今日の臨床サポート

赤芽球癆

著者: 石田文宏 信州大学医学部保健学科

監修: 木崎昌弘 埼玉医科大学総合医療センター

著者校正/監修レビュー済:2022/11/09
患者向け説明資料

概要・推奨   

  1. 赤芽球癆の診断は骨髄赤芽球低形成に基づく赤血球産生低下により生じている貧血であることを証明し、病歴や検査所見によって病因診断を行うことが重要である(推奨度1)
  1. 赤芽球癆の初期治療は急性型と慢性型の鑑別を行うための方針決定と赤血球輸血の適応判断である(推奨度1)
  1. 基礎疾患の治療により貧血が改善しない後天性慢性赤芽球癆と特発性赤芽球癆に対して、免疫抑制薬の使用を考慮する(推奨度1)
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、 著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※同効薬・小児・妊娠および授乳中の注意事項等は、海外の情報も掲載しており、日本の医療事情に適応しない場合があります。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適応の査定において保険適応及び保険適応外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適応の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
石田文宏 : 特に申告事項無し[2022年]
監修:木崎昌弘 : 講演料(武田薬品工業,ヤンセンファーマ,小野薬品工業,ブリストル・マイヤーズスクイブ),研究費・助成金など(武田薬品工業),奨学(奨励)寄付など(協和キリン,旭化成ファーマ,第一三共,中外製薬,日本新薬,武田薬品工業)[2022年]

改訂のポイント:
  1. 定期レビューを行い、疾患情報について加筆修正した。 

病態・疫学・診察

疾患情報  
  1. 赤芽球癆(pure red cell aplasia、PRCA)は正球性または大球性貧血( 貧血 )と網赤血球の著減および骨髄赤芽球の著減を特徴とする造血器疾患である。<図表><図表>
  1. 赤芽球癆の病因は多様である。大きく先天性と後天性の病型に分けられ、後天性はその発症様式から急性型と慢性型に分類される。<図表>
  1. 先天性のものはDiamond-Blackfan貧血が知られ、25%の症例にリボゾーム蛋白S19をコードする遺伝子異常を有している。
  1. 後天性慢性赤芽球癆には特発性赤芽球癆と、 胸腺腫 あるいは 大顆粒リンパ球性白血病 などに伴う続発性赤芽球癆があり、その鑑別は重要である。
  1. 通常白血球数および血小板数は正常であるが、続発性の場合には基礎疾患によって異なる。
  1. 赤芽球癆の治療は病型・病因によって異なり、基礎疾患の治療に反応しない後天性慢性赤芽球癆に対して免疫抑制療法が行われる。
  1. 後天性赤芽球癆は、指定難病であり、重症度分類がStage3以上(ただし薬物療法を行っていてヘモグロビン濃度10g/dl以上の者は対象外)などでは、申請し認定されると医療費の自己負担分の一部が公費負担として助成される。(平成27年7月施行)
  1. 難病法に基づく医療費助成制度
 
  1. 日本人に最も多い後天性慢性赤芽球癆の病型は特発性(69.1%)である。続発性慢性赤芽球癆のなかで多い原因は胸腺腫関連赤芽球癆(9.3%)および大顆粒リンパ球性白血病関連赤芽球癆(2.5%)である(推奨度1、O)
  1. まとめ:後天性赤芽球癆は急性と慢性に区分される。慢性赤芽球癆は原因不明の特発性と基礎疾患を有する続発性に分類される。特発性赤芽球癆は続発性赤芽球癆に属さないものを指し、その頻度は後天性慢性赤芽球癆全体の約70%と推定されている[1][2][3]
  1. 代表事例:特発性造血障害調査研究班が2004年と06年に行った全国調査によれば、ヒトパルボウイルスB19感染によらない成人の後天性赤芽球癆185例中、特発性が73例(39.5%)で、残りが続発性であった。続発性赤芽球癆の基礎疾患としては、胸腺腫、リンパ系腫瘍、自己免疫疾患が多くみられた[3]。日本血液学会疾患登録データベースで2013年から2019年の登録症例では69.1%が特発性であった。
  1. 結論:続発性赤芽球癆の原因は多様であり、基礎疾患を丁寧に探すことが重要である。
問診・診察のポイント  
  1. 急性型と慢性型の鑑別のために、 貧血 およびそれに関連する症状がいつ出現したかを確認する。

