Reduced intensity conditioning allogeneic stem cell transplantation for patients with acute myeloid leukemia: long term results of a ‘donor’ versus ‘no donor’ comparison

Standard myeloablative allogeneic stem cell transplantation (allo-SCT) is a well-established therapy for patients with acute myeloid leukemia (AML). However, because of the high incidence of transplant-related mortality (TRM), this procedure is limited to younger patients in good medical condition.1 Reduced-intensity conditioning (RIC) regimens have emerged as an attractive modality to decrease TRM.2, 3 However, the issue of possible higher relapse rate after RIC-allo-SCT is still under debate,4, 5, 6 and no randomized studies between RIC-allo-SCT for AML and chemotherapy alone are yet available.7

This updated analysis describes the long-term results of 95 previously reported8 consecutive AML patients, diagnosed between 1999 and 2003 in a single institution, and who were considered as potential candidates for RIC-allo-SCT. Detailed methods were previously published.8 Using a genetic randomization through a ‘donor’ versus ‘no donor’ comparison, the aim of this updated analysis was to assess the benefit of RIC-allo-SCT for adult AML and its impact on clinical outcome. In this series, 35 patients (37%; ‘donor’ group) had an ‘identified’ HLA-identical sibling donor, while the remaining 60 patients had no HLA-matched related donor (‘no donor’ group). As per institutional policy, HLA-matched unrelated donors were not considered during the study period.8

No significant differences in patients or AML features were found between the two groups (Table 1). In the ‘donor’ group, 25 patients (71%; median age, 51 (range, 26–60)) could actually proceed to the RIC-allo-SCT. The 10 remaining patients with an identified donor did not receive allo-SCT because of early relapse after complete remission (n=2), patient or donor refusal (n=6) and psychiatric disorders appearing before allo-SCT (n=2). The latest median follow-up is 4.8 (range, 3.5–7.2) years. In an ‘intention-to-treat’ analysis, leukemia-free survival (LFS) was significantly higher in the ‘donor’ group as compared with the ‘no donor’ group (P=0.003; 60 versus 23% at 7 years). When restricting the analysis to patients who could actually receive the RIC-allo-SCT, the difference in LFS was also significant between this group of 25 patients (‘transplant’ group) and the remaining 70 patients (‘no transplant’ group) who did not receive allo-SCT (P=0.0002; 72 versus 24% at 7 years). In the ‘transplant’ group, RIC-allo-SCT was performed at a median of 209 (range, 119–413) days after diagnosis. No major toxicities were encountered during RIC administration, and only three patients died from TRM, for a cumulative incidence of TRM of 12% (95% CI, 3–32%). This relatively low TRM translated towards a significantly higher overall survival (OS) in the ‘transplant’ group as compared with the ‘no transplant’ group (P=0.0003). In the ‘intention-to-treat’ analysis, OS was still significantly higher in the ‘donor’ group as compared with the ‘no donor’ group (P=0.003; Figure 1). After controlling for all relevant factors, in the multivariate analysis, only actual performance of RIC-allo-SCT (P=0.0005; RR=4.1; 95% CI, 1.8–9.1), was significantly predictive of an improved LFS.

Table 1 Patients' characteristics and acute myeloid leukemia features
Figure 1
figure1

Survival after RIC-allo-SCT for AML. (a) Comparison of leukemia-free survival (LFS) between the ‘donor’ (solid line) and ‘no donor’ (dashed line) groups; (b) Comparison of LFS between the ‘transplant’ (solid line) and ‘no transplant’ (dashed line) groups; (c) Comparison of overall survival (OS) between the ‘transplant’ (solid line) and ‘no transplant’ (dashed line) groups; (d) Comparison of OS between the ‘donor’ (solid line) and ‘no donor’ (dashed line) groups. Probabilities of LFS and OS were estimated from the time of diagnosis using the Kaplan–Meier product-limit estimates.

