Relapse of childhood acute lymphoblastic leukemia and outcomes at a reference center in Latin America: organomegaly at diagnosis is a significant clinical predictor

Figures & data

Figure 1. Consort diagram showing relapse percentage, sites and time of relapse for 246 children with ALL. For clarity, one patient who relapsed to the testis is not shown. Fourteen patients (5%) abandoned treatment and 13 (4.8%) received chemotherapy at other institutions.

Table 1. Characteristics of the 246 children with ALL included in the study.

Characteristics	n (%)
Age, median (years)	5
Sex
Male	131 (53.3)
Female	115 (46.7)
Adenopathy
Yes	58 (23.6)
No	188 (76.4)
Organomegaly
Yes	91 (37)
No	155 (63)
WBC × 10^9 /l
<50 000/µl	194 (78.9)
>50 000/µl	52 (21.1)
Initial CNS involvement
Present	21 (8.5)
Absent	225 (91.5)
Immunophenotype
B-cell	234 (95.1)
T-cell	12 (4.9)
PDN response
Good	222 (90.2)
Poor	24 (9.8)
Risk at diagnosis
High risk	137 (55.7)
Standard risk	109 (44.3)

Figure 2. EFS at 5 years in 246 children newly diagnosed with ALL without organomegaly at diagnosis was 72.1% (95% CI 72.02–72.18) vs. 24.5% (95% CI 24.39–24.61) in those with organomegaly, p < 0.001.

Table 2. Time and causes of death for 75 children with ALL.

Timing of death	n (%)	Median (range)
Death during induction (%)	15 (20)	0.87 (0.14–1.17)
During CR	9 (12)	10.51 (2.69–41.30)
In relapsed patients (%)	51 (68)	23.35 (4.14–130.04)
Causes of death	n (%)	Median (range), months
Septic shock (%)	32 (42.67)	13.78 (0.46–118.77)
Intracranial hemorrhage	8 (10.67)	20.02 (0.72–49.22)
Gastrointestinal bleeding	6 (8)	23.65 (1.35–54.05)
Pulmonary hemorrhage	6 (8)	10.80 (1.38–53.59)
Pulmonary edema	5 (6.67)	21.24 (1.31–129.61)
Heart failure	2 (2.67)	24.52 (11.10–37.95)
Pneumonia	2 (2.67)	11.43 (0.69–22.18)
Acute respiratory insufficiency	1 (1.33)	11.10
DIC	1 (1.33)	53.52
Leukoencephalopathy	1 (1.33)	23.36
Tumor lysis syndrome	1 (1.33)	0.62
Unspecified	10 (13.33)	38.20 (0.99–130.04)

Note: CR: complete remission, DIC: disseminated intravascular coagulation.

Table 3. HR for death (s OS) and treatment failure (-f EFS) according to uni- and multivariate Cox’s proportional regression analysis for ALL in children and its association with clinical and laboratory characteristics.

Factors	n	OS					EFS
		% 5 year OS	Univariate HR	p	Multivariate HR	p	% 5 year EFS	Univariate HR	p	Multivariate HR	p
Age at diagnosis (years)
1–10	163	71	1.88 (1.19–2.99)	0.007	0.80 (0.28–2.27)	0.68	54.5	1.59 (1.09–2.33)	0.01	1.23 (0.47–3.19)	0.67
<1 or >10	83	50.9					35.1
Gender
Male	131	57.6	1.30 (0.82–2.06)	0.26	0.98 (0.42–2.27)	0.96	40.7	1.77 (1.20–2.62)	0.004	1.68 (0.87–3.22)	0.12
Female	115	70.7					56.2
WBC at diagnosis
<50 000	52	69	2.31 (1.40–3.79)	0.001	0.67 (0.20–2.20)	0.51	54.1	2.30 (1.53–3.48)	<0.001	0.51 (0.21–1.24)	0.14
>50 000	194	43.4					22.1
immunophenotype
B	234	66.7	3.75 (1.85–7.60)	<0.001	1.07 (0.14–8.10)	0.94	48.4	1.88 (0.87–4.05)	0.108	0.69 (0.04–5.64)	0.73
T	12	13.6					37.5
ICNS
Yes	21	69.6	0.96 (0.43–2.12)	0.92	0.36 (0.07–1.85)	0.22	36.7	1.33 (0.70–2.51)	0.37	1.37 (0.48–3.92)	0.55
No	225	63.2					48.5
Adenopathy
Yes	58	66.1	1.07 (0.60–1.94)	0.82	0.78 (0.30–2.03)	0.60	36.3	1.33 (0.86–2.06)	0.20	0.95 (0.47–1.89)	0.88
No	188	64					50.1
Organomegaly
Yes	91	53.8	1.75 (1.10–2.77)	0.017	1.85 (0.73–4.73)	0.20	21.7	2.79 (1.91–4.07)	<0.001	2.65 (1.28–5.49)	0.008
No	155	69.5					62.4
CD10 antigen
Yes	216	69.2	2.96 (1.75–5.00)	<0.001	2.00 (0.40–9.93)	0.40	49.2	1.36 (0.72–2.56)	0.35	1.08 (0.23–4.96)	0.92
No	30	38.9					39.7
Risk at diagnosis
High risk	137	51	3.33 (1.91–5.81)	<0.001	4.84 (1.31–17.93)	0.02	33.9	2.47 (1.64–3.74)	<0.001	1.72 (0.65–4.59)	0.27
Standard risk	109	80.9					66.3
Steroid response
Good	222	66.6	3.04 (1.54–6.00)	0.001	1.23 (0.37–4.08)	0.73	51.4	3.16 (1.87–5.36)	<0.001	2.56 (1.05–6.25)	0.03
Poor	24	17.3					15.2
MRD (n = 126)
Positive	48	43.4	1.07 (0.50–2.26)	0.866	0.72 (0.32–1.64)	0.44	43.5	1.27 (0.73–2.22)	0.39	1.18 (0.64–2.17)	0.58
Negative	78	58					53.0

Note: WBC: white blood cell count, ICNS: infiltrated central nervous system, MRD: minimal residual disease.

Figure 3. Five-year OS in BM relapsed patients was significantly lower, 11.2% (95% CI 11.09–11.31) vs. 50.8% (95% CI 50.63–50.97) in extramedullary or combined relapse, p < 0.001.