Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Acute Leukemia

T-replete haploidentical allogeneic transplantation using post-transplantation cyclophosphamide in advanced AML and myelodysplastic syndromes

Bone Marrow Transplantation volume 51, pages 194–198 (2016)Cite this article

Subjects

Abstract

Unmanipulated haploidentical transplantation (Haplo-SCT) using post-transplantation cyclophosphamide (PT-Cy) represents an alternative for patients with high-risk diseases lacking HLA-identical donor. Although it provides low incidences of GVHD, the efficacy of Haplo-SCT is still questioned, especially for patients with myeloid malignancies. Thus, we analyzed 60 consecutive patients with refractory (n=30) or high-risk CR (n=30) AML or myelodysplastic syndromes (MDSs) who underwent PT-Cy Haplo-SCT. The median age was 57 years (22–73 years), hematopoietic cell transplantation comorbidity index was ⩾3 in 38 patients (63%) and Haplo-SCT was the second allogeneic transplantation for 10 patients (17%). Although most of patients received PBSC as graft source (n=48, 80%), we found low incidences of grade 3–4 acute (2%) and severe chronic GVHD (4%). Among patients with high-risk CR diseases, 1-year non-relapse mortality, cumulative incidence of relapse, progression-free and overall survivals were 20%, 32%, 47% and 62%, respectively. In patients with refractory disease, corresponding results were 34%, 35%, 32% and 37%, respectively. We conclude that PT-Cy Haplo-SCT could provide promising anti-leukemic effect even in the setting of very advanced diseases. Thus, it represents a viable alternative for high-risk AML/MDS patients without HLA-identical donor.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Luznik L, O’Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant 2008; 14: 641–650.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bashey A, Zhang X, Sizemore CA, Manion K, Brown S, Holland HK et al. T-cell-replete HLA-haploidentical hematopoietic transplantation for hematologic malignancies using post-transplantation cyclophosphamide results in outcomes equivalent to those of contemporaneous HLA-matched related and unrelated donor transplantation. J Clin Oncol 2013; 31: 1310–1316.

    Article  CAS  PubMed  Google Scholar 

  3. Brunstein CG, Fuchs EJ, Carter SL, Karanes C, Costa LJ, Wu J et al. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood 2011; 118: 282–288.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Raiola A, Dominietto A, Varaldo R, Ghiso A, Galaverna F, Bramanti S et al. Unmanipulated haploidentical BMT following non-myeloablative conditioning and post-transplantation CY for advanced Hodgkin’s lymphoma. Bone Marrow Transplant 2014; 49: 190–194.

    Article  CAS  PubMed  Google Scholar 

  5. Garciaz S, Castagna L, Bouabdallah R, Fürst S, Bramanti S, Coso D et al. Familial haploidentical challenging unrelated donor Allo-SCT in advanced non-Hodgkin lymphomas when matched related donor is not available. Bone Marrow Transplant 2015; 50: 865–867.

    Article  CAS  PubMed  Google Scholar 

  6. Burroughs LM, O’Donnell PV, Sandmaier BM, Storer BE, Luznik L, Symons HJ et al. Comparison of outcomes of HLA-matched related, unrelated, or HLA-haploidentical related hematopoietic cell transplantation following nonmyeloablative conditioning for relapsed or refractory Hodgkin lymphoma. Biol Blood Marrow Transplant 2008; 14: 1279–1287.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010; 115: 453–474.

    Article  PubMed  Google Scholar 

  8. Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood 2012; 120: 2454–2465.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Prentice RL, Kalbfleisch JD, Peterson AV, Flournoy N, Farewell VT, Breslow NE . The analysis of failure times in the presence of competing risks. Biometrics 1978; 34: 541–554.

    Article  CAS  PubMed  Google Scholar 

  10. Gray RJ . A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Statist 1988; 16: 1141–1154.

    Article  Google Scholar 

  11. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  PubMed  Google Scholar 

  12. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11: 945–956.

