Donor lymphocyte infusions in adolescents and young adults for control of advanced pediatric sarcoma

Sebastian J. Schober; Irene von Luettichau; Angela Wawer; Maximilian Steinhauser; Christoph Salat; Wolfgang Schwinger; Marek Ussowicz; Petar Antunovic; Luca Castagna; Hans Jochem Kolb; Stefan E.G. Burdach; Uwe Thiel

doi:10.18632/oncotarget.25228

Donor lymphocyte infusions in adolescents and young adults for control of advanced pediatric sarcoma

Sebastian J. Schober
, Irene von Luettichau
, Angela Wawer
, Maximilian Steinhauser
, Christoph Salat
, Wolfgang Schwinger
, Marek Ussowicz
, Petar Antunovic
, Luca Castagna
, Hans Jochem Kolb
, Stefan E.G. Burdach
, Uwe Thiel

Technical University of Munich
Medical Center for Hematology and Oncology Munich MVZ
Medical University of Graz
Wroclaw Medical University
University Hospital Linköping
Humanitas University
Comprehensive Cancer Center

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Background: Allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusions (DLI) may induce a graft-versus-tumor effect in pediatric sarcoma patients. Here, we describe general feasibility, toxicity and efficacy of DLI after allo-SCT. Results: 4 of 8 patients responded. ES#4 had stable disease (SD) for 9 months after DLI and RMS#4 partial response for 8 months with combined hyperthermia/ chemotherapy. In ES#4, DLI led to SD for 6 months and reverted residual disease before allo-SCT into complete remission. After DLI, ES#4 and RMS#4 developed acute GvHD (°III-°IV), ES#4 also developed chronic GvHD. 5 patients including ES#4 lived longer than expected. Median survival after allo-SCT was 2.3 years, post-relapse survival (PRS) was 13 months. Off note, HLA-mismatched DLI were associated with a trend towards increased survival after allo-SCT and increased PRS compared to HLA-matched DLI (23 versus 3 months). Materials and Methods: We studied eight adolescents and young adults (AYAs) with advanced Ewing sarcoma (ES#1-4) and rhabdomyosarcoma (RMS#1-4) who received DLI. Escalating doses ranged from 2.5 x 104 to 1 x 10⁸ CD3⁺ cells/kg body weight. AYAs were evaluated for response to DLI, graft-versus-host disease (GvHD) and survival. Conclusions: DLI after allo-SCT may control advanced pediatric sarcoma in AYAs with controllable toxicity.

Original language	English
Pages (from-to)	22741-22748
Number of pages	8
Journal	Oncotarget
Volume	9
Issue number	32
DOIs	https://doi.org/10.18632/oncotarget.25228
State	Published - 27 Apr 2018

Keywords

Allogeneic stem cell transplantation
Alloimmunity and transplantation
Donor lymphocyte infusion
Ewing sarcoma
Rhabdomyosarcoma

Access to Document

10.18632/oncotarget.25228

Cite this

@article{e0852946a05a4a64a113af4b85a8611b,

title = "Donor lymphocyte infusions in adolescents and young adults for control of advanced pediatric sarcoma",

abstract = "Background: Allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusions (DLI) may induce a graft-versus-tumor effect in pediatric sarcoma patients. Here, we describe general feasibility, toxicity and efficacy of DLI after allo-SCT. Results: 4 of 8 patients responded. ES\#4 had stable disease (SD) for 9 months after DLI and RMS\#4 partial response for 8 months with combined hyperthermia/ chemotherapy. In ES\#4, DLI led to SD for 6 months and reverted residual disease before allo-SCT into complete remission. After DLI, ES\#4 and RMS\#4 developed acute GvHD (°III-°IV), ES\#4 also developed chronic GvHD. 5 patients including ES\#4 lived longer than expected. Median survival after allo-SCT was 2.3 years, post-relapse survival (PRS) was 13 months. Off note, HLA-mismatched DLI were associated with a trend towards increased survival after allo-SCT and increased PRS compared to HLA-matched DLI (23 versus 3 months). Materials and Methods: We studied eight adolescents and young adults (AYAs) with advanced Ewing sarcoma (ES\#1-4) and rhabdomyosarcoma (RMS\#1-4) who received DLI. Escalating doses ranged from 2.5 x 104 to 1 x 108 CD3+ cells/kg body weight. AYAs were evaluated for response to DLI, graft-versus-host disease (GvHD) and survival. Conclusions: DLI after allo-SCT may control advanced pediatric sarcoma in AYAs with controllable toxicity.",

keywords = "Allogeneic stem cell transplantation, Alloimmunity and transplantation, Donor lymphocyte infusion, Ewing sarcoma, Rhabdomyosarcoma",

