陽生台中榮民總醫院 血液腫瘤科

Paroxysmal nocturnal hemoglobinuria是一種罕見的溶血性貧血，其臨床診斷除溶血 外 ， 常 伴 有 low LAP score 及 positive sugar water test 。 據 知 其 係 因glycosylphosphatidylinositol-class A(PIG-A)基因異常所致。根據文獻報告 PNH之 PIG-A gene突變，目前已知總共有 174個位置 somatic mutation被發現，其中有 158個位置是獨特(unique mutation)，僅有 16個位置是重覆出現(recurrent mutation)。

因此，近三年來吾人針對 11個 PNH 病人的 PIG-A gene做DNA定序，發現其中三個病人各自有獨特突變(unique mutation)，分別在 Exon2(568-577) GAAAATACTG的Deletion，Exon2(628-636) GTAGATCCT 的 Deletion 和 A 的 Insertion，兩者皆造成frameshift，另一病人在 Intron 1(-2)發生 AG轉變，造成 splice site被改變。另外在所有病人皆發現 Intron 1(+15) GCGC以及其中９個病人發現 promter(-472) CG，此二位置在正常人亦有相同情形，此二位置應屬於 species variation。

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Retinoblastoma—the Experience of a Single Medical Center In North Taiwan惡性視神經母細胞瘤---北台灣單一醫學中心之經驗

張家堯、洪君儀、謝玉林*、黃碧桃台北榮民總醫院 兒童醫學部

Purpose: As a referal center, we aim describe the susvival and clinical characteristics of 50 retinoblastoma cases, who visit or are treated at Taipei Veteran General Hospital between 1982 and 2004.

Methods: We retrospectively analyzed the clinical record of 50 children diagnosed as retinoblastoma in our hospital between 1982 to 2004. Information on sex, laterality, age at diagosis, presenting signs, spread of tumor, treatment modality, survival rate, and family history were collected.

Result: Thirty cases is referal cases. 40(80%) cases were unilateral and 10(20%) cases were bilateral. The mean age at the time of diagnosis was 25.89 months; in unilateral cases, 28.58 months(in 19 right cases, 26.47 months; in 21 left cases, 30.8 months); and in bilateral cases, 15.08 months. The most common presenting signs were leukocoria(33 cases, 66%), strabismus(6 cases, 12%), blurred vision(4 cases, 8%), red painful or tearing eye(5 cases, 10%), proptosis(1 case, 2%). The average time of presenting signs before diagnosis is 3.5 months. Only 2 case in 46 cases(4.3%) were familial cases. At least 7 cases had optic nerve involvement initially, ? cases had CNS invasion, at least 3 cases had bone marrow involvement. The 3-year cumulative survival rate will be shown at oral presentation.

Conclusion: Some results are not similar to report at CGMH in 2001. Detailed aspects will be discussed in oral presentation.

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Successful treatment of a steroid-refractory Kasabach-Merritt syndrome using anti-platelet agents

吳孟哲 黃芳亮 陳靜鈺 張德高臺中榮民總醫院兒童醫學部 兒童血液腫瘤科

A 5 M/O female infant was found having erythematous nodule about 3 x 3 cm in size over left thigh since she was 2 M/O. The lesion progressively increased size to about 10 x 12 cm. She was sent to a community hospital where interferon and prednisolone were prescribed but in vain. Because of severe thrombocytopenia and easy bruising, she was transferred to our hospital. After admission, laboratory data showed platelet 2K, DIC profile: fibrinogen < 40, FDP > 40, D-dimer > 5, PT: 12.3 sec, APTT: 40 sec, Kasabach-Merritt syndrome with consumption coagulopathy was impressed. Steroid pulse therapy with platelet and FFP transfusion were arranged. Unfortunately, there was no obvious improvement. Oncovin and Endoxan were ever used in the following days. Interferon-alpha was added later, but still in vain. One month after admission, the symptoms of thrombocytopenia with consumption coagulopathy were still present and the size of left thigh hemangioma was unchanged. Anti-platelet agents including tapal and persantin were then given. During the first week of treatment, thrombocytopenia was dramatically improved, the huge hemangioma decreased in size gradually. Ten days later, she was discharged and OPD followed up under anti-platelet agents. After 1 year and 4 months of follow-up, no more thrombocytopenia was found, and the hemangioma decreased in size also. Successfully use of anti-platelet agents with tapal and persantin in the treatment of steroid-refractory Kasabach-Merritt syndrome was noted in our case experience.