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文献 

D A Clark, E N Dessypris, S B Krantz
Studies on pure red cell aplasia. XI. Results of immunosuppressive treatment of 37 patients.
Blood. 1984 Feb;63(2):277-86.
Abstract/Text Thirty-seven patients with pure red cell aplasia (PRCA) were seen between 1966 and 1982. Ten patients had accompanying diseases described in association with PRCA, while the remainder had primary PRCA. All but two patients were treated with some form of immune manipulation, including corticosteroids, cytotoxic drugs, antithymocyte globulin, splenectomy, thymectomy, and plasmapheresis. Twenty-three patients (66%) had a remission induced by immunosuppression. In addition, there were 5 spontaneous remissions (14%). Cytotoxic drugs administered in combination with corticosteroids were the most effective form of treatment, producing 18/32 remissions (56%). Twelve of these remissions were in patients resistant to corticosteroids or in patients who had relapsed while taking them. Thirteen of the 23 patients in whom remissions were induced and one-fifth of the patients with spontaneous remissions have relapsed to date. However, with additional treatment, a second remission was induced in 10/13. Fifty-four percent of the patients with induced remissions remained transfusion-free during most of the follow-up period. Median survival in patients with primary PRCA was greater than 10 yr, whereas in patients with secondary PRCA, it was 4 yr. Infection was a major cause of morbidity and mortality. This study demonstrates the value of a variety of immunosuppressive treatments of patients with PRCA.

PMID 6581839
Abstract/Text From 1980 through 1994, we identified 47 adult patients with acquired pure red cell aplasia (median age, 64 years; range, 22 to 84 years). Associated clinical disorders included T-cell large granular lymphocytic (LGL) leukemia, thymoma, chronic lymphocytic leukemia, and non-Hodgkin's lymphoma. Review of bone marrow findings in 40 patients showed absence of erythroid precursors in 14 patients and rare pronormoblasts in 26. None had morphologic evidence of myelodysplasia. T-cell receptor gene rearrangement studies with Southern blot technique in 14 patients showed clonal rearrangements in nine. Karyotypic analyses performed in 28 patients showed clonal abnormalities in four. Overall, 28 of 47 patients (60%) responded to immunosuppressive therapy, but none were the patients with cytogenetic abnormalities. There was a trend toward superior response to immunosuppressive agents in the patients with T-cell LGL leukemia. Cyclophosphamide, with or without corticosteroids, was the most useful treatment agent. Cyclosporine A was effective for refractory disease. Neither the presence of an associated clinical disorder nor the existence of detectable erythroid precursors affected overall survival. We conclude that (1) T-cell LGL leukemia is the disorder most commonly associated with pure red cell aplasia, (2) the presence of clonal cytogenetic abnormality predicts poor response to immunosuppressive therapy, and (3) oral cyclophosphamide and cyclosporine A are effective treatment regimens.

