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. 2023 Feb 21:13:1064190.
doi: 10.3389/fonc.2023.1064190. eCollection 2023.

Haploidentical hematopoietic stem cell transplantation as individual treatment option in pediatric patients with very high-risk sarcomas

Thomas Eichholz  1 , Michaela Döring  1 , Stefano Giardino  2 , Bernd Gruhn  3 , Christian Seitz  1 , Tim Flaadt  1 , Wolfgang Schwinger  4 , Martin Ebinger  1 , Ursula Holzer  1 , Markus Mezger  1 , Heiko-Manuel Teltschik  5 , Monika Sparber-Sauer  5   6 , Ewa Koscielniak  5   6 , Michael Abele  1 , Rupert Handgretinger  1 , Peter Lang  1
Affiliations

Haploidentical hematopoietic stem cell transplantation as individual treatment option in pediatric patients with very high-risk sarcomas

Thomas Eichholz et al. Front Oncol. .

Abstract

Background: Prognosis of children with primary disseminated or metastatic relapsed sarcomas remains dismal despite intensification of conventional therapies including high-dose chemotherapy. Since haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of hematological malignancies by mediating a graft versus leukemia effect, we evaluated this approach in pediatric sarcomas as well.

Methods: Patients with bone Ewing sarcoma or soft tissue sarcoma who received haplo-HSCT as part of clinical trials using CD3+ or TCRα/β+ and CD19+ depletion respectively were evaluated regarding feasibility of treatment and survival.

Results: We identified 15 patients with primary disseminated disease and 14 with metastatic relapse who were transplanted from a haploidentical donor to improve prognosis. Three-year event-free survival (EFS) was 18,1% and predominantly determined by disease relapse. Survival depended on response to pre-transplant therapy (3y-EFS of patients in complete or very good partial response: 36,4%). However, no patient with metastatic relapse could be rescued.

Conclusion: Haplo-HSCT for consolidation after conventional therapy seems to be of interest for some, but not for the majority of patients with high-risk pediatric sarcomas. Evaluation of its future use as basis for subsequent humoral or cellular immunotherapies is necessary.

Keywords: Ewing sarcoma; haploidentical hematopoietic stem cell transplantation; pediatric sarcoma; rhabdomyosarcoma; soft tissue sarcoma.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Immune reconstitution after haploidentical HSCT (mean and standard deviation), calculated from total lymphocyte cell count and flow cytometry results. (A) Reconstitution of CD56+ NK and CD19+ B cells. (B) Reconstitution of CD3+ T cells (CD4+ and CD8+). (C) Comparison of the recovery of CD3+ T cells in patients with or without relapse. (D) Comparison of the recovery of CD56+ NK cells in patients with or without relapse.
Figure 2
Figure 2
Cumulative Incidence (CI) of relapse, GvHD and transplant related mortality from haploidentical HSCT. (A) CI of relapse in patients who reach CR or VGPR after pre-transplant therapy compared to patients with either PR or NR. (B) CI of relapse in patients achieving first CR, VGPR or PR pre-transplant compared to patients in CR or PR who were transplanted after relapse. (C) CI of relapse in patients with Ewing Sarcoma or Rhabdomyosarcoma. (D) CI of relapse according to occurrence of aGvHD °I-IV or no aGvHD. (E) CI of aGvHD °II-IV and cGvHD. (F) CI of transplant related mortality.
Figure 3
Figure 3
Survival, counted from haploidentical HSCT. (A) Probability of Overall Survival (OS) and Event Free Survival of the entire cohort. (B) EFS according to pre-transplant remission status CR/VGPR vs. PR or NR. (C) EFS of patients achieving first PR or better compared to patients in CR/PR, who were transplanted after relapse. (D) EFS in accordance with the occurrence of aGvHD.
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