Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2020; 19: 94-101
Аллогенная трансплантация гемопоэтических стволовых клеток при альвеолярной рабдомиосаркоме. Описание первого опыта гаплоидентичной трансплантации в клинической практике
https://doi.org/10.24287/1726-1708-2020-19-4-94-101Аннотация
В данной статье представлено описание проведения аллогенной трансплантации гемопоэтических стволовых клеток (ТГСК) пациентке с метастатической формой альвеолярной рабдомиосаркомы. Представленный клинический случай имеет несколько особенностей манифестации заболевания, диагностики, а также выбора тактики терапии. Данное исследование одобрено независимым этическим комитетом и утверждено решением ученого совета ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России. За последние десятилетия не произошло существенного улучшения выживаемости пациентов с метастатическими формами злокачественных новообразований, в том числе больных с мягкотканными саркомами. Прогноз для таких пациентов остается крайне неблагоприятным, несмотря на интенсификацию химиотерапии и проведение лучевой терапии. Применение аутологичной ТГСК не привело к изменению в результатах лечения. В целях улучшения прогноза для пациентов группы очень высокого риска разрабатываются экспериментальные методы терапии, включающие иммунотерапевтические технологии. Данный случай описан ввиду применения нестандартного подхода терапии с получением положительного ответа в виде длительного контроля за болезнью и отсутствия системной прогрессии заболевания. Он показывает, что аллогенная ТГСК рассматривается как один из возможных перспективных методов для интенсификации терапии, главным образом, за счет существования эффекта «трансплантат против опухоли». Родители дали согласие на использование информации, в том числе фотографий ребенка, в научных исследованиях и публикациях.
Список литературы
1. Schlegel P., Feuchtinger T., NitschkeGérard C. Favorable NK cell activity after haploidentical hematopoietic stem cell transplantation in stage IV relapsed Ewing’s sarcoma patients. Bone Marrow Transplant 2015; 50 (2): 72–6. DOI: 10.1038/bmt.2015.100
2. De Casterléa I., Billiaua A.D., Sprangers B. Recipient and donor cells in the graft-versus-solid tumor effect: It takes two to tango. Blood Rev 2018; 32 (6): 449–56. DOI: 10.1016/j.blre.2018.04.002
3. Blaise D., Bregni M. Allogeneic stem cell transplantation for solid tumors: which way forward? Biol Blood Marrow Transplant 2007; 13: 73–5. DOI: 10.1016/j.bbmt.2006.10.022
4. Goldman J.M., Schmitz N., Neithammer D., Gratwohl A. Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe in 1998. Bone Marrow Transplant 1998; 21 (1): 1–7. DOI: 10.1038/sj.bmt.1701089
5. Goldman J.M., Horowitz M.M. The international bone marrow transplant registry. Int J Hematol 2002; 76 (1): 393–7. DOI: 10.1007/BF03165291
6. Ljungman P., Bregni M., Brune M., Cornelissen J., de Witte T., Dini G., et al. Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe 2009. Bone Marrow Transplant 2010; 45 (2): 219–34. DOI: 10.1038/bmt.2009.141
7. Carnevale-Schianca F., Ricchiardi A., Capaldi A., Bucci A.R., Grignani G., Rota-Scalabrini D., et al. Allogeneic Hemopoietic stem cell transplantation in solid tumors. Transplantation Proc 2005; 37 (6): 2664–6. DOI: 10.1016/j.transproceed.2005.06.050
8. Lang P., Pfeiffer M., Müller I., Schumm M., Ebinger M., Koscielniak E., et al. Haploidentical stem cell transplantation in patients with pediatric solid tumors: preliminary results of a pilot study and analysis of graft versus tumor effects. Klin Padiatr 2006; 218 (6): 321–6. DOI: 10.1055/s-2006-942256
9. Moscovitch M., Slavin S. Anti-tumor effects of allogeneic bone marrow transplantation in (NZB X NZW) F1 hybrids with spontaneous lymphosarcoma. J Immunol 1984; 132 (2): 997–1000.
