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.

Immunology

Sirolimus-based graft-versus-host disease prophylaxis promotes the in vivo expansion of regulatory T cells and permits peripheral blood stem cell transplantation from haploidentical donors

Leukemia volume 29, pages 396–405 (2015)Cite this article

Subjects

Abstract

Hematopoietic stem cell transplantation (HSCT) from human leukocyte antigen (HLA) haploidentical family donors is a promising therapeutic option for high-risk hematologic malignancies. Here we explored in 121 patients, mostly with advanced stage diseases, a sirolimus-based, calcineurin-inhibitor-free prophylaxis of graft-versus-host disease (GvHD) to allow the infusion of unmanipulated peripheral blood stem cell (PBSC) grafts from partially HLA-matched family donors (TrRaMM study, Eudract 2007-5477-54). Conditioning regimen was based on treosulfan and fludarabine, and GvHD prophylaxis on antithymocyte globulin Fresenius (ATG-F), rituximab and oral administration of sirolimus and mycophenolate. Neutrophil and platelet engraftment occurred in median at 17 and 19 days after HSCT, respectively, and full donor chimerism was documented in patients’ bone marrow since the first post-transplant evaluation. T-cell immune reconstitution was rapid, and high frequencies of circulating functional T-regulatory cells (Treg) were documented during sirolimus prophylaxis. Incidence of acute GvHD grade II–IV was 35%, and occurrence and severity correlated negatively with Treg frequency. Chronic GvHD incidence was 47%. At 3 years after HSCT, transpant-related mortality was 31%, relapse incidence 48% and overall survival 25%. In conclusion, GvHD prophylaxis with sirolimus–mycophenolate–ATG-F–rituximab promotes a rapid immune reconstitution skewed toward Tregs, allowing the infusion of unmanipulated haploidentical PBSC grafts.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

References

  1. Copelan EA . Hematopoietic stem-cell transplantation. N Engl J Med 2006; 354: 1813–1826.

    Article  CAS  PubMed  Google Scholar 

  2. Zuckerman T, Rowe JM . Alternative donor transplantation in acute myeloid leukemia: which source and when? Curr Opin Hematol 2007; 14: 152–161.

    Article  PubMed  Google Scholar 

  3. Reisner Y, Hagin D, Martelli MF . Haploidentical hematopoietic transplantation: current status and future perspectives. Blood 2011; 118: 6006–6017.

    Article  CAS  PubMed  Google Scholar 

  4. Beatty PG, Clift RA, Mickelson EM, Nisperos BB, Flournoy N, Martin PJ et al. Marrow transplantation from related donors other than HLA-identical siblings. N Engl J Med 1985; 313: 765–771.

    Article  CAS  PubMed  Google Scholar 

  5. Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med 1998; 339: 1186–1193.

    Article  CAS  PubMed  Google Scholar 

  6. Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S et al. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol 2005; 23: 3447–3454.

    Article  PubMed  Google Scholar 

  7. Kennedy-Nasser AA, Brenner MK . T-cell therapy after hematopoietic stem cell transplantation. Curr Opin Hematol 2007; 14: 616–624.

    Article  PubMed  Google Scholar 

  8. Ciceri F, Bonini C, Stanghellini MT, Bondanza A, Traversari C, Salomoni M et al. Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial): a non-randomised phase I-II study. Lancet Oncol 2009; 10: 489–500.

    Article  PubMed  Google Scholar 

  9. Ciceri F, Labopin M, Aversa F, Rowe JM, Bunjes D, Lewalle P et al. A survey of fully haploidentical hematopoietic stem cell transplantation in adults with high-risk acute leukemia: a risk factor analysis of outcomes for patients in remission at transplantation. Blood 2008; 112: 3574–3581.

    Article  CAS  PubMed  Google Scholar 

  10. 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, post-transplantation cyclophosphamide. Biol Blood Marrow Transplant 2008; 14: 641–650.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. 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 2012; 19: 117–122.

    Article  PubMed  Google Scholar 

  12. Di Bartolomeo P, Santarone S, De Angelis G, Picardi A, Cudillo L, Cerretti R et al. Haploidentical, unmanipulated, G-CSF-primed bone marrow transplantation for patients with high-risk hematologic malignancies. Blood 2013; 121: 849–857.

    Article  CAS  PubMed  Google Scholar 

  13. Appelbaum FR . Pursuing the goal of a donor for everyone in need. N Engl J Med 2012; 367: 1555–1556.

    Article  CAS  PubMed  Google Scholar 

  14. Battaglia M, Stabilini A, Migliavacca B, Horejs-Hoeck J, Kaupper T, Roncarolo MG . Rapamycin promotes expansion of functional CD4+CD25+FOXP3+ regulatory T cells of both healthy subjects and type 1 diabetic patients. J Immunol 2006; 177: 8338–8347.

