Establishment of early donor engraftment after reduced-intensity allogeneic hematopoietic stem cell transplantation to potentiate the graft-versus-lymphoma effect against refractory lymphomas.

Michael R. Bishop, Jeannie Whit Shan Hou, Wyndham H. Wilson, Seth M. Steinberg, Jeanne Odom, Kathleen Castro, Claude Sportes, Juan Gea-Banacloche, Donna Marchigiani, Ronald Gress, Daniel H. Fowler

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Reduced-intensity allogeneic hematopoietic stem cell transplantation (alloHSCT), which typically results in mixed chimerism initially after transplantation, has had limited efficacy in chemotherapy-refractory lymphomas. We hypothesized that the rapid establishment of complete donor chimerism would potentiate a graft-versus-lymphoma effect. Fifteen patients with chemotherapy-refractory lymphoma initially received induction with a conventional chemotherapy regimen (etoposide, prednisone, vincristine, cyclophosphamide, adriamycin, fludarabine [EPOCH-F]) to deplete host T cells and provide disease control prior to alloHSCT. Patients then received conditioning with fludarabine and cyclophosphamide followed by alloHSCT from HLA-matched siblings. Graft-versus-host disease prophylaxis consisted of cyclosporine alone. EPOCH-F resulted in 73% of patients having partial responses or stable disease. EPOCH-F depleted host CD4(+) T cells from a median of 235 cells/microL to 56 cells/microL. Fourteen patients underwent alloHSCT, and all had >95% donor engraftment by day 14 after transplantation. The incidence of Grade II to III acute graft-versus-host disease was 71%. There were two therapy-related deaths. There were 8 partial responses and 3 complete responses (CRs) at day 28. Five additional CRs were observed at day 100 without withdrawal of cyclosporine or donor lymphocyte infusion. The rate of CRs for all 15 patients was 60%. The 1-year progression-free survival rate from time of study entry is 67% with only 1 relapse among 9 CRs. At a median potential follow-up of 28 months, the overall survival rate is 53%. These data demonstrate that a potent and durable graft-versus-lymphoma effect can occur against chemotherapy-refractory lymphomas and suggest that this effect may be associated with rapid, complete donor chimerism after reduced-intensity alloHSCT.

Original languageEnglish (US)
Pages (from-to)162-169
Number of pages8
JournalBiology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
Volume9
Issue number3
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

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Hematopoietic Stem Cell Transplantation
Lymphoma
Cyclophosphamide
Chimerism
Tissue Donors
Transplants
Vincristine
Etoposide
Prednisone
Doxorubicin
Drug Therapy
Graft vs Host Disease
Cyclosporine
Survival Rate
Transplantation
T-Lymphocytes
Time and Motion Studies
Disease-Free Survival
Siblings
Lymphocytes

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Establishment of early donor engraftment after reduced-intensity allogeneic hematopoietic stem cell transplantation to potentiate the graft-versus-lymphoma effect against refractory lymphomas. / Bishop, Michael R.; Hou, Jeannie Whit Shan; Wilson, Wyndham H.; Steinberg, Seth M.; Odom, Jeanne; Castro, Kathleen; Sportes, Claude; Gea-Banacloche, Juan; Marchigiani, Donna; Gress, Ronald; Fowler, Daniel H.

In: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, Vol. 9, No. 3, 01.01.2003, p. 162-169.

Research output: Contribution to journalArticle

Bishop, Michael R. ; Hou, Jeannie Whit Shan ; Wilson, Wyndham H. ; Steinberg, Seth M. ; Odom, Jeanne ; Castro, Kathleen ; Sportes, Claude ; Gea-Banacloche, Juan ; Marchigiani, Donna ; Gress, Ronald ; Fowler, Daniel H. / Establishment of early donor engraftment after reduced-intensity allogeneic hematopoietic stem cell transplantation to potentiate the graft-versus-lymphoma effect against refractory lymphomas. In: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2003 ; Vol. 9, No. 3. pp. 162-169.
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abstract = "Reduced-intensity allogeneic hematopoietic stem cell transplantation (alloHSCT), which typically results in mixed chimerism initially after transplantation, has had limited efficacy in chemotherapy-refractory lymphomas. We hypothesized that the rapid establishment of complete donor chimerism would potentiate a graft-versus-lymphoma effect. Fifteen patients with chemotherapy-refractory lymphoma initially received induction with a conventional chemotherapy regimen (etoposide, prednisone, vincristine, cyclophosphamide, adriamycin, fludarabine [EPOCH-F]) to deplete host T cells and provide disease control prior to alloHSCT. Patients then received conditioning with fludarabine and cyclophosphamide followed by alloHSCT from HLA-matched siblings. Graft-versus-host disease prophylaxis consisted of cyclosporine alone. EPOCH-F resulted in 73{\%} of patients having partial responses or stable disease. EPOCH-F depleted host CD4(+) T cells from a median of 235 cells/microL to 56 cells/microL. Fourteen patients underwent alloHSCT, and all had >95{\%} donor engraftment by day 14 after transplantation. The incidence of Grade II to III acute graft-versus-host disease was 71{\%}. There were two therapy-related deaths. There were 8 partial responses and 3 complete responses (CRs) at day 28. Five additional CRs were observed at day 100 without withdrawal of cyclosporine or donor lymphocyte infusion. The rate of CRs for all 15 patients was 60{\%}. The 1-year progression-free survival rate from time of study entry is 67{\%} with only 1 relapse among 9 CRs. At a median potential follow-up of 28 months, the overall survival rate is 53{\%}. These data demonstrate that a potent and durable graft-versus-lymphoma effect can occur against chemotherapy-refractory lymphomas and suggest that this effect may be associated with rapid, complete donor chimerism after reduced-intensity alloHSCT.",
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AU - Wilson, Wyndham H.

AU - Steinberg, Seth M.

AU - Odom, Jeanne

AU - Castro, Kathleen

AU - Sportes, Claude

AU - Gea-Banacloche, Juan

AU - Marchigiani, Donna

AU - Gress, Ronald

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