author = "Schober, \{Sebastian J.\} and \{von Luettichau\}, Irene and Angela Wawer and Maximilian Steinhauser and Christoph Salat and Wolfgang Schwinger and Marek Ussowicz and Petar Antunovic and Luca Castagna and Kolb, \{Hans Jochem\} and Burdach, \{Stefan E.G.\} and Uwe Thiel",

note = "Publisher Copyright: {\textcopyright} Schober et al.",

year = "2018",

month = apr,

day = "27",

doi = "10.18632/oncotarget.25228",

language = "English",

volume = "9",

pages = "22741--22748",

journal = "Oncotarget",

issn = "1949-2553",

publisher = "Impact Journals LLC",

number = "32",

}

TY - JOUR

T1 - Donor lymphocyte infusions in adolescents and young adults for control of advanced pediatric sarcoma

AU - Schober, Sebastian J.

AU - von Luettichau, Irene

AU - Wawer, Angela

AU - Steinhauser, Maximilian

AU - Salat, Christoph

AU - Schwinger, Wolfgang

AU - Ussowicz, Marek

AU - Antunovic, Petar

AU - Castagna, Luca

AU - Kolb, Hans Jochem

AU - Burdach, Stefan E.G.

AU - Thiel, Uwe

N1 - Publisher Copyright: © Schober et al.

PY - 2018/4/27

Y1 - 2018/4/27

N2 - Background: Allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusions (DLI) may induce a graft-versus-tumor effect in pediatric sarcoma patients. Here, we describe general feasibility, toxicity and efficacy of DLI after allo-SCT. Results: 4 of 8 patients responded. ES#4 had stable disease (SD) for 9 months after DLI and RMS#4 partial response for 8 months with combined hyperthermia/ chemotherapy. In ES#4, DLI led to SD for 6 months and reverted residual disease before allo-SCT into complete remission. After DLI, ES#4 and RMS#4 developed acute GvHD (°III-°IV), ES#4 also developed chronic GvHD. 5 patients including ES#4 lived longer than expected. Median survival after allo-SCT was 2.3 years, post-relapse survival (PRS) was 13 months. Off note, HLA-mismatched DLI were associated with a trend towards increased survival after allo-SCT and increased PRS compared to HLA-matched DLI (23 versus 3 months). Materials and Methods: We studied eight adolescents and young adults (AYAs) with advanced Ewing sarcoma (ES#1-4) and rhabdomyosarcoma (RMS#1-4) who received DLI. Escalating doses ranged from 2.5 x 104 to 1 x 108 CD3+ cells/kg body weight. AYAs were evaluated for response to DLI, graft-versus-host disease (GvHD) and survival. Conclusions: DLI after allo-SCT may control advanced pediatric sarcoma in AYAs with controllable toxicity.

AB - Background: Allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusions (DLI) may induce a graft-versus-tumor effect in pediatric sarcoma patients. Here, we describe general feasibility, toxicity and efficacy of DLI after allo-SCT. Results: 4 of 8 patients responded. ES#4 had stable disease (SD) for 9 months after DLI and RMS#4 partial response for 8 months with combined hyperthermia/ chemotherapy. In ES#4, DLI led to SD for 6 months and reverted residual disease before allo-SCT into complete remission. After DLI, ES#4 and RMS#4 developed acute GvHD (°III-°IV), ES#4 also developed chronic GvHD. 5 patients including ES#4 lived longer than expected. Median survival after allo-SCT was 2.3 years, post-relapse survival (PRS) was 13 months. Off note, HLA-mismatched DLI were associated with a trend towards increased survival after allo-SCT and increased PRS compared to HLA-matched DLI (23 versus 3 months). Materials and Methods: We studied eight adolescents and young adults (AYAs) with advanced Ewing sarcoma (ES#1-4) and rhabdomyosarcoma (RMS#1-4) who received DLI. Escalating doses ranged from 2.5 x 104 to 1 x 108 CD3+ cells/kg body weight. AYAs were evaluated for response to DLI, graft-versus-host disease (GvHD) and survival. Conclusions: DLI after allo-SCT may control advanced pediatric sarcoma in AYAs with controllable toxicity.

KW - Allogeneic stem cell transplantation

KW - Alloimmunity and transplantation

KW - Donor lymphocyte infusion

KW - Ewing sarcoma

KW - Rhabdomyosarcoma

UR - https://www.scopus.com/pages/publications/85046103063

U2 - 10.18632/oncotarget.25228

DO - 10.18632/oncotarget.25228

M3 - Article

AN - SCOPUS:85046103063

SN - 1949-2553

VL - 9

SP - 22741

EP - 22748

JO - Oncotarget

JF - Oncotarget

IS - 32

ER -

Donor lymphocyte infusions in adolescents and young adults for control of advanced pediatric sarcoma

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this