Skip to main content
Log in

Impact of gemtuzumab ozogamicin consolidation on hematopoietic stem cells (HSCs) mobilization in AML: analysis of 20 patients

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Gemtuzumab ozogamicin (GO), is an anti-CD33 monoclonal antibody, approved for AML CD33 + , those patients with low and intermediate-risk who obtain a complete response may also be candidated for consolidation with autologous stem cell transplantation (ASCT). However, there are scant data on the mobilization of hemopoietic stem cells (HSC) after fractionated GO. We retrospectively studied data from five Italian centers and identified 20 patients (median age 54 years, range 29–69, 15 female, 15 NPM1mutated) that attempted HSC mobilization after fractionated doses of GO + “7 + 3” regimen and 1–2 cycles of consolidation (GO + HDAC + daunorubicin). After chemotherapy and standard G-CSF, 11/20 patients (55%) reached the threshold of 20 CD34 + /µL, and HSC were successfully harvested, while 9 patients (45%) failed. The median day of apheresis was Day + 26 from the start of chemotherapy (range 22–39 days). In good mobilizer patients, the median circulating CD34 + cells were 35.9 cells/µL and the median CD34 + harvested were 4.65 × 106/kg of patients’ body weight. With a median follow-up of 12.7 months, at 24 months from the first diagnosis, 93.3% of all 20 patients were alive and the median overall survival was 25 months. The 2-year RFS rate from the timepoint of the first CR was 72.6%, while the median RFS was not reached. However, only five patients underwent ASCT and achieved full engraftment.

In conclusion, in our cohort of patients, the addition of GO reduced HSC mobilization and harvesting, which was reached in about 55% of patients. Nevertheless, further studies are warranted to evaluate the effects of fractionated doses of GO on HSC mobilization and ASCT outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

Anonymized data not published within this article will be made available by request from any qualified investigator.

References

  1. Molica M, Perrone S, Mazzone C et al (2021) Cd33 expression and gentuzumab ozogamicin in acute myeloid leukemia: two sides of the same coin. Cancers (Basel) 13:3214

    Article  CAS  PubMed  Google Scholar 

  2. Weigert N, Rowe JM, Lazarus HM, Salman MY (2022) Consolidation in AML: abundant opinion and much unknown. Blood Rev 51:100873. https://doi.org/10.1016/j.blre.2021.100873

  3. Heuser M, Ofran Y, Boissel N et al (2020) Acute myeloid leukaemia in adult patients: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 31:697–712. https://doi.org/10.1016/j.annonc.2020.02.018

    Article  CAS  PubMed  Google Scholar 

  4. Kapp-Schwoerer S, Weber D, Corbacioglu A et al (2020) Impact of gemtuzumab ozogamicin on MRD and relapse risk in patients with NPM1-mutated AML: results from the AMLSG 09–09 trial. Blood 136:3041–3050. https://doi.org/10.1182/blood.2020005998

    Article  CAS  PubMed  Google Scholar 

  5. Jawad M, Seedhouse C, Mony U et al (2010) Analysis of factors that affect in vitro chemosensitivity of leukaemic stem and progenitor cells to gemtuzumab ozogamicin (Mylotarg) in acute myeloid leukaemia. Leukemia 24:74–80. https://doi.org/10.1038/leu.2009.199

    Article  CAS  PubMed  Google Scholar 

  6. Lambert J, Pautas C, Terré C et al (2019) Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica 104:113–119. https://doi.org/10.3324/haematol.2018.188888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Yamashita M, Dellorusso PV, Olson OC, Passegué E (2020) Dysregulated haematopoietic stem cell behaviour in myeloid leukaemogenesis. Nat Rev Cancer 20:365–382. https://doi.org/10.1038/s41568-020-0260-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. EMA EPAR - Summary for mylotarg - epar product information public. https://www.ema.europa.eu/en/documents/product-information/mylotarg-epar-product-information_en.pdf. Accessed 17 Oct 2020

  9. Castaigne S, Pautas C, Terré C et al (2012) Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet 379:1508–1516. https://doi.org/10.1016/S0140-6736(12)60485-1

