Skip to main content

Advertisement

SpringerLink
Log in

Donor compatibility and performance status affect outcome of allogeneic haematopoietic stem cell transplant in patients with relapsed or refractory acute myeloid leukaemia

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

Abstract

We retrospectively analysed 78 patients with relapsed (n = 38), primary refractory (n = 34) or untreated (n = 6) acute myeloid leukaemia (AML) who underwent allogeneic HSCT at our Institution between 2002 and 2011, to verify outcome and to identify factors that can affect long-term outcome. Myeloablative conditioning regimens were used in 48 patients (24 siblings, 24 matched unrelated donor (MUD)), while 30 patients (18 siblings, 12 MUD) received reduced-intensity conditioning. Acute graft versus host disease (GVHD) developed in 37 (47 %) patients, while chronic GVHD occurred in 19 of the 65 evaluable patients (29 %). With a median follow-up time of 5 years, 13 of 78 patients (17 %) are alive and in complete remission (CR), while 64 have died. Cause of death was disease recurrence in 37 patients (58 %), infection in ten patients (16 %) and GVHD in six (9 %). One-year non-relapse mortality was 35 %. In multivariate analysis, performance status ≥80 % WHO and a full-matched donor were associated with a better outcome: these two variables allowed for risk stratification, identifying three groups with significantly different survival after transplant (P = 0.0001). Considering post-transplant variables, only CR at recovery and development of cGVHD were correlated with a longer survival. Our data confirm the capacity of allogeneic transplant to prolong survival in a significant proportion of extremely high-risk AML patients.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Appelbaum FR, Gundacker H, Head DR, Slovak ML, Willman CL, Godwin JE, Anderson JE, Petersdorf SH (2006) Age and acute myeloid leukemia. Blood 107(9):3481–3485

    Article  PubMed  CAS  Google Scholar 

  2. Walter RB, Appelbaum FR, Tallman MS, Weiss NS, Larson RA, Estey EH (2010) Shortcomings in the clinical evaluation of new drugs: acute myeloid leukemia as paradigm. Blood 116(14):2420–2428

    Article  PubMed  CAS  Google Scholar 

  3. Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, Wheatley K, Harrison CJ, Burnett AK (2010) Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 116(3):354–365

    Article  PubMed  CAS  Google Scholar 

  4. Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Lowenberg B, Bloomfield CD (2010) Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 115(3):453–474

    Article  PubMed  Google Scholar 

  5. Breems DA, Boogaerts MA, Dekker AW, Van Putten WL, Sonneveld P, Huijgens PC, Van der Lelie J, Vellenga E, Gratwohl A, Verhoef GE, Verdonck LF, Lowenberg B (2005) Autologous bone marrow transplantation as consolidation therapy in the treatment of adult patients under 60 years with acute myeloid leukaemia in first complete remission: a prospective randomized Dutch-Belgian Haemato-Oncology Co-operative Group (HOVON) and Swiss Group for Clinical Cancer Research (SAKK) trial. Br J Haematol 128(1):59–65

    Article  PubMed  Google Scholar 

  6. Armistead PM, de Lima M, Pierce S, Qiao W, Wang X, Thall PF, Giralt S, Ravandi F, Kantarjian H, Champlin R, Estey E (2009) Quantifying the survival benefit for allogeneic hematopoietic stem cell transplantation in relapsed acute myelogenous leukemia. Biol Blood Marrow Transplant 15(11):1431–1438

    Article  PubMed  Google Scholar 

  7. Gratwohl A, Stern M, Brand R, Apperley J, Baldomero H, de Witte T, Dini G, Rocha V, Passweg J, Sureda A, Tichelli A, Niederwieser D (2009) Risk score for outcome after allogeneic hematopoietic stem cell transplantation: a retrospective analysis. Cancer 115(20):4715–4726

    Article  PubMed  Google Scholar 

  8. Hemmati PG, Terwey TH, le Coutre P, Vuong LG, Massenkeil G, Dorken B, Arnold R (2011) A modified EBMT risk score predicts the outcome of patients with acute myeloid leukemia receiving allogeneic stem cell transplants. Eur J Haematol 86(4):305–316