    PubMed  Google Scholar 

  13. Kaplan E, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  14. Devillier R, Crocchiolo R, Castagna L, Fürst S, Cheikh JEl, Faucher C et al. The increase from 2.5 to 5 mg/kg of rabbit anti-thymocyte-globulin dose in reduced intensity conditioning reduces acute and chronic GVHD for patients with myeloid malignancies undergoing allo-SCT. Bone Marrow Transplant 2012; 47: 639–645.

    Article  CAS  PubMed  Google Scholar 

  15. Holtan SG, DeFor TE, Lazaryan A, Bejanyan N, Arora M, Brunstein CG et al. Composite endpoint of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood 2015; 125: 133–138.

    Article  Google Scholar 

  16. Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 2005; 106: 2912–2919.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Castagna L, Crocchiolo R, Furst S, Bramanti S, Cheikh JEl, Sarina B et al. Bone marrow compared with peripheral blood stem cells for haploidentical transplantation with a nonmyeloablative conditioning regimen and post-transplantation cyclophosphamide. Biol Blood Marrow Transplant 2014; 20: 724–729.

    Article  PubMed  Google Scholar 

  18. Schmid C, Schleuning M, Ledderose G, Tischer J, Kolb H-J . Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol 2005; 23: 5675–5687.

    Article  PubMed  Google Scholar 

  19. Krejci M, Doubek M, Dusek J, Brychtova Y, Racil Z, Navratil M et al. Combination of fludarabine, amsacrine, and cytarabine followed by reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia. Ann Hematol 2013; 92: 1397–1403.

    Article  CAS  PubMed  Google Scholar 

  20. Kanakry CG, O’Donnell PV, Furlong T, de Lima MJ, Wei W, Medeot M et al. Multi-institutional study of post-transplantation cyclophosphamide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning. J Clin Oncol 2014; 32: 3497–3505.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kanakry CG, Tsai H-L, Bolaños-Meade J, Smith BD, Gojo I, Kanakry JA et al. Single-agent GVHD prophylaxis with posttransplantation cyclophosphamide after myeloablative, HLA-matched BMT for AML, ALL, and MDS. Blood 2014; 124: 3817–3827.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Roberto A, Castagna L, Zanon V, Bramanti S, Crocchiolo R, McLaren JE et al. Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation. Blood 2015; 125: 2855–2864.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Noviello M, Forcina A, Veronica V, Crocchiolo R, Stanghellini MTL, Carrabba M et al. Early recovery of CMV immunity after HLA-haploidentical hematopoietic stem cell transplantation as a surrogate biomarker for a reduced risk of severe infections overall. Bone Marrow Transplant 2015; 50: 1262–1264.

    Article  CAS  PubMed  Google Scholar 

  24. Oudin C, Chevallier P, Furst S, Guillaume T, Cheikh JEl, Delaunay J et al. Reduced-toxicity conditioning prior to allogeneic stem cell transplantation improves outcome in patients with myeloid malignancies. Haematologica 2014; 99: 1762–1768.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Raiola AM, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F et al. Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning. Biol Blood Marrow Transplant 2013; 19: 117–122.

    Article  CAS  PubMed  Google Scholar 

  26. Di Stasi A, Milton DR, Poon LM, Hamdi A, Rondon G, Chen J et al. Similar transplantation outcomes for acute myeloid leukemia and myelodysplastic syndrome patients with haploidentical versus 10/10 human leukocyte antigen-matched unrelated and related donors. Biol Blood Marrow Transplant 2014; 20: 1975–1981.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Tischer J, Stemmler HJ, Engel N, Hubmann M, Fritsch S, Prevalsek D et al. Feasibility of clofarabine cytoreduction followed by haploidentical hematopoietic stem cell transplantation in patients with relapsed or refractory advanced acute leukemia. Ann Hematol 2013; 92: 1379–1388.