    Article  CAS  PubMed  Google Scholar 

  15. Sakaguchi S . Regulatory T cells: history and perspective. Methods Mol Biol 2011; 707: 3–17.

    Article  CAS  PubMed  Google Scholar 

  16. Trenado A, Charlotte F, Fisson S, Yagello M, Klatzmann D, Salomon BL et al. Recipient-type specific CD4+CD25+ regulatory T cells favor immune reconstitution and control graft-versus-host disease while maintaining graft-versus-leukemia. J Clin Invest 2003; 112: 1688–1696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Edinger M, Hoffmann P, Ermann J, Drago K, Fathman CG, Strober S et al. CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med 2003; 9: 1144–1150.

    Article  CAS  PubMed  Google Scholar 

  18. Kanakry CG, Ganguly S, Zahurak M, Bolanos-Meade J, Thoburn C, Perkins B et al. Aldehyde dehydrogenase expression drives human regulatory T cell resistance to post-transplantation cyclophosphamide. Sci Transl Med 2013; 5: 211ra157.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Brunstein CG, Miller JS, Cao Q, McKenna DH, Hippen KL, Curtsinger J et al. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood 2011; 117: 1061–1070.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Di Ianni M, Falzetti F, Carotti A, Terenzi A, Castellino F, Bonifacio E et al. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood 2011; 117: 3921–3928.

    Article  CAS  PubMed  Google Scholar 

  21. Teachey DT, Grupp SA, Brown VI . Mammalian target of rapamycin inhibitors and their potential role in therapy in leukaemia and other haematological malignancies. Br J Haematol 2009; 145: 569–580.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. von Reyn Cream L, Ehmann WC, Rybka WB, Claxton DF . Sirolimus in unmanipulated haploidentical cell transplantation. Bone Marrow Transplant 2008; 42: 765–766.

    Article  CAS  PubMed  Google Scholar 

  23. Armand P, Gibson CJ, Cutler C, Ho VT, Koreth J, Alyea EP et al. A disease risk index for patients undergoing allogeneic stem cell transplantation. Blood 2012; 120: 905–913.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. 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 

  25. Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 2002; 295: 2097–2100.

    Article  CAS  PubMed  Google Scholar 

  26. Mazzi B, Clerici TD, Zanussi M, Lupo Stanghellini MT, Vago L, Sironi E et al. Genomic typing for patient-specific human leukocyte antigen-alleles is an efficient tool for relapse detection of high-risk hematopoietic malignancies after stem cell transplantation from alternative donors. Leukemia 2008; 22: 2119–2122.

    Article  CAS  PubMed  Google Scholar 

  27. Sacre K, Carcelain G, Cassoux N, Fillet AM, Costagliola D, Vittecoq D et al. Repertoire, diversity, and differentiation of specific CD8 T cells are associated with immune protection against human cytomegalovirus disease. J Exp Med 2005; 201: 1999–2010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wieczorek G, Asemissen A, Model F, Turbachova I, Floess S, Liebenberg V et al. Quantitative DNA methylation analysis of FOXP3 as a new method for counting regulatory T cells in peripheral blood and solid tissue. Cancer Res 2009; 69: 599–608.

    Article  CAS  PubMed  Google Scholar 

  29. Apperley J, Carreras E, Gluckman E, Masszi T . ESH-EBMT Handbook on Haematopoietic Stem Cell Transplantation. Forum Service Editore: Genova, Italy, 2012.

    Google Scholar 

  30. Gooley TA, Leisenring W, Crowley J, Storer BE . Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Statist Med 1999; 18: 695–706.

    Article  CAS  Google Scholar 

  31. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18: 295–304.

    Article  CAS  PubMed  Google Scholar 

  32. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980; 69: 204–217.

    Article  CAS  PubMed  Google Scholar 

  33. Pavletic SZ, Kumar S, Mohty M, de Lima M, Foran JM, Pasquini M et al. NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: report from the Committee on the Epidemiology and Natural History of Relapse following Allogeneic Cell Transplantation. Biol Blood Marrow Transplant 2010; 16: 871–890.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Vago L, Perna SK, Zanussi M, Mazzi B, Barlassina C, Stanghellini MT et al. Loss of mismatched HLA in leukemia after stem-cell transplantation. N Engl J Med 2009; 361: 478–488.

