Phase II Study of Sequential Infusion of Donor Lymphocyte Infusion and Cytokine-Induced Killer Cells for Patients Relapsed after Allogeneic Hematopoietic Stem Cell Transplantation

Martino Introna, Federico Lussana, Alessandra Algarotti, Elisa Gotti, Rut Valgardsdottir, Caterina Micò, Anna Grassi, Chiara Pavoni, Maria Luisa Ferrari, Federica Delaini, Elisabetta Todisco, Irene Cavattoni, Sara Deola, Ettore Biagi, Adriana Balduzzi, Attilio Rovelli, Matteo Parma, Sara Napolitano, Giusy Sgroi, Emanuela MarroccoPaolo Perseghin, Daniela Belotti, Benedetta Cabiati, Giuseppe Gaipa, Josée Golay, Andrea Biondi, Alessandro Rambaldi

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Seventy-four patients who relapsed after allogeneic stem cell transplantation were enrolled in a phase IIA study and treated with the sequential infusion of donor lymphocyte infusion (DLI) followed by cytokine-induced killer (CIK) cells. Seventy-three patients were available for the intention to treat analysis. At least 1 infusion of CIK cells was given to 59 patients, whereas 43 patients received the complete cell therapy planned (58%). Overall, 12 patients (16%) developed acute graft-versus-host disease (aGVHD) of grades I to II in 7 cases and grades III to IV in 5). In 8 of 12 cases, aGVHD developed during DLI treatment, leading to interruption of the cellular program in 3 patients, whereas in the remaining 5 cases aGVHD was controlled by steroids treatment, thus allowing the subsequent planned administration of CIK cells. Chronic GVHD (cGVHD) was observed in 11 patients (15%). A complete response was observed in 19 (26%), partial response in 3 (4%), stable disease in 8 (11%), early death in 2 (3%), and disease progression in 41 (56%). At 1 and 3 years, rates of progression-free survival were 31% and 29%, whereas rates of overall survival were 51% and 40%, respectively. By multivariate analysis, the type of relapse, the presence of cGVHD, and a short (<6 months) time from allogeneic hematopoietic stem cell transplantation to relapse were the significant predictors of survival. In conclusion, a low incidence of GVHD is observed after the sequential administration of DLI and CIK cells, and disease control can be achieved mostly after a cytogenetic or molecular relapse.

Original languageEnglish
Pages (from-to)2070-2078
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume23
Issue number12
DOIs
Publication statusPublished - 1 Dec 2017
Externally publishedYes

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Cytokine-Induced Killer Cells
Hematopoietic Stem Cell Transplantation
Tissue Donors
Lymphocytes
Graft vs Host Disease
Recurrence
Intention to Treat Analysis
Stem Cell Transplantation
Cell- and Tissue-Based Therapy
Cytogenetics
Disease-Free Survival
Disease Progression
Multivariate Analysis
Survival Rate
Steroids
Survival
Incidence

Keywords

  • Cytokine-induced killer (CIK) cells
  • DLI
  • Passive immunotherapy
  • Relapse after allo-BMT

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Phase II Study of Sequential Infusion of Donor Lymphocyte Infusion and Cytokine-Induced Killer Cells for Patients Relapsed after Allogeneic Hematopoietic Stem Cell Transplantation. / Introna, Martino; Lussana, Federico; Algarotti, Alessandra; Gotti, Elisa; Valgardsdottir, Rut; Micò, Caterina; Grassi, Anna; Pavoni, Chiara; Ferrari, Maria Luisa; Delaini, Federica; Todisco, Elisabetta; Cavattoni, Irene; Deola, Sara; Biagi, Ettore; Balduzzi, Adriana; Rovelli, Attilio; Parma, Matteo; Napolitano, Sara; Sgroi, Giusy; Marrocco, Emanuela; Perseghin, Paolo; Belotti, Daniela; Cabiati, Benedetta; Gaipa, Giuseppe; Golay, Josée; Biondi, Andrea; Rambaldi, Alessandro.

In: Biology of Blood and Marrow Transplantation, Vol. 23, No. 12, 01.12.2017, p. 2070-2078.