10. Ueno N.T., Rondon G., Mirza N.Q., Geisler D.K., Anderlini P., Giralt S.A., et al. Allogeneic peripheral-blood progenitor-cell transplantation for poor-risk patients with metastatic breast cancer. J Clin Oncol 1998; 16 (3): 986–93. DOI: 10.1200/JCO.1998.16.3.986
11. Margolin K., Morishima C., Velcheti V., Miller J.S., Lee S.M., Silk A.W., et al. Phase I Trial of ALT-803, A Novel Recombinant IL15 Complex, in Patients with Advanced Solid Tumors. Clin Cancer Res 2018; 24 (22): 5552–61. DOI: 10.1158/1078-0432.CCR-18-0945
12. Haworth K.B., Leddon J.L., Chen C.-Y., Horwitz E.M., Mackall C.L., Cripe T.P. Going back to class I: MHC and immunotherapies for childhood cancer. Pediatr Blood Cancer 2015; 62 (4): 571–6. DOI: 10.1002/pbc.25359
13. Lundqvist A., Childs R. Allogeneic hematopoietic cell transplantation as immunotherapy for solid tumors current status and future directions. J Immunother 2005; 28 (4): 281–8. DOI: 10.1002/pbc.25359
14. Miller J.S., Soignier Y., Panoskaltsis-Mortari A., McNearney S.A., Yun G.H., Fautsch S.K., et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 2005; 105 (8): 3051–7. DOI: 10.1182/blood-2004-07-2974
15. Minard-Colin V., Ichante J.L., Nguyen L., Paci A., Orbach D., Bergeron C., et al. Phase II study of vinorelbine and continuous low doses cyclophosphamide in children and young adults with a relapsed or refractory malignant solid tumour: good tolerance profile and efficacy in rhabdomyosarcoma – a report from the Société Française des Cancers et leucémies de l'Enfant et de l'adolescent (SFCE). Eur J Cancer 2012; 48 (15): 2409–16. DOI: 10.1016/j.ejca.2012.04.012
16. Oberlin O., Rey A., Lyden E., Bisogno G., Stevens M.C., Meyer W.H., et al. Prognostic factors in metastatic rhabdomyosarcomas: results of a pooled analysis from United States and European cooperative groups. J Clin Oncol 2008; 26 (14): 2384– 9. DOI: 10.1200/JCO.2007.14.7207
17. Thiel U., Koscielniak E., Blaeschke F., Grunewald T.G.P., Badoglio M., Diaz M.A., et al. Allogeneic stem cell transplantation for patients with advanced rhabdomyosarcoma: a retrospective assessment. Br J Cancer 2013; 109 (10): 2523–32. DOI: 10.1038/bjc.2013.630
Pediatric Hematology/Oncology and Immunopathology. 2020; 19: 94-101
Allogeneic hematopoietic stem cell transplantation for alveolar rhabdomyosarcoma: the first clinical experience of haploidentical transplantation
https://doi.org/10.24287/1726-1708-2020-19-4-94-101Abstract
This article describes the use of allogeneic hematopoietic stem cell transplantation (HSCT) for the treatment of a patient with metastatic alveolar rhabdomyosarcoma. The reported case is unusual in terms of its presentation, diagnosis, and choice of treatment. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. In the last decades, the survival rates of patients with metastatic malignant neoplasms, including those with soft-tissue sarcomas, have not improved significantly. The prognosis for these patients remains extremely poor despite the intensification of chemotherapy and the application of radiation therapy. The use of autologous HSCT has not brought about any positive changes in treatment outcomes. Experimental approaches to treatment, including immunotherapeutic techniques, aimed at improving the prognosis for very high-risk patients are currently under development. We chose to report this case because of the unconventional treatment approach that had helped to achieve long-term control over the disease and to prevent systemic progression. It demonstrates that allogeneic HSCT can be regarded as one of the promising options for treatment intensification mainly due to the “graftversus-tumour” effect. The patients' parents gave their consent to the use of their child's data, including photographs, for research purposes and in publications.
