Haploidentical stem cell transplantation after a reduced-intensity conditioning regimen for the treatment of advanced hematologic malignancies

Posttransplantation CD8-depleted donor lymphocyte infusions contribute to improve T-cell recovery

Anna Dodero, Cristiana Carniti, Anna Raganato, Antonio Vendramin, Lucia Farina, Francesco Spina, Carmelo Carlo-Stella, Simona Di Terlizzi, Marco Milanesi, Paolo Longoni, Lorenza Gandola, Claudia Lombardo, Paolo Corradini

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Haploidentical hematopoietic stem cell transplantation provides an option for patients with advanced hematologic malignancies lacking a compatible donor. In this prospective phase 1/2 trial, we evaluated the role of reduced-intensity conditioning (RIC) followed by early add-backs of CD8-depleted donor lymphocyte infusions (DLIs). The RIC regimen consisted of thiotepa, fludarabine, cyclophosphamide, and 2 Gy total body irradiation. Twenty-eight patients with advanced lymphoproliferative diseases (n = 24) or acute myeloid leukemia (n = 4) were enrolled. Ex vivo and in vivo T-cell depletion was carried out by CD34+ cell selection and alemtuzumab treatment. The 2-year cumulative incidence of nonrelapse mortality was 26% and the 2-year overall survival (OS) was 44%, with a better outcome for patients with chemosensitive disease (OS, 75%). Overall, 54 CD8-depleted DLIs were administered to 23 patients (82%) at 3 different dose levels without loss of engraftment or acute toxicities. Overall, 6 of 23 patients (26%) developed grade II-IV graft-versus-host disease, mainly at dose level 2. In conclusion, our RIC regimen allowed a stable engraftment with a rather low nonrelapse mortality in poor-risk patients; OS is encouraging with some long-term remissions in lymphoid malignancies. CD8-depleted DLIs are feasible and promote the immune reconstitution.

Original languageEnglish
Pages (from-to)4771-4779
Number of pages9
JournalBlood
Volume113
Issue number19
DOIs
Publication statusPublished - 2009

Fingerprint

T-cells
Lymphocytes
Stem Cell Transplantation
Hematologic Neoplasms
Stem cells
Tissue Donors
T-Lymphocytes
Recovery
Thiotepa
Grafts
Cyclophosphamide
Survival
Toxicity
Therapeutics
Irradiation
Mortality
Whole-Body Irradiation
Hematopoietic Stem Cell Transplantation
Graft vs Host Disease
Acute Myeloid Leukemia

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

@article{6f48cd40bd5344d8a6d3c1ae3329f831,
title = "Haploidentical stem cell transplantation after a reduced-intensity conditioning regimen for the treatment of advanced hematologic malignancies: Posttransplantation CD8-depleted donor lymphocyte infusions contribute to improve T-cell recovery",
abstract = "Haploidentical hematopoietic stem cell transplantation provides an option for patients with advanced hematologic malignancies lacking a compatible donor. In this prospective phase 1/2 trial, we evaluated the role of reduced-intensity conditioning (RIC) followed by early add-backs of CD8-depleted donor lymphocyte infusions (DLIs). The RIC regimen consisted of thiotepa, fludarabine, cyclophosphamide, and 2 Gy total body irradiation. Twenty-eight patients with advanced lymphoproliferative diseases (n = 24) or acute myeloid leukemia (n = 4) were enrolled. Ex vivo and in vivo T-cell depletion was carried out by CD34+ cell selection and alemtuzumab treatment. The 2-year cumulative incidence of nonrelapse mortality was 26{\%} and the 2-year overall survival (OS) was 44{\%}, with a better outcome for patients with chemosensitive disease (OS, 75{\%}). Overall, 54 CD8-depleted DLIs were administered to 23 patients (82{\%}) at 3 different dose levels without loss of engraftment or acute toxicities. Overall, 6 of 23 patients (26{\%}) developed grade II-IV graft-versus-host disease, mainly at dose level 2. In conclusion, our RIC regimen allowed a stable engraftment with a rather low nonrelapse mortality in poor-risk patients; OS is encouraging with some long-term remissions in lymphoid malignancies. CD8-depleted DLIs are feasible and promote the immune reconstitution.",
author = "Anna Dodero and Cristiana Carniti and Anna Raganato and Antonio Vendramin and Lucia Farina and Francesco Spina and Carmelo Carlo-Stella and {Di Terlizzi}, Simona and Marco Milanesi and Paolo Longoni and Lorenza Gandola and Claudia Lombardo and Paolo Corradini",
year = "2009",
doi = "10.1182/blood-2008-10-183723",
language = "English",
volume = "113",
pages = "4771--4779",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "19",

