Relapse risk factors during allogeneic stem cell transplantation in children, adolescents and young adults with acute lymphoblastic leukemia
https://doi.org/10.29235/1814-6023-2021-18-3-375-384
Abstract
More than 20–25 % of patients with acute leukemia underwent transplantation of HSC from HLA-identical sibling or unrelated donor had relapse.
Therefore, the purpose of this study was to evaluate the influence of different factors on the risk of post-transplantation relapse in children and teenagers with acute lymphoblastic leukemia (ALL).
The gender, the age of a donor at the time of transplantation; the gender, the age of a recipient at the time of transplantation; the type, the number of relapses of previous HSCTs; the type of conditioning; the type of transplantation; the source of stem cells; transplant parameters; the acute (aGVHD) and chronic (cGVHD) graft-versus-host disease or its absence; the KIRalloreactivity of donor NK cells were estimated as risk factors for the disease relapse in our study.
We established that the recipient’s age of less than 4 years at the time of transplantation (p = 0.0042); the time of relapse (very early and early) (p = 0.0047); the absence of aGVHD (p = 0.0183) or cGVHD (p = 0.0384) have been the important factors for the disease relapse of patients with ALL after allogeneic HSC transplantation.
About the Authors
D. V. Prudnikau
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
Belarus
Belarus
Dmitry V. Prudnikau – Hematologist
43, Frunzenskaya Str., 223053, v. Borovliany, Minsk region
N. P. Kirsanava
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
Belarus
Belarus
Natalia P. Kirsanava – Ph. D. (Med.), Hematologist
43, Frunzenskaya Str., 223053, v. Borovliany, Minsk region
Yu. E. Mareika
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
Belarus
Belarus
Yulia E. Mareika – Hematologist
43, Frunzenskaya Str., 223053, v. Borovliany, Minsk region
N. V. Minakovskaya
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
Belarus
Belarus
Nina V. Minakovskaya – Ph. D. (Med.), Associate Professor, Hematologist, Head of the Department
43, Frunzenskaya Str., 223053, v. Borovliany, Minsk region
O. V. Aleinikova
Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
Belarus
Belarus
Olga V. Aleinikova – Corresponding Member, D. Sc. (Med.), Professor, Chief Researcher
43, Frunzenskaya Str., 223053, v. Borovliany, Minsk region
References
1. Miano M., Labopin M., Hartmann O., Angelucci E., Cornish J., Gluckman E. [et al.]. Haematopoietic stem cell transplantation trends in children over the last three decades: a survey by the paediatric diseases working party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplantation, vol. 39, no. 2, pp. 89‒99. https://doi.org/10.1038/sj.bmt.1705550
2. Peters C., Schrappe M., von Stackelberg A., Schrauder A., Bader P., Ebell W. [et al.]. Stem-Cell Transplantation in Children with Acute Lymphoblastic Leukemia: A Prospective International Multicenter Trial Comparing Sibling Donors with Matched Unrelated Donors ‒ The ALL-SCT-BFM-2003 Trial. Journal of Clinical Oncology, 2015, vol. 33, no. 11, pp. 1265‒1273. https://doi.org/10.1200/JCO.2014.58.9747
3. Pui C-H., Evans W. E. Acute lymphoblastic leukemia. New England Journal of Medicine, 1998, vol. 339, no. 9, pp. 605–615. https://doi.org/10.1056/NEJM199808273390907
4. Pavletic S. Z., Kumar S., Mohty M., de Lima M., Foran J. M., Pasquini M., Zhang M. J., Giralt S., Bishop M. R., Weisdorf D. NCI first international workshop on the biology, prevention and treatment of relapse after allogeneic hematopoietic cell transplantation: report from the committee on prevention of relapse following allogeneic cell transplantation for hematologic malignancies. Biology of Blood and Marrow Transplantation, 2010, vol. 16, no. 8, pp. 1037–1069. https://doi.org/10.1016/j.bbmt.2010.04.004
5. Chiaretti S., Vitale A., Cazzaniga G., Orlando S. M., Silvestri D., Fazi P. [et al.]. Clinico-biological features of 5202 patients with acute lymphoblastic leukemia enrolled in the Italian AIEOP and GIMEMA protocols and stratified in age cohorts. Haematologica, 2013, vol. 98, no. 11, pp. 1702‒1710. https://doi.org/10.3324/haematol.2012.080432
6. Matsumoto K., Yamamoto W., Ogusa E., Ishigatsubo Y., Kanamori H. Prognostic index for relapsed acute leukemia after allogeneic stem cell transplant. Leukemia and Lymphoma, 2014, vol. 55, no. 12, pp. 2808–2812. https://doi.org/10.3109/10428194.2014.896004
