Intervention Review

Corticosteroids for preventing graft-versus-host disease after allogeneic myeloablative stem cell transplantation

  1. Susanne Quellmann1,*,
  2. Guido Schwarzer2,
  3. Kai Hübel3,
  4. Alexander Greb4,
  5. Andreas Engert1,
  6. Julia Bohlius1

Editorial Group: Cochrane Haematological Malignancies Group

Published Online: 16 JUL 2008

Assessed as up-to-date: 27 JAN 2007

DOI: 10.1002/14651858.CD004885.pub2


How to Cite

Quellmann S, Schwarzer G, Hübel K, Greb A, Engert A, Bohlius J. Corticosteroids for preventing graft-versus-host disease after allogeneic myeloablative stem cell transplantation. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD004885. DOI: 10.1002/14651858.CD004885.pub2.

Author Information

  1. 1

    University Hospital of Cologne, Cochrane Haematological Malignancies Group, Department I of Internal Medicine, Cologne, Germany

  2. 2

    German Cochrane Center, Department of Medical Biometry and Statistics, Freiburg, Germany

  3. 3

    University Hospital of Cologne, Department I of Internal Medicine, Center of Integrated Oncology Köln Bonn, Cologne, Germany

  4. 4

    Cologne, Germany

*Susanne Quellmann, Cochrane Haematological Malignancies Group, Department I of Internal Medicine, University Hospital of Cologne, Kerpener Str. 62, Cologne, 50924, Germany. s.quellmann@email.de.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 16 JUL 2008

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Despite ongoing progress, acute and chronic GvHD still represent major drawbacks in the context of allogeneic myeloablative haematopoietic stem cell transplantation (HSCT) due to their high morbidity and mortality. Corticosteroids are used as first-line treatment of acute and chronic GvHD. However, their role for preventing GvHD is unclear as the published study results are controversial.

Objectives

To determine the effectiveness of corticosteroids used for the prophylaxis of GvHD in adults following allogeneic myeloablative HSCT. in improving overall survival, disease-free survival, relapse incidence, non-relapse mortality, acute GvHD grade I to IV, II to IV and III to IV, chronic GvHD, incidence of infectious complications, other adverse effects and cause of deaths.

Search methods

We searched the Cochrane Haematological Malignancies Group trials register, CENTRAL (The Cochrane Library Issue 2, 2004), MEDLINE (January 1999 to February 2006), EMBASE (January 1999 to 2004), LILACS covering publications until 2004, as well as handsearched conference proceedings, including citations until 2005.

Selection criteria

Randomised controlled trials (RCT) comparing the addition of corticosteroids to a GvHD prophylaxis regimen in adult patients having undergone allogeneic myeloablative HSCT were included into the review. All types and stages of the underlying disease as well as all types of possible HLA-matching were considered.

Data collection and analysis

Trial eligibility and quality assessment, data extraction and analysis were done in duplicate.

Main results

Five RCTs involving 604 people were included. The pooled results revealed that the addition of corticosteroids reduces statistically significant the risk for acute GvHD grade I to IV (HR 0.58; 95% CI 0.45 to 0.76) and II to IV (HR 0.69; 95% CI 0.51 to 0.92). No evidence was found that it has any clinical relevance on overall survival (HR 0.99; 95% CI 0.79 to 1.25) or disease-free survival (HR 0.95; 95% CI 0.74 to 1.23). As well, no statistically significant influence was found for acute GvHD grade III to IV (HR 0.78; 95% CI 0.52 to 1.15), chronic GvHD (HR 1.21;95% CI 0.89 to 1.65]), relapse incidence (HR 0.82; 95% CI 0.57 to 1.18) or non-relapse mortality (HR 0.88;95% CI 0.61 to 1.26). No clear evidence was found that the rate of infectious complications (under the concomitant use of antiviral or antibacterial medication or both) increases with the addition of corticosteroids. With respect to the other outcomes no significant differences could be detected.

Authors' conclusions

The addition of corticosteroids reduces the incidences of acute GvHD grade I to IV and II to IV. This reduction, however, did not show any effect on overall survival and disease-free survival. Further randomised controlled studies are needed to evaluate if the timing of steroid administration has a significant influence on the outcome; data on quality of life should be assessed systematically.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Corticosteroids for preventing graft-versus-host disease after allogeneic myeloablative stem cell transplantation

Some types of blood cancer can be treated by transplanting stem cells from the patient's blood relatives or siblings. Unfortunately, transplanted stem cells (also called the 'graft') can sometimes induce an inflammatory reaction in the patient (or the 'host'). This reaction is called 'graft-versus-host disease' (GvHD), and once it occurs it is difficult to treat. GvHD can adversely affect the patient's quality of life and often causes death. Drug therapies have been developed to prevent GvHD. Even so, many patients still suffer this complication. Preventive therapy against GvHD must be optimised. Since corticosteroids are the first-line treatment used after GvHD occurs, it is a hypothesis that if used in prophylaxis regimens, corticosteroids can decrease the occurrence of GvHD and improve patient survival rates.

