演題詳細

特別講演 / Special Lecture

【E】特別講演 (Special Lecture)

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日程
2013年10月11日(金)
時間
13:00 - 13:45
会場
第1会場 / Room No.1 (さっぽろ芸文館 1F ニトリ文化ホール)
座長・司会
髙久 史麿 (Fumimaro Takaku):1
1:President, The Japanese Association of Medical Sciences/Honorary President, Jichi Medical University, Japan
 
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Acquired pure red cell aplasia (PRCA): 45 year experience

演題番号 : -

Sanford B. Krantz:1

1:Department of Hematology / Oncology, Vanderbilt University Medical Center, USA

 

 Acquired PRCA is a severe anemia with an almost complete absence of erythroblasts in the marrow, but with normal granulopoiesis and thrombopoiesis. When I was a Hematology Fellow we were referred a PRCA patient and I put his marrow cells into a newly constructed culture system that responded to erythropoietin. To our surprise hemoglobin synthesis increased 5-fold and new erythroblasts were formed suggesting that the cells were freed from an inhibitor. Subsequent cultures demonstrated that PRCA lgG inhibited this increase and later tests from multiple patients showed that the lgG inhibitors could inhibit development of CFU-E and/or BFU-E, or be cytotoxic to erythroblasts. We treated our first patient with 6-mercaptopurine and he went into complete remission. We have since treated 37 PRCA patients with cytotoxic chemotherapy plus prednisone and 56% have had a remission after relapsing or failing with prednisone alone. 13/23 patients who responded have relapsed at least once, but retreatment was successful in 10/13. By retreating several times or initiating maintenance immunosuppression, 9/13 relapsing patients and 54% of all patients remained transfusion free during follow-up. Totterman was the first to report responses to cyclosporine A (CsA). While his patients did not remain in remission after CsA was stopped, the remissions were maintained with low dose CsA with or without low dose steroids. We have treated 9 PRCA patients, refractory to other immunosuppressive agents, with oral CsA plus 30 mg of prednisone daily. We obtain a trough CsA level 7 days after starting, when it is fully equilibrated, and aim for 200-300 ng/ml. 6 patients responded to CsA in 2-12 weeks and remained in remission for 4-19 months. Recently Dr Ken-lchi Sawada and the Japan PRCA Collaborative Study Group conducted a very important nationwide survey in Japan. From 185 patients 62 with primary acquired PRCA were evaluated in the largest and longest follow-up study so far. 23/31 remissions occurred with CsA. After discontinuation, 12/14 relapsed while only 3/27 relapsed during CsA maintenance. We studied 12 cases of transient erythroblastopenia of childhood and demonstrated an lgG inhibitor of patientsʼ CFU-E or BFU-E in 8/12 which disappeared upon remission. Further studies by other investigators have shown that PRCA in Tor B cell chronic lymphocytic leukemia is associated with T¥ cells that inhibit the patientsʼ own CFU- E. Tefferi found that T cell large granular lymphocytic leukemia was the most common secondary association with PRCA and that these patients responded to CsA or cytotoxic chemotherapy. Another form of secondary PRCA is due to drug administration and our laboratory showed that in a case of diphenylhydantoin PRCA the patientʼs lgG markedly inhibited his own CFU-E only in the presence of the drug. Over many years many drugs have been implicated as a cause of secondary PRCA and when these drugs are withdrawn the PRCA generally remits in 1-4weeks. In 45 years we have come a long way, from one PRCA patient with an unknown pathogenesis, to a classification of PRCA into a great many groups and a demonstration of an immune pathogenesis in many that responds to a variety of immunos,uppressive therapies.

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