The impact of the graft-versus-leukemia effect on survival in acute lymphoblastic leukemia

被引：63

作者：

Yeshurun, Moshe ^{[1
,2
]}

Weisdorf, Daniel ^{[3
]}

Rowe, Jacob M. ^{[4
]}

Tallman, Martin S. ^{[5
]}

Zhang, Mei-Jie ^{[6
,7
]}

Wang, Hai-Lin ^{[6
]}

Saber, Wael ^{[6
]}

de Lima, Marcos ^{[8
]}

Sandmaier, Brenda M. ^{[9
,10
]}

Uy, Geoffrey ^{[11
]}

Kamble, Rammurti T. ^{[12
]}

Cairo, Mitchell S. ^{[13
]}

Cooper, Brenda W. ^{[14
]}

Cahn, Jean-Yves ^{[15
]}

Ganguly, Siddhartha ^{[16
]}

Camitta, Bruce ^{[17
,18
]}

Verdonck, Leo F. ^{[19
]}

Dandoy, Christopher ^{[20
]}

Angel Diaz, Miguel ^{[21
]}

Savani, Bipin N. ^{[22
]}

George, Biju ^{[23
]}

Liesveld, Jane ^{[24
]}

McGuirk, Joseph ^{[16
]}

Byrne, Michael ^{[22
]}

Grunwald, Michael R. ^{[25
]}

Drobyski, William R. ^{[26
]}

Pulsipher, Michael A. ^{[27
]}

Abdel-Azim, Hisham ^{[27
]}

Prestidge, Tim ^{[28
]}

Wieduwilt, Matthew J. ^{[29
]}

Martino, Rodrigo ^{[30
]}

Norkin, Maxim ^{[31
]}

Beitinjaneh, Amer ^{[32
]}

Seo, Sachiko ^{[33
]}

Nishihori, Taiga ^{[34
]}

Wirk, Baldeep ^{[35
]}

Frangoul, Haydar ^{[36
,37
]}

Bashey, Asad ^{[38
]}

Mori, Shahram ^{[39
]}

Marks, David I. ^{[40
]}

Bachanova, Veronika ^{[41
]}

机构：

[1] Rabin Med Ctr, Inst Haematol, Davidoff Canc Ctr, 39 Jabotinsky St, IL-49141 Petah Tiqwa, Israel

[2] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel

[3] Univ Minnesota, Med Ctr, Dept Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA

[4] Shaare Zedek Med Ctr, Dept Hematol, Jerusalem, Israel

[5] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, 1275 York Ave, New York, NY 10021 USA

[6] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA

[7] Med Coll Wisconsin, Div Biostat, Inst Hlth & Soc, Milwaukee, WI 53226 USA

[8] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Dept Med, Cleveland, OH USA

[9] Univ Washington, Div Med Oncol, Seattle, WA 98195 USA

[10] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA

[11] Washington Univ, Sch Med, Div Oncol, St Louis, MO USA

[12] Baylor Coll Med, Ctr Cell & Gene Therapy, Div Hematol & Oncol, Houston, TX 77030 USA

[13] New York Med Coll, Dept Pediat, Div Pediat Hematol Oncol & Stem Cell Transplantat, Valhalla, NY 10595 USA

[14] Univ Hosp Case Med Ctr, Dept Med Hematol & Oncol, Cleveland, OH USA

[15] Ctr Hosp Univ Grenoble Alpes, Dept Hematol, Grenoble, France

[16] Univ Kansas Hlth Syst, Div Hematol Malignancy & Cellular Therapeut, Kansas City, KS USA

[17] Med Coll Wisconsin, Midwest Ctr Canc & Blood Disorders, Milwaukee, WI 53226 USA

[18] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA

[19] Isala Clin, Dept Hematol Oncol, Zwolle, Netherlands

[20] Cincinnati Childrens Hosp Med Ctr, Div Bone Marrow Transplant & Immune Deficiency, Cincinnati, OH 45229 USA