    Article  CAS  PubMed  Google Scholar 

  28. Bacigalupo A, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F et al. Unmanipulated haploidentical bone marrow transplantation and post-transplant cyclophosphamide for hematologic malignanices following a myeloablative conditioning: an update. Bone Marrow Transplant 2015; 50: S37–S39.

    Article  CAS  PubMed  Google Scholar 

  29. Ciurea SO, Zhang M-J, Bacigalupo AA, Bashey A, Appelbaum FR, Aljitawi OS et al. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. Blood 2015; 126: 1033–1040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ciurea SO, Saliba R, Rondon G, Pesoa S, Cano P, Fernandez-Vina M et al. Reduced-intensity conditioning using fludarabine, melphalan and thiotepa for adult patients undergoing haploidentical SCT. Bone Marrow Transplant 2010; 45: 429–436.

    Article  CAS  PubMed  Google Scholar 

  31. Wang Y, Liu D-H, Liu K-Y, Xu L-P, Zhang X-H, Han W et al. Long-term follow-up of haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of leukemia: nine years of experience at a single center. Cancer 2013; 119: 978–985.

    Article  PubMed  Google Scholar 

  32. Wang Y, Liu D-H, Liu K-Y, Xu L-P, Zhang X-H, Han W et al. Impact of pretransplantation risk factors on post transplantation outcome of patients with acute myeloid leukemia in remission after haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2013; 19: 283–290.

    Article  PubMed  Google Scholar 

  33. Yahng S-A, Kim J-H, Jeon Y-W, Yoon J-H, Shin S-H, Lee S-E et al. A well-tolerated regimen of 800cGy TBI-fludarabine-busulfan-ATG for reliable engraftment after unmanipulated haploidentical peripheral blood stem cell transplantation in adult patients with acute myeloid leukemia. Biol Blood Marrow Transplant 2015; 21: 119–129.

    Article  CAS  PubMed  Google Scholar 

  34. Shin S-H, Kim J-H, Jeon Y-W, Yoon J-H, Yahng S-A, Lee S-E et al. Feasible outcomes of T cell-replete haploidentical stem cell transplantation with reduced-intensity conditioning in patients with myelodysplastic syndrome. Biol Blood Marrow Transplant 2015; 21: 342–349.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the nursing staff for providing excellent care for our patients and the ‘Association pour la Recherche contre le Cancer’.

Author information

Author notes

  1. R Devillier, S Bramanti, L Castagna and D Blaise: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, Institut Paoli Calmettes, Marseille, France

    R Devillier, S Fürst, J El-Cheikh, A Granata, S Harbi, C Faucher, P-J Weiller, N Vey & D Blaise

  2. Aix-Marseille University, Medicine Faculty, Marseille, France

    R Devillier, C Chabannon, P-J Weiller, N Vey & D Blaise

  3. Department of Hematology, Humanitas Cancer Center, Rozzano, Italy

    S Bramanti, B Sarina, R Crocchiolo, L Morabito, A Santoro, C Carlo-Stella & L Castagna

  4. Cell Therapy Facility, Institut Paoli Calmettes, Marseille, France

    C Chabannon

Authors
  1. R Devillier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S Bramanti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Fürst
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B Sarina
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J El-Cheikh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R Crocchiolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A Granata
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C Chabannon
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. L Morabito
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. S Harbi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. C Faucher
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A Santoro
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. P-J Weiller
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. N Vey
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. C Carlo-Stella
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. L Castagna
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. D Blaise
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D Blaise.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on Bone Marrow Transplantation website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Devillier, R., Bramanti, S., Fürst, S. et al. T-replete haploidentical allogeneic transplantation using post-transplantation cyclophosphamide in advanced AML and myelodysplastic syndromes. Bone Marrow Transplant 51, 194–198 (2016). https://doi.org/10.1038/bmt.2015.270

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2015.270

This article is cited by

Search

Advanced search

Quick links