Impact of Cytogenetics on Outcome of AML after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Gindina Tatiana L , Mamaev Nikolay N , Afanasyev Boris V , Bondarenko Sergey N , Alyanskiy Alexander , Slesarchuk Olga , Moiseev Ivan S , Razumova Svetlana V , Zubarovskaya Lyudmila 
Published: November 2019

Background. Chromosomal abnormalities (CA) are the most prognostic factor in acute myeloid leukemia (AML). However, it is still not clear whether the cytogenetic risk groups established for patients (pts), treated by standard chemotherapy, are so optimal for pts undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT). Recent studies have confirmed negative effects of both monosomal and complex karyotypes (MK, CK) on outcomes after alloHSCT [1,2]. Meantime, some investigators consider that immune effects of alloHSCT can reduce negative impact of these CA [3].

Aim. To evaluate impact of the CA in AML pts with adverse cytogenetic risk group on outcome after alloHSCT.

Material and Methods. In this study, outcomes of alloHSCT, which were performed in a single institution between 2009 and 2014 years for 97 AML pts have been analyzed. Patients and transplantation characteristics are presented in Table I. The probabilities of overall survival (OS), leukemia free survival (LFS), cumulative incidence of relapse (CIR) were evaluated for different cytogenetic groups.

Results. According to univariateanalysis, the probabilities of 4-year OS in pts with 5q-, KMT2A translocations and monosomy 7 were 66%, 59% and 56%, respectively. At the same time, OS in pts with CK, 7q- and 3q26 rearrangements were lower i.e. 33%, 25% and 25%, respectively (p=0.01). Multivariate analysis showed, that clinical stage at HSCT, age and HSC source are independent predictors of OS in AML pts (Table 2). Four-year LFS were various in pts with different CA. The higher LFS was noted in pts with 5q- and KMT2A translocations (66% and 52%, respectively), whereas lower LFS were in pts with 3q26 rearrangements, CK, monosomy 7 and 7q- (0, 18%, 23% and 37%, respectively) (Fig. 1). Besides, LFS distinguished between groups with CK+ and CK- (18% vs 41%, p=0.008), as well as with MK+ and MK- (17% vs 30%, p=0.04). Multivariate analysis evidenced clinical stage at HSCT, cytogenetic groups, MK and number of transplanted CD34+ cells to be independent predictor of LFS in AML pts (Table 2).Cumulative incidence of relapses in pts transplanted in remission (n=42) was higher in those with CK+ (55% vs 14%, p=0.03) and MK+ (75% vs 31%, p=0.013).

Discussion. The study showed that 4-year OS in AML pts with 5q-, KMT2A translocations and monosomy 7 significantly distinguished from those with CK, 7q- and 3q26 rearrangements. Furthermore, OS depended on clinical stage at HSCT, patient's age and HSC source. On the other hand, EFS differed from all above-mentioned cytogenetic groups, including MK. Finally EFS depended on clinical stage at HSCT and number of transplanted CD34+ cells.

Conclusion. On the basis of this data, a conclusion may be drawn that alloHSCT in AML pts with adverse CA should be performed at complete remission, with bone marrow as HSC source and enough number of transplanted CD34+ cells.

Reference.

1. Hemmatti et al. Eur J Haematol. 2013; 92:102-10.

2. Fang et al. Blood 2011; 118:1490-4.

3. Guo et al. Biol Blood Marrow Transplant 2014; 20: 690-5.

Table 1. Patients and Transplant characteristics Patients, n (%) 97 (100) Gender, n (%)MaleFemale 53 (54.6)44 (45.4) Age at HSCT, median, (range) years 25 (1.5-60) Cytogenetics, n (%) 3q26 rearrangementsDeletion 5q (sole)Monosomy 7 (sole)Deletion 7q (sole)KMT2A translocationComplex karyotype ³3 CA Monosomal karyotype 4 (4)10 (10.3)12 (12.4)4 (4)11 (11.3)56 (58)18 (18.5) Time from diagnosis to HSCT, median (range) days 477 (47 - 3482) Clinical stage at HSCT, n (%)CR1³CR2Active disease 29 (30)13 (13)55 (57) HSC source, n (%)Bone marrowPeripheral bloodBM+PB 54 (56)34 (35)9 (9) Conditioning regimen, n (%)MANon-MA 35 (36)62 (64) Donor type, n (%)HLA-id siblingMatched unrelatedHaploidentical 17 (17.5)53 (54.6)27 (27.8) Number of transplanted CD34+ cellsmedian (range), x106/kg 6.1 (1.5-17.9)

Table 2. Multivariate analyses HR 95% CI P Overall survival Clinical stage at HSCT 2.65 1.72-4.09 0.00001 Median age<18 years) 2.05 1.05-3.99 0.034 HSC source 1.66 1.12-2.45 0.011 Cytogeneticgroups 1.72 0.81-3.66 0.15 Median number of transplanted CD34+ cells>6x106/kg 1.77 0.91-3.42 0.08 Leukemia-free survival Clinical stage at HSCT 2.59 1.8-3.7 0.0001 Cytogeneticgroups 1.31 1.03-1.69 0.031 Monosomal karyotype 1.88 0.97-3.66 0.044 Median number of transplanted CD34+ cells>6x106/kg 2.78 1.51-5.11 0.0003

Figure 1. Leukemia-free survival for AML patients with different cytogenetic groups after alloHSCT Figure 1. Leukemia-free survival for AML patients with different cytogenetic groups after alloHSCT

Disclosures

No relevant conflicts of interest to declare.