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Stammzelltransplantation bei pädiatrischen soliden Tumoren

Stem cell transplantation in pediatric solid tumors

  • Leitthema
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Der Onkologe Aims and scope

Zusammenfassung

Hintergrund

Die Hochdosischemotherapie mit autologem Stammzellsupport, auch autologe Stammzelltransplantation (SZT) genannt, hat seit ihrer Einführung zur Behandlung solider Tumoren eine deutliche Fokussierung der Indikationsstellung erlebt. Für bestimmte Entitäten in der Primärtherapie und für definierte Entitäten in der Rückfallsituation stellt sie jedoch einen fest etablierten Therapiebaustein dar, mit dessen Hilfe die Prognose deutlich verbessert werden konnte.

Ziel

In der vorliegenden Arbeit werden derzeitige Indikationen für die autologe SZT beschrieben und zudem der aktuelle Stand der allogenen SZT bei soliden Tumoren erörtert.

Material und Methoden

Dazu erfolgte eine selektive Literaturrecherche, die Analyse von Empfehlungen der Fachgesellschaft (Gesellschaft für Pädiatrische Onkologie und Hämatologie, GPOH) sowie Auswertung eigener Patientenkollektive.

Ergebnisse und Schlussfolgerung

Die autologe SZT ist v. a. bei Neuroblastomen, Ewing-Sarkomen, Medulloblastomen und anderen Hirntumoren, Rhabdoidtumoren, Burkitt-Lymphomen sowie bei Keimzelltumoren indiziert und verbessert nachweislich das krankheitsfreie Überleben. Dennoch muss mit einer signifikanten Anzahl von Rezidiven gerechnet werden, die meist eine schlechte Prognose haben. Die allogene Stammzelltransplantation stellt hier eine Therapieoption dar, die für einen Teil dieser Patienten kurativ sein kann. Zudem bietet sie die Möglichkeit, ein vom Spender stammendes Immunsystem zu etablieren, welches potenziell Anti-Tumor-Effekte vermitteln kann. Weitere immunologische Ansätze, insbesondere therapeutische Antikörper, können diese Effekte klinisch nachweisbar verstärken.

Abstract

Background

Indications for high-dose chemotherapy with autologous stem cell support, also known as autologous stem cell transplantation (SCT), have been increasingly limited to specific tumor entities in recent years. In those tumors, autologous SCT is a well-established therapeutic option which can improve survival rates in case of primary or relapsed disease.

Aim

We summarize current indications for high-dose chemotherapy with autologous stem cell support and also report on the use of allogeneic SCT in pediatric solid tumors.

Materials and methods

For this purpose, a selective literature search, analysis of the recommendations of medical associations (German Association for Pediatric Oncology and Hematology), and evaluation of our own patient cohorts were performed.

Results and conclusions

The use of autologous SCT is indicated in particular in neuroblastomas, Ewing sarcomas, medulloblastomas and other brain tumors, rhabdoid tumors, Burkitt lymphomas and germinal cell tumors and leads to an improvement of survival rates. However, a significant number of relapses still occur posttransplant, which are generally associated with a poor prognosis. In this situation, allogeneic SCT can be a curative therapeutic option for at least a portion of these patients. Moreover, allogeneic SCT offers the possibility to exert antitumor effects based on the new, donor-derived immune system. Additional immunological approaches such as use of therapeutic antibodies can clinically improve these effects.

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Literatur

  1. Ringden O, Karlsson H, Olsson R, Omazic B, Uhlin M (2009) The allogeneic graft-versus-cancer effect. Br J Haematol 147(5):614–633

    Article  Google Scholar 

  2. Pfeiffer MM, Feuchtinger T, Teltschik HM et al (2010) Reconstitution of natural killer cell receptors influences natural killer activity and relapse rate after haploidentical transplantation of T‑ and B‑cell depleted grafts in children. Haematologica 95(8):1381–1388