7. Liu J., Wang Y., Xu L. P., Liu D. H., Qin Y. Z., Chang Y. J., Liu K. Y., Huang X. J. Monitoring mixed lineage leukemia expression may help identify patients with mixed lineage leukemia–rearranged acute leukemia who are at high risk of relapse after allogeneic hematopoietic stem cell transplantation. Biology of Blood and Marrow Transplantation, 2014, vol. 20, no. 7, pp. 929–936. https://doi.org/10.1016/j.bbmt.2014.03.008
8. Eapen M., Raetz E., Zhang M. J., Muehlenbein C., Devidas M., Abshire T. [et al.]. Outcomes after HLA-matched sibling transplantation or chemotherapy in children with B-precursor acute lymphoblastic leukemia in a second remission: a collaborative study of the Children’s Oncology Group and the Center for International Blood and Marrow Transplant Research. Blood, 2006, vol. 107, no. 12, pp. 4961–4967. https://doi.org/10.1182/blood-2005-12-4942
9. Ceppi F., Duval M., Leclerc J. M., Laverdiere C., Delva Y. L., Cellot S., Teira P., Bittencourt H. Improvement of the outcome of relapsed or refractory acute lymphoblastic leukemia in children using a risk-based treatment strategy. PLoS ONE, 2016, vol. 11, no. 9, p. e0160310. https://doi.org/10.1371/journal.pone.0160310
10. Tomblyn M. B., Arora M., Baker K. S., Blazar B. R., Brunstein C. G., Burns L. J. [et al.]. Myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia: analysis of graft sources and long-term outcome. Journal of Clinical Oncology, 2009, vol. 27, no. 22, pp. 3634–3641. https://doi.org/10.1200/JCO.2008.20.2960
11. Marks D. I., Forman S. J., Blume K. G., Pérez W. S., Weisdorf D. J., Keating A. [et al.]. A comparison of cyclophosphamide and total body irradiation with etoposide and total body irradiation as conditioning regimens for patients undergoing sibling allografting for acute lymphoblastic leukemia in first or second complete remission. Biology of Blood and Marrow Transplantation, 2006, vol. 12, no. 4, pp. 438–453. https://doi.org/10.1016/j.bbmt.2005.12.029
12. Willasch A. M., Salzmann-Manrique E., Krenn T., Duerken M., Faber J., Opper J. [et al.]. Treatment of relapse after allogeneic stem cell transplantation in children and adolescents with ALL: the Frankfurt experience. Bone Marrow Transplantation, 2017, vol. 52, no. 2, pp. 201–208. https://doi.org/10.1038/bmt.2016.224
13. Ceppi F., Cazzaniga G., Colombini A., Biondi A., Conter V. Risk factors for relapse in childhood acute lymphoblastic leukemia: prediction and prevention. Expert Review of Hematology, 2015, vol. 8, no. 1, pp. 57–70. https://doi.org/10.1586/17474086.2015.978281
14. Beck J. C., Cao Q., Trotz B., Smith A. R., Weigel B. J., Verneris M. R., Burke M. J. Allogeneic hematopoietic cell transplantation outcomes for children with B-precursor acute lymphoblastic leukemia and early or late BM relapse. Bone Marrow Transplantation, 2011, vol. 46, no. 7, pp. 950–955. https://doi.org/10.1038/bmt.2010.217
15. Pulsipher M. A., Wayne A. S., Schultz K. R. New frontiers in pediatric Allo-SCT: novel approaches for children and adolescents with ALL. Bone Marrow Transplantation, 2014, vol. 49, no. 10, pp. 1259‒1265. https://doi.org/10.1038/bmt.2014.114
16. Remberger M., Mattsson J., Hentschke P., Aschan J., Barkholt L., Svennilson J., Ljungman P., Ringdén O. The graftversus-leukaemia effect in haematopoietic stem cell transplantation using unrelated donors. Bone Marrow Transplantation, 2002, vol. 30, no. 7, pp. 761–768. https://doi.org/10.1038/sj.bmt.1703735
17. Locatelli F., Zecca M., Rondelli R., Bonetti F., Dini G., Prete A. [et al.]. Graft versus host disease prophylaxis with low-dose cyclosporine-A reduces the risk of relapse in children with acute leukemia given HLA-identical sibling bone marrow transplantation: results of a randomized trial. Blood, 2000, vol. 95, no. 5, pp. 1572‒1579. https://doi.org/10.1182/blood.v95.5.1572.005k12_1572_1579
18. Gustafsson Jernberg A., Remberger M., Ringd’en O., Winiarski J. Graft-versus-leukaemia effect in children: chronic GVHD has a significant impact on relapse and survival. Bone Marrow Transplantation, 2003, vol. 31 (3), pp. 175‒181. https://doi.org/10.1038/sj.bmt.1703808