}

TY - JOUR

T1 - Haploidentical stem cell transplantation after a reduced-intensity conditioning regimen for the treatment of advanced hematologic malignancies

T2 - Posttransplantation CD8-depleted donor lymphocyte infusions contribute to improve T-cell recovery

AU - Dodero, Anna

AU - Carniti, Cristiana

AU - Raganato, Anna

AU - Vendramin, Antonio

AU - Farina, Lucia

AU - Spina, Francesco

AU - Carlo-Stella, Carmelo

AU - Di Terlizzi, Simona

AU - Milanesi, Marco

AU - Longoni, Paolo

AU - Gandola, Lorenza

AU - Lombardo, Claudia

AU - Corradini, Paolo

PY - 2009

Y1 - 2009

N2 - Haploidentical hematopoietic stem cell transplantation provides an option for patients with advanced hematologic malignancies lacking a compatible donor. In this prospective phase 1/2 trial, we evaluated the role of reduced-intensity conditioning (RIC) followed by early add-backs of CD8-depleted donor lymphocyte infusions (DLIs). The RIC regimen consisted of thiotepa, fludarabine, cyclophosphamide, and 2 Gy total body irradiation. Twenty-eight patients with advanced lymphoproliferative diseases (n = 24) or acute myeloid leukemia (n = 4) were enrolled. Ex vivo and in vivo T-cell depletion was carried out by CD34+ cell selection and alemtuzumab treatment. The 2-year cumulative incidence of nonrelapse mortality was 26% and the 2-year overall survival (OS) was 44%, with a better outcome for patients with chemosensitive disease (OS, 75%). Overall, 54 CD8-depleted DLIs were administered to 23 patients (82%) at 3 different dose levels without loss of engraftment or acute toxicities. Overall, 6 of 23 patients (26%) developed grade II-IV graft-versus-host disease, mainly at dose level 2. In conclusion, our RIC regimen allowed a stable engraftment with a rather low nonrelapse mortality in poor-risk patients; OS is encouraging with some long-term remissions in lymphoid malignancies. CD8-depleted DLIs are feasible and promote the immune reconstitution.

AB - Haploidentical hematopoietic stem cell transplantation provides an option for patients with advanced hematologic malignancies lacking a compatible donor. In this prospective phase 1/2 trial, we evaluated the role of reduced-intensity conditioning (RIC) followed by early add-backs of CD8-depleted donor lymphocyte infusions (DLIs). The RIC regimen consisted of thiotepa, fludarabine, cyclophosphamide, and 2 Gy total body irradiation. Twenty-eight patients with advanced lymphoproliferative diseases (n = 24) or acute myeloid leukemia (n = 4) were enrolled. Ex vivo and in vivo T-cell depletion was carried out by CD34+ cell selection and alemtuzumab treatment. The 2-year cumulative incidence of nonrelapse mortality was 26% and the 2-year overall survival (OS) was 44%, with a better outcome for patients with chemosensitive disease (OS, 75%). Overall, 54 CD8-depleted DLIs were administered to 23 patients (82%) at 3 different dose levels without loss of engraftment or acute toxicities. Overall, 6 of 23 patients (26%) developed grade II-IV graft-versus-host disease, mainly at dose level 2. In conclusion, our RIC regimen allowed a stable engraftment with a rather low nonrelapse mortality in poor-risk patients; OS is encouraging with some long-term remissions in lymphoid malignancies. CD8-depleted DLIs are feasible and promote the immune reconstitution.

UR - http://www.scopus.com/inward/record.url?scp=66549125203&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66549125203&partnerID=8YFLogxK

U2 - 10.1182/blood-2008-10-183723

DO - 10.1182/blood-2008-10-183723

M3 - Article

VL - 113

SP - 4771

EP - 4779

JO - Blood

JF - Blood

SN - 0006-4971

IS - 19

ER -