Page 55 - 2019_02-Haematologica-web

Aplastic anemia in the elderly
Table 2. Population characteristics according to first-line treatment (n=88).
n(%) or median [IQR]
Male
Age (years)
Weight (kg)
Charlson comorbidity index Performance status
Blood count
PMN (x109/L) Lymphocytes (x109/L) Hemoglobin (g/dL) MCV (fL) Reticulocytes (x109/L) Platelets (x109/L)
AA severity Mild
Severe
Very severe
Myelogram cellularity
Markedly increased Increased
Average
Reduced
Poor
Unknown or failure
Paroxysmal Nocturnal Hemoglobinuria.
Table 3. Impact of treatment on outcome (overall response and mortality) after adjustment for treatment line, disease severity and performance status.
ATG-CsA (n=44)
17 (39%)
66 [62;70] 66.5 [61;78] 1.5 [1;2.25] 1 [0;1]
0.51 [0.195;1.1] 1.5 [0.999;1.95] 7.9 [6.98;8.65] 92 [88;98] 20 [11.92;41.25] 8 [4;13]
16 (36.5%) 16 (36.5%) 12 (27%)
1 (2%)
1 (2%)
11 (25%)
18 (41%)
10 (23%)
3 (7%)
3 (7%)
CsA alone (n=18)
9 (50%)
71.5 [65;74] 73 [61;79.5] 2 [1;2]
1 [1;1]
0.915 [0.25;1.43] 1.29 [1;1.585] 8.65 [7.23;9.2] 92.5 [89;101.2] 23 [16;40]
12 [6;16.75]
7 (39%) 6 (33%) 5 (28%)
71.5 [68.5;76]
69.5 [65.75;80] 0.62
1.5 [1;2.75] 0.96 1 [0;1.75] 0.26
0.8 [0.5;1.513] 0.12 1.2 [0.8;1.5] 0.46 8.85 [6.98;10.1] 0.11
Others (n=26) P 19 (73%) 0.02
0.007
100.3 [95.5;104]
28 [19.5;43.5] 0.48
0.095
15 [7.25;37.75]
0.025
0 (0%) 0 (0%) 4 (22%) 11 (61%) 3 (17%) 0 (0%) 3 (17%)
15 (58%) 0.11 10 (38%)
1 (4%)
0 (0%) 1 (4%)
3 (12%) 0.88 15 (58%)
4 (15%)
3 (11%)
PNH clone ≥ 5%
AA: Aplastic Anemia; ATG: Anti-Thymocyte Globulin; CsA: Cyclosporine-A; IQR: Inter-Quartile range; MCV: Mean Corpuscular Volume; PMN: Polymorphonuclear Neutrophils; PNH:
1 (4%) 0.33
ATG-CsA
CsA alone Eltrombopag alone Androgens alone EPO
G-CSF
HR (CI95%)
0.44 (0.13;1.45)
2.84 (0.93;8.61)
0.80 (0.08;7.71)
1.33 (0.36;4.88)
1.12 (0.35;3.58)
1.28 (0.50;3.29)
P
0.18
0.066
0.85
0.67
0.84
0.61
Overall response OR (CI95%) P
4.18 (1.93;9.09) 0.0003
0.73 (0.28;1.91) 0.52 0.34 (0.08;1.36) 0.13 0.44 (0.14;1.33) 0.15
2.05 (0.91;4.6) 0.082 1.32 (0.59;2.93) 0.5
Mortality
In analyses, EPO and G-CSF were considered to be supportive care treatments rather than treatment lines. ATG: Anti-thymocyte Globulin; CI: Confidence Interval; CsA: Cyclosporine-A; EPO: Erythropoietin; G-CSF: Granulocyte-Colony Stimulating Factor; HR: Hazard Ratio; OR: Odds Ratio.
0.35 (0.13;0.96), P=0.042), eltrombopag (OR 0.12 (0.03;0.54), P=0.0057) and androgens (OR 0.17 (0.05;0.58), P=0.0047) were all individually associated with lower response rates than an ATG-CsA regimen (Table 4).
The main treatment-associated complications were infections, with 35% of treatment lines complicated by at least one grade-III/IV infection, including 9 deaths (5%), and renal issues, with grade-III/IV acute kidney failure after 29% of treatment lines. Other grade-III/IV complica- tions were hepatic or digestive (11%), cardiovascular (9%), hemorrhagic (9%, including 4 deaths (2%)) and neu- rological (2%). In comparison with other treatments, ATG-CsA was associated with significantly more infec- tious (72% vs. 24%, P<0.0001) and cardiovascular compli- cations (32% vs. 15%, P=0.01) and acute kidney failure
(43% vs. 22%, P=0.003). Interestingly, patients aged 70 and over receiving ATG-CsA did not seem to experience any more complications than younger patients, and only one patient in this subgroup died during ATG-CsA treat- ment (Table 5). Four clonal evolutions were recorded: two abnormal karyotypes (1 monosomy of chromosome 7 and 1 t(3;4)), one case of acute myeloid leukemia, and one case of myelodysplastic syndrome with 17% excess blasts.
Overall survival at three years was 74.7%, with median survival of 7.36 years (Figure 1) and a total of 24 patient deaths from the following causes: nine infections (38%), five deaths in palliative care or after active treatment had finished (21%), four hemorrhagic complications (17%), and six miscellaneous causes. Univariate analysis showed that mortality was significantly higher in patients with
haematologica | 2019; 104(2)
259