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Topic: Successful adult dual unit Cord Blood Transplantation complicated with fatal EBV-associated Post Transplant Lymphoproliferative Disease (PTLD)

傅雪美 蕭樑材 林鵬展 趙大中 陳博明台北榮民總醫院 內科部腫瘤科

Epstein-Barr virus associated post-transplant lymphoproliferative disease (PTLD) has been well documented as an unique iatrogenic complication after allogeneic stem celltransplantation. Few cases of pediatric PTLD after CBSCT have been reported. Thiscase is the first to describe disseminated PTLD (nodal and extranodal) in an adult after unrelated dual-unit CBSCT for severe aplastic anemia (SAA).Biopsy proven EBV-associated PTLD (DLBCL) over nasopharyngeal mass was identified on D+120 post CBSCT. High spiking fever , lymphadenopathies over neck, axillary and inguinal were also noted in association with the development of intractable gastrointestinal bleeding. An abdominal CT scan revealed multiple hypodense lesions over liver, spleen , kidney as well as intestinal wall thickening, esp. over distal jejunum and proximal ileum, suggestive of diffuse lymphoma involvement. Unfortunately, no appreciable clinical response was noted after immune suppression reduction, weekly Rituximab, IVIG or even final addition of systemic chemotherapy with COP. The patient died 30 days after the diagnosis of PTLD on account of intractable GI bleeding, neutropenic sepsis and multiple organ failure.This case demonstrates that disseminated PTLD carries high mortality despite aggressive and prompt management. The role of Rituximab alone in disseminated PTLD seems inadequate to control disease progression and further effective combination therapy is warranted in future cases.

Keywords: post transplant lymphoproliferative disease , cord blood stem cell transplantation, COP ( cyclophosphamide ,oncovin, prednisolone)

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Two units umbilical cord blood transplant to chronic myelogenous leukemia: a case report

台北榮民總醫院內科部腫瘤科 兒童醫學部 1

邱宗傑 洪君儀 1 張家堯 1 鄧豪偉 陳博明 黃碧桃 1

Tzeon-Jye Chiou, Giun-Yi Hung1, Chia-Yau Chang1, Hao-Wei Dan, Po-Min Chen, Betau Hwang1