PMID 8639922
Ken-ichi Sawada, Makoto Hirokawa, Naohito Fujishima, Masanao Teramura, Masami Bessho, Kazuo Dan, Hisashi Tsurumi, Shinji Nakao, Akio Urabe, Mitsuhiro Omine, Keiya Ozawa, PRCA Collaborative Study Group
Long-term outcome of patients with acquired primary idiopathic pure red cell aplasia receiving cyclosporine A. A nationwide cohort study in Japan for the PRCA Collaborative Study Group.
Haematologica. 2007 Aug;92(8):1021-8. Epub 2007 Jul 20.
Abstract/Text BACKGROUND AND OBJECTIVES: Cyclosporine A (CsA) has become one of the leading agents for the treatment of pure red cell aplasia (PRCA). However, further studies are necessary to determine the relapse-free survival (RFS) and overall survival (OS) of patients treated with this drug, the minimum duration of therapy for induction of remission, and whether or not there is need for maintenance treatment.
DESIGN AND METHODS: We conducted a nationwide survey in Japan. From a total of 185 patients (with 73 primary idiopathic PRCA and 112 with secondary PRCA), we evaluated 62 patients with primary idiopathic PRCA for this report.
RESULTS: The remission induction therapy for these patients included CsA (n=31), corticosteroids (CS) (n=20) or other drugs (n=11). CsA and CS produced remissions in 23 (74%) and 12 (60%) patients, respectively. The salvage treatment produced remissions in 58 patients (94%). Forty-one and 15 patients were maintained on CsA+/-CS (CsA-containing group) or CS alone (CS group), respectively. The median RFS in the CsA-containing group was 103 months, longer than that seen in the CS group (33 months) (p<0.01). Of 14 patients whose CsA was discontinued, 12 patients (86%) relapsed after a median of 3 months (range 1.5 to 40 months), while only 3 of 27 patients (11%) relapsed during CsA-containing maintenance therapy. Thus, the discontinuance of maintenance therapy was strongly correlated with relapse (p<0.001). Four patients in the CsA-containing group died; however, the OS of this group was not significantly different from that of the CS-groups (p=0.104).
INTERPRETATION AND CONCLUSIONS: CsA-containing regimens sustain prolonged RFS more effectively than CS in primary idiopathic PRCA and seem to be important to prevent relapse.

PMID 17640861
Muneeb A Choudry, Bryan K Moffett, Damian A Laber
Pure red-cell aplasia secondary to pregnancy, characterization of a syndrome.
Ann Hematol. 2007 Apr;86(4):233-7. doi: 10.1007/s00277-006-0211-4. Epub 2007 Jan 30.
Abstract/Text The aim of this study was to characterize the syndrome of pure red-cell aplasia (PRCA) secondary to pregnancy. All published cases of PRCA induced by pregnancy were reviewed. Additionally, we reported a patient who developed PRCA on three occasions; two were triggered by pregnancy and one after medroxyprogesterone administration. Ten patients with 13 pregnancy-induced PRCA episodes were reported. The PRCA occurred at any gestational age. All patients received blood transfusions, and six of them were treated corticosteroids. The PRCA resolved in all subjects postpartum. Five women had subsequent pregnancies; three were complicated by PRCA, one was normal, and one had spontaneous abortion without PRCA. One subject developed a PRCA after long-term exposure to medroxyprogesterone. Infant blood values were normal in the nine reported cases. Pregnancy-induced PRCA is a self-limited syndrome with a high risk for relapse during subsequent pregnancies. It can be managed by blood transfusions. Progestins might cause PRCA in these women.

PMID 17262194
P Fisch, R Handgretinger, H E Schaefer
Pure red cell aplasia.
Br J Haematol. 2000 Dec;111(4):1010-22.
Abstract/Text
PMID 11167735
R S Go, C Y Li, A Tefferi, R L Phyliky
Acquired pure red cell aplasia associated with lymphoproliferative disease of granular T lymphocytes.
Blood. 2001 Jul 15;98(2):483-5.
Abstract/Text Acquired pure red cell aplasia (PRCA) can be associated with lymphoproliferative disease of granular T lymphocytes (T-LDGL), also known as T-cell large granular lymphocyte leukemia. Fifteen adult patients with PRCA associated with T-LDGL comprise this study. Neutropenia and rheumatoid arthritis were uncommon. All patients responded to immunosuppressive therapy. The 2 most commonly used treatments were prednisone and cyclophosphamide +/- corticosteroids, producing overall response rates of 50% and 60%, respectively. Treatment with cyclophosphamide was associated with a more durable remission (median, 60 versus 7.5 months). After a median follow-up of 67 months, 2 patients died of treatment-related complications, one from myelodysplasia and another from cyclosporine-induced renal failure. The clinical course and treatment responses of PRCA associated with T-LDGL in this series were similar to the general group of PRCA. Because T-LDGL is frequently underdiagnosed, it is likely that a significant proportion of idiopathic or primary PRCA is in fact secondary to T-LDGL.