    Article  PubMed  Google Scholar 

  9. Sorror ML, Sandmaier BM, Storer BE, Maris MB, Baron F, Maloney DG, Scott BL, Deeg HJ, Appelbaum FR, Storb R (2007) Comorbidity and disease status based risk stratification of outcomes among patients with acute myeloid leukemia or myelodysplasia receiving allogeneic hematopoietic cell transplantation. J Clin Oncol 25(27):4246–4254

    Article  PubMed  Google Scholar 

  10. Vigorito AC, Campregher PV, Storer BE, Carpenter PA, Moravec CK, Kiem HP, Fero ML, Warren EH, Lee SJ, Appelbaum FR, Martin PJ, Flowers ME (2009) Evaluation of NIH consensus criteria for classification of late acute and chronic GVHD. Blood 114(3):702–708

    Article  PubMed  CAS  Google Scholar 

  11. Scrucca L, Santucci A, Aversa F (2007) Competing risk analysis using R: an easy guide for clinicians. Bone Marrow Transplant 40(4):381–387

    Article  PubMed  CAS  Google Scholar 

  12. Kim DH, Sohn SK, Kim JG, Lee NY, Sung WJ, Baek JH, Suh JS, Lee KS, Lee KB (2005) Parameters for predicting allogeneic PBSCT outcome of acute myeloid leukemia: cytogenetics at presentation versus disease status at transplantation. Ann Hematol 84(1):25–32

    Article  PubMed  Google Scholar 

  13. Kurosawa S, Yamaguchi T, Miyawaki S, Uchida N, Sakura T, Kanamori H, Usuki K, Yamashita T, Okoshi Y, Shibayama H, Nakamae H, Mawatari M, Hatanaka K, Sunami K, Shimoyama M, Fujishima N, Maeda Y, Miura I, Takaue Y, Fukuda T (2010) Prognostic factors and outcomes of adult patients with acute myeloid leukemia after first relapse. Haematologica 95(11):1857–1864

    Article  PubMed  Google Scholar 

  14. Duval M, Klein JP, He W, Cahn JY, Cairo M, Camitta BM, Kamble R, Copelan E, de Lima M, Gupta V, Keating A, Lazarus HM, Litzow MR, Marks DI, Maziarz RT, Rizzieri DA, Schiller G, Schultz KR, Tallman MS, Weisdorf D (2010) Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol 28(23):3730–3738

    Article  PubMed  Google Scholar 

  15. Naik S, Wong R, Arai S, Brown J, Laport G, Lowsky R, Miklos D, Shizuru J, Blume K, Negrin R, Johnston L (2011) Long-term outcomes in patients with high-risk myeloid malignancies following matched related donor hematopoietic cell transplantation with myeloablative conditioning of BU, etoposide and CY. Bone Marrow Transplant 46(2):192–199

    Article  PubMed  CAS  Google Scholar 

  16. Valcarcel D, Martino R, Caballero D, Martin J, Ferra C, Nieto JB, Sampol A, Bernal MT, Pinana JL, Vazquez L, Ribera JM, Besalduch J, Moraleda JM, Carrera D, Brunet MS, Perez-Simon JA, Sierra J (2008) Sustained remissions of high-risk acute myeloid leukemia and myelodysplastic syndrome after reduced-intensity conditioning allogeneic hematopoietic transplantation: chronic graft-versus-host disease is the strongest factor improving survival. J Clin Oncol 26(4):577–584

    Article  PubMed  CAS  Google Scholar 

  17. Koh H, Nakamae H, Hagihara K, Nakane T, Manabe M, Hayashi Y, Nishimoto M, Umemoto Y, Nakamae M, Hirose A, Inoue E, Inoue A, Yoshida M, Bingo M, Okamura H, Aimoto R, Aimoto M, Terada Y, Koh KR, Yamane T, Ohsawa M, Hino M (2011) Factors that contribute to long-term survival in patients with leukemia not in remission at allogeneic hematopoietic cell transplantation. J Exp Clin Cancer Res 30:36

    Article  PubMed  Google Scholar 

  18. Oyekunle AA, Kroger N, Zabelina T, Ayuk F, Schieder H, Renges H, Fehse N, Waschke O, Fehse B, Kabisch H, Zander AR (2006) Allogeneic stem-cell transplantation in patients with refractory acute leukemia: a long-term follow-up. Bone Marrow Transplant 37(1):45–50

