Prognostic significance of leukopenia during the induction phase in adult B cell acute lymphoblastic leukemia

Figures & data

Figure 1 Flow chart of the patients.

Abbreviations: CR, complete remission; HSCT, hematopoietic stem cell transplantation.

Table 1 Patient characteristics in adult B-ALL cohorts

Variable	All patients (N=51)	WBC-15 <0.40×10^9/L (N=26)	WBC-15 ≥0.40×10^9/L (N=25)	P-value
WBC-15 (×10^9/L), median (range)	0.39 (0.03–18.27)	0.2 (0.03–0.39)	1.2 (0.4–18.27)	0.0000
Age (years), median (range)	38 (14–64)	39 (14–64)	34 (16–57)	0.5214
Age, n (%)
≤35 years	24 (47.1)	10 (38.5)	14 (56.0)	0.210
>35 years	27 (52.9)	16 (61.5)	11 (44.0)
Sex, n (%)
Male	17 (33.3)	8 (30.8)	9 (36.0)	0.692
Female	34 (66.7)	18 (69.2)	16 (64.0)
WBC at diagnosis (×10^9/L), median (range)	11.5 (0.74–972.4)	10.18 (0.74–972.4)	14.4 (1.3–658.41)	0.1317
WBC at diagnosis, n (%)
≤30×10^9/L	35 (68.6)	20 (76.9)	15 (60.0)	0.193
>30×10^9/L	16 (31.4)	6 (23.1)	10 (40.0)
Immunophenotype, n (%)
Pro-B	7 (13.7)	3 (11.5)	4 (16.0)	0.643
Common/pre-B	44 (86.3)	23 (88.5)	21 (84.0)
Cytogenetics, n (%)
Favorable	1 (2.0)	1 (3.8)	0 (0)	0.320
Intermediate	28 (54.9)	12 (46.2)	16 (64.0)
Unfavorable	22 (43.1)	13 (50.0)	9 (36.0)
Risk group, n (%)
Higha	41 (80.4)	20 (76.9)	21 (84.0)	0.525
Standard	10 (19.6)	6 (23.1)	4 (16.0)
Early BM response (day 15)b, n (%)
M1 marrow	21 (41.2)	10 (38.5)	11 (44.0)	0.414
M2 marrow	7 (13.7)	4 (15.4)	3 (12.0)
M3 marrow	5 (9.8)	1 (3.8)	4 (16.0)
Missing data	18 (35.3)	11 (42.3)	7 (28.0)
CR achieved after first induction, n (%)	39 (76.5)	20 (76.9)	19 (76.0)	0.938
Postconsolidation treatment,c n (%)
HSCT	15 (39.5)	8 (38.1)	7 (41.2)	0.847
Maintenance	23 (60.5)	13 (61.9)	10 (58.8)

Notes:

a High-risk group was defined by the presence of at least 1 of the following parameters: age >35 years, WBC count at diagnosis >30×10⁹/L, pro-B phenotype, 2 courses of induction required to achieve CR, and unfavorable cytogenetic features.

b Early BM responses to the treatment on day 15 of induction therapy were defined as follows: M1 marrow <5%, M2 marrow ≤25% and ≥5%, M3 marrow >25%.

c Only patients who completed consolidation in CR are considered.

Abbreviations: B-ALL, B cell acute lymphoblastic leukemia; BM, bone marrow; CR, complete remission; HSCT, hematopoietic stem cell transplantation; WBC, white blood cell; WBC-15, WBC count on day 15.

Figure 2 Kaplan–Meier estimates of EFS and OS in adult patients with B cell acute lymphoblastic leukemia.

Notes: Patients with a WBC-15 <0.40×10⁹/L vs. patients with a WBC-15 ≥0.40×10⁹/L. (A) The 2-year EFS was 52.0%±13.9% (N=26, 95% CI: 23.3%–74.5%) vs. 4.3%±4.2% (N=25, 95% CI: 0.3%–18.2%), respectively, P=0.0020. (B) The 3-year OS was 66.4%±10.8% (N=26, 95% CI: 41.1%–82.8%) vs. 11.2%±7.1% (N=25, 95% CI: 2.1%–29.0%), respectively, P=0.0111. P-values were based on the log-rank test. WBC-15 indicates WBC count on day 15 during induction therapy.

Abbreviations: EFS, event-free survival; OS, overall survival; WBC, white blood cell.