PMID 11435321
Makoto Hirokawa, Ken-ichi Sawada, Naohito Fujishima, Shinji Nakao, Akio Urabe, Kazuo Dan, Shin Fujisawa, Yuji Yonemura, Fumio Kawano, Mitsuhiro Omine, Keiya Ozawa, PRCA Collaborative Study Group
Long-term response and outcome following immunosuppressive therapy in thymoma-associated pure red cell aplasia: a nationwide cohort study in Japan by the PRCA collaborative study group.
Haematologica. 2008 Jan;93(1):27-33. doi: 10.3324/haematol.11655.
Abstract/Text BACKGROUND: Thymoma-associated pure red cell aplasia (PRCA) accounts for a significant proportion of cases of secondary PRCA and immunosuppressive therapy has been reported to be useful in this condition. However, because of its rarity, the long-term response and relapse rates after immunosuppressive therapy are largely unknown, and optimal management of this disorder remains unclear. The aim of this study was to collect more information on the outcome of patients with thymoma-associated PRCA.
DESIGN AND METHODS: We conducted a nationwide survey in Japan. From a total of 185 patients, comprising 73 with idiopathic and 112 with secondary PRCA, 41 patients with thymoma were evaluated for this report. End-points of this study were the response rate, duration of the response after immunosuppressive therapy and overall survival.
RESULTS: Surgical removal of thymoma was reported in 36 patients, 16 of whom developed PRCA at a median of 80 months post-thymectomy. First remission induction therapy was effective in 19 of 20 patients treated with cyclosporine, 6 of 13 patients treated with corticosteroids and 1 of 1 treated with cyclophosphamide. No cyclosporine-responders relapsed within a median observation period of 18 months (range; 1 to 118 months). Relapse of anemia was observed in three corticosteroid-responders who did not receive additional cyclosporine. Only two patients were in remission after stopping therapy for 19 and 67 months. The estimated median overall survival time of all patients was 142 months.
CONCLUSIONS: Thymoma-associated PRCA showed an excellent response to cyclosporine and cyclosporine-containing regimens were effective in preventing relapse of anemia. It does, however, remain uncertain whether cyclosporine can induce a maintenance-free hematologic response.

PMID 18166782
Naohito Fujishima, Ken-ichi Sawada, Makoto Hirokawa, Kazuo Oshimi, Koichi Sugimoto, Akira Matsuda, Masanao Teramura, Masamitsu Karasawa, Ayako Arai, Yuji Yonemura, Shinji Nakao, Akio Urabe, Mitsuhiro Omine, Keiya Ozawa, PRCA Collaborative Study Group
Long-term responses and outcomes following immunosuppressive therapy in large granular lymphocyte leukemia-associated pure red cell aplasia: a Nationwide Cohort Study in Japan for the PRCA Collaborative Study Group.
Haematologica. 2008 Oct;93(10):1555-9. doi: 10.3324/haematol.12871. Epub 2008 Jul 18.
Abstract/Text Large granular lymphocyte leukemia-associated pure red cell aplasia accounts for a significant portion of secondary pure red cell aplasia cases. However, because of its rarity, long-term responses and relapse rates after immunosuppressive therapy are largely unknown. We conducted a nationwide survey in Japan and collected 185 evaluable patients. Fourteen patients with large granular lymphocyte leukemia-associated pure red cell aplasia were evaluated. Cyclophosphamide, cyclosporine A and prednisolone produced remissions in 6/8, 1/4 and 0/2 patients respectively. Seven and 5 patients were maintained on cyclophosphamide or cyclosporine A respectively. Two patients relapsed after stopping cyclophosphamide, and 2 patients relapsed during maintenance therapy with cyclosporine A. The median relapse-free survival in the cyclophosphamide - and the cyclosporine A groups was 53 and 123 months respectively. Large granular lymphocyte leukemia-associated pure red cell aplasia showed a good response to either cyclophosphamide or cyclosporine A. Most patients continued to receive maintenance therapy and it remains uncertain whether cyclophosphamide or cyclosporine A can induce a maintenance-free hematologic response in large granular lymphocyte leukemia-associated pure red cell aplasia.

