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

Background: Acute 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.

Methods: To 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.

Results: One 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.

Conclusions: In 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.

Keywords: 17p abnormalities; Acute myeloid leukaemia; First remission; Stem cell transplantation; Survival.

Fig. 1

Cumulative incidence of chronic GvHD. The 2-year cumulative incidence of chronic GvHD was 21% [95% CI 14.2–29.5]

Fig. 2

Non-relapse mortality (NRM) (a) and relapse incidence (RI) (b). The 2-year cumulative incidence of NRM was 15% [95% CI 8.9–21.8] (a) and the 2-year cumulative incidence of relapse was 61.3% [95% CI 51.5–69.7] (b)

Fig. 3

Overall survival (OS) (a) and leukaemia-free survival (LFS) (b). In the whole cohort, the 2-year probability of OS was 28% [95% CI 19.7–37.1] (a) and the 2-year probability of LFS was 24% [95% CI 15.7–31.9] (b)

Fig. 4

Overall survival (OS) (a) and leukaemia-free survival (LFS) (b) by cytogenetics subgroup. Mono5 refers as the presence of monosomy 5 or loss of 5q and mono7 refers as the presence of monosomy 7. Absence of Mono5 was associated to a better OS (2-year OS 47% [95% CI 30–65] and 31% [95% CI 0–63] in patients without and with mono7, respectively) compared to the subset of patients harbouring mono5 (2-year OS: 16% [95% CI 1–31] and 10% [95% CI 0–22], according to simultaneous mono7 or not, respectively) (a). The deleterious impact of mono5 on LFS was independent of presence of additional mono7, with a 2-year LFS of 11% [95% CI 0–23] (mono5 without mono7) and 13% [95% CI 0–27] (mono5 with mono7) vs 38% [95% CI 9–67] (absence of mono5 with mono7) and 37% [95% CI 20–53] (absence of both abnormalities, p = 0.007) (b)