On the basis of these long-term results, and other studies with comparable long follow-up,9, 10 we conclude that if a matched-related donor is identified, RIC-allo-SCT should be proposed because it represents a valid and potentially curative option for AML patients not eligible for standard myeloablative allo-SCT.

References

  1. 1

    Sorror ML, Giralt S, Sandmaier BM, De Lima M, Shahjahan M, Maloney DG et al. Hematopoietic cell transplantation specific comorbidity index as an outcome predictor for patients with acute myeloid leukemia in first remission: combined FHCRC and MDACC experiences. Blood 2007; 110: 4606–4613.

    CAS  Article  Google Scholar 

  2. 2

    Champlin R, Khouri I, Kornblau S, Molldrem J, Giralt S . Reinventing bone marrow transplantation. Nonmyeloablative preparative regimens and induction of graft-vs-malignancy effect. Oncology (Huntingt) 1999; 13: 621–628; discussion 631, 635–638, 641.

    CAS  Google Scholar 

  3. 3

    Storb R . Can reduced-intensity allogeneic transplantation cure older adults with AML? Best Pract Res Clin Haematol 2007; 20: 85–90.

    Article  Google Scholar 

  4. 4

    Lazarus HM, Rowe JM . Reduced-intensity conditioning for acute myeloid leukemia: is this strategy correct. Leukemia 2006; 20: 1673–1682.

    CAS  Article  Google Scholar 

  5. 5

    Martino R, Iacobelli S, Brand R, Jansen T, van Biezen A, Finke J et al. Retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA-identical sibling donors in myelodysplastic syndromes. Blood 2006; 108: 836–846.

    CAS  Article  Google Scholar 

  6. 6

    Blaise D, Vey N, Faucher C, Mohty M . Current status of reduced-intensity-conditioning allogeneic stem cell transplantation for acute myeloid leukemia. Haematologica 2007; 92: 533–541.

    Article  Google Scholar 

  7. 7

    Shimoni A, Nagler A . Allogeneic hematopoietic stem-cell transplantation in patients with acute myeloid leukemia in first complete remission: new answers for an old question. Leukemia 2005; 19: 891–893.

    CAS  Article  Google Scholar 

  8. 8

    Mohty M, de Lavallade H, Ladaique P, Faucher C, Vey N, Coso D et al. The role of reduced intensity conditioning allogeneic stem cell transplantation in patients with acute myeloid leukemia: a donor vs no donor comparison. Leukemia 2005; 19: 916–920.

    CAS  Article  Google Scholar 

  9. 9

    Hegenbart U, Niederwieser D, Sandmaier BM, Maris MB, Shizuru JA, Greinix H et al. Treatment for acute myelogenous leukemia by low-dose, total-body, irradiation-based conditioning and hematopoietic cell transplantation from related and unrelated donors. J Clin Oncol 2006; 24: 444–453.

    CAS  Article  Google Scholar 

  10. 10

    Valcarcel D, Martino R, Caballero D, Martin J, Ferra C, Nieto JB et al. 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 2008; 26: 577–584.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We thank the nursing staff for providing excellent care for our patients and the physicians of the Hematology Department at the Institut Paoli-Calmettes for their important study contributions and dedicated patient care. We also thank the ‘Association pour la Recherche sur le Cancer (ARC)’ (Pole ARECA), the ‘Fondation de France’, the ‘Fondation contre la Leucémie’, the ‘Agence de Biomédecine’, the ‘Association Cent pour Sang la Vie’ and the ‘Association Laurette Fuguain’ for their generous and continuous support for our clinical and basic research work. We were supported by several grants from the French Ministry of Health as part of the ‘Programme Hospitalier de Recherche Clinique (PHRC)’.

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Mohty, M., de Lavallade, H., El-Cheikh, J. et al. Reduced intensity conditioning allogeneic stem cell transplantation for patients with acute myeloid leukemia: long term results of a ‘donor’ versus ‘no donor’ comparison. Leukemia 23, 194–196 (2009). https://doi.org/10.1038/leu.2008.164

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