PMID 18641028
Carrie A Thompson, David P Steensma
Pure red cell aplasia associated with thymoma: clinical insights from a 50-year single-institution experience.
Br J Haematol. 2006 Nov;135(3):405-7. doi: 10.1111/j.1365-2141.2006.06295.x.
Abstract/Text Acquired pure red cell aplasia (PRCA) is a rare disorder of erythropoiesis that can develop in association with a thymoma. Optimal management of this subgroup is unclear, and there have been few series reporting long-term clinical outcomes. Here, we report features of 13 patients treated for PRCA associated with thymoma over 50 years at our institution. Surgical resection of the thymoma was insufficient for normalisation of erythropoiesis in all cases. T-cell gene rearrangement studies did not routinely demonstrate a clonal process, and ciclosporin and anti-thymocyte globulin were effective adjuvant treatments. However, treatment-related morbidity was high, with frequent infectious complications.

PMID 17032177
Makoto Hirokawa, Ken-ichi Sawada, Naohito Fujishima, Fumio Kawano, Akiro Kimura, Takashi Watanabe, Ayako Arai, Toshimitsu Matsui, Shinji Nakao, Akio Urabe, Mitsuhiro Omine, Keiya Ozawa
Acquired pure red cell aplasia associated with malignant lymphomas: a nationwide cohort study in Japan for the PRCA Collaborative Study Group.
Am J Hematol. 2009 Mar;84(3):144-8. doi: 10.1002/ajh.21354.
Abstract/Text Pure red cell aplasia (PRCA) has been reported in association with lymphoma as one of the autoimmune diseases seen during the course of lymphoid malignancies. However, the relation of PRCA with the underlying lymphomas remains unclear. The aim of this study was to clarify the histologic subtypes of lymphomas, the chronological sequence of anemia and lymphoma, and the response to treatment. We conducted a nationwide survey in Japan. From a cohort of 185 PRCA patients, 8 patients with lymphoma were evaluated. Histologic subtypes varied and the lymphoma was of the B-cell type in four cases and of the T-cell type in four. Four patients simultaneously developed PRCA and lymphoma. Three patients developed PRCA following lymphoma, two of whom developed anemia during remission of lymphoma. PRCA preceded lymphoma in one patient. Effective chemotherapy was associated with remission of anemia in concurrent lymphoma and PRCA. Overall, anemia responded to chemotherapy and/or immunosuppressive therapy in seven patients. In four responding patients, PRCA remained in durable remission without maintenance immunosuppressive therapy, which is different from a recurrent feature of idiopathic PRCA. We suggest that the mechanism of lymphoma-associated PRCA is heterogeneous and that durable maintenance-free remission of anemia can be obtained in some patients.

PMID 19195037
V R Sharma, D R Fleming, S P Slone
Pure red cell aplasia due to parvovirus B19 in a patient treated with rituximab.
Blood. 2000 Aug 1;96(3):1184-6.
Abstract/Text Rituximab is a chimeric monoclonal antibody directed against CD20 and used in the treatment of B-cell non-Hodgkin's lymphoma. Due to its ability to deplete B lymphocytes, rituximab can interfere with humoral immunity, causing it to be suppressed for several months after treatment. The reported case depicts a serious consequence of this effect of rituximab therapy: pure red cell aplasia resulting from chronic parvovirus B19 infection. The point of interest in this case is not only the association between rituximab therapy and pure red cell aplasia, but the diagnostic and therapeutic utility of the knowledge of parvovirus B19 as the likely etiologic link between the two. Given the known efficacy of intravenous immunoglobulin (IVIg) in the treatment of chronic parvovirus B19 infection, this therapy can cure some of these patients and successfully render most others transfusion-independent until recovery of their own humoral immune system.

