Intervention Review

Immunoglobulin prophylaxis in hematological malignancies and hematopoietic stem cell transplantation

  1. Pia Raanani1,*,
  2. Anat Gafter-Gvili2,
  3. Mical Paul3,
  4. Isaac Ben-Bassat4,
  5. Leonard Leibovici2,
  6. Ofer Shpilberg1

Editorial Group: Cochrane Haematological Malignancies Group

Published Online: 8 OCT 2008

Assessed as up-to-date: 21 JUL 2008

DOI: 10.1002/14651858.CD006501.pub2


How to Cite

Raanani P, Gafter-Gvili A, Paul M, Ben-Bassat I, Leibovici L, Shpilberg O. Immunoglobulin prophylaxis in hematological malignancies and hematopoietic stem cell transplantation. Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD006501. DOI: 10.1002/14651858.CD006501.pub2.

Author Information

  1. 1

    Rabin Medical Center, Institute of Hematology, Petah-Tikva, Israel

  2. 2

    Beilinson Campus, Rabin Medical Center, Department of Medicine E, Petah-Tiqva, Israel

  3. 3

    Rabin Medical Center, Infectious Diseases Unit and Department of Medicine E, Petah-Tikva, Israel

  4. 4

    Sheba Medical Center, Tel-Hashomer, Institute of Hematology, Tel-Hashomer, Israel

*Pia Raanani, Institute of Hematology, Rabin Medical Center, Institute of Hematology, Rabin Medical Center, Campus Beilinson, Petah-Tikva, 49100, Israel. praanani@012.net.il.

Publication History

  1. Publication Status: New
  2. Published Online: 8 OCT 2008

SEARCH

 

Abstract

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

Background

Patients undergoing hematopoietic stem cell transplantation (HSCT) and those with lymphoproliferative disorders (LPD) have a higher incidence of infections due to secondary hypogammaglobulinemia. One approach is the prophylactic administration of intravenous immunoglobulins (IVIG). Randomized controlled trials (RCTs) showed conflicting results in terms of type, schedule, dose and hematological patients benefiting from IVIG. We therefore performed a systematic review and meta-analysis to evaluate the role of IVIG in these patients.

Objectives

To determine whether prophylaxis with IVIG reduces mortality or affects other outcomes in patients with hematological malignancies.

Search methods

PubMed (January 1966 to December 2007), CENTRAL (The Cochrane Library, up to 2007, issue 1), LILACS and conference proceedings published between 2002-2007 were searched. The terms "immunoglobulins" or "gammaglobulins" or specific gammaglobulins and similar and the terms "hematologic neoplasms" or "hematologic malignancies" or "transplant" or "autotransplant" or "allotransplant" or "bone marrow transplant" or "peripheral stem cell transplant" and similar were selected. References of all included trials and reviews identified were scanned for additional trials.

Selection criteria

All RCTs comparing prophylaxis of IVIG with placebo, no treatment or another immunoglobulin preparation, different administration schedules or doses for patients with hematological malignancies were included. One author screened all abstracts identified through the search strategy and two reviewers independently inspected each reference identified by the search and applied inclusion criteria.

Data collection and analysis

For each trial, results were expressed as relative risks (RR) with 95% confidence intervals (CI) for dichotomous data and weighted mean differences for continuous data. We conducted meta-analysis, where enough similar trials were available, using the fixed- effects model, unless significant heterogeneity was present. We performed sensitivity analyses to assess the effect of individual methodological quality measures on effect estimates, including allocation generation, concealment and blinding.

Main results

Forty trials were included: thirty included HSCT patients and ten included patients LPD. When polyvalent immunoglobulins or hyperimmune cytomegalovirus (CMV)-IVIG was compared to control for HSCT, there was no difference in all-cause mortality. Polyvalent immunoglobulins significantly reduced the risk for interstitial pneumonitis but increased the risk for veno-occlusive disease and adverse events. In LPD, no benefit in terms of mortality IVIG could be demonstrated but there was a decrease in clinically and microbiologically documented infections.

Authors' conclusions

In patients undergoing HSCT, routine prophylaxis with IVIG is not supported. Its use may be considered in LPD patients with hypogammaglobulinemia and recurrent infections, for reduction of clinically documented infections.

