Mutational patterns in therapy-related acute lymphoblastic leukemia subgroups: one step closer to unveiling the genetic odyssey

Figures & data

Table 1. Patient characteristics in trALL and dnALL.

	trALL	dnALL
	n = 19	n = 112	p value
Median age – years (range)	60 (31–73)	40 (18–76)	<0.001
Female – no. (%)	9 (47)	51 (46)	1.000
Leukemia phenotype – no. (%)
T-ALL	4 (21)	20 (18)	0.751
B-ALL	15 (79)	92 (82)
Cytogenetics – no. (%)
Ph + B-ALL	7 (37)	20 (18)	0.075
KMT2A-rearranged	3 (16)	7 (6)	0.149
normal	4 (21)	21 (19)	0.532
del (5) or monosomy	0 (0)	1 (1)	1.000
del (7) or monosomy	3 (16)	10 (9)	0.404
del 17p	1 (5)	2 (2)	0.381
High hyperdiploidy (51-65 chromosomes)	1 (5)	6 (5)	1.000
Low hypodiploidy (30-39 chromosomes)	1 (5)	4 (4)	0.553
Hypodiploid	0 (0)	2 (2)	1.000
Complex karyotype	4 (21)	46 (41)	0.119
NA	1 (5)	7 (6)	1.000
Comorbidities – no. (%)
None	0 (0)	52 (46)	<0.001
Cardiovascular	3 (16)	21 (19)	1.000
Pulmonary	2 (11)	9 (8)	0.661
Rheumatologic	2 (11)	3 (3)	0.153
Gastrointestinal	0 (0)	8 (7)	0.602
Chronic renal failure	0 (0)	0 (0)	1.000
Endocrine and metabolic	5 (26)	26 (23)	1.000
Neurologic	1 (5)	7 (6)	1.000
Psychiatric	0 (0)	3 (3)	1.000
Oncologic (prior)	19 (100)	9 (8)	<0.001
Other*	3 (16)	9 (8)	0.428
Clinical characteristics at diagnosis**
Hemoglobin – g/l (range)	108 (66–141)	96 (46–169)	0.401
Platelets – G/l (range)	99 (16–253)	63 (1–761)	0.518
Leucocytes – G/l (range)	7.8 (0.6–196)	10.7 (0.5–613)	0.775
Neutrophils – G/l (range)	2.5 (0.1–68)	1.5 (0–32)	0.283
Peripheral blasts – % (range)	20 (0–92)	40 (0–95)	0.181
Bone marrow infiltration – % (range)	87 (30–97)	90 (23–100)	0.262
Splenomegaly – no. (%)	8 (42)	59 (53)	0.302
Lymphadenopathy – no. (%)	3 (16)	42 (38)	0.036
Central nervous system involvement – no. (%)	1 (5)	12 (11)	0.687

Outline of primary cancer treatment, latency to traLL, and cytogenetic abnormalities. A p-value of <0.05 was considered significant.* Other comorbidities include gynecologic, infectious, dermatologic and congenital diseases.** Data given as median with range unless otherwise stated.NA Not available Ph Philadelphia chromosome

Figure 1. Outline of primary cancer treatment, latency to trALL, and cytogenetic abnormalities. Gray shading indicates failed karyotype. * T-lymphoblastic phenotype.

Figure 2. Oncoplot for visualization of mutations in trALL each column represents a patient sample and each row a different gene. The bottom barplot shows the corresponding cytogenetic and immunophenotypic profile. Percentages are rounded to 5% increments. Chr chromosome NA not available Ph Philadelphia chromosome TMB total mutation burden.

Figure 3. Overall survival in trALL shown are Kaplan–Meier plots for overall survival in trALL and dnALL (A) and in the subgroups of Philadelphia chromosome-positive trALL and dnALL (B). Overall survival in patients with and without allogeneic stem cell transplantation is depicted in C. Plots are calculated as the time to death or lost to follow-up, and p values are calculated by the log-rank test. Tick marks indicate censored data.

Data availability statement

A dataset on all trALL patients is provided in the supplementary material. Further requests for data sharing may be submitted to Corinne C. Widmer ([email protected]).