PMID 10910942
Kevin W Song, Peter Mollee, Bruce Patterson, William Brien, Michael Crump
Pure red cell aplasia due to parvovirus following treatment with CHOP and rituximab for B-cell lymphoma.
Br J Haematol. 2002 Oct;119(1):125-7.
Abstract/Text A 26-year-old woman, diagnosed with diffuse large B-cell lymphoma, was treated with CHOP (cyclophosphamide, hydroxydaunomycin, oncovin, prednisone), rituximab and radiotherapy. She developed transfusion-dependant anaemia, which persisted following chemotherapy. Bone marrow aspirate and biopsy were consistent with pure red cell aplasia and parvovirus infection. Serology was negative for previous or acute infection but parvovirus DNA was detected by polymerase chain reaction. Administration of intravenous immunoglobulin (1 g/kg) resulted in reticulocytosis and recovery of her haemoglobin. We hypothesize that rituximab caused depletion of her normal B cells, resulting in an inability to mount a primary immune response to parvovirus infection.

PMID 12358915
Yasushi Isobe, Koichi Sugimoto, Yumi Shiraki, Miho Nishitani, Kengo Koike, Kazuo Oshimi
Successful high-titer immunoglobulin therapy for persistent parvovirus B19 infection in a lymphoma patient treated with rituximab-combined chemotherapy.
Am J Hematol. 2004 Dec;77(4):370-3. doi: 10.1002/ajh.20200.
Abstract/Text A 40-year-old female diagnosed with follicular lymphoma was treated with rituximab-combined chemotherapy. Although she achieved complete remission, she developed progressive anemia and reticulocytopenia. Bone marrow examination revealed features of pure red cell aplasia and hemophagocytosis. In addition, the appearance of large pronormoblasts suggested that she was infected with parvovirus B19. Excess viral DNA in her bone marrow confirmed that her illness was caused by persistent parvovirus B19 infection. Serum immunoglobulin levels decreased beyond the lower normal limit, which indicated that her humoral immunity was impaired after rituximab-combined chemotherapy. Although she had been infected with parvovirus B19, she was re-infected and failed to control the viral expansion. High-titer immunoglobulin against parvovirus B19 was intravenously administrated and resulted in remarkable reticulocytosis and improvement of anemia. High-titer immunoglobulin, which contained a sufficient amount of neutralizing antibodies against parvovirus B19, likely inactivated most viruses in vivo. We successfully eradicated the virus after 2 courses of high-dose therapy at 0.5 g/kg/day every week followed by 8 courses of maintenance therapy at 0.1 g/kg/day every other week. It is important to consider that parvovirus B19 infection is a possible cause of progressive anemia in B-cell lymphoma patients treated with rituximab-combined chemotherapy. We propose that the use of high-titer immunoglobulin against parvovirus B19 may enable such immunocompromised patients to eradicate the virus before sufficient immune system reconstruction.

2004 Wiley-Liss, Inc.
PMID 15558805
Ranjit Nair, Shereen Gheith, Suresh G Nair
Immunotherapy-Associated Hemolytic Anemia with Pure Red-Cell Aplasia.
N Engl J Med. 2016 Mar 17;374(11):1096-7. doi: 10.1056/NEJMc1509362.
Abstract/Text
PMID 26981948
Atsushi Isoda, Yuri Miyazawa, Kenichi Tahara, Masahiro Mihara, Akio Saito, Morio Matsumoto, Morio Sawamura
Pembrolizumab-induced Pure Red Cell Aplasia Successfully Treated with Intravenous Immunoglobulin.
Intern Med. 2020 Aug 15;59(16):2041-2045. doi: 10.2169/internalmedicine.4467-20. Epub 2020 May 8.
Abstract/Text We herein report a 64-year-old man who was treated with pembrolizumab for relapsed Hodgkin lymphoma. After the third administration of pembrolizumab, he showed acute anemia with a positive direct anti-globulin test. Because of the markedly erythroid hypoplasia, he was diagnosed with pure red cell aplasia (PRCA) caused by pembrolizumab. He was initially treated with prednisolone, but the reticulocytes decreased after tapering prednisolone. He then received high-dose intravenous immunoglobulin (IVIG) with prednisolone, and PRCA was successfully treated. Although the pathogenesis of PRCA caused by immune checkpoint inhibitors (CPIs) remains unclear, IVIG treatment may be effective for some steroid-refractory CPI-induced PRCA cases.

