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Tandem versus single autologous peripheral blood stem cell transplantation as post-remission therapy in adult acute myeloid leukemia patients under 60 in first complete remission: results of the multicenter prospective phase III GOELAMS LAM-2001 trial

Leukemia volume 24, pages 1380–1385 (2010)Cite this article

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The capacity to harvest a graft after the miniconsolidation or the early intensification was similar between both groups (arm A: 59% versus arm B: 54%, and arm A: 63% versus arm B: 57%). Thus, the ability to obtain at least one (>2 × 106 CD34+ cells/kg) or two (⩾4 × 106 CD34+ cells/kg) graft(s) was similar in both arms (arm A: n=168 (81%) versus arm B: n=162 (79.5%), and arm A: n=132 (64%) versus arm B: n=134 (66%)). Interestingly, the first randomization had a significant impact on the amount of stem cells collected (median 9.8 (0.9–100) × 106/kg for daunorubicin versus 6.7 (0.3–307) × 106/kg for idarubicin, P<0.0001). Patients who received daunorubicin were also more liable to achieve the planned auto-HSCT program (P=0.04 in both arms). As required by the protocol, the majority of patients in arm A (75%) and in arm B (77%) received a graft collected only after the early intensification. The median number of CD34+ stem cells collected after this early intensification was significantly higher in arm B compared with arm A (5.9 (range 0–90.5) × 106/kg versus 5.2 (range 0–308) × 106/kg, P=0.04). As shown in Table 3, none of the significantly different outcomes was related to the time of graft collection.

The main objective of this phase III randomized study was to compare one (arm A) versus two (arm B) auto-HSCT(s) as post-remission therapy in adult AML patients lesser than 60 years old in first CR. The outcomes reported here compare favorably with those of previously randomized studies1, 2 and confirm the safety of a double auto-HSCT procedure with only 5% of treatment-related mortality.3 However, similar results were obtained in both arms, either in an intent-to-treat analysis or when considering only patients who effectively received the full planned schedule. Moreover, no benefit from receiving two rather than one auto-HSCT as post-remission therapy was identified in any of the prognostic subgroups of patients. These results could be explained, first, by the planned rescue strategies that were applied when auto-HSCT could not be performed as expected. Second, the feasibility of the full auto-HSCT procedure was unquestionably worse in arm B (44 versus 75% in arm A), mainly because of an unexpected threefold higher incidence of relapse in arm B between CR and auto-HSCT. There is no clear evidence to explain this phenomenon, as the incidence of high-risk patients was equally distributed between both arms. Keating et al.4 have reported that the capacity to harvest high numbers of CD34+ cells can be considered as an independent poor prognosis factor, reflecting a low sensitivity for chemotherapy with less efficient in vivo purging of leukemic stem cells. In this study, most of the patients (75%) in each arm received a graft collected after early intensification, and the capacity of mobilization was indeed significantly higher in arm B. Finally, the timing of the second auto-HSCT in arm B could also explain the lack of superiority of the double auto-HSCT schedule. Several patients in arm A did receive another auto-HSCT at relapse because of the availability of a graft collected in first-line therapy. The poor outcome of AML patients who relapse after auto-HSCT has previously been shown to be improved by a second auto-HSCT.5 Consistent with the results reported in this study, this raises the question of delaying the second auto-HSCT until relapse rather than proposing two successive auto-HSCTs straightaway. Although a recent relatively large study showed the feasibility of good CD34+ mobilization at relapse in AML patients,6 the availability of a previously collected graft could alleviate mobilization in retreated patients, and limit the risk of harvesting more resistant cells. Auto-HSCT results were particularly poor in patients with high-risk cytogenetics or in those who achieved CR after two courses of induction. The dismal prognosis of such patients suggests that they would rather benefit from allogeneic transplantation.7 Conversely, the study reported here confirms the good results of auto-HSCT in AML patients with favorable cytogenetics and no sibling donor.8

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Authors and Affiliations

  1. Department of Hematology, CHU Hôtel-Dieu, Nantes, France

    P Chevallier & J-L Harousseau

  2. Department of Hematology, CHRU, Strasbourg, France

    L Fornecker & B Lioure

  3. Department of Hematology/Biology, CHU, Nancy, France

    M C Béné

  4. Department of Hematology, Hopital Haut-Leveque, CHU, Bordeaux, France

    A Pigneux

  5. Department of Hematology, Hopital de Purpan, CHU, Toulouse, France

    C Recher

  6. Department of Hematology, CHU, Nancy, France

    B Witz

  7. Department of Hematology, CHU Saint Eloi, Montpellier, France

    N Fegueux

  8. Department of Hematology, Hopital Michallon, CHU Grenoble, France

    C-E Bulabois

  9. Department of Hematology/Biology, Hopital Robert Debre, Reims, France

    S Daliphard & I Luquet

  10. Department of Hematology, Hopital Cochin, Paris, France

    D Bouscary

  11. Department of Hematology, Institut Paoli-Calmette, Marseille, France

    N Vey

  12. Department of Hematology, Hopital Bretonneau, Tours, France

    M Delain

  13. Department of Hematology, CHU, Clermont-Ferrand, France

    J-O Bay

  14. Department of Hematology, CHRU, Limoges, France

    P Turlure

  15. Department of Hematology, CHU, Rennes, France

    M Bernard

  16. Department of Hematology, Hopital Robert Debre, Reims, France

    C Himberlin

  17. Department of Hematology, CHRU, Angers, France

    N Ifrah

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Chevallier, P., Fornecker, L., Lioure, B. et al. Tandem versus single autologous peripheral blood stem cell transplantation as post-remission therapy in adult acute myeloid leukemia patients under 60 in first complete remission: results of the multicenter prospective phase III GOELAMS LAM-2001 trial. Leukemia 24, 1380–1385 (2010). https://doi.org/10.1038/leu.2010.111

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