References
1. Schlegel P., Feuchtinger T., NitschkeGérard C. Favorable NK cell activity after haploidentical hematopoietic stem cell transplantation in stage IV relapsed Ewing’s sarcoma patients. Bone Marrow Transplant 2015; 50 (2): 72–6. DOI: 10.1038/bmt.2015.100
2. De Casterléa I., Billiaua A.D., Sprangers B. Recipient and donor cells in the graft-versus-solid tumor effect: It takes two to tango. Blood Rev 2018; 32 (6): 449–56. DOI: 10.1016/j.blre.2018.04.002
3. Blaise D., Bregni M. Allogeneic stem cell transplantation for solid tumors: which way forward? Biol Blood Marrow Transplant 2007; 13: 73–5. DOI: 10.1016/j.bbmt.2006.10.022
4. Goldman J.M., Schmitz N., Neithammer D., Gratwohl A. Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe in 1998. Bone Marrow Transplant 1998; 21 (1): 1–7. DOI: 10.1038/sj.bmt.1701089
5. Goldman J.M., Horowitz M.M. The international bone marrow transplant registry. Int J Hematol 2002; 76 (1): 393–7. DOI: 10.1007/BF03165291
6. Ljungman P., Bregni M., Brune M., Cornelissen J., de Witte T., Dini G., et al. Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe 2009. Bone Marrow Transplant 2010; 45 (2): 219–34. DOI: 10.1038/bmt.2009.141
7. Carnevale-Schianca F., Ricchiardi A., Capaldi A., Bucci A.R., Grignani G., Rota-Scalabrini D., et al. Allogeneic Hemopoietic stem cell transplantation in solid tumors. Transplantation Proc 2005; 37 (6): 2664–6. DOI: 10.1016/j.transproceed.2005.06.050
8. Lang P., Pfeiffer M., Müller I., Schumm M., Ebinger M., Koscielniak E., et al. Haploidentical stem cell transplantation in patients with pediatric solid tumors: preliminary results of a pilot study and analysis of graft versus tumor effects. Klin Padiatr 2006; 218 (6): 321–6. DOI: 10.1055/s-2006-942256
9. Moscovitch M., Slavin S. Anti-tumor effects of allogeneic bone marrow transplantation in (NZB X NZW) F1 hybrids with spontaneous lymphosarcoma. J Immunol 1984; 132 (2): 997–1000.
10. Ueno N.T., Rondon G., Mirza N.Q., Geisler D.K., Anderlini P., Giralt S.A., et al. Allogeneic peripheral-blood progenitor-cell transplantation for poor-risk patients with metastatic breast cancer. J Clin Oncol 1998; 16 (3): 986–93. DOI: 10.1200/JCO.1998.16.3.986
11. Margolin K., Morishima C., Velcheti V., Miller J.S., Lee S.M., Silk A.W., et al. Phase I Trial of ALT-803, A Novel Recombinant IL15 Complex, in Patients with Advanced Solid Tumors. Clin Cancer Res 2018; 24 (22): 5552–61. DOI: 10.1158/1078-0432.CCR-18-0945
12. Haworth K.B., Leddon J.L., Chen C.-Y., Horwitz E.M., Mackall C.L., Cripe T.P. Going back to class I: MHC and immunotherapies for childhood cancer. Pediatr Blood Cancer 2015; 62 (4): 571–6. DOI: 10.1002/pbc.25359
13. Lundqvist A., Childs R. Allogeneic hematopoietic cell transplantation as immunotherapy for solid tumors current status and future directions. J Immunother 2005; 28 (4): 281–8. DOI: 10.1002/pbc.25359
14. Miller J.S., Soignier Y., Panoskaltsis-Mortari A., McNearney S.A., Yun G.H., Fautsch S.K., et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 2005; 105 (8): 3051–7. DOI: 10.1182/blood-2004-07-2974
15. Minard-Colin V., Ichante J.L., Nguyen L., Paci A., Orbach D., Bergeron C., et al. Phase II study of vinorelbine and continuous low doses cyclophosphamide in children and young adults with a relapsed or refractory malignant solid tumour: good tolerance profile and efficacy in rhabdomyosarcoma – a report from the Société Française des Cancers et leucémies de l'Enfant et de l'adolescent (SFCE). Eur J Cancer 2012; 48 (15): 2409–16. DOI: 10.1016/j.ejca.2012.04.012
16. Oberlin O., Rey A., Lyden E., Bisogno G., Stevens M.C., Meyer W.H., et al. Prognostic factors in metastatic rhabdomyosarcomas: results of a pooled analysis from United States and European cooperative groups. J Clin Oncol 2008; 26 (14): 2384– 9. DOI: 10.1200/JCO.2007.14.7207
17. Thiel U., Koscielniak E., Blaeschke F., Grunewald T.G.P., Badoglio M., Diaz M.A., et al. Allogeneic stem cell transplantation for patients with advanced rhabdomyosarcoma: a retrospective assessment. Br J Cancer 2013; 109 (10): 2523–32. DOI: 10.1038/bjc.2013.630