INTRODUCTION: From the first successful case of umbilical cord bood transplantation in 1988, the accumulated experience in the world has reached thousands of examples. Umbilical cord blood was proved to be a feasible source of hematopoietic stem cells other than bone marrow and peripheral blood. However, it is just initiated in Taiwan with less than ten successfully transplanted cases. To our knowledge, this is the first case report in Taiwan demonstrated of two units umbilical cord blood transplant to a boy of chronic myelogenous leukemia with body weight as high as 68.5 kg at transplant.CASE REPORT: A 12-year-4-month old boy diagnosed as CML in Oct. 2003, with the initial WBC: 520,200/ul. He searched for medical help because of blurred vision. Leukemic retinopathy and massive splenomegaly were found by physical examination. Laboratory data revealed LDH 1376 u/l, LAP score: 2 scores. Positive of Philadelphia chromosome: 46,XY,t(9,22)(q34;q11.2). His condition was controlled by oral hydroxyurea. Since no HLA-matched sibling or unrelated bone marrow donors could be found, cord blood transplant was planned 4 months after starting hydroxyurea treatment.The Cord bloods were donated by StemCyte Taiwan Company, LTD. There were two units with 1 and 2 loci HLA mismatch and total nucleated cell dose were 1.92 and 4.67 x 10 7/kg of patient’s body weight, respectively. The condition regimen included busulphan 1mg/kg qid, day-7~day-4; and endoxan 60mg/kg/d, day-3~day-2. For GVHD prophylaxis, ATG (15mg/kg/d, day-2~day0), methotrexate, and cyclosporin-A were prescribed. The patient developed UGI bleeding, neutropenic fever, Herpes Simplex stomatitis and severe mucositis reguiring TPN supplement during transplantation. At fifth week he suffered from fever and dry cough, symptoms improved after treatment with Zithromax. The nadir of WBC was 10/ul on day+7, and absolute neutrophil count (ANC)>200/ul on day+15, >500/ul on day+20, >1000/ul on day+21. Time of neutrophil engraftment (ANC>500/ul for 3 consecutive days) was day+22. Time of platelet engraftment (without blood transfusion in previous 7 days) was day+41 for platelet >20,000/ul; day+43 for platelet>50,000/ul; and day+51 for platelet>100,000/ul. Chimerism is demonstrated by DNA-STR typing, which revealed 98% recipient’s type on day+7, but turned to 89% donor’s type on day+14, and 100% donor’s type on day+35. Of the two units of cord blood, only one unit engrafted successfully. The other unit was detected during day+7~+14 with minimal percentage, and can’t be detected since day+35.CONCLUSION: Umbilical cord blood transplantation is a feasible treatment for CML when no suitable bone marrow or PBSC donor could be found. Two units of cord blood can be considered for high body weight children or adult patients.

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Prevention of transmission of hepatitis C virus in allogeneic peripheral blood stem cell transplantation by treating seropositive donor with peginterferon alfa-2b and ribavirin

曾士賓 余明隆* 蔡慧珍 劉益昌 蕭惠樺 劉大智 張肇松 陳田柏 林勝豐Shih-Bin Tseng, Ming-Lung Yu* , Hui-Jen Tsai , Yi-Chang Liu, Hui-Hua Hsiao, Ta-Chih Liu,

Chao-Sung Chang, Tyen-Po Chen, Sheng-Fung Lin

高雄醫學大學 血液腫瘤內科、肝膽胰內科*

There is limited information on the clinical course of transplantation from hepatitis C virus (HCV)-positive donors. Studies have shown that immunocompromised patients infected with HCV have a high incidence of chronic infection and rapid progression to cirrhosis. Here we report a case of allogeneic peripheral blood stem cell transplantation (PBSCT) in chronic myeloid leukemia (CML) patient from HCV-positive donor. To prevent HCV transmission, the donor received peginterferon alfa-2b and ribavirin treatment before transplantation.

The 34 year-old male was a case of CML with blast crisis diagnosed on March 2003. The initial presentation was gastrointestinal bleeding and complete blood count showed leukocytosis, anemia and thrombocytopenia. The patient received imatinib treatment at first and both complete cytogenetic and molecular response were achieved. Then, the patient received allogeneic PBSCT on September 2003 from HCV seropositive donor.

The laboratory survey before transplantation of both donor and recipient showed:

AST/ALT (u/L) HBsAg Anti-HBs Anti-HCV Abdominal echo

Recipient 28 / 20 (-) (+) (-) Fatty liver Donor 30 / 30 (-) (+) (+) Fatty liver

Further survey of donor showed: HCV RNA qualitative positive and genotyping 1b. To prevent HCV transmission during PBSCT, the donor received Peg-Intron 100 ug SC once on day –6 and Ribavirin 1200 mg per day since day –6 and through out the course of transplantation. Total nucleated cell harvested was 22.9 x 10^8/kg (CD34+ cell 3.45 x 10^6/kg) during 3 consecutive days. Absolute neutrophil count > 500/ul achieved on day+10 after transplantation. Abnormal AST/ALT and anti-HCV positive were noted in recipient on day+29, however, the anti-HCV became negative spontaneously without specific treatment after day+200. The periodic HCV RNA qualitative of recipient showed negative during day+29~+200.

