幹細胞為嚴重的移植物抗宿主反應帶來一線希望


  December 12, 2006 (奧蘭多) — 使用間葉幹細胞於治療嚴重急性移植物抗宿主反應 (GvHD) 可以「救命」,且為原本認為無治療希望、面對死亡的病患帶來一線希望;來自Pennsylvania大學的Stephen Emerson醫師,在美國血液學會(ASH)第48屆年會暨研討會中聽到一項52位病患的試驗報告後,向Medscape提出上述看法。
  
  此一研究結果係由Karolinska大學醫院Katrina LeBlanc的醫師所發表,她指出,發生嚴重急性GvHD的病患對類固醇沒有治療反應者,死亡率是100%;在第3期臨床試驗試過的其他治療方式有PUVA、血漿減除術,或間白血球素-2併腫瘤壞死因子,都未顯示有效。
  
  她的團隊決定試著使用間葉幹細胞,作為對抗小分子之更廣泛的治療方法;細胞來源是捐贈者的骨髓,主要來自未配對骨髓,但有些來自親戚,使用間葉幹細胞的配對情況看來比使用造血幹細胞較不困難。
  
  所發表的研究結果來自52位病患 (摘要中報告的是其中40位),LeBlanc醫師指出,在其中35位有治療反應(整體反應率為 68%),這之中有22位病患仍存活,11位健康良好,有11位仍有慢性GvHD。
  
  其他30位病患死亡,8位有治療反應,但是因為其GvHD頗為嚴重導致發生嚴重感染;2位出現多重器官衰竭,1位出現新發作的急性骨髓性白血病,2 位是復發白血病。
  
  另外17位病患沒有治療反應,LeBlanc醫師表示,目前為止,不知道為什麼有些病患有治療反應,而有些則沒有。
  
  研究者推測,間葉幹細胞發揮了抗發炎反應(在體外試驗已顯示有效),且促進了腸胃道的癒合,原本接受靜脈營養輸注的病患可以恢復自行進食,顯示可以快速恢復GI上皮功能。
  
  LeBlanc醫師表示,基於這些結果,我們對間葉幹細胞可以實質幫助修復人類組織感到樂觀;結果顯示此一方法可以有效且安全的治療嚴重急性GvHD,但是她強調,此方法必須以隨機臨床試驗進行檢測;她的研究團隊目前正計畫第三期試驗。
  
  ASH 48th Annual Meeting and Exposition: Abstract 753. Presented December 11, 2006.

Stem Cells Offer Hope in Sever

By Zosia Chustecka
Medscape Medical News

December 12, 2006 (Orlando) ??The use of mesenchymal stem cells in the treatment of severe acute graft-vs-host disease (GvHD) is a "lifesaving advance" and offers hope to a patient population that would otherwise be without hope, facing almost certain death. This was the reaction of Stephen Emerson, MD, PhD, from the University of Pennsylvania, in Philadelphia, speaking to Medscape after hearing the results from a trial of 52 patients at the American Society of Hematology (ASH) 48th Annual Meeting and Exposition.

The results were presented by Katrina LeBlanc, MD, PhD, from the Karolinska University Hospital Huddinge, in Stockholm, Sweden. She noted that patients who develop severe acute GvHD and who do not respond to steroids have a 100% mortality rate. Other treatment approaches that have been tried, such as PUVA, plasmapheresis, or interleukin-2 with tumor necrosis factor, have not shown efficacy in phase 3 clinical trials, she told Medscape.

Her team decided to try mesenchymal stem cells "as a more global way to deliver a therapy as opposed to a small molecule." The cells were collected from donated bone marrow. The majority came from mismatched bone marrow, although some came from relatives. "It appears that with mesenchymal stem cells, the degree of matching is less crucial than with hemopoietic stem cells," she commented.

Presenting results from 52 patients (an update on the 40 patients reported in the abstract), Dr. LeBlanc said that responses were seen in 35 patients (overall response rate, 68%). Of these, 22 patients are still alive: 11 are well, but 11 continue to have chronic GvHD.

The other 30 patients died. Eight patients responded but had such severe GvHD that they developed severe infections. Two patients had multiple organ failure, 1 patient developed de novo acute myeloid leukemia, and 2 had leukemia relapses.

A further 17 patients did not respond. "At present, there is no indication as to why some patients did respond to the treatment while others didn't," Dr. LeBlanc commented.

The researchers speculate that the mesenchymal stem cells exert anti-inflammatory effects (which have been demonstrated in vitro) and also that they promote healing of the gastrointestinal tract. "Some patients who were previously receiving intravenous nutrition were able to resume eating," she said. "It appears that there was a rapid recovery of the GI epithelium."

"Based on these results, we are optimistic that mesenchymal stem cells do in fact have measurable value in repairing human tissues," Dr. LeBlanc commented. This approach appears to offer an effective and safe way to treat severe acute GvHD, she added, but she emphasized that the approach must be tested in a randomized clinical trial. Her team is now planning a phase 3 study.

ASH 48th Annual Meeting and Exposition: Abstract 753. Presented December 11, 2006.

    
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