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Editorials
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reduced deaths from other causes, and non-relapse mor- tality is significantly increased in the long-term.
Another debated issue is the comparison between reduced intensity and myeloablative conditioning regi- mens, and their effect on relapse and survival.4-5 The authors found that reduced intensity conditioning regi- mens protect patients from early non-relapse mortality (as expected), but this effect is lost after 4 months, and its competing event, relapse, unfortunately, increases con- stantly over time. Thus, when using a reduced intensity conditioning regimen, the clinician must be aware that the beneficial effect is short-lived and that in the long- term there is no protection against non-relapse mortality, with significantly greater risk of relapse.
In the era of personalized medicine the statistical approach suggested by Fuerst et al. provides a tool to dis- entangle the effects of different transplant components. This in turn gives new answers, sometimes unexpected, to important questions, such as the lack of reduced relapse risk using peripheral blood cells, or the significant- ly increased risk of relapse with reduced intensity condi-
Figure 1. Time-dependent effect of peripheral blood grafts compared to bone marrow grafts. The box plots rep- resent the hazard ratio (HR) for non- relapse mortality (NRM) <8 months from transplant (0.75; range, 0.68- 0.84) (P<0.001), for NRM >8 months from transplant (1.38; range, 1.14- 1.66) (P<0.001) and for relapse any time after transplantation (1.04; range, 0.94-1.15) (P=0.4). This analysis illus- trates a protective effect of peripheral blood (PB) on NRM early after trans- plant; a detrimental effect of PB on NRM later on, and no effect of PB on relapse, when compared to bone mar- row (BM) as a source of stem cells.
tioning regimens. A better understanding of these compo- nents lays the basis for a reconsideration of transplant protocols and the design of tailored clinical trials.
References
1. Fuerst D, Frank S, Mueller C, et al. Competing-risk outcomes after hematopoietic stem cell transplantation from the perspective of time- dependent effects. Haematologica. 2018;103(9):1527-1534.
2. Friedrichs B, Tichelli A, Bacigalupo A, et al. Long-term outcome and late effects in patients transplanted with mobilised blood or bone mar- row: a randomised trial. Lancet Oncol. 2010;11(4):331-338.
3. Anasetti C, Logan BR, Lee SJ, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med. 2012;367(16):1487- 1496.
4. Bornhäuser M, Kienast J, Trenschel R, et al. Reduced-intensity condi- tioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012;13(10):1035–1044.
5. ScottBL,PasquiniMC,LoganBR,etal.Myeloablativeversusreduced- intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes. J Clin Oncol. 2017;35 (11):1154-1161.
haematologica | 2018; 103(9)