[21] Hosp Infantil Univ Nino Jesus, Dept Hematol Oncol, Madrid, Spain

[22] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA

[23] Christian Med Coll & Hosp, Dept Clin Hematol, Vellore, Tamil Nadu, India

[24] Univ Rochester, Med Ctr, Dept Med, Rochester, NY 14642 USA

[25] Atrium Hlth, Levine Canc Inst, Dept Hematol Oncol & Blood Disorders, Charlotte, NC USA

[26] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA

[27] USC, Keck Sch Med, Childrens Hosp Los Angeles, Div Hematol Oncol & Blood & Marrow Transplantat, Los Angeles, CA USA

[28] Starship Childrens Hosp, Blood & Canc Ctr, Auckland, New Zealand

[29] Univ Calif San Diego, Med Ctr, Moores Canc Ctr, La Jolla, CA 92093 USA

[30] Hosp Santa Creu & Sant Pau, Div Clin Hematol, Barcelona, Spain

[31] Univ Florida, Coll Med, Div Hematol Oncol, Gainesville, FL USA

[32] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Stem Cell Transplant & Cellular Therapy Program, Miami, FL 33136 USA

[33] Natl Canc Res Ctr East, Dept Hematol & Oncol, Chiba, Japan

[34] H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL USA

[35] Seattle Canc Care Alliance, Div Bone Marrow Transplant, Seattle, WA USA

[36] TriStar Centennial, Childrens Hosp, Nashville, TN USA

[37] Sarah Cannon Res Inst, Nashville, TN USA

[38] Northside Hosp, Blood & Marrow Transplant Program, Atlanta, GA USA

[39] Florida Hosp Med Grp, Blood & Marrow Transplant Ctr, Orlando, FL USA

[40] Univ Hosp Bristol NHS Trust, Adult Bone Marrow Transplant, Bristol, Avon, England

[41] Univ Minnesota, Med Ctr, Bone & Marrow Transplant Program, Minneapolis, MN 55455 USA

来源：

BLOOD ADVANCES | 2019年 / 3卷 / 04期

关键词：

BONE-MARROW-TRANSPLANTATION; HOST-DISEASE; ALLOGENEIC TRANSPLANTATION; INTERNATIONAL-BLOOD; REMISSION; RELAPSE; RISK;

D O I：

10.1182/bloodadvances.2018027003

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Allogeneic hematopoietic cell transplant is a potential curative therapy for acute lymphoblastic leukemia (ALL). Delineating the graft-versus-leukemia (GVL) effect as a function of graft-versus-host disease (GVHD) offers the potential to improve survival. We examined 5215 transplant recipients with ALL reported to the Center for International Blood and Marrow Transplant Research registry. Overall survival (OS) was compared according to the presence and severity of GVHD and evaluated in 3 cohorts: 2593 adults in first or second complete remission (CR1/CR2), 1619 pediatric patients in CR1/CR2, and 1003 patients with advanced (CR >= 3 or active disease) ALL. For patients in CR1/CR2, development of acute GVHD (aGVHD) or chronic GVHD (cGVHD) was associated with lower risk of relapse than no GVHD (hazard ratio [HR], 0.49-0.69). Patients with advanced ALL developing grades III and IV aGVHD or cGVHD were also at lower risk of relapse (HRs varied from 0.52 to 0.67). Importantly, adult and children in CR1/CR2 with grades I and II aGVHD without cGVHD experienced the best OS compared with no GVHD (reduction of mortality with HR, 0.83-0.76). Increased nonrelapse mortality accompanied grades III and IV aGVHD (HRs varied from 2.69 to 3.91) in all 3 cohorts and abrogated any protection from relapse, resulting in inferior OS. Patients with advanced ALL had better OS (reduction in mortality; HR, 0.69-0.73) when they developed cGVHD with or without grades I and II aGVHD. In conclusion, GVHD was associated with an increased GVL effect in ALL. GVL exerted a net beneficial effect on OS only if associated with low-grade aGVHD in CR1/CR2 or with cGVHD in advanced ALL.

引用

页码：670 / 680

页数：11

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