Allogeneic cell therapy (act) after relapse from autologous stem cell transplantation (autosct)

D. Porter, S. Luger, K. Duffy, Gregory Orloff, D. Tsai, E. Stadtmauer, G. Laport, S. Schuster, K. McDaid

Research output: Contribution to journalArticle

Abstract

Allogeneic donor leukocytes can be used after non-myeloablative conditioning to exploit their GVT activity in a setting of reduced conditioning regimen toxicity. Chimerism, hématologie recovery, toxicity, and GVT induction may depend on the conditioning regimen, prior therapy, and tumor type. Incomplete immune recovery after prior autoSCT may increase the likelihood of engraftment but toxicity may also be enhanced. To assess the role of ACT after failed autoSCT, we treated 14 patients (pts) with relapsed Hodgkin's disease (HD) (n=ll), myeloma (n=2) and NHL (n=l) on 2 sequential trials of ACT. ACT was administered 24-202 wks (median 45 wk.) after autoSCT. 4 pts received unmobilized donor leukocyte infusions (DLI) as primary therapy without GVHD prophylaxis. 10 pts received fludarabine/ cytoxan as conditioning followed by DLI (n=3) or GCSF mobilized blood stem cells (n=7). These 10 pts received cyclosporine for GVHD prophylaxis. All but 1 had detectable donor cells by day 30 after ACT and 8 had 80% donor chimerism at some time after ACT. Median donor chimerism at days 30, 45, 60, and 90 after ACT was 8.5% (0-99%), 37% (0-99%), 74% (0-100%), and 30% (0-100%) respectively. 5/7 recipients of DLI as ACT had 1-5% chimerism at least 30 days after ACT. The 7 recipients of PBSC had 16-100% (median, 99%) donor chimerism 16-187 days after ACT. Acute GVHD developed in 11 cases including 8 with grade II-IV GVHD (5/8 had received CSA). 5 pts entered CR (3 HD; l NHL; l myeloma) and 4 had a PR (3 HD; l myeloma). 3 patients did not respond and 2 early deaths were not évaluable. The median follow-up is 15 wks (4-174). 6 are alive 11-179 wk. after ACT, 4 with continued PR and 2 with active disease. 8 died 4-61 wks (median 15 wk.) after ACT including 4 related to therapy (GVHD and/or infection) and 4 from progressive disease. 3 pts died in CR. These data show that ACT for relapse after autoSCT results in mixed or complete chimerism in most pts, and can result in sustained remissions. This confirms that ACT can induce a direct GVT effect against HD, NHL and myeloma. AutoSCT followed by ACT may be useful in diseases susceptible to both high dose therapy and immunologie control; however in heavily pretreated patients it may be associated with significant toxicity and should be performed on carefully designed trials.

Original languageEnglish (US)
JournalBlood
Volume96
Issue number11 PART I
StatePublished - Dec 1 2000
Externally publishedYes

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Stem Cell Transplantation
Cell- and Tissue-Based Therapy
Stem cells
Chimerism
Tissue Donors
Recurrence
Toxicity
Hodgkin Disease
Leukocytes
Recovery
Cyclophosphamide
Cyclosporine
Tumors
Therapeutics
Blood
Blood Cells
Stem Cells
Infection

ASJC Scopus subject areas

  • Hematology

Cite this

Porter, D., Luger, S., Duffy, K., Orloff, G., Tsai, D., Stadtmauer, E., ... McDaid, K. (2000). Allogeneic cell therapy (act) after relapse from autologous stem cell transplantation (autosct). Blood, 96(11 PART I).

Allogeneic cell therapy (act) after relapse from autologous stem cell transplantation (autosct). / Porter, D.; Luger, S.; Duffy, K.; Orloff, Gregory; Tsai, D.; Stadtmauer, E.; Laport, G.; Schuster, S.; McDaid, K.

In: Blood, Vol. 96, No. 11 PART I, 01.12.2000.

Research output: Contribution to journalArticle

Porter, D, Luger, S, Duffy, K, Orloff, G, Tsai, D, Stadtmauer, E, Laport, G, Schuster, S & McDaid, K 2000, 'Allogeneic cell therapy (act) after relapse from autologous stem cell transplantation (autosct)', Blood, vol. 96, no. 11 PART I.
Porter D, Luger S, Duffy K, Orloff G, Tsai D, Stadtmauer E et al. Allogeneic cell therapy (act) after relapse from autologous stem cell transplantation (autosct). Blood. 2000 Dec 1;96(11 PART I).
Porter, D. ; Luger, S. ; Duffy, K. ; Orloff, Gregory ; Tsai, D. ; Stadtmauer, E. ; Laport, G. ; Schuster, S. ; McDaid, K. / Allogeneic cell therapy (act) after relapse from autologous stem cell transplantation (autosct). In: Blood. 2000 ; Vol. 96, No. 11 PART I.
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AU - Luger, S.

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AU - Tsai, D.

AU - Stadtmauer, E.

AU - Laport, G.

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N2 - Allogeneic donor leukocytes can be used after non-myeloablative conditioning to exploit their GVT activity in a setting of reduced conditioning regimen toxicity. Chimerism, hématologie recovery, toxicity, and GVT induction may depend on the conditioning regimen, prior therapy, and tumor type. Incomplete immune recovery after prior autoSCT may increase the likelihood of engraftment but toxicity may also be enhanced. To assess the role of ACT after failed autoSCT, we treated 14 patients (pts) with relapsed Hodgkin's disease (HD) (n=ll), myeloma (n=2) and NHL (n=l) on 2 sequential trials of ACT. ACT was administered 24-202 wks (median 45 wk.) after autoSCT. 4 pts received unmobilized donor leukocyte infusions (DLI) as primary therapy without GVHD prophylaxis. 10 pts received fludarabine/ cytoxan as conditioning followed by DLI (n=3) or GCSF mobilized blood stem cells (n=7). These 10 pts received cyclosporine for GVHD prophylaxis. All but 1 had detectable donor cells by day 30 after ACT and 8 had 80% donor chimerism at some time after ACT. Median donor chimerism at days 30, 45, 60, and 90 after ACT was 8.5% (0-99%), 37% (0-99%), 74% (0-100%), and 30% (0-100%) respectively. 5/7 recipients of DLI as ACT had 1-5% chimerism at least 30 days after ACT. The 7 recipients of PBSC had 16-100% (median, 99%) donor chimerism 16-187 days after ACT. Acute GVHD developed in 11 cases including 8 with grade II-IV GVHD (5/8 had received CSA). 5 pts entered CR (3 HD; l NHL; l myeloma) and 4 had a PR (3 HD; l myeloma). 3 patients did not respond and 2 early deaths were not évaluable. The median follow-up is 15 wks (4-174). 6 are alive 11-179 wk. after ACT, 4 with continued PR and 2 with active disease. 8 died 4-61 wks (median 15 wk.) after ACT including 4 related to therapy (GVHD and/or infection) and 4 from progressive disease. 3 pts died in CR. These data show that ACT for relapse after autoSCT results in mixed or complete chimerism in most pts, and can result in sustained remissions. This confirms that ACT can induce a direct GVT effect against HD, NHL and myeloma. AutoSCT followed by ACT may be useful in diseases susceptible to both high dose therapy and immunologie control; however in heavily pretreated patients it may be associated with significant toxicity and should be performed on carefully designed trials.

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