Abstract
Background: Procedures to prevent severe graft-versus-host disease (GVHD) delay immune reconstitution secondary to transplants of haploidentical haemopoietic stem cells for the treatment of leukaemia, leading to high rates of late infectious mortality. We aimed to systematically add back genetically engineered donor lymphocytes to facilitate immune reconstitution and prevent late mortality. Methods: In a phase I-II, multicentre, non-randomised trial of haploidentical stem-cell transplantation, we infused donor lymphocytes expressing herpes-simplex thymidine kinase suicide gene (TK-cells) after transplantation. The primary study endpoint was immune reconstitution defined as circulating CD3+ count of 100 cells per μL or more for two consecutive observations. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00423124. Findings: From Aug 13, 2002, to March 26, 2008, 50 patients (median age 51 years, range 17-66) received haploidentical stem-cell transplants for high-risk leukaemia. Immune reconstitution was not recorded before infusion of TK-cells. 28 patients received TK-cells starting 28 days after transplantation; 22 patients obtained immune reconstitution at median 75 days (range 34-127) from transplantation and 23 days (13-42) from infusion. Ten patients developed acute GVHD (grade I-IV) and one developed chronic GVHD, which were controlled by induction of the suicide gene. Overall survival at 3 years was 49% (95% CI 25-73) for 19 patients who were in remission from primary leukaemia at the time of stem-cell transplantation. After TK-cell infusion, the last death due to infection was at 166 days, this was the only infectious death at more than 100 days. No acute or chronic adverse events were related to the gene-transfer procedure. Interpretation: Infusion of TK-cells might be effective in accelerating immune reconstitution, while controlling GVHD and protecting patients from late mortality in those who are candidates for haploidentical stem-cell transplantation. Funding: MolMed SpA, Italian Association for Cancer Research.
| Original language | English |
|---|---|
| Pages (from-to) | 489-500 |
| Number of pages | 12 |
| Journal | The Lancet Oncology |
| Volume | 10 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2009 |
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ASJC Scopus subject areas
- Oncology
Cite this
Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial) : a non-randomised phase I-II study. / Ciceri, Fabio; Bonini, Chiara; Stanghellini, Maria Teresa Lupo; Bondanza, Attilio; Traversari, Catia; Salomoni, Monica; Turchetto, Lucia; Colombi, Scialini; Bernardi, Massimo; Peccatori, Jacopo; Pescarollo, Alessandra; Servida, Paolo; Magnani, Zulma; Perna, Serena K.; Valtolina, Veronica; Crippa, Fulvio; Callegaro, Luciano; Spoldi, Elena; Crocchiolo, Roberto; Fleischhauer, Katharina; Ponzoni, Maurilio; Vago, Luca; Rossini, Silvano; Santoro, Armando; Todisco, Elisabetta; Apperley, Jane; Olavarria, Eduardo; Slavin, Shimon; Weissinger, Eva M.; Ganser, Arnold; Stadler, Michael; Yannaki, Evangelia; Fassas, Athanasios; Anagnostopoulos, Achilles; Bregni, Marco; Stampino, Corrado Gallo; Bruzzi, Paolo; Bordignon, Claudio.
In: The Lancet Oncology, Vol. 10, No. 5, 05.2009, p. 489-500.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial)
T2 - a non-randomised phase I-II study
AU - Ciceri, Fabio
AU - Bonini, Chiara
AU - Stanghellini, Maria Teresa Lupo
AU - Bondanza, Attilio
AU - Traversari, Catia
AU - Salomoni, Monica
AU - Turchetto, Lucia
AU - Colombi, Scialini
AU - Bernardi, Massimo
AU - Peccatori, Jacopo
AU - Pescarollo, Alessandra
AU - Servida, Paolo
AU - Magnani, Zulma
AU - Perna, Serena K.
AU - Valtolina, Veronica
AU - Crippa, Fulvio
AU - Callegaro, Luciano
AU - Spoldi, Elena
AU - Crocchiolo, Roberto
AU - Fleischhauer, Katharina
AU - Ponzoni, Maurilio
AU - Vago, Luca
AU - Rossini, Silvano
AU - Santoro, Armando
AU - Todisco, Elisabetta
AU - Apperley, Jane
AU - Olavarria, Eduardo
AU - Slavin, Shimon
AU - Weissinger, Eva M.
