HAPLOIDENTICAL TRANSPLANT WITH POST-TRANSPLANT CYCLOPHOSPHAMIDE FOR ACUTE MYELOID LEUKAEMIA AND MYELODYSPLASTIC SYNDROMES PATIENTS: THE ROLE OF PREVIOUS LINES OF THERAPY.

Main Article Content

Daniele Avenoso
Fabio Serpenti
Liron Barnea Slonim
Styliani Bouziana
Francesco Dazzi
Guy Hannah
Michelle Kenyon
Varun Mehra
Austin Kulasekararaj
Pramila Krishnamurthy
Mili Naresh Shah
Sharon Lionel
Antonio Pagliuca
Victoria Potter

Keywords

Haplo-identical stem cell transplantation, AML, MDS

Abstract

Background: Allogeneic haematopoietic stem-cell transplant is a potentially curative option for high-risk acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) patients. Post-transplant cyclophosphamide administration allows for selection of haploidentical donors in patients who are eligible for the procedure, but do not have a fully matched donor, since it can overcome the HLA barrier. There is still an active debate on whether intensification of the conditioning regimen is necessary with haploidentical donors when peripheral blood stem cells are used as the source of the graft.  


Herein we report our decennial experience of haploidentical stem-cell transplant using peripheral blood stem cells at King’s College Hospital.


Objectives: The primary objective was to evaluate overall survival (OS) for patients with less than two previous lines of therapy. Secondary objectives were total OS, OS according to cytomegalovirus (CMV) reactivation, incidence of transplant-related mortality (TRM), graft-versus-host disease (GVHD) and GVHD-relapse-free survival (GRFS).


Results: One-year and three-year total OS were 62% and 43%, respectively, with a median OS of 22 months. One-year and three-year OS for patients with ≤2 and in patients with >2 previous lines of therapy were 72% and 55%, and 60% and 22%, respectively (p-value=0.04). The median OS in patients with >2 previous lines of therapy and ≤2 lines of therapy was 16 and 49 months, respectively. Cumulative incidence (CI) of relapse was 25% with a median time to relapse of 5 months (range 1 – 38 months).


Conclusions: Haploidentical haematopoietic stem-cell transplant is potentially curative in chemo-sensitive AML and MDS and offers a high rate of prolonged remission. Our cohort further confirms the role of consolidative haploidentical transplant in patients in complete remission and highlights that patients with heavily pre-treated disease may not benefit from this strategy.


 

Downloads

Download data is not yet available.


Abstract 563
PDF Downloads 362
HTML Downloads 47

References

1. Sweeney, C. & Vyas, P. The Graft-Versus-Leukemia Effect in AML. Front. Oncol. 9, 1217 (2019).
2. Döhner, H. et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood 140, 1345–1377 (2022).
3. Nagler, A. & Mohty, M. In 2022, which is preferred: haploidentical or cord transplant? Hematology 2022, 64–73 (2022).
4. Milano, F. et al. Cord-Blood Transplantation in Patients with Minimal Residual Disease. N. Engl. J. Med. 375, 944–953 (2016).
5. Luznik, L. et al. HLA-Haploidentical Bone Marrow Transplantation for Hematologic Malignancies Using Nonmyeloablative Conditioning and High-Dose, Posttransplantation Cyclophosphamide. Biol. Blood Marrow Transplant. 14, 641–650 (2008).
6. Ruggeri, A. et al. Bone marrow versus mobilized peripheral blood stem cells in haploidentical transplants using posttransplantation cyclophosphamide. Cancer 124, 1428–1437 (2018).
7. Castagna, L. et al. Bone Marrow Compared with Peripheral Blood Stem Cells for Haploidentical Transplantation with a Nonmyeloablative Conditioning Regimen and Post-transplantation Cyclophosphamide. (2014) doi:10.1016/j.bbmt.2014.02.001.
8. O’Donnell, P. V. et al. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol. Blood Marrow Transplant. J. Am. Soc. Blood Marrow Transplant. 8, 377–86 (2002).
9. Raiola, A. M. et al. Unmanipulated Haploidentical Bone Marrow Transplantation and Posttransplantation Cyclophosphamide for Hematologic Malignancies after Myeloablative Conditioning. Biol. Blood Marrow Transplant. 19, 117–122 (2013).
10. Solomon, S. R. et al. Haploidentical transplantation using T cell replete peripheral blood stem cells and myeloablative conditioning in patients with high-risk hematologic malignancies who lack conventional donors is well tolerated and produces excellent relapse-free survival: results of a prospective phase II trial. Biol. Blood Marrow Transplant. J. Am. Soc. Blood Marrow Transplant. 18, 1859–1866 (2012).
11. Sammassimo, S. A Cellular Therapy with Haploidentical Peripheral Hematopoietic STEM CELL Transplantation MAY be a Therapeutic Option in Patients with Relapsed Lymphoma with Chemorefractory Disease. (2018).
12. Ciurea, S. O. et al. Improved early outcomes using a T cell replete graft compared with T cell depleted haploidentical hematopoietic stem cell transplantation. Biol. Blood Marrow Transplant. J. Am. Soc. Blood Marrow Transplant. 18, 1835–1844 (2012).
13. Piemontese, S. et al. A survey on unmanipulated haploidentical hematopoietic stem cell transplantation in adults with acute leukemia. Leukemia 29, 1069–1075 (2015).
14. Rashidi, A. et al. Outcomes of haploidentical vs matched sibling transplantation for acute myeloid leukemia in first complete remission. Blood Adv. 3, 1826–1836 (2019).
15. Khoury, J. D. et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia 36, 1703–1719 (2022).
16. Armand, P. et al. Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation. Blood 123, 3664–3671 (2014).
17. Blouin, A. G., Ye, F., Williams, J. & Askar, M. A Practical Guide To Chimerism Analysis: Review of The Literature and Testing Practices Worldwide. Hum. Immunol. 82, 838–849 (2021).
18. Toubai, T., Sun, Y. & Reddy, P. GVHD pathophysiology: is acute different from chronic? Best Pract. Res. Clin. Haematol. 21, 101–117 (2008).
19. Appelbaum, F. R. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia when a matched related donor is not available. Hematol. Am. Soc. Hematol. Educ. Program 412–417 (2008) doi:10.1182/asheducation-2008.1.412.
20. McCurdy, S. R. & Fuchs, E. J. Selecting the best haploidentical donor. Semin. Hematol. 53, 246–251 (2016).
21. Devillier, R. et al. Reduced intensity versus non-myeloablative conditioning regimen for haploidentical transplantation and post-transplantation cyclophosphamide in complete remission acute myeloid leukemia: a study from the ALWP of the EBMT. Bone Marrow Transplant. 57, 1421–1427 (2022).
22. Fuchs, E. J. et al. Double unrelated umbilical cord blood vs HLA-haploidentical bone marrow transplantation: the BMT CTN 1101 trial. Blood 137, 420–428 (2021).