Outcomes and adverse events in older acute lymphoblastic Leukemia patients treated with a pediatric-inspired protocol with Pegylated or native Asparaginase

Figures & data

Table 1. Patients’ characteristics.

	N = 73	EC-ASP (52)	PEG-ASP (21)	p
Gender, Male % (N)	47.9% (35)	50% (26)	42.9% (9)	0.5803^a
Age Median (range)	67.0 (60-86)	67 (60–86)	68 (60-77)	0.9513^b
Age (<70 Years old) % (N)	60.3% (44)	61.5% (32)	57.1% (12)	0.7283^a
Ploidy %, (N)
Hypodiploid	14.9% (7)	17.1% (6)	8.3% (1)	0.8487^c
Diploid	76.6% (36)	74.3% (26)	83.3% (10)
Hyperdiploid	8.5% (4)	8.6% (3)	8.3% (1)
Phenotype, % (N)
B-ALL	82.2% (60)	84.6% (44)	76.2% (16)	0.6807^c
MPAL	6.8% (5)	5.7% (3)	9.5% (2)
T-ALL	11.0% (8)	9.6% (5)	14.3% (3)
Prior malignancy, % (N)	21.9% (16)	25% (13)	14.3% (3)	0.3697^c
EM disease % (N)	18.1% (13)	17.6% (9)	19.0% (4)	1.0000^c
MLL, mut % (N)	5.9% (4)	8.3% (4)	0% (0)-	0.3121^c
CRLF2, yes	2/25	0/7	2/18	1.0000^c
%, (n)	8%	0%	11.1%
Hb, median (range) g/L	91 (59–162)	90.5 (64–162)	91 (59–128)	0.6607^b
WBC, median (IQR) 10*9/L	3.8 (1.9–12.9)	5.4 (2.3–17.9)	1.8 (1.5–3.6)	0.0034^b
WBC count (low) %, N	72.6% (53)	65.4% (34)	90.5% (19)	0.0415^c
PLT, median (IQR) 10*9/L	74.0 (28–144)	75 (25.5–168.5)	73 (30–140)	0.8502^b
BM blasts, median (range) %	76 (0-98)	80 (0-98)	65 (0–97)	0.2172^b
Charlson, %(N)
0–1	63% (46)	61.5% (32)	66.7% (14)	0.6812^a
> = 2	37% (27)	38.5% (20)	33.3% (7)

^a Chi-Square p-value.

^b Wilcoxon rank sum p-value.

^c Fisher Exact p-value.

*EM: extramedullary disease; MLL, mut: mixed-lineage leukemia gene-positivity; CRLF2: Cytokine receptor-like factor 2 overexpression; Hb: Hemoglobin; WBC: White blood cells counts; PLT: Platelets count; BM blasts: bone marrow blasts percentage.

Figure 1. Number of adverse events recorded in the overall population.

Table 2. Adverse event rates at any phase during therapy.

	N = 73
Febrile neutropenia, %(N)	38.4% (N = 28)
Thrombosis, %(N)	35.6% (N = 26)
Transaminitis, %(N)	34.2% (N = 25)
Total bilirubin increase, %(N)	17.8% (N = 13)
Hypo fibrinogen %(N)	31.5% (N = 23)
Pancreatitis	5.5% (N = 4)
Neuropathy	19.2% (N = 14)

Figure 2. Comparison of adverse event rates between patients who received EC-ASP vs PEG-ASP. This figure presents a side-by-side comparison of the adverse events elucidating a comparison between the two formulations.

Figure 3. Overall survival and leukemia-free survival analysis.

Figure 4. (a) Overall survival (OS) by age group. Stratification by age, with a specific focus on patients aged 70 years or older, who had worse OS rates (p = 0.0134), indicating the impact of age on treatment outcomes. (b) Overall survival (OS) by white blood cell count (WBC). Categorizing according to white blood cell count, revealed that patients with a WBC count greater than 30 x 10⁹/L exhibited poorer OS (p = 0.0069), underscoring the prognostic value of WBC count. (c) Overall survival by history of previous malignancy. Patients with a history of malignancy had poorer OS (p = 0.0353), which highlights the influence of pre-existing conditions on treatment efficacy. (d) Overall survival by measurable residual Disease (MRD) status post-induction. This figure evaluates overall survival rates based on MRD status after induction therapy, demonstrating that MRD-positive patients had significantly poorer OS (p = 0.0056), emphasizing the prognostic importance of MRD status.

Figure 5. Overall survival and leukemia-free survival by type of asparaginase used, noting no significant differences in outcomes.

Table 3. Univariate and multivariable overall survival analysis.

Variables associated with overall survival (OS)	Univariate		Multivariable
	% (95%CI)	P (log-rank)	HR (95%CI)	P (Cox model)
MRD status post induction (OS at 12 m)
Negative (26)	85% (64.0–93.9)	p = 0.0056`
Positive (26)	57% (36.4–73.8)
Previous malignancy (OS 24m)
No (n = 57)	65% (51.0–76.3)	p = 0.0353
Yes (n = 16)	44% (17.9–67.9)
Asparaginase (OS 24m)
Peg-asparaginase (21)	66% (95% CI: 37.2–84.1)	p = 0.5703	ref	p = 0.7242
EC- asparaginase (52)	59% (95% CI: 44.4–71.1)		1.17 (0.49–2.76)
Older age (OS at 24m)
<70 years old (n = 44)	73% (56.6–84.2)	p = 0.0134	ref	p = 0.0159
>70 years old (n = 29)	42% (23.4–59.8)		2.28 (1.17–4.47)
WBC count (OS at 24m)
<11 × 10e9/L (low WBC, n = 53)	70% (55.1–80.8)	P = 0.0069	ref	p = 0.0134
>11 × 10e9/L (high WBC, n = 20)	39% (18.6–59.7)		2.43 (1.20–4.92)

*MRD: measurable residual disease; WBC: white blood cell counts.