Table 2 Univariate analysis for event-free and overall survival

Variables	Event-free survival			Overall survival
	HR	95% CI	P-value	HR	95% CI	P-value
WBC-15 (×10^9/L) (≥0.40 vs. <0.40)	2.95	1.40–6.23	0.004	2.92	1.23–6.93	0.015
WBC at diagnosis (×10^9/L) (>30 vs. ≤30)	1.34	0.63–2.83	0.442	1.42	0.63–3.18	0.394
Sex (female vs. male)	0.98	0.47–2.03	0.951	0.71	0.32–1.55	0.386
Age (years) (>35 vs. ≤35)	0.93	0.47–1.86	0.837	1.38	0.64–2.96	0.406
Cytogenetics (unfavorable vs. other)	0.96	0.48–1.94	0.917	0.81	0.37–1.78	0.608
Immunophenotype (Pro-B vs. common/pre-B)	0.43	0.13–1.40	0.161	0.43	0.10–1.81	0.248
Early BM response (day 15) (M2/M3 marrow vs. M1 marrow)a	2.03	0.87–4.73	0.102	0.70	0.26–1.88	0.480
Risk group (high vs. standard)	1.50	0.58–3.91	0.407	1.21	0.42–3.55	0.723
Postconsolidation treatment (HSCT vs. maintenance)	0.62	0.25–1.59	0.322	0.49	0.16–1.44	0.191

Notes:

a Only including 33 patients with available data on early BM response at day 15 of the induction therapy.

Abbreviations: BM, bone marrow; HR, hazard ratio; HSCT, hematopoietic stem cell transplantation; WBC, white blood cell; WBC-15, WBC count on day 15.

Table 3 Multivariate analysis for event-free and overall survival

Covariate	Event-free survival			Overall survival
	HR	95% CI	P-value	HR	95% CI	P-value
WBC-15 (≥0.40×10^9/L vs. <0.40×10^9/L)	3.29	1.28–8.49	0.014	3.29	1.07–10.09	0.038
Early BM response (day 15) (M2/M3 marrow vs. M1 marrow)a	2.00	0.85–4.70	0.114	0.62	0.23–1.66	0.339

Notes:

a Only including 33 patients with available data on early BM response at day 15 of the induction therapy.

Abbreviations: BM, bone marrow; HR, hazard ratio; WBC, white blood cell; WBC-15, WBC count on day 15.