    Article  CAS  PubMed  Google Scholar 

  35. Vago L, Forno B, Sormani MP, Crocchiolo R, Zino E, Di Terlizzi S et al. Temporal, quantitative, and functional characteristics of single-KIR-positive alloreactive natural killer cell recovery account for impaired graft-versus-leukemia activity after haploidentical hematopoietic stem cell transplantation. Blood 2008; 112: 3488–3499.

    Article  CAS  PubMed  Google Scholar 

  36. Elmaagacli AH, Steckel NK, Koldehoff M, Hegerfeldt Y, Trenschel R, Ditschkowski M et al. Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients. Blood 2011; 118: 1402–1412.

    Article  CAS  PubMed  Google Scholar 

  37. Green ML, Leisenring WM, Xie H, Walter RB, Mielcarek M, Sandmaier BM et al. CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia. Blood 2013; 122: 1316–1324.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Duval M, Klein JP, He W, Cahn JY, Cairo M, Camitta BM et al. Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol 2010; 28: 3730–3738.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Craddock C, Labopin M, Pillai S, Finke J, Bunjes D, Greinix H et al. Factors predicting outcome after unrelated donor stem cell transplantation in primary refractory acute myeloid leukaemia. Leukemia 2011; 25: 808–813.

    Article  CAS  PubMed  Google Scholar 

  40. Todisco E, Ciceri F, Oldani E, Boschini C, Mico C, Vanlint MT et al. The CIBMTR score predicts survival of AML patients undergoing allogeneic transplantation with active disease after a myeloablative or reduced intensity conditioning: a retrospective analysis of the Gruppo Italiano Trapianto Di Midollo Osseo. Leukemia 2013; 27: 2086–2091.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Marty FM, Bryar J, Browne SK, Schwarzberg T, Ho VT, Bassett IV et al. Sirolimus-based graft-versus-host disease prophylaxis protects against cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation: a cohort analysis. Blood 2007; 110: 490–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Perruccio K, Tosti A, Burchielli E, Topini F, Ruggeri L, Carotti A et al. Transferring functional immune responses to pathogens after haploidentical hematopoietic transplantation. Blood 2005; 106: 4397–4406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Amrolia PJ, Muccioli-Casadei G, Huls H, Adams S, Durett A, Gee A et al. Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation. Blood 2006; 108: 1797–1808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med 2012; 367: 1487–1496.

    Article  CAS  PubMed  Google Scholar 

  45. Ringden O, Labopin M, Beelen DW, Volin L, Ehninger G, Finke J et al. Bone marrow or peripheral blood stem cell transplantation from unrelated donors in adult patients with acute myeloid leukaemia, an Acute Leukaemia Working Party analysis in 2262 patients. J Intern Med 2012; 272: 472–483.

    Article  CAS  PubMed  Google Scholar 

  46. Favre G, Beksac M, Bacigalupo A, Ruutu T, Nagler A, Gluckman E et al. Differences between graft product and donor side effects following bone marrow or stem cell donation. Bone Marrow Transplant 2003; 32: 873–880.

    Article  CAS  PubMed  Google Scholar 

  47. Vago L, Toffalori C, Ciceri F, Fleischhauer K . Genomic loss of mismatched human leukocyte antigen and leukemia immune escape from haploidentical graft-versus-leukemia. Semin Oncol 2012; 39: 707–715.

    Article  PubMed  Google Scholar 

  48. Platzbecker U, Wermke M, Radke J, Oelschlaegel U, Seltmann F, Kiani A et al. Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial. Leukemia 2012; 26: 381–389.

    Article  CAS  PubMed  Google Scholar 

  49. Provasi E, Genovese P, Lombardo A, Magnani Z, Liu PQ, Reik A et al. Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer. Nat Med 2012; 18: 807–815.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kochenderfer JN, Dudley ME, Carpenter RO, Kassim SH, Rose JJ, Telford WG et al. Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Blood 2013; 122: 4129–4139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was supported by the Italian Ministry of Health, by the Italian Ministry of University and Research, by the Cariplo Foundation (to KF), by the Associazione Italiana per la Ricerca sul Cancro (My First AIRC Grant to AB, Start-Up Grant to LV, Investigator Grant to ChB and to KF), and by the European Community (ERANET-TRANSCAN grant to AB). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.

Author contributions

JP and FC designed the study and analyzed the data. JP, AFo, DC, LV, MTLS, CM, AC, AA, SMar, SMas, FG, AL, EG, FLu, MC, MT, MGR, SR, MBe, CC, MM, FP, MZ, FLo and FC contributed to patient clinical care and data collection. AFo, LV, MN, SO, MBa, AFe, MRC, GO, KF, AB and ChB contributed to the immune monitoring data collection and interpretation. RC and LC performed the statistical analyses. JP, AFo, LV, AB, ChB and FC wrote the paper.