Research output: Contribution to journalArticle

Introna, M, Lussana, F, Algarotti, A, Gotti, E, Valgardsdottir, R, Micò, C, Grassi, A, Pavoni, C, Ferrari, ML, Delaini, F, Todisco, E, Cavattoni, I, Deola, S, Biagi, E, Balduzzi, A, Rovelli, A, Parma, M, Napolitano, S, Sgroi, G, Marrocco, E, Perseghin, P, Belotti, D, Cabiati, B, Gaipa, G, Golay, J, Biondi, A & Rambaldi, A 2017, 'Phase II Study of Sequential Infusion of Donor Lymphocyte Infusion and Cytokine-Induced Killer Cells for Patients Relapsed after Allogeneic Hematopoietic Stem Cell Transplantation', Biology of Blood and Marrow Transplantation, vol. 23, no. 12, pp. 2070-2078. https://doi.org/10.1016/j.bbmt.2017.07.005
Introna, Martino ; Lussana, Federico ; Algarotti, Alessandra ; Gotti, Elisa ; Valgardsdottir, Rut ; Micò, Caterina ; Grassi, Anna ; Pavoni, Chiara ; Ferrari, Maria Luisa ; Delaini, Federica ; Todisco, Elisabetta ; Cavattoni, Irene ; Deola, Sara ; Biagi, Ettore ; Balduzzi, Adriana ; Rovelli, Attilio ; Parma, Matteo ; Napolitano, Sara ; Sgroi, Giusy ; Marrocco, Emanuela ; Perseghin, Paolo ; Belotti, Daniela ; Cabiati, Benedetta ; Gaipa, Giuseppe ; Golay, Josée ; Biondi, Andrea ; Rambaldi, Alessandro. / Phase II Study of Sequential Infusion of Donor Lymphocyte Infusion and Cytokine-Induced Killer Cells for Patients Relapsed after Allogeneic Hematopoietic Stem Cell Transplantation. In: Biology of Blood and Marrow Transplantation. 2017 ; Vol. 23, No. 12. pp. 2070-2078.
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T1 - Phase II Study of Sequential Infusion of Donor Lymphocyte Infusion and Cytokine-Induced Killer Cells for Patients Relapsed after Allogeneic Hematopoietic Stem Cell Transplantation

AU - Introna, Martino

AU - Lussana, Federico

AU - Algarotti, Alessandra

AU - Gotti, Elisa

AU - Valgardsdottir, Rut

AU - Micò, Caterina

AU - Grassi, Anna

AU - Pavoni, Chiara

AU - Ferrari, Maria Luisa

AU - Delaini, Federica

AU - Todisco, Elisabetta

AU - Cavattoni, Irene

AU - Deola, Sara

AU - Biagi, Ettore

AU - Balduzzi, Adriana

AU - Rovelli, Attilio

AU - Parma, Matteo

AU - Napolitano, Sara

AU - Sgroi, Giusy

AU - Marrocco, Emanuela

AU - Perseghin, Paolo

AU - Belotti, Daniela

AU - Cabiati, Benedetta

AU - Gaipa, Giuseppe

AU - Golay, Josée

AU - Biondi, Andrea

AU - Rambaldi, Alessandro

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Seventy-four patients who relapsed after allogeneic stem cell transplantation were enrolled in a phase IIA study and treated with the sequential infusion of donor lymphocyte infusion (DLI) followed by cytokine-induced killer (CIK) cells. Seventy-three patients were available for the intention to treat analysis. At least 1 infusion of CIK cells was given to 59 patients, whereas 43 patients received the complete cell therapy planned (58%). Overall, 12 patients (16%) developed acute graft-versus-host disease (aGVHD) of grades I to II in 7 cases and grades III to IV in 5). In 8 of 12 cases, aGVHD developed during DLI treatment, leading to interruption of the cellular program in 3 patients, whereas in the remaining 5 cases aGVHD was controlled by steroids treatment, thus allowing the subsequent planned administration of CIK cells. Chronic GVHD (cGVHD) was observed in 11 patients (15%). A complete response was observed in 19 (26%), partial response in 3 (4%), stable disease in 8 (11%), early death in 2 (3%), and disease progression in 41 (56%). At 1 and 3 years, rates of progression-free survival were 31% and 29%, whereas rates of overall survival were 51% and 40%, respectively. By multivariate analysis, the type of relapse, the presence of cGVHD, and a short (<6 months) time from allogeneic hematopoietic stem cell transplantation to relapse were the significant predictors of survival. In conclusion, a low incidence of GVHD is observed after the sequential administration of DLI and CIK cells, and disease control can be achieved mostly after a cytogenetic or molecular relapse.

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KW - Cytokine-induced killer (CIK) cells

KW - DLI

KW - Passive immunotherapy

KW - Relapse after allo-BMT

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