    Article  CAS  Google Scholar 

  3. Ruggeri L, Capanni M, Urbani E et al (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295(5562):2097–2100

    Article  CAS  Google Scholar 

  4. Oevermann L, Michaelis SU, Mezger M et al (2014) KIR B haplotype donors confer a reduced risk for relapse after haploidentical transplantation in children with ALL. Blood 124(17):2744–2747

    Article  CAS  Google Scholar 

  5. Schlegel P, Feuchtinger T, Nitschke-Gerard C et al (2015) Favorable NK cell activity after haploidentical hematopoietic stem cell transplantation in stage IV relapsed Ewing’s sarcoma patients. Bone Marrow Transplant 50(2):S72–6

    Article  CAS  Google Scholar 

  6. Koscielniak E, Gross-Wieltsch U, Treuner J et al (2005) Graft-versus-Ewing sarcoma effect and long-term remission induced by haploidentical stem-cell transplantation in a patient with relapse of metastatic disease. J Clin Oncol 23(1):242–244

    Article  Google Scholar 

  7. Kanold J, Paillard C, Tchirkov A et al (2008) Allogeneic or haploidentical HSCT for refractory or relapsed solid tumors in children: toward a neuroblastoma model. Bone Marrow Transplant 42(2):S25–30

    Article  Google Scholar 

  8. Matthay KK, Seeger RC, Reynolds CP et al (1994) Allogeneic versus autologous purged bone marrow transplantation for neuroblastoma: a report from the childrens cancer group. J Clin Oncol 12(11):2382–2389

    Article  CAS  Google Scholar 

  9. Ladenstein R, Lasset C, Hartmann O et al (1994) Comparison of auto versus allografting as consolidation of primary treatments in advanced neuroblastoma over one year of age at diagnosis: report from the European group for bone marrow transplantation. Bone Marrow Transplant 14(1):37–46

    CAS  PubMed  Google Scholar 

  10. Hale GA, Arora M, Ahn KW et al (2013) Allogeneic hematopoietic cell transplantation for neuroblastoma: the CIBMTR experience. Bone Marrow Transplant 48(8):1056–1064

    Article  CAS  Google Scholar 

  11. Illhardt T, Toporski J, Feuchtinger T et al (2018) Haploidentical stem cell transplantation for refractory/relapsed neuroblastoma. Biol Blood Marrow Transplant 24(5):1005–1012

    Article  Google Scholar 

  12. Burdach S, van Kaick B, Laws HJ et al (2000) Allogeneic and autologous stem-cell transplantation in advanced ewing tumors. An update after long-term follow-up from two centers of the European intergroup study EICESS. Stem-cell transplant programs at Dusseldorf university medical center, Germany and St. Anna Kinderspital, Vienna, Austria. Ann Oncol 11(11):1451–1462

    Article  CAS  Google Scholar 

  13. Flaadt PL, Ebinger M, Schlegel P, Illhardt T, Feuchtinger T, Fuchs J, Warmann S, Schaefer J, Ladenstein R, Lode H, Schwinger W, Urban C, Handgretinger R (2020) Haploidentical stem cell transplantation and subsequent immunotherapy with antiGD2 antibody for patients with relapsed metastatic neuroblastoma. Pediatr Blood Cancer 67(S4):1545–5009

    Google Scholar 

  14. Passweg JR, Baldomero H, Peters C et al (2014) Hematopoietic SCT in Europe: data and trends in 2012 with special consideration of pediatric transplantation. Bone Marrow Transplant 49(6):744–750

    Article  Google Scholar 

  15. Berthold F, Boos J, Burdach S et al (2005) Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial. Lancet Oncol 6(9):649–658

    Article  CAS  Google Scholar 

  16. Matthay KK, Reynolds CP, Seeger RC et al (2009) Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children’s oncology group study. J Clin Oncol 27(7):1007–1013

    Article  CAS  Google Scholar 

  17. Pritchard J, Cotterill SJ, Germond SM, Imeson J, de Kraker J, Jones DR (2005) High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European neuroblastoma study group. Pediatr Blood Cancer 44(4):348–357

    Article  Google Scholar 

  18. Ladenstein R, Potschger U, Pearson ADJ et al (2017) Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial. Lancet Oncol 18(4):500–514

