Get access

Alkylating agents for Waldenstrom's macroglobulinaemia

  • Review
  • Intervention




Waldenstrom's macroglobulinaemia (WM) is an uncommon B-cell lymphoproliferative disorder characterized by bone marrow infiltration and production of monoclonal immunoglobulin. Uncertainty remains if alkylating agents, such as chlorambucil, melphalan or cyclophosphamide, are an effective form of management.


To assess the effects and safety of the alkylating agents on Waldenstrom's macroglobulinaemia (WM).

Search methods

We searched the Cochrane Central Register of Controlled Trials (Issue1, 2008), MEDLINE (1966 to 2008), EMBASE (1980 to 2008), the Chinese Biomedical Base (1982 to 2008) and reference lists of articles.We also handsearched relevant conference proceedings from 1990 to 2008.

Selection criteria

Randomised controlled trials (RCTs) comparing alkylating agents given concomitantly with radiotherapy, splenectomy, plasmapheresis, stem-cell transplantation in patients with a confirmed diagnosis of WM.

Data collection and analysis

Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials.

Main results

One trial involving 92 participants with pretreated/relapsed WM compared the effect of fludarabine versus the combination of cyclophosphamide (the alkylating agent), doxorubicin and prednisone (CAP). Compared to CAP, the Hazard ratio (HR) for deaths of treatment with fludarabine was estimated to be 1.04, with a standard error of 0.30 (95% CI 0.58 to 1.48) and it indicated that the mean difference of median survival time was -4.00 months, and 16.00 months for response duration. The relative risks (RR) of response rate was 2.80 (95% CI 1.10 to 7.12). There were no statistically difference in overall survival rate and median survival months, while on the basis of response rate and response duration, fludarabine seemed to be superior to CAP for pretreated/relapsed patients with macroglobulinaemia.

Authors' conclusions

Although alkylating agents have been used for decades they have never actually been tested in a proper randomised trial. This review demonstrated that there is currently no evidence to suggest that alkylating agents are effective in treating Waldenstrom's macroglobulinaemia.



烷基化劑藥物(Alkylating agents)使用於瓦爾登斯特倫巨球蛋白血症(Waldenstrom's macroglobulinaemia)

瓦爾登斯特倫巨球蛋白血症是一種少見的B細胞淋巴組織增生性疾病, 其特點是骨髓浸潤及產生單株免疫球蛋白. 而烷基化劑藥物, 例如苯丁酸氮芥(chlorambucil), 馬法蘭(melphalan)或環磷醯胺(cyclophosphamide), 是否有療效仍然還不確定.




我們搜尋了Cochrane Central Register of Controlled Trials (Issue1, 2008), MEDLINE (1966年至2008年), EMBASE (1980年至2008年), Chinese Biomedical Base (1982年至2008年)和文章列出之參考文獻. 我們也利用手工搜尋相關1990年至2008年參考文獻之會議記錄.


利用隨機對照試驗(Randomised controlled trials, RCTs), 比較烷基化劑藥物治療合併放射性治療, 脾臟切除, 血漿置換, 或幹細胞移植於確診為瓦爾登斯特倫巨球蛋白血症之病人.


由兩位作者獨立評估各個試驗的品質及其摘錄的數據. 我們亦聯繫研究的作者以獲得更多訊息. 我們也從各個試驗中收集副作用的資料.


其中一個試驗, 共含92個新診斷或復發的瓦爾登斯特倫巨球蛋白血症患者, 比較其使用弗達拉濱藥物(fludarabine)與合併環磷醯胺(為一種烷基化劑藥物), 力得(doxorubicin)及潑尼松(prednisone)(合稱CAP)之治療效果. 和CAP組比起來, 用弗達拉濱藥物治療病人造成死亡的危險比(HR)為1.04, 其標準誤(standard error)為0.30(95%信賴區間為0.58到1.48), 及其中間存活時間的平均差為負4個月, 和16個月的治療反應期. 其治療反應率的相對風險(relative risks, RR)為2.80(95%信賴區間為1.10到7.12). 且其總生存率和中位生存月在統計上並無差異.且根據治療反應率及反應時程, 弗達拉濱藥物使用在新診斷或復發的瓦爾登斯特倫巨球蛋白血症患者的效果似乎優於烷基化劑藥物.


雖然烷基化劑藥物已被使用數十年, 但他們從來沒有用於隨機試驗中. 這審查發現目前沒有證據使用烷基化劑藥物於治療瓦爾登斯特倫巨球蛋白血症上是有效的.



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


烷基化劑藥物使用於瓦爾登斯特倫巨球蛋白血症: 瓦爾登斯特倫巨球蛋白血症是一種少見的B細胞淋巴組織增生性疾病, 其特點是骨髓浸潤及產生單株免疫球蛋白. 它是一種可導致死亡之非霍奇金淋巴瘤. 烷基化劑藥物被認為可有效的治療在瓦爾登斯特倫巨球蛋白血症上, 其可減輕症狀和延長存活時間. 審查的作者發現一個隨機對照試驗, 於92個實驗者中, 認為對於治療新診斷或復發的瓦爾登斯特倫巨球蛋白血症患者, 使用弗達拉濱藥物的效果優於烷基化劑藥物.

Plain language summary

Alkylating agents for Waldenstrom's macroglobulinaemia

Waldenstrom's macroglobulinaemia (WM) is an uncommon B-cell lymphoproliferative disorder characterised by bone marrow infiltration and production of monoclonal immunoglobulin. It is a kind of non-Hodgkin's lymphoma which can lead to death. Alkylating agents are believed to be effective in treatment of Waldenstrom's macroglobulinaemia for alleviating symptoms and elongating survival time. The review authors found one randomised controlled trial with 92 participants that considered fludarabine was superior to the alkylating agents-containing regimen for pretreated/relapsed patients with Waldenstrom's macroglobulinaemia.