THE EFFICACY OF HIGH-DOSE CONSOLIDATION AND AUTOLOGOUS BONE MARROW TRANSPLANTATION IN FIRST REMISSION OF ACUTE MYELOID LEUKEMIA

Introduction. The question of the most adequate treatment strategy of AML in cases when it is impossible to perform allogeneic HSCT because of any reason still remains open.

The aim of this study was to assess the long-term survival of patients with AML who received chemotherapy (CT) or autologous HSCT as consolidation in the first remission of the disease. It was included 135 patients aged 18 to 67 years, with a verified diagnosis of AML (except FAB M3) in the study. Of these, 100 patients received only CT, 35 patients received consolidation with autologous bone marrow transplantation. Patients who achieved remission after completion of induction CT courses received one of three treatment options as consolidation: 1) chemotherapy of standard-intensity (sCT), 2) high-dose chemotherapy (HDCT), 3) autologous HSCT (autoHSCT) conducted after 1–2 courses of high-dose CT. Adverse prognostic factors were identified as: age over 40 years, hyperleucocytosis more than 50,0 × 10 9/L and unfavorable cytogenetic and molecular-biological risk group.

Materials and methods. Depending on the number of prognostic factors at the onset of disease relapse-free survival (RFS) was 47 % in their absence, 45 % in the presence of 1 factor, in the presence of 2 factors – 14 % (p = 0,000), regardless of the variant of consolidation therapy (sCT, HDCT, autoHSCT). A high level of white blood cells adversely affects OS (38 % vs. 22 %) and increases the frequency of relapse (52 % vs. 69 %) when performing only CT (sCT and HDCT). At initial white blood cells level more than 50,0 × 10 9/L the 5-year OS was 60 % when performing both autoHSCT and HDCT. Performance of autoHSCT at failure to achieve remission after the 1st induction course CT is associated with the best 2-year OS (62 % vs. 35 %, p = 0,05), EFS (50 % vs. 22 %, p = 0,05) and RFS (50 % vs. 37 %, p = 0,05) in comparison with HDCT and sCT. In favorable cytogenetic risk group 5-year RFS was 80 % when performing autoHSCT and 67 % when performing HDCT; the 5-year OS was 80 % regardless of consolidation therapy option.

Conclusion. AutoHSCT is the preferred consolidation option in favorable risk group patients, and after failure to achieve remission after the 1st CT course.

1. Bondarenko S. N., Moiseev I. S., Samorodova I. A. et al. Comparison of chemotherapy and allogeneic hematopoietic stem cells transplantation efficacy in first remission of acute myeloid leukemia in adults. Uchenye zapiski SPbGMU im. Akad. I. P. Pavlova = The Scientific Notes of the I. P. Pavlov St. Petersburg State Medical University 2015, XXII(3);66–72 (In Russ.). DOI: 10.24884/1607‑4181‑2015‑22‑3‑66‑80.

2. Cornelissen J. J., van Putten W. L.J., Verdonck L. F. et al. Results of a HOVON/ SAKK donor versus no-donor analysis of myeloablative HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom? Blood 2007;109:3658–66. DOI: 10.1182/blood-2006‑06‑025627. PMID: 17213292.

3. Afanasiev B. V., Zubarovskaya L. S., Semenova E. V. et al. The experience of allogeneic unrelated hematopoietic stem cells transplantation in the bone marrow transplantation clinic of Pavlov First St. Petersburg State Medical University. Terapevticheskiy arkhiv = Therapeutic archive 2007;79(7):36–43 (In Russ.).

4. Cornelissen J. J., Gratwohl A., Schlenk R. F. et al. The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated_risk adapted approach. Nat Rev Clin Oncol 2012;9(10):579–90. DOI: 10.1038/nrclinonc.2012.150. PMID: 22949046.