PMID 32389947
Ilyssa O Gordon, Takisha Wade, Kevin Chin, Jerome Dickstein, Thomas F Gajewski
Immune-mediated red cell aplasia after anti-CTLA-4 immunotherapy for metastatic melanoma.
Cancer Immunol Immunother. 2009 Aug;58(8):1351-3. doi: 10.1007/s00262-008-0627-x. Epub 2008 Dec 4.
Abstract/Text
PMID 19052742
Charles F Thomas, Andrew H Limper
Pneumocystis pneumonia.
N Engl J Med. 2004 Jun 10;350(24):2487-98. doi: 10.1056/NEJMra032588.
Abstract/Text
PMID 15190141
Elliott Vichinsky, Onyinye Onyekwere, John Porter, Paul Swerdlow, James Eckman, Peter Lane, Beatrice Files, Kathryn Hassell, Patrick Kelly, Felicia Wilson, Françoise Bernaudin, Gian Luca Forni, Iheanyi Okpala, Catherine Ressayre-Djaffer, Daniele Alberti, Jaymes Holland, Peter Marks, Ellen Fung, Roland Fischer, Brigitta U Mueller, Thomas Coates, Deferasirox in Sickle Cell Investigators
A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease.
Br J Haematol. 2007 Feb;136(3):501-8. doi: 10.1111/j.1365-2141.2006.06455.x.
Abstract/Text Deferasirox is a once-daily, oral iron chelator developed for treating transfusional iron overload. Preclinical studies indicated that the kidney was a potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, the primary objective of this randomised, open-label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population. Assessment of efficacy, as measured by change in liver iron concentration (LIC) using biosusceptometry, was a secondary objective. A total of 195 adult and paediatric patients received deferasirox (n = 132) or deferoxamine (n = 63). Adverse events most commonly associated with deferasirox were mild, including transient nausea, vomiting, diarrhoea, abdominal pain and skin rash. Abnormal laboratory studies with deferasirox were occasionally associated with mild non-progressive increases in serum creatinine and reversible elevations in liver function tests. Discontinuation rates from deferasirox (11.4%) and deferoxamine (11.1%) were similar. Over 1 year, similar dose-dependent LIC reductions were observed with deferasirox and deferoxamine. Once-daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease.

PMID 17233848
Takahiro Suzuki, Masao Tomonaga, Yasushi Miyazaki, Shinji Nakao, Kazuma Ohyashiki, Itaru Matsumura, Yutaka Kohgo, Yoshiro Niitsu, Seiji Kojima, Keiya Ozawa
Japanese epidemiological survey with consensus statement on Japanese guidelines for treatment of iron overload in bone marrow failure syndromes.
Int J Hematol. 2008 Jul;88(1):30-5. doi: 10.1007/s12185-008-0119-y. Epub 2008 Jun 27.
Abstract/Text Many patients with bone marrow failure syndromes need frequent transfusions of red blood cells, and most of them eventually suffer from organ dysfunction induced by excessively accumulated iron. The only way to treat transfusion-induced iron overload is iron chelating therapy. However, most patients have not been treated effectively because daily/continuous administration of deferoxamine is difficult for outpatients. Recently, a novel oral iron chelator, deferasirox, has been developed, and introduction of the drug may help many patients benefit from iron chelation therapy. In this review, we will discuss the current status of iron overload in transfusion-dependent patients, and the development of Japanese guidelines for the treatment of iron overload in Japan, which were established by the National Research Group on Idiopathic Bone Marrow Failure Syndromes in Japan.

PMID 18581199

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