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Case Report：Limbic Encephalitis in a Patient Undergoing Umbilical Cord Blood Transplantation

Tran-Der, Tan*, MD., Bowen, Chen, MD., Kuo-Jang-Kao, MD., Andrew T. Huang*, MDDepartment of Hematology and Medical Oncology*., Division of Pediatric Hematology and

Oncology., Division of Pediatric Hematology and Oncology

Koo Foundation Sun Yat-Sen Cancer Center

譚傳德醫師 陳博文醫師 高國彰醫師 黃達夫醫師辜公亮基金會和信治癌中心醫院 血液腫瘤科 小兒血液腫瘤科 血庫

We present our first patient undergoing umbilical cord blood transplantation, who is a patient of refractory acute myeloid leukemia. Because of no available matched sibling donor and unrelated bone marrow donor, we performed umbilical cord blood transplantation for this patient and neutrophil engraftment occurred on 21st day but complicated with limbic encephalitis with short-term memory loss.

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Thromboembolic Thrombocytopenic Purpura Induced By Cyclosporin-A After Allogeneic Peripheral Blood Stem Cell Transplantation: A Case Report

黃馨慧 林振源 葉士芃 廖裕民 沈盈君 邱昌芳中國醫藥大學血液腫瘤科

Allogeneic hematopoietic stem cell transplantation (HSCT) is an important therapy to cure chemo-sensitive hematological malignancies at present. Graft-versus-host disease (GVHD), though providing graft-versus-malignancy effect, is still the most serious complication to be overcome after allogeneic HSCT. Cyclosporin-A (CSA) plays the major role in preventing and treating GVHD, acute or chronic. Renal toxicity and gastrointestinal disturbance are the most frequent side effects of CSA. Thromboembolic thrombocytopenic purpura (TTP) is one of the rare but serious adverse effects of CSA. Mortality rate of TTP can be at least 50% according to the previous reports. We report a 23-year-old female patient with myelodysplastic syndrome in leukemic transformation receiving allogeneic peripheral blood stem cell transformation developed TTP 56 days later when taking CSA for GVHD prevention. The condition of the disease progressed though CSA was discontinued, so plasma exchange was performed. After six courses of plasma exchange, schistocyte and level of lactic dehydrogenase (LDH) decreased, and cytopenia was improved. Instead of CSA, mycophenolate is her present medication for preventing GVHD. Till now (114 days after transplantation), TTP does not recur after the above management, though CSA was reloaded due to deterioration of acute GVHD.

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Pure red cell aplasia due to parvovirus B19 infection in a renal transplantation recipient ; patient report

蕭培靜★ 威廉貝爾★★ 連榮達★★★中山醫學大學附設醫院內科部血液科★腎臟科★★★

美國霍普金斯大學醫學院內科部★★A 36-year-old male patient, a renal transplant recipient with triple immunosuppressive agents (Prednisolone 20 mg p.o. qd, Cellceft 1000 mg p.o. bid and Prograf 7 mg p.o.bid ) experienced pure red cell aplasia (PRCA) secondary to parvovirus B19 infection one year after transplantation. This was confirmed by PCR, serologic studies demonstrated an IgM and IgG response. He received packed RBC 4u each month on average for anemia and rhEPO 8000Us.c.three times a week After PRCA was identified 3 months, post-transplant diabetes mellitus (PTDM) was also noted . DM was controlled by Mixtard 20u s.c. q a.m. and Actose 0.5 mg p.o. qd. Prograf and Cellceft were replaced by Cyclosporin 125 mg p.o. bid and Rapamune 3 mg p.o. qd after identification of DM. Anemia persisted, so Cylcosporin was discontinued and replaced by Imuran (Azathioprine) 50 mg p.o. bid . Approximately 2 months later, hemoglobin concentration remained normal and DM subsided. It has been reported in PRCA induced by B19 infection that intravenous IVIG results in resolution of anemia. However in this patient, we discontinued Cyclosporin and instituted Imuran 50 mg p.o. qd; Prednisolone 5mg p.o. qd and Rapamune 2 mg p.o. qd in the absence of IVIG and this was beneficial to the patient.

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