5. Suciu S., Mandelli F., de Witte T. et al. Allogeneic compared with autologous stem cell transplantation in the treatment of patients younger than 46 years with acute myeloid leukemia (AML) in first complete remission (CR1): an intention-to-treat analysis of the EORTC/GIMEMAAML-10 trial. Blood 2003;102(4):1232–40. DOI 10.1182/blood-2002‑12‑3714. PMID: 12714526.

6. Mohty M. The EBMT Handbook 2012, Ch. 19, pp. 317–27.

7. Sureda A., Bader P., Cesaro S. et al. Indications for alloand auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe. Bone Marrow Transplantation 2015;50(8):1037–56. DOI: 10.1038/bmt.2015.6. PMID: 25798672.

8. Melkova K. N., Petrova G. D. Materials of the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation (April, 2016, Valencia). Klinicheskaya onkogematologiya = Clinical Oncohematology 2016;9(4):485–93 (In Russ.).

9. Cornelissen J. J., Blaise D. Hematopoietic stem cell transplantation for patients with AML in first remission. Blood 2016;127(1):62–70. DOI: 10.1182/blood-2015‑07‑604546. PMID: 26660427.

10. Breems D. A., Lowenberg B. Autologous stem cell transplantation in the treatment of adults with acute myeloid leukaemia. British Journal of Haematology 2005;130:825–33.

11. DOI:10.1111/j.1365-2141.2005.05628.x. PMID: 16156852.

12. Varaldo R., Frassoni F. The EBMT Handbook, 2008, pp. 357–70.

13. Proceedings of the European Bone Marrow Transplantation Conference (EBMT), 2008. Klinicheskaya onkogematologiya = Clinical oncohematology 2008;1(2):183–5 (In Russ.).

14. Savchenko V. G., Parovichnikova E. N., Afanasiev B. V. et al. National clinical guidelines for the diagnosis and treatment of AML in adults. Gematologiya i transfuziologiya = Hematology and Transfusiology 2014;59(S2):2–29 (In Russ.).

15. Savchenko V. G., Parovichnikova E. N., Afanasiev B. V. et al. Russian experts’ clinical guidelines for acute myeloid leukemia treatment in patients less than 60 years of age. Terapevticheskiy arkhiv = Therapeutic archive 2014;86(7):4–13 (In Russ.).

16. Sekeres M., Elson P., Kalaycio M. E. et al. Time from diagnosis to treatment initiation predicts survival in younger, but not older, acute myeloid leukemia patients. Blood 2009;113(1):28–36. DOI: 10.1182/blood-2008‑05‑157065. PMID: 18827183.

17. Bertoli S., Berard E., Huguet F. et al. Time from diagnosis to intensive chemotherapy initiation does not adversely impact the outcome of patients with acute myeloid leukemia. Blood 2013;121(14):2618–26. DOI: 10.1182/blood-2012‑09‑454553 PMID: 23365464.

18. Buchner T., Hiddemann W., Berdel W. E. et al. 6-Thioguanine, cytarabine, and daunorubicin (TAD) and high-dose cytarabine and mitoxantrone (HAM) for induction, TAD for consolidation, and either prolonged maintenance by reduced monthly TAD or TAD-HAM-TAD and one course of intensive consolidation by sequential HAM in adult patients at all ages with de novo acute myeloid leukemia(AML): a randomized trial of the German AML Cooperative Group. J Clin Oncol 2003;21(24):4496–504. DOI: 10.1200/JCO.2003.02.133. PMID: 14673036.

19. Parovichnikova E. N., Troitskaya V. V., Klyasova G. A. et al. Clinical protocol AML-01.10 on the treatment of acute myeloid leukemia in adults. In: Program treatment of blood diseases. V.G. Savchenko (ed.). Moscow: Praktika, 2012. P. 153–206 (In Russ.).

20. Bloomfield С. D., Lawrence D., Byrd J. C. et al. Frequency of Prolonged Remission Duration after High-Dose Cytarabine Intensification in Acute Myeloid Leukemia Varies by Cytogenetic Subtype. Cancer Research 1998;58(18):4173–79. PMID: 9751631.