19. Nakamura R., Auayporn N., Smith D. D., Palmer J., Sun J. Y., Schriber J. [et al.]. Impact of graft cell dose on transplant outcomes following unrelated donor allogeneic peripheral blood stem cell transplantation: Higher CD34+ cell doses are associated with decreased relapse rates. Biology of Blood and Marrow Transplantation, 2008, vol. 14, no. 4, pp. 449–457. https://doi.org/10.1016/j.bbmt.2008.02.005
20. Pulsipher M. A., Chitphakdithai P., Logan B. R., Leitman S. F., Anderlini P., Klein J. P., Horowitz M. M., Miller J. P., King R. J., Confer D. L. Donor, recipient, and transplant characteristics as risk factors after unrelated donor PBSC transplantation: beneficial effects of higher CD34+ cell dose. Blood, 2009, vol. 114, no. 3, pp. 2606–2616. https://doi.org/10.1182/blood-2009-03-208355
21. Kałwak K., Porwolik J., Mielcarek M., Gorczyńska E., Owoc-Lempach J., Ussowicz M. [et al.]. Higher CD34+ and CD3+ cell doses in the graft promote long-term survival, and have no impact on the incidence of severe acute or chronic graft-versus-host disease after in vivo T cell-depleted unrelated donor hematopoietic stem cell transplantation in children. Biology of Blood and Marrow Transplantation, 2010, vol. 16, no. 10, pp. 1388–1401. https://doi.org/10.1016/j.bbmt.2010.04.001
22. Pulsipher M. A., Langholz B., Wall D. A., Schultz K. R., Bunin N., Carroll W. [et al.]. Risk factors and timing of relapse after allogeneic transplantation in Pediatric ALL: for whom and when should interventions be tested? Bone Marrow Transplantation, 2015, vol. 50, no. 9, pp. 1173–1179. https://doi.org/10.1038/bmt.2015.103
23. Bader P., Kreyenberg H., Henze G. H., Eckert C., Reising M., Willasch A. [et al.]. Prognostic value of minimal residual disease quantification before allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia: the ALL-REZ BFM Study Group. Journal of Clinical Oncology, 2009, vol. 27, no. 3, pp. 377–384. https://doi.org/10.1200/JCO.2008.17.6065
24. Athale U. H., Gibson P. J., Bradley N. M., Malkin D. M., Hitzler J. Minimal residual disease and childhood leukemia: standard of care recommendations from the Pediatric Oncology Group of Ontario MRD Working Group. Pediatric Blood and Cancer, 2016, vol. 63, no. 6, pp. 973–982. https://doi.org/10.1002/pbc.25939
25. Willasch A. M., Peters C., Sedláček P., Dalle J. H., Kitra-Roussou V., Yesilipek A. [et al.]. Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy? ‒ A multicenter EBMT-PDWP study. Bone Marrow Transplantation, 2020, vol. 55, no. 8, pp. 1540–1551. https://doi.org/10.1038/s41409-020-0854-0
26. Bresters D., Lawitschka A., Cugno C., Pötschger U., Dalissier A., Michel G. [et al.]. Incidence and severity of crucial late effects after allogeneic HSCT for malignancy under the age of 3 years: TBI is what really matters. Bone Marrow Transplantation, 2016, vol. 51, no. 11, pp. 1482–1489. https://doi.org/10.1038/bmt.2016.139
27. Dalle J.-H., Lucchini G., Balduzzi A., Ifversen M., Jahnukainen K., Macklon K. T. [et al.]. State-of the-art fertility preservation in children and adolescents undergoing haematopoietic stem cell transplantation: a report on the expert meeting of the Paediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) in Baden, Austria, 29‒30 September 2015. Bone Marrow Transplantation, 2017, vol. 52, no. 7, pp. 1029–1035. https://doi.org/10.1038/bmt.2017.21
28. Pfeiffer M. M., Feuchtinger T., Teltschik H. M., Schumm M., Müller I., Handgretinger R., Lang P. 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, 2010, vol. 95, no. 8, pp. 1381‒1388. https://doi.org/10.3324/haematol.2009.021121
29. Farag S. S., Bacigalupo A., Eapen M., Hurley C., Dupont B., Caligiuri M. A. [et al.]. The effect of KIR ligand incompatibility on the outcome of unrelated donor transplantation: a report from the center for international blood and marrow transplant research, the European blood and marrow transplant registry, and the Dutch registry. Biology of Blood and Marrow Transplantation, 2006, vol. 12, no. 8, pp. 876–884. https://doi.org/10.1016/j.bbmt.2006.05.007
Review
For citations:
Prudnikau D.V., Kirsanava N.P., Mareika Yu.E., Minakovskaya N.V., Aleinikova O.V. Relapse risk factors during allogeneic stem cell transplantation in children, adolescents and young adults with acute lymphoblastic leukemia. Proceedings of the National Academy of Sciences of Belarus, Medical series. 2021;18(3):375-384. (In Russ.) https://doi.org/10.29235/1814-6023-2021-18-3-375-384
Views: 539
Email this article 