Table S1 Treatment and follow-up of the 51 adult B-ALL patients

Group	Case	Therapy	Response	Status	OS (months)
WBC-15 <0.40×10^9/L	1	Induction	CR	Alive	70.7
		Consolidation	CR
		HSCT	CR
WBC-15 <0.40×10^9/L	2	Induction	CR	Alive	32.1
		Consolidation	CR
		HSCT	CR
WBC-15 <0.40×10^9/L	3	Induction	Non-CR	Dead	16.0
		Reinduction	CR
		Consolidation	Relapse
WBC-15 <0.40×10^9/L	4	Induction	Non-CR	Dead	15.8
		Reinduction	CR
		Consolidation	CR
		Maintenance	Relapse
WBC-15 <0.40×10^9/L	5	Induction	CR	Alive	21.7
		Consolidation	CR
		Maintenance	CR
WBC-15 <0.40×10^9/L	6	Induction	CR	Dead	6.7
		Consolidation	Relapse
WBC-15 <0.40×10^9/L	7	Induction	CR	Alive	19.3
		Consolidation	CR
		Maintenance	CR
WBC-15 <0.40×10^9/L	8	Induction	CR	Alive	19.0
		Consolidation	CR
		Maintenance	CR
WBC-15 <0.40×10^9/L	9	Induction	CR	Alive	18.9
		Consolidation	CR
		Maintenance	CR
WBC-15 <0.40×10^9/L	10	Induction	CR	Dead	13.6
		Consolidation	CR
		Maintenance	Relapse
WBC-15 <0.40×10^9/L	11	Induction	CR	Alive	17.0
		Consolidation	CR
		HSCT	CR
WBC-15 <0.40×10^9/L	12	Induction	Non-CR	Alive	15.5
		Reinduction	CR
		Consolidation	CR
		Maintenance	CR
WBC-15 <0.40×10^9/L	13	Induction	CR	Alive	14.5
		Consolidation	CR
		Maintenance	CR
WBC-15 <0.40×10^9/L	14	Induction	CR	Alive	13.3
		Consolidation	CR
		Maintenance	CR
WBC-15 <0.40×10^9/L	15	Induction	NA	Dead	0.8
WBC-15 <0.40×10^9/L	16	Induction	CR	Alive	49.4
		Consolidation	CR
		HSCT	CR
WBC-15 <0.40×10^9/L	17	Induction	Non-CR	Dead	5.0
		Reinduction	CR
		Consolidation	CR
WBC-15 <0.40×10^9/L	18	Induction	CR	Alive	36.6
		Consolidation	CR
		HSCT	CR
WBC-15 <0.40×10^9/L	19	Induction	CR	Alive	36.3
		Consolidation	CR
		Maintenance	Relapse
WBC-15 <0.40×10^9/L	20	Induction	CR	Dead	9.9
		Consolidation	Relapse
WBC-15 <0.40×10^9/L	21	Induction	Non-CR	Alive	45.9
		Reinduction	CR
		Consolidation	CR
		HSCT	CR
WBC-15 <0.40×10^9/L	22	Induction	CR	Alive	8.6
		Consolidation	CR
		HSCT	CR
WBC-15 <0.40×10^9/L	23	Induction	CR	Alive	8.3
		Consolidation	CR
		Maintenance	CR
WBC-15 <0.40×10^9/L	24	Induction	CR	Alive	12.7
		Consolidation	CR
		HSCT	CR
WBC-15 <0.40×10^9/L	25	Induction	CR	Alive	6.8
		Consolidation	CR
		Maintenance	CR
WBC-15 <0.40×10^9/L	26	Induction	CR	Alive	6.6
		Consolidation	CR
		Maintenance	CR
WBC-15 ≥0.40×10^9/L	27	Induction	CR	Dead	22.1
		Consolidation	CR
		HSCT	Relapse
WBC-15 ≥0.40×10^9/L	28	Induction	Non-CR	Dead	24.4
		Reinduction	CR
		Consolidation	CR
		Maintenance	CR
WBC-15 ≥0.40×10^9/L	29	Induction	CR	Dead	14.5
		Consolidation	CR
		Maintenance	Relapse
WBC-15 ≥0.40×10^9/L	30	Induction	CR	Dead	23.7
		Consolidation	CR
		Maintenance	Relapse
WBC-15 ≥0.40×10^9/L	31	Induction	CR	Dead	20.4
		Consolidation	CR
		HSCT	Relapse
WBC-15 ≥0.40×10^9/L	32	Induction	CR	Dead	5.7
		Consolidation	Relapse
WBC-15 ≥0.40×10^9/L	33	Induction	CR	Dead	7.2
		Consolidation	CR
		Maintenance	CR
WBC-15 ≥0.40×10^9/L	34	Induction	non-CR	Dead	2.8
		Reinduction	Non-CR
WBC-15 ≥0.40×10^9/L	35	Induction	CR	Dead	11.8
		Consolidation	Relapse
WBC-15 ≥0.40×10^9/L	36	Induction	CR	Dead	21.5
		Consolidation	CR
		HSCT	CR
WBC-15 ≥0.40×10^9/L	37	Induction	CR	Dead	8.2
		Consolidation	CR
		Maintenance	CR
WBC-15 ≥0.40×10^9/L	38	Induction	CR	Dead	10.0
		Consolidation	Relapse
WBC-15 ≥0.40×10^9/L	39	Induction	Non-CR	Alive	53.6
		Reinduction	CR
		Consolidation	CR
		HSCT	CR
WBC-15 ≥0.40×10^9/L	40	Induction	CR	Dead	3.4
		Consolidation	CR
WBC-15 ≥0.40×10^9/L	41	Induction	CR	Alive	26.3
		Consolidation	CR
		Maintenance	CR
WBC-15 ≥0.40×10^9/L	42	Induction	CR	Dead	14.8
		Consolidation	Relapse
WBC-15 ≥0.40×10^9/L	43	Induction	Non-CR	Alive	10.4
		Reinduction	Non-CR
WBC-15 ≥0.40×10^9/L	44	Induction	CR	Dead	24.6
		Consolidation	CR
		HSCT	Relapse
WBC-15 ≥0.40×10^9/L	45	Induction	CR	Alive	48.5
		Consolidation	CR
		Maintenance	Relapse
WBC-15 ≥0.40×10^9/L	46	Induction	CR	Dead	14.0
		Consolidation	CR
		HSCT	Relapse
WBC-15 ≥0.40×10^9/L	47	Induction	Non-CR	Dead	16.1
		Reinduction	CR
		Consolidation	CR
		Maintenance	CR
WBC-15 ≥0.40×10^9/L	48	Induction	CR	Dead	31.1
		Consolidation	CR
		Maintenance	Relapse
WBC-15 ≥0.40×10^9/L	49	Induction	CR	Dead	27.4
		Consolidation	CR
		Maintenance	Relapse
WBC-15 ≥0.40×10^9/L	50	Induction	CR	Alive	8.9
		Consolidation	CR
		HSCT	CR
WBC-15 ≥0.40×10^9/L	51	Induction	NA	Dead	1.0

Abbreviations: B-ALL, B cell acute lymphoblastic leukemia; CR, complete remission; HSCT, hematopoietic stem cell transplantation; NA, not available; OS, overall survival; WBC, white blood cell; WBC-15, WBC count on day 15.