    PubMed  CAS  Google Scholar 

  19. Shimoni A, Nagler A (2011) Optimizing the conditioning regimen for allogeneic stem-cell transplantation in acute myeloid leukemia; dose intensity is still in need. Best Pract Res Clin Haematol 24(3):369–379

    Article  PubMed  Google Scholar 

  20. Andersson BS, Valdez BC, de Lima M, Wang X, Thall PF, Worth LL, Popat U, Madden T, Hosing C, Alousi A, Rondon G, Kebriaei P, Shpall EJ, Jones RB, Champlin RE (2011) Clofarabine +/− fludarabine with once daily i.v. busulfan as pretransplant conditioning therapy for advanced myeloid leukemia and MDS. Biol Blood Marrow Transplant 17(6):893–900

    Article  PubMed  CAS  Google Scholar 

  21. Birninger N, Bornhauser M, Schaich M, Ehninger G, Schetelig J (2011) The hematopoietic cell transplantation-specific comorbidity index fails to predict outcomes in high-risk AML patients undergoing allogeneic transplantation—investigation of potential limitations of the index. Biol Blood Marrow Transplant 17(12):1822–1832

    Article  PubMed  Google Scholar 

  22. Michallet M, Thomas X, Vernant JP, Kuentz M, Socie G, Esperou-Bourdeau H, Milpied N, Blaise D, Rio B, Reiffers J, Jouet JP, Cahn JY, Bourhis JH, Lioure B, Leporrier M, Sotto JJ, Souillet G, Sutton L, Bordigoni P, Dreyfus F, Tilly H, Gratecos N, Attal M, Leprise PY, Demeocq F, Michel G, Buzyn A, Delmas-Marsalet B, Bernaudin F, Ifrah N, Sadoun A, Guyotat D, Cavazzana-Cavo M, Caillot D, De Revel T, Vannier JP, Baruchel A, Fegueux N, Tanguy ML, Thiebaut A, Belhabri A, Archimbaud E (2000) Long-term outcome after allogeneic hematopoietic stem cell transplantation for advanced stage acute myeloblastic leukemia: a retrospective study of 379 patients reported to the Societe Francaise de Greffe de Moelle (SFGM). Bone Marrow Transplant 26(11):1157–1163

    Article  PubMed  CAS  Google Scholar 

  23. Sierra J, Radich J, Hansen JA, Martin PJ, Petersdorf EW, Bjerke J, Bryant E, Nash RA, Sanders JE, Storb R, Sullivan KM, Appelbaum FR, Anasetti C (1997) Marrow transplants from unrelated donors for treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 90(4):1410–1414

    PubMed  CAS  Google Scholar 

  24. Schlenk RF, Dohner K, Mack S, Stoppel M, Kiraly F, Gotze K, Hartmann F, Horst HA, Koller E, Petzer A, Grimminger W, Kobbe G, Glasmacher A, Salwender H, Kirchen H, Haase D, Kremers S, Matzdorff A, Benner A, Dohner H (2010) Prospective evaluation of allogeneic hematopoietic stem-cell transplantation from matched related and matched unrelated donors in younger adults with high-risk acute myeloid leukemia: German-Austrian trial AMLHD98A. J Clin Oncol 28(30):4642–4648

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology and Bone Marrow Transplantation & Department of Experimental and Clinical Medical Sciences, Azienda Ospedaliero-Universitaria di Udine, P.zzale S. M. Misericordia, 15, 33100, Udine, Italy

    Daniela Damiani, Mario Tiribelli, Antonella Geromin, Michela Cerno, Alessandra Sperotto, Eleonora Toffoletti, Erica Simeone, Angela Michelutti, Margherita Cavallin & Renato Fanin

Authors
  1. Daniela Damiani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mario Tiribelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Antonella Geromin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michela Cerno
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alessandra Sperotto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eleonora Toffoletti
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Erica Simeone
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Angela Michelutti
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Margherita Cavallin
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Renato Fanin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniela Damiani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Damiani, D., Tiribelli, M., Geromin, A. et al. Donor compatibility and performance status affect outcome of allogeneic haematopoietic stem cell transplant in patients with relapsed or refractory acute myeloid leukaemia. Ann Hematol 91, 1937–1943 (2012). https://doi.org/10.1007/s00277-012-1551-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-012-1551-x

Keywords

Search

Navigation