Allogeneic stem cell transplantation in adult patients with acute myeloid leukaemia and 17p abnormalities in first complete remission: a study from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Abstract

BackgroundAcute myeloid leukaemia (AML) with 17p abnormalities (abn(17p)) carries a very poor prognosis due to high refractoriness to conventional chemotherapy, and allogeneic stem cell transplantation (allo-SCT) appears as the only potential curative option.MethodsTo address outcomes after allo-SCT in patients with abn(17p), we retrospectively analysed de novo or secondary AML undergoing SCT between 2000 and 2013 from the EBMT registry.ResultsOne hundred thirty-nine patients with confirmed abn(17p) have been selected. At the time of transplant, one hundred twenty-five were in first remission (CR1). Median age was 54 years old. Abn(17p) was associated with a monosomal karyotype in 83% of patients, complex karyotype in 91%, monosomy 5 or 5q deletion (-5/5q-) in 55%, monosomy 7 (-7) in 39% and both -5/5q and -7 in 27%. Seventy-three patients (59%) had a reduced-intensity conditioning regimen. The 2-year overall survival (OS) and leukaemia-free survival (LFS) were 28 and 24%, respectively. The 2-year non-relapse mortality (NRM) was 15%, and 2-year relapse incidence (RI) was 61%. The cumulative incidence of grade II to IV acute graft-versus-host disease (GvHD) was 24% and that of chronic GvHD was 21%. In multivariate analysis, the presence of a -5/5q- in addition to abn(17p) was significantly and independently associated with worse OS, LFS and higher RI. Age and donor types did not correlate with outcome. Conditioning intensity was not statistically associated with OS, LFS and NRM when adjusted for patients’ age.ConclusionsIn contrast to the dismal prognosis reported for AML patients harbouring abn(17p) undergoing conventional chemotherapy, allogeneic SCT provides responses in about 25% of those patients transplanted in CR1.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0393-3) contains supplementary material, which is available to authorized users.

The impact of concomitant cytogenetic abnormalities on acute myeloid leukemia with monosomy 7 or deletion 7q after HLA‐matched allogeneic stem cell transplantation

“…26 We also found that sAML was significantly associated with increased NRM and decreased OS as previously described, 27,28 So, -7/7q-is the most frequent cytogenetic feature reported as sole abnormality, 23 which is well illustrated within our population with 42% of the patients harboring -7/7q-without CK, MK, -5/5q-, abn (17p) and inv (3). As suggested by our previous dataset, 18 we hypothesized that the prognosis of our cohort would be dictated by the presence of additional adverse cytogenetic abnormalities. While CK did not show an impact on outcomes in multivariate analysis, we found a significantly worse survival in patients harboring MK, -5/5q-, abn(17p) and inv ( SCT in high-risk AML.…”

“…38,39 Our "abn(17p)" group translated into a 2-year probability of LFS of only 19% if transplanted in CR1, which is worse than previously published data. 18,40 These worse results might be related to the presence of 66% -5/5q-within the "abn(17p)" group, which supports our previous observation of the deleterious effect of the combination of -5/5q-and abn(17p) on outcomes after SCT. 18 To further support the negative combinatorial impact of -5/5q-and abn(17p), we subsequently studied separately -5/5q-, abn(17p) and the combination of -5/5q-with abn(17p).…”

“…The 2-year cumulative incidence of relapse was 36.7% for the "-7/7q-± CK group," 47.8% for the "MK group," 51% for the "-5/5qgroup," 62.9% and 68.4% for the "inv(3) group" (P < .001, Figure 2A), which translated into a 2-year probability of LFS of 48%, 36.4%, 28.4%, 19.1% and 17.3% for the "-7/7q-± CK," "MK," "-5/5q-," "abn(17p)" and "inv(3)" groups, respectively (P < .001, Figure 2C). The 2-year NRM was similar across our five cytogenetic <.0001 20 (16)(17)(18)(19)(20)(21)(22)(23)(24) .99 23 (18)(19)(20)(21)(22)(23)(24)(25)(26)(27) <.0001 27 (22)(23)(24)(25)(26)(27)(28)(29)(30)(31) <.0001 13 (10)(11)(12)(13)(14)(15)(16) <.0001 26 (22)(23)(24)(25)(26)(27)(28)(29)…”

“…15 20 (12-28) . 32 (29)(30)(31)(32)(33)(34)(35) 7q-vs -7 7q-44 (38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49) .005 21 (17)(18)(19)(20)(21)(22)(23)(24)(25)(26) .72 35 (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41) .004 42 (36)(37)(38)(39)(40)(41)(42)(43)(44)(45)…”

“…Interestingly, the co-occurrence of -7 without -5/5q-translated into a much better survival than the frequent combination of -5/5q-and abn (17p). 18 This raises the questions of a potential better outcome after SCT for patients with -7/7q-, and the influence of concomitant cytogenetic abnormalities. Subsequently, we studied a cohort of 501 patients with -5/5q-in which we were not able to demonstrate any impact of -7/7q-on outcomes after SCT.…”