    Article  CAS  Google Scholar 

  19. Simon T, Hero B, Schulte JH et al (2017) 2017 GPOH guidelines for diagnosis and treatment of patients with neuroblastic tumors. Klin Padiatr 229(3):147–167

    Article  Google Scholar 

  20. Marabelle A, Merlin E, Halle P et al (2011) CD34+ immunoselection of autologous grafts for the treatment of high-risk neuroblastoma. Pediatr Blood Cancer 56(1):134–142

    Article  Google Scholar 

  21. Yanik GA, Villablanca JG, Maris JM et al (2015) 131I-metaiodobenzylguanidine with intensive chemotherapy and autologous stem cell transplantation for high-risk neuroblastoma. A new approaches to neuroblastoma therapy (NANT) phase II study. Biol Blood Marrow Transplant 21(4):673–681

    Article  CAS  Google Scholar 

  22. Ladenstein R, Potschger U, Le Deley MC et al (2010) Primary disseminated multifocal Ewing sarcoma: results of the Euro-EWING 99 trial. J Clin Oncol 28(20):3284–3291

    Article  CAS  Google Scholar 

  23. Klingebiel T, Boos J, Beske F et al (2008) Treatment of children with metastatic soft tissue sarcoma with oral maintenance compared to high dose chemotherapy: report of the HD CWS-96 trial. Pediatr Blood Cancer 50(4):739–745

    Article  Google Scholar 

  24. Burkhardt B, Woessmann W (2012) BFM registry 2012 - registry of the NHL-BFM study goup for all subtypes of non-Hodgkin lymphoma diagnosed in children and adolescents. Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH),

    Google Scholar 

  25. Rutkowski S, Cohen B, Finlay J et al (2010) Medulloblastoma in young children. Pediatr Blood Cancer 54(4):635–637

    Article  Google Scholar 

  26. Bartelheim K, Nemes K, Seeringer A et al (2016) Improved 6‑year overall survival in AT/RT - results of the registry study Rhabdoid 2007. Cancer Med 5(8):1765–1775

    Article  CAS  Google Scholar 

  27. Bouffet E (2010) The role of myeloablative chemotherapy with autologous hematopoietic cell rescue in central nervous system germ cell tumors. Pediatr Blood Cancer 54(4):644–646

    Article  Google Scholar 

  28. Warmuth-Metz M, Blashofer S, von Bueren AO et al (2011) Recurrence in childhood medulloblastoma. J Neurooncol 103(3):705–711

    Article  Google Scholar 

  29. Dunkel IJ, Gardner SL, Garvin JH Jr., Goldman S, Shi W, Finlay JL (2010) High-dose carboplatin, thiotepa, and etoposide with autologous stem cell rescue for patients with previously irradiated recurrent medulloblastoma. Neuro Oncol 12(3):297–303

    Article  CAS  Google Scholar 

  30. Daw S, Hasenclever D, Mascarin M et al (2020) Risk and response adapted treatment guidelines for managing first relapsed and refractory classical Hodgkin lymphoma in children and young people. Recommendations from the Euronet pediatric Hodgkin lymphoma group. Hemasphere 4(1):e329

    Article  Google Scholar 

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Authors and Affiliations

  1. Kinder- und Jugendmedizin, Pädiatrische Hämatologie/Onkologie und Stammzelltransplantation, Universitätsklinik, Hoppe-Seyler-Str. 1, 72076, Tübingen, Deutschland

    Peter Lang

  2. Pädiatrische Hämatologie/Onkologie und Stammzelltransplantation, Universitätskinderklinik, Würzburg, Deutschland

    Paul-Gerhardt Schlegel

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  1. Peter Lang
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Correspondence to Peter Lang.

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Interessenkonflikt

P. Lang und P.-G. Schlegel geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Lang, P., Schlegel, PG. Stammzelltransplantation bei pädiatrischen soliden Tumoren. Onkologe 27, 464–469 (2021). https://doi.org/10.1007/s00761-021-00927-6

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  • DOI: https://doi.org/10.1007/s00761-021-00927-6

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