AU - Ganser, Arnold
AU - Stadler, Michael
AU - Yannaki, Evangelia
AU - Fassas, Athanasios
AU - Anagnostopoulos, Achilles
AU - Bregni, Marco
AU - Stampino, Corrado Gallo
AU - Bruzzi, Paolo
AU - Bordignon, Claudio
PY - 2009/5
Y1 - 2009/5
N2 - Background: Procedures to prevent severe graft-versus-host disease (GVHD) delay immune reconstitution secondary to transplants of haploidentical haemopoietic stem cells for the treatment of leukaemia, leading to high rates of late infectious mortality. We aimed to systematically add back genetically engineered donor lymphocytes to facilitate immune reconstitution and prevent late mortality. Methods: In a phase I-II, multicentre, non-randomised trial of haploidentical stem-cell transplantation, we infused donor lymphocytes expressing herpes-simplex thymidine kinase suicide gene (TK-cells) after transplantation. The primary study endpoint was immune reconstitution defined as circulating CD3+ count of 100 cells per μL or more for two consecutive observations. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00423124. Findings: From Aug 13, 2002, to March 26, 2008, 50 patients (median age 51 years, range 17-66) received haploidentical stem-cell transplants for high-risk leukaemia. Immune reconstitution was not recorded before infusion of TK-cells. 28 patients received TK-cells starting 28 days after transplantation; 22 patients obtained immune reconstitution at median 75 days (range 34-127) from transplantation and 23 days (13-42) from infusion. Ten patients developed acute GVHD (grade I-IV) and one developed chronic GVHD, which were controlled by induction of the suicide gene. Overall survival at 3 years was 49% (95% CI 25-73) for 19 patients who were in remission from primary leukaemia at the time of stem-cell transplantation. After TK-cell infusion, the last death due to infection was at 166 days, this was the only infectious death at more than 100 days. No acute or chronic adverse events were related to the gene-transfer procedure. Interpretation: Infusion of TK-cells might be effective in accelerating immune reconstitution, while controlling GVHD and protecting patients from late mortality in those who are candidates for haploidentical stem-cell transplantation. Funding: MolMed SpA, Italian Association for Cancer Research.
AB - Background: Procedures to prevent severe graft-versus-host disease (GVHD) delay immune reconstitution secondary to transplants of haploidentical haemopoietic stem cells for the treatment of leukaemia, leading to high rates of late infectious mortality. We aimed to systematically add back genetically engineered donor lymphocytes to facilitate immune reconstitution and prevent late mortality. Methods: In a phase I-II, multicentre, non-randomised trial of haploidentical stem-cell transplantation, we infused donor lymphocytes expressing herpes-simplex thymidine kinase suicide gene (TK-cells) after transplantation. The primary study endpoint was immune reconstitution defined as circulating CD3+ count of 100 cells per μL or more for two consecutive observations. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00423124. Findings: From Aug 13, 2002, to March 26, 2008, 50 patients (median age 51 years, range 17-66) received haploidentical stem-cell transplants for high-risk leukaemia. Immune reconstitution was not recorded before infusion of TK-cells. 28 patients received TK-cells starting 28 days after transplantation; 22 patients obtained immune reconstitution at median 75 days (range 34-127) from transplantation and 23 days (13-42) from infusion. Ten patients developed acute GVHD (grade I-IV) and one developed chronic GVHD, which were controlled by induction of the suicide gene. Overall survival at 3 years was 49% (95% CI 25-73) for 19 patients who were in remission from primary leukaemia at the time of stem-cell transplantation. After TK-cell infusion, the last death due to infection was at 166 days, this was the only infectious death at more than 100 days. No acute or chronic adverse events were related to the gene-transfer procedure. Interpretation: Infusion of TK-cells might be effective in accelerating immune reconstitution, while controlling GVHD and protecting patients from late mortality in those who are candidates for haploidentical stem-cell transplantation. Funding: MolMed SpA, Italian Association for Cancer Research.
UR - http://www.scopus.com/inward/record.url?scp=65349157330&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65349157330&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(09)70074-9
DO - 10.1016/S1470-2045(09)70074-9
M3 - Article
C2 - 19345145
AN - SCOPUS:65349157330
VL - 10
SP - 489
EP - 500
JO - The Lancet Oncology
JF - The Lancet Oncology
SN - 1470-2045
IS - 5
ER -