Author information

Authors and Affiliations

  1. Division of Regenerative Medicine, Hematology and Bone Marrow Transplantation Unit, Gene Therapy and Stem Cells, IRCCS San Raffaele Scientific Institute, Milan, Italy

    J Peccatori, A Forcina, D Clerici, R Crocchiolo, L Vago, M T L Stanghellini, C Messina, A Crotta, A Assanelli, S Marktel, S Mastaglio, F Giglio, L Crucitti, A Lorusso, E Guggiari, F Lunghi, M Carrabba, M Tassara, M Bernardi, C Corti, M Marcatti, A Bondanza & F Ciceri

  2. Division of Immunology, Experimental Hematology Unit, Infectious Diseases and Transplants, IRCCS San Raffaele Scientific Institute, Milan, Italy

    A Forcina, M Noviello, M R Carbone, G Oliveira & C Bonini

  3. Humanitas Cancer Center, Rozzano, Italy

    R Crocchiolo

  4. Division of Regenerative Medicine, Unit of Molecular and Functional Immunogenetics, Gene Therapy and Stem Cells, IRCCS San Raffaele Scientific Institute, Milan, Italy

    L Vago & K Fleischhauer

  5. Epiontis GmbH, Berlin, Germany

    S Olek

  6. Division of Immunology, San Raffaele Diabetes Research Institute, Infectious Diseases and Transplants, IRCCS San Raffaele Scientific Institute, Milan, Italy

    M Battaglia & A Ferraro

  7. Division of Regenerative Medicine, Pediatric Immunology, Hematology and Bone Marrow Transplantation Unit, Gene Therapy and Stem Cells, IRCCS San Raffaele Scientific Institute, Milan, Italy

    M G Roncarolo

  8. Division of Regenerative Medicine, San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Gene Therapy and Stem Cells, San Raffaele Scientific Institute, Milan, Italy

    M G Roncarolo

  9. ‘Vita-Salute’ San Raffaele University, Milan, Italy

    M G Roncarolo & C Bordignon

  10. Division of Regenerative Medicine, Immunohematology and Transfusion Medicine Service, Gene Therapy and Stem Cells, IRCCS San Raffaele Scientific Institute, Milan, Italy

    S Rossini

  11. Clinica Ematologica, Policlinico Universitario, Udine, Italy

    F Patriarca

  12. Policlinico San Matteo, Pavia, Italy

    M Zecca

  13. IRCCS Ospedale Bambino Gesù, Roma, Italy

    F Locatelli

  14. MolMed SpA, Milan, Italy

    C Bordignon

  15. Division of Regenerative Medicine, Leukemia Immunotherapy Group, Gene Therapy and Stem Cells, IRCCS San Raffaele Scientific Institute, Milan, Italy

    A Bondanza

Authors
  1. J Peccatori
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Forcina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Clerici
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R Crocchiolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L Vago
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M T L Stanghellini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M Noviello
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C Messina
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A Crotta
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A Assanelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. S Marktel
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. S Olek
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. S Mastaglio
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. F Giglio
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. L Crucitti
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. A Lorusso
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. E Guggiari
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. F Lunghi
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. M Carrabba
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. M Tassara
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. M Battaglia
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. A Ferraro
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. M R Carbone
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. G Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. M G Roncarolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. S Rossini
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. M Bernardi
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. C Corti
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. M Marcatti
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. F Patriarca
    View author publications

    You can also search for this author in PubMed Google Scholar

  31. M Zecca
    View author publications

    You can also search for this author in PubMed Google Scholar

  32. F Locatelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  33. C Bordignon
    View author publications

    You can also search for this author in PubMed Google Scholar

  34. K Fleischhauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  35. A Bondanza
    View author publications

    You can also search for this author in PubMed Google Scholar

  36. C Bonini
    View author publications

    You can also search for this author in PubMed Google Scholar

  37. F Ciceri
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F Ciceri.

Ethics declarations

Competing interests

Dr Chiara Bonini is a scientific consultant of MolMed SpA, Milan, Italy. Professor Claudio Bordignon is an employee of MolMed SpA, Milan, Italy. The remaining authors declare no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Peccatori, J., Forcina, A., Clerici, D. et al. Sirolimus-based graft-versus-host disease prophylaxis promotes the in vivo expansion of regulatory T cells and permits peripheral blood stem cell transplantation from haploidentical donors. Leukemia 29, 396–405 (2015). https://doi.org/10.1038/leu.2014.180

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2014.180

This article is cited by

Search

Advanced search

Quick links