    Article  CAS  Google Scholar 

  10. Döhner H, Estey E, Grimwade D et al (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129:424–447. https://doi.org/10.1182/blood-2016-08-733196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Muta T, Kato K, Oku S et al (2007) Successful mobilization of peripheral blood stem cells in an acute promyelocytic leukemia patient after gemtuzumab ozogamicin. Bone Marrow Transplant 40:287–288. https://doi.org/10.1038/sj.bmt.1705715

    Article  CAS  PubMed  Google Scholar 

  12. Rosati S, Gurnari C, Breccia M et al (2021) Acute promyelocytic leukemia (APL) in very old patients: real-life behind protocols. Acta Oncol 60:1520–1526. https://doi.org/10.1080/0284186X.2021.1971291

    Article  CAS  PubMed  Google Scholar 

  13. Candoni A, Papayannidis C, Martinelli G et al (2018) Flai (fludarabine, cytarabine, idarubicin) plus low-dose gemtuzumab ozogamicin as induction therapy in CD33-positive AML: final results and long term outcome of a phase II multicenter clinical trial. Am J Hematol 93:655–663. https://doi.org/10.1002/ajh.25057

    Article  CAS  PubMed  Google Scholar 

  14. Eom K-S, Kim H-J, Cho B-S et al (2011) Hematopoietic stem cell transplant following remission induction chemotherapy including gemtuzumab ozogamicin is a feasible and effective treatment option in elderly patients with acute myeloid leukemia. Leuk Lymphoma 52:2321–2328. https://doi.org/10.3109/10428194.2011.587562

    Article  CAS  PubMed  Google Scholar 

  15. Mandelli F, Vignetti M, Suciu S et al (2009) Daunorubicin versus mitoxantrone versus idarubicin as induction and consolidation chemotherapy for adults with acute myeloid leukemia: the EORTC and GIMEMA groups study AML-10. J Clin Oncol 27:5397–5403. https://doi.org/10.1200/JCO.2008.20.6490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Venditti A, Piciocchi A, Candoni A et al (2019) GIMEMA AML1310 trial of risk-adapted, MRD-directed therapy for young adults with newly diagnosed acute myeloid leukemia. Blood 134:935–945. https://doi.org/10.1182/blood.2018886960

    Article  CAS  PubMed  Google Scholar 

  17. Sakashita AM, Kondo AT, Ribeiro AAF et al (2011) Factors affecting autologous peripheral blood hematopoietic stem cell collections by large-volume leukapheresis: a single center experience. Einstein (São Paulo) 9:196–200. https://doi.org/10.1590/s1679-45082011ao1932

    Article  PubMed  Google Scholar 

  18. Capelli D, Chiarucci M, Poloni A et al (2014) Mobilization-driven postconsolidation therapy in elderly patients with acute myeloid leukemia: feasibility and efficacy of autologous stem cell transplantation versus low-dose gemtuzumab ozogamicin. Biol Blood Marrow Transplant 20:1399–1406. https://doi.org/10.1016/j.bbmt.2014.05.019

    Article  CAS  PubMed  Google Scholar 

  19. Blum V, Heini AD, Novak U et al (2017) Hematopoietic stem cell remobilization with vinorelbine and filgrastim in AML. Bone Marrow Transplant 52:786–788

    Article  CAS  PubMed  Google Scholar 

  20. Shumilov E, Novak U, Jeker B, et al (2019) Hematopoietic stem cell mobilization with plerixafor is safe and effective in poorly mobilizing acute myeloid leukemia patients. Hemasphere 3:e176. https://doi.org/10.1097/HS9.0000000000000176

  21. To LB, Levesque J-P, Herbert KE (2011) How I treat patients who mobilize hematopoietic stem cells poorly. Blood 118:4530–4540. https://doi.org/10.1182/blood-2011-06-318220

    Article  CAS  PubMed  Google Scholar 

  22. Bakeer M, Zubair AC, Roy V (2020) Low baseline platelet count predicts poor response to plerixafor in patients with multiple myeloma undergoing autologous stem cell mobilization. Cytotherapy 22:16–20. https://doi.org/10.1016/j.jcyt.2019.10.008

