Impact of immune modulation with anti–T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies

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BlankImpact of immune modulation with anti–T-cell antibodies on the outcome of

reduced-intensity allogeneic hematopoietic stem cell transplantation for

hematologic malignancies

1.. J. Soiffer1,

2.. LeRademacher2,

3.. Ho1,

4.. Fangyu Kan3,

5.. Artz4,

6.. E. Champlin5,

7.. Devine6,

8.. Isola7,

9.. Hillard M. Lazarus8,

10.. I. Marks9,

11.. L. Porter10,

12.. Edmund K. Waller11,

13.. M. Horowitz2, and

14.. Eapen2

+ Author Affiliations

1.. 1Dana-Farber Cancer Institute, Boston, MA;

2.. 2Center for International Blood and Marrow Transplant Research, Medical

College of Wisconsin, Milwaukee, WI;

3.. 3National Marrow Donor Program, Minneapolis, MN;

4.. 4University of Chicago Medical Center, Chicago, IL;

5.. 5M. D. Cancer Center, Houston, TX;

6.. 6The Ohio State University, Columbus, OH;

7.. 7Mount Sinai Hospital, New York, NY;

8.. 8Case Western Reserve University, Cleveland, OH;

9.. 9United Bristol Health Care Trust, Bristol, United Kingdom;

10.. 10University of Pennsylvania, Philadelphia, PA; and

11.. 11Emory University, Atlanta, GA

Abstract

The success of reduced intensity conditioning (RIC) transplantation is largely

dependent on alloimmune effects. It is critical to determine whether immune

modulation with anti–T-cell antibody infusion abrogates the therapeutic benefits

of transplantation. We examined 1676 adults undergoing RIC transplantation for

hematologic malignancies. All patients received alkylating agent plus

fludarabine; 792 received allografts from a human leukocyte antigen-matched

sibling, 884 from a 7 or 8 of 8 HLA-matched unrelated donor. Using

regression, outcomes after in vivo T-cell depletion (n = 584 antithymocyte

globulin [ATG]; n = 213 alemtuzumab) were compared with T cell– replete (n =

879) transplantation. Grade 2 to 4 acute GVHD was lower with alemtuzumab

compared with ATG or T cell– replete regimens (19% vs 38% vs 40%, P < .0001) and

chronic GVHD, lower with alemtuzumab, and ATG regimens compared with T-replete

approaches (24% vs 40% vs 52%, P < .0001). However, relapse was more frequent

with alemtuzumab and ATG compared with T cell–replete regimens (49%, 51%, and

38%, respectively, P < .001). Disease-free survival was lower with alemtuzumab

and ATG compared with T cell–replete regimens (30%, 25%, and 39%, respectively,

P < .001). Corresponding probabilities of overall survival were 50%, 38%, and

46% (P = .008). These data suggest adopting a cautious approach to routine use

of in vivo T-cell depletion with RIC regimens.