Five RCTs involving 604 people were included in this review. Analyses of these studies showed that the incidence of moderate forms of GvHD can be reduced by prophylactic corticosteroid regimens. However, there is no evidence that the incidence of life-threatening forms or patient mortality can be reduced. Effects on quality of life could not be estimated because this information was not systematically collected during these studies. Further studies are needed to determine if the timing of steroid administration influences the outcomes of GvHD.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

以皮脂類固醇預防殲滅性異體幹細胞移植後之移植物對抗宿主疾病

即使醫療不斷進展,急性與慢性移植物對抗宿主疾病(GvHD)仍然因為它的高致病率與死亡率,而代表了殲滅性異體造血幹細胞移植(HSCT)的主要缺點。皮脂類固醇是治療急性與慢性移植物對抗宿主疾病的第一線藥物。然而,目前已發表的結果仍有許多爭議,故他們在預防的角色仍不明確。

目標

確認皮脂類固醇用在預防成人殲滅性異體造血幹細胞移植後的急性與慢性移植物對抗宿主疾病,在改善整體存活、無病存活、復發機率、非復發死亡率、第一到四級、二到四級與第三到四級的急性移植物對抗宿主疾病、慢性移植物對抗宿主疾病、感染併發症的機率,其他副作用與死亡原因的有效程度。

搜尋策略

我們搜尋了考科藍血液惡性疾病組研究登記、CENTRAL(考科藍實證醫學資料庫2004年第二期)、醫學文獻資料庫(1999年一月到2006年二月)、醫藥學文獻資料庫(1999年一月到2004年)、2004年以前LILACS的封面文章,同時也進行人工搜尋,2005年以前的會議記錄與引用文獻。

選擇標準

額外以皮脂類固醇用在成人殲滅性異體造血幹細胞移植,作為預防移植物對抗宿主疾病治療之隨機對照試驗,皆納入此回顧。既有疾病所有類型的分類與分期,和所有可能的人類白血球抗原配對的試驗,皆納入考慮。

資料收集與分析

所有試驗的參與條件、品質評估、資料提取與分析都經過重複確認。

主要結論

五個隨機臨床試驗,包含604個病患被納入此回顧。集中後的結果顯示,額外的皮脂類固醇,在統計上有意義的減少急性第一到四級(危險比0.58; 95% 信賴區間是 0.45 至 0.76),與第二到四級(危險比0.69; 95%信賴區間是 0.51 至 0.92)移植物對抗宿主疾病。沒有證據顯示它的使用在整體存活(危險比 0.99; 95% 信賴區間是 0.79 至 1.25) 或無病存活(危險比 0.95; 95% 信賴區間是 0.74 至 1.23) 有任何臨床關連。同樣的,在急性第三到四級移植物對抗宿主疾病(危險比 0.78; 95% 信賴區間是 0.52 至 1.15)、慢性移植物對抗宿主疾病(危險比 1.21; 95% 信賴區間是 0.89 至 1.65)、疾病復發(危險比 0.82; 95% 信賴區間是 0.57 至 1.18)或非復發死亡率(危險比 0.88; 95% 信賴區間是 0.61 至 1.26)並無統計上有意義的影響。沒有明顯的證據顯示,額外使用皮脂類固醇會增加感染併發症的比例(在同時使用抗病毒及抗菌藥物的時候)。至於其他的治療結果亦無發現顯著的不同。

作者結論

額外的使用皮脂類固醇,可減少第一到四級與第二到四級移植物對抗宿主疾病。然而這樣的改善,對整體存活和無病存活並沒有顯現任何效果。需要更進一步的隨機試驗,來評估使用類固醇的時機,對移植成果是否有顯著影響;生活品質的評估,亦須有系統的來探討。

翻譯人

本摘要由慈濟醫院王佐輔翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

有些類型的血液癌症可以用患者兄弟姊妹或親人的幹細胞移植來治療。不幸的是,移植的幹細胞(也稱為移植物)有時會在病患(或稱為宿主)身上引發一種發炎反應。這種反應叫做移植物對抗宿主疾病,而一但它發生了以後便很難治療。移植物對抗宿主疾病會對病患的生活品質有負面的影響且常常造成死亡。目前許多藥物被研發來預防移植物對抗宿主疾病。即便如此,許多患者仍遭受到此併發症。移植物對抗宿主疾病的預防性治療需要改善。既然皮脂類固醇是移植物對抗宿主疾病的第一線治療,在預防性的處方使用它可降低移植物對抗宿主疾病的發生率並改善病患的存活是一個合理的假設。五個隨機臨床試驗包含604個病患被納入此回顧。這些研究的分析發現中度的移植物對抗宿主疾病可被皮脂類固醇所預防。然而,沒有證據顯示可能致命的移植物對抗宿主疾病或是病患死亡可以被減少。對生活品質的影響則因為這些研究在進行時無有系統的收集此類資料,故目前無法評估。仍須近一步的研究來決定可影響移植物對抗宿主疾病的類固醇使用時機。