    Article  PubMed  Google Scholar 

  23. Walter RB, Ofran Y, Wierzbowska A et al (2021) Measurable residual disease as a biomarker in acute myeloid leukemia: theoretical and practical considerations. Leukemia 35:1529–1538. https://doi.org/10.1038/s41375-021-01230-4

    Article  PubMed  Google Scholar 

  24. de Benito A de S, Jeker B, Gfeller E, et al (2020) Molecular minimal residual disease negativity and decreased stem cell mobilization potential predict excellent outcome after autologous transplant in NPM1 mutant acute myeloid leukemia. Haematologica 105:e9–e12. https://doi.org/10.3324/haematol.2019.216457

  25. Gorin NC, Labopin M, Reiffers J et al (2010) Higher incidence of relapse in patients with acute myelocytic leukemia infused with higher doses of CD34 + cells from leukapheresis products autografted during the first remission. Blood 116:3157–3162. https://doi.org/10.1182/blood-2009-11-252197

    Article  CAS  PubMed  Google Scholar 

  26. Grubovic RM, Georgievski B, Cevreska L et al (2017) Analysis of factors that influence hematopoietic recovery in autologous transplanted patients with hematopoietic stem cells from peripheral blood. Open Access Maced J Med Sci 5:324–331. https://doi.org/10.3889/oamjms.2017.039

    Article  PubMed  PubMed Central  Google Scholar 

  27. Fernandez HF, Sun Z, Litzow MR et al (2011) Autologous transplantation gives encouraging results for young adults with favorable-risk acute myeloid leukemia, but is not improved with gemtuzumab ozogamicin. Blood 117:5306–5313. https://doi.org/10.1182/blood-2010-09-309229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Passweg JR, Baldomero H, Chabannon C et al (2020) The EBMT activity survey on hematopoietic-cell transplantation and cellular therapy 2018: CAR-T’s come into focus. Bone Marrow Transplant 55:1604–1613. https://doi.org/10.1038/s41409-020-0826-4

    Article  PubMed  PubMed Central  Google Scholar 

  29. Shumilov E, Shakhanova I, Flach J et al (2022) Feasibility and efficacy of salvage allogeneic stem cell transplantation in AML patients relapsing after autologous stem cell transplantation. Bone Marrow Transplant 57:224–231. https://doi.org/10.1038/s41409-021-01521-5

    Article  CAS  PubMed  Google Scholar 

  30. Passweg JR, Labopin M, Christopeit M et al (2020) Postremission consolidation by autologous hematopoietic cell transplantation (HCT) for acute myeloid leukemia in first complete remission (CR) and negative implications for subsequent allogeneic HCT in second CR: a study by the acute leukemia working party of the european society for blood and marrow transplantation (EBMT). Biol Blood Marrow Transplant 26:659–664. https://doi.org/10.1016/j.bbmt.2019.11.021

    Article  CAS  PubMed  Google Scholar 

  31. Ferrara F, Picardi A (2019) Is there still a role for autologous stem cell transplantation for the treatment of acute myeloid leukemia? Cancers (Basel) 12:59. https://doi.org/10.3390/cancers12010059

    Article  CAS  PubMed  Google Scholar 

  32. Capria S, Trisolini SM, Diverio D et al (2022) Autologous stem cell transplantation in favorable-risk acute myeloid leukemia: single-center experience and current challenges. Int J Hematol 116:586–593. https://doi.org/10.1007/s12185-022-03370-4

Download references

Acknowledgements

Paolo Lopedote and Nadezda Zhdanovskaya for critical revising this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Salvatore Perrone.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Perrone, S., Capria, S., Bernardi, M. et al. Impact of gemtuzumab ozogamicin consolidation on hematopoietic stem cells (HSCs) mobilization in AML: analysis of 20 patients. Ann Hematol 102, 769–775 (2023). https://doi.org/10.1007/s00277-023-05129-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-023-05129-1

Keywords

Navigation