 

Plain language summary

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

The role of prophylactic immunoglobulins in hematological malignancies

Patients with hematological malignancies are prone to infections due to defects in their immune system. One of the main defects is a reduction in the level of immunoglobulins. For many years, the notion was that administration of pooled immunoglobulins from healthy donors might reverse this defect. However, randomized controlled trials showed different results in terms of prolongation of survival, reduction of infections and side effects of treatments. We conducted a systematic review assessing the role of administration of immunoglobulins from healthy donors as prophylaxis in patients with hematological malignancies. Our review showed that in the context of bone marrow transplantation the administration of immunoglobulins did not have an effect on survival or other outcomes. On the other hand, in patients with lymphoproliferative disorders like chronic lymphocytic leukemia or multiple myeloma, it reduced substantially the rate of infections. Despite their high cost, prophylactic immunoglobulins might prove cost-effective in this population.

 

摘要

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

背景

在血液惡性疾病與造血幹細胞移植的預防性免疫球蛋白之使用

接受造血幹細胞移植患者與罹患淋巴增生性疾病的病人會因為次發性的低伽瑪球蛋白症而導致較高的感染率。預防性的使用靜脈注射免疫球蛋白(IVIG)是一種可行的方式。在隨機分派的對照試驗中發現在不同劑型、療程、劑量與血液疾病病患中,免疫球蛋白治療好處有不一致的結論。因此我們進行了系統性的回顧與統合分析(metaanalysis)來評估免疫球蛋白在這類病患的角色。

目標

決定預防性的免疫球蛋白在血液惡性疾病的病患中是否降低死亡率或影響其他結果。

搜尋策略

我們搜尋MEDLINE (1966年一月到2007年十二月)、CENTRAL (Cochrane圖書館至2007年第一期)、 LILACS與發表於2002到2007年的會議記錄。免疫球蛋白或伽瑪球蛋白或是特定的伽瑪球蛋白與相似的字,還有血液腫瘤、血液惡性疾病、移植、自體移植、異體移植、骨髓移植或周邊血幹細胞移植與相似的字都被選擇。所有納入的研究和綜論之參考文獻都被掃描起來以供其他的研究。

選擇標準

所有比較預防性靜脈注射免疫球蛋白與安慰劑、無治療、其他劑型的球蛋白、不同療程或劑量用於血液惡性疾病病患的隨機臨床試驗都被納入。由一位作者篩選所有以搜尋策略找到的摘要而另兩位審閱者獨立的檢視每一篇搜尋到且符合納入條件的參考文獻。

資料收集與分析

每一篇研究的結果都以相對風險(RR) 與95% CI來表達二分法的資料並以加權均數差值來表達連續資料。若相似的研究夠多時我們執行統合分析並以固定影響模型分析,除非有顯著的異質性。我們施行靈敏度分析去評估每一個方法學的品質之效果估計,包含分配族群、隱瞞與盲法。

主要結論

四十個試驗被納入:其中三十個為造血幹細胞移植病患之研究,另外十個是淋巴增生性疾病的病人。用在造血幹細胞移植病患時,多價的免疫球蛋白或巨細胞病毒的超免疫免疫球蛋白與對照組比較起來並沒有減少所有原因之死亡。多價的免疫球蛋白可有意義的減少間質性肺炎但會增加肝小靜脈拴塞疾病和其他副作用。在淋巴增生性疾病的病人,免疫球蛋白無法證實對死亡率有任何幫忙,但是可減少臨床上及細菌學上證實的感染。

作者結論

在進行造血幹細胞移植的病患,常規的預防性使用免疫球蛋白並不被支持。但它的使用在淋巴增生性疾病的病人合併有低伽瑪球蛋白症與反覆感染時,為了減少臨床上證實的感染可考慮使用。

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

預防性使用免疫球蛋白在血液惡性疾病的角色:血液惡性疾病的患者因為他們的免疫系統的缺陷而容易感染,其中一個主要的缺陷即是免疫球蛋白的減少。多年以來,一般的觀念是注射由健康捐者收集來的免疫球蛋白可以校正這個缺陷。然而,隨機的對照試驗顯示在延長存活、減少感染與治療副作用等方面有不同的結果。我們實行這個系統性的回顧評估在血液惡性疾病患者預防性使用收集自健康捐者的免疫球蛋白。我們的分析顯示在骨髓移植的情況下使用免疫球蛋白對存活與其他結果沒有任何效果。另一方面,在淋巴增生性疾病的病人如:慢性淋巴性白血病或多發性骨髓瘤,它可以減少實質上感染的機率。姑且不管它很昂貴,預防性的免疫球蛋白在這個族群可能是划算的。