Selective depletion of alloreactive donor lymphocytes

A novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation

Scott R. Solomon, Stephan Mielke, Bipin N. Savani, Aldemar Montera, Laura Wisch, Richard Childs, Nancy Hensel, John Schindler, Victor Ghetie, Susan F. Leitman, Thao Mai, Charles S. Carter, Roger Kurlander, Elizabeth J. Read, Ellen S. Vitetta, A. John Barrett

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

We have selectively depleted host-reactive donor T cells from peripheral blood stem cell (PBSC) transplant allografts ex vivo using an anti-CD25 immunotoxin. We report a clinical trial to decrease graft-versus-host disease (GVHD) in elderly patients receiving selectively depleted PBSC transplants from HLA-identical sibling donors. Sixteen patients (median age, 65 years [range, 51-73 years]), with advanced hematologic malignancies underwent transplantation following reduced-intensity conditioning with fludarabine and either cyclophosphamide (n = 5), melphalan (n = 5), or busulfan (n = 6). Cyclosporine was used as sole GVHD prophylaxis. The allograft contained a median of 4.5 × 106 CDSA cells/kg (range, 3.4-7.3 × 106 CD34 cells/kg) and 1.0 × 108/kg (range, 0.2-1.5 × 10 8/kg) selectively depleted T cells. Fifteen patients achieved sustained engraftment. The helper T-lymphocyte precursor (HTLp) frequency assay demonstrated successful (mean, 5-fold) depletion of host-reactive donor T cells, with conservation of third-party response in 9 of 11 cases tested. Actuarial rates of acute GVHD were 46% ± 13% for grades II to IV and 12% ± 8% for grades III to IV. These results suggest that allodepletion of donor cells ex vivo is clinically feasible in older patients and may reduce the rate of severe acute GVHD. Further studies with selectively depleted transplants to evaluate graft-versus-leukemia (GVL) and survival are warranted.

Original languageEnglish (US)
Pages (from-to)1123-1129
Number of pages7
JournalBlood
Volume106
Issue number3
DOIs
StatePublished - Aug 1 2005

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Lymphocytes
Stem Cell Transplantation
Graft vs Host Disease
Stem cells
Grafts
T-cells
Siblings
Transplants
Tissue Donors
T-Lymphocytes
Allografts
Immunotoxins
Blood
Busulfan
Melphalan
Hematologic Neoplasms
Helper-Inducer T-Lymphocytes
Cyclophosphamide
Cyclosporine
Leukemia

ASJC Scopus subject areas

  • Hematology

Cite this

Selective depletion of alloreactive donor lymphocytes : A novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation. / Solomon, Scott R.; Mielke, Stephan; Savani, Bipin N.; Montera, Aldemar; Wisch, Laura; Childs, Richard; Hensel, Nancy; Schindler, John; Ghetie, Victor; Leitman, Susan F.; Mai, Thao; Carter, Charles S.; Kurlander, Roger; Read, Elizabeth J.; Vitetta, Ellen S.; Barrett, A. John.

In: Blood, Vol. 106, No. 3, 01.08.2005, p. 1123-1129.

Research output: Contribution to journalArticle

Solomon, SR, Mielke, S, Savani, BN, Montera, A, Wisch, L, Childs, R, Hensel, N, Schindler, J, Ghetie, V, Leitman, SF, Mai, T, Carter, CS, Kurlander, R, Read, EJ, Vitetta, ES & Barrett, AJ 2005, 'Selective depletion of alloreactive donor lymphocytes: A novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation', Blood, vol. 106, no. 3, pp. 1123-1129. https://doi.org/10.1182/blood-2005-01-0393
Solomon, Scott R. ; Mielke, Stephan ; Savani, Bipin N. ; Montera, Aldemar ; Wisch, Laura ; Childs, Richard ; Hensel, Nancy ; Schindler, John ; Ghetie, Victor ; Leitman, Susan F. ; Mai, Thao ; Carter, Charles S. ; Kurlander, Roger ; Read, Elizabeth J. ; Vitetta, Ellen S. ; Barrett, A. John. / Selective depletion of alloreactive donor lymphocytes : A novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation. In: Blood. 2005 ; Vol. 106, No. 3. pp. 1123-1129.
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abstract = "We have selectively depleted host-reactive donor T cells from peripheral blood stem cell (PBSC) transplant allografts ex vivo using an anti-CD25 immunotoxin. We report a clinical trial to decrease graft-versus-host disease (GVHD) in elderly patients receiving selectively depleted PBSC transplants from HLA-identical sibling donors. Sixteen patients (median age, 65 years [range, 51-73 years]), with advanced hematologic malignancies underwent transplantation following reduced-intensity conditioning with fludarabine and either cyclophosphamide (n = 5), melphalan (n = 5), or busulfan (n = 6). Cyclosporine was used as sole GVHD prophylaxis. The allograft contained a median of 4.5 × 106 CDSA cells/kg (range, 3.4-7.3 × 106 CD34 cells/kg) and 1.0 × 108/kg (range, 0.2-1.5 × 10 8/kg) selectively depleted T cells. Fifteen patients achieved sustained engraftment. The helper T-lymphocyte precursor (HTLp) frequency assay demonstrated successful (mean, 5-fold) depletion of host-reactive donor T cells, with conservation of third-party response in 9 of 11 cases tested. Actuarial rates of acute GVHD were 46{\%} ± 13{\%} for grades II to IV and 12{\%} ± 8{\%} for grades III to IV. These results suggest that allodepletion of donor cells ex vivo is clinically feasible in older patients and may reduce the rate of severe acute GVHD. Further studies with selectively depleted transplants to evaluate graft-versus-leukemia (GVL) and survival are warranted.",
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AU - Mielke, Stephan

AU - Savani, Bipin N.

AU - Montera, Aldemar

AU - Wisch, Laura

AU - Childs, Richard

AU - Hensel, Nancy

AU - Schindler, John

AU - Ghetie, Victor

AU - Leitman, Susan F.

AU - Mai, Thao

AU - Carter, Charles S.

AU - Kurlander, Roger

AU - Read, Elizabeth J.

AU - Vitetta, Ellen S.

AU - Barrett, A. John

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