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When is second allogeneic HSCT for relapse of acute leukaemia an option?

Bone Marrow Transplantation volume 51, pages 184–185 (2016)Cite this article

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Patients with acute leukaemia who relapse after allogeneic haematopoietic stem cell transplantation (allo-HSCT) face limited treatment options.1 Commonly, chemotherapy, novel agents like epigenetic modifiers, donor lymphocyte infusions (DLI), second allogeneic HSCT (allo-HSCT2), or combinations thereof are employed therapeutically.1, 2 In general, outcome of patients with acute leukaemia relapsing after allo-HSCT remains poor.1 The approach to relapse after allo-HSCT frequently is an individual one. The lack of head-to-head comparisons and small group sizes in the single analyses are an obstacle to evidence-based recommendations. Clearly, outcomes of cell-based therapy (DLI or allo-HSCT2) after successful induction of CR by conventional chemotherapy are superior to conventional chemotherapy alone if relapse occurred after reduced-intensity conditioning (RIC)-based allo-HSCT.3 Recently, hypomethylating drugs as standalone agents or combined with DLI were shown to induce responses in 30–33% of patients.4, 5 In addition, HDAC inhibitors, tyrosine-kinase inhibitors and Abs/Ab–conjugate combinations are in clinical tests at present. The value of allo-HSCT2 remains controversial. It is the one option with a documented long-time survival—10 year overall survival (OS) after myeloablative conditioning-based second allogeneic stem cell transplantation (allo-HSCT2) performed between 1985 and 2000 is 10±2%.6 Yet, what are the risk factors for successful allo-HSCT2 for relapse of acute leukaemia? Can choice of pretreatment, conditioning, immunosuppression or donor influence outcome?

Patients in CR at allo-HSCT2, relapsing no earlier than 10 months after allo-HSCT and transplanted using TBI-based conditioning at allo-HSCT2 reached a 10-year OS of 36±10%.6 Two of these favourable risk factors, ability to induce CR after haematological relapse after allo-HSCT1 and duration of remission, are factors commonly found to be prognostic for successful cell-based treatment, perhaps reflecting favourable disease biology. Risk factors for allo-HSCT2 have been evaluated in the myeloablative setting at allo-HSCTC7, 8, 9 and in multicenter studies analysing both myeloablative and RIC regimens at allo-HSCT1/2.10, 11, 12 Risk factors beyond duration of remission and ability to reach a next CR before allo-HSCT2 are less clear. Conducting allo-HSCT2 from an alternative donor in order to allow for an immune effect that was not provided by cells from the initial donor has not been proven to be beneficial.9, 10, 13 Yet, the recent large study by Ruutu et al.13 found a reduction in tumour-related mortality when an alternative donor was asked to donate. This was antagonised by lower non-relapse mortality (NRM) when the second graft was collected from the initial donor.13 Due to small patient numbers in respective subgroups, valid statistical proof supporting or declassing the concept of changing the donor for individuals who had been in remission for a long time, who had not experienced GvHD after allo-HSCT1 and who do reach CR before allo-HSCT2 is lacking. The European Society for Blood and Marrow Transplantation (EBMT) risk score14 at allo-HSCT2 was found to be of prognostic impact in several studies,13, 15 excluding our own.10 There still is considerable debate on the impact of the conditioning regimen chosen. In lower toxicity regimens at allo-HSCT2, NRM is frequently found to be reduced.13, 16 Relapse incidence is sometimes documented to be increased.9 Comparability between regimens throughout the transplant community is low due to little uniformity and results as to whether one or the other approach or even specific regimen trumps the other are to be viewed with caution.

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  1. Department of Stem Cell Transplantation, University Medical Center Hamburg, Hamburg, Germany

    M Christopeit

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Christopeit, M. When is second allogeneic HSCT for relapse of acute leukaemia an option?. Bone Marrow Transplant 51, 184–185 (2016). https://doi.org/10.1038/bmt.2015.285

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