Tyrosine kinase inhibitors and reduced-dose chemotherapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia

Figures & data

Table 1. Chemotherapy regimens.

Treatment phases	Drugs	Doses	Route	Schedules
Prephase	Prednisone	60 mg/d	PO	D-3 to −1
	Cyclophosphamide	200 mg/m^2	IV	D-3 to −1
Frontline induction (4 weeks)
Standard chemotherapy	Vincristine	2 mg/d	IV	D1,8,15,22
(VDCP)	Danuorubicin	40 mg/m^2/d	IV	D1-3
	Cyclophosphamide	750 mg/m^2	IV	D1
	Prednisone	1 mg/m^2/d	PO	D1-14,15-28(2/3dose)
Reduced-dose chemotherapy	Vincristine	2 mg/d	IV	D1,8,15,22
(VP)	Prednisone	1 mg/m^2/d	PO	D1-14,15-28(2/3dose)
Early-stage consolidation block
CAM	Cyclophosphamide	750 mg/m^2	IV	D1,8
	Cytarabine	100 mg/m^2/d	IV	D1-3,8-10
	Mercaptopurine	60 mg/m^2/d	PO	D1-7
HD-MTX + VP	Methotrexate	3 g/m^2	IV	D1
	Vincristine	2 mg/d	IV	D8
	Dexamethasone	6 mg/m^2/d	IV	D8-15
MA	Mitoxatrone	8 mg/m^2/d	IV	D1-3
	Cytarabine	750 mg/m^2	IV	D1-3
Late-stage consolidation block
VDCD	Vincristine	2 mg/d	IV	D1,8,15,22
	Danuorubicin*	40 mg/m^2/d	IV	D1-3
	Cyclophosphamide	750 mg/m^2	IV	D1, D15
	Dexamethasone	8 mg/m^2/d	PO	D1-7, D15-21
COAD	Cyclophosphamide	750 mg/m^2	IV	D1
	Vincristine	2 mg/d	IV	D1
	Cytarabine	100 mg/m^2/d	IV	D1-7
	Teniposide	100 mg/m^2/d	IV	D1-4
	Dexamethasone	8 mg/m^2/d	IV	D1-7
HD-MTX	Methotrexate	3 g/m^2	IV	D1
	Vincristine	2 mg/d	IV	D8
	Dexamethasone	6 mg/m^2/d	IV	D8-15
TA	Teniposide	100 mg/m^2/d	IV	D1-4
	Cytarabine	100 mg/m^2/d	IV	D1-7
Long-term maintenance (until 36 months)	Methotrexate	2 mg/m^2/week	PO	D8 for every 4 weeks
	6-Mercaptopurine	40 mg/m^2/d	PO	D1-7 for every 4 weeks

IV, intravenous; IM, intramuscular; PO, oral. *Or idarubicin 8 mg/(m2/d). Intrathecal (IT) chemotherapy: cytarabine (50 mg) and/ormethotrexate (10 mg), and dexamethasone (5 mg). Patients received at least 8 intrathecal chemotherapy treatments administered during the consolidationcourses as a prophylactic for relapse in the CNS.

Table 2. Patient characteristics.

Group	Standard chemotherapy group(n = 143)	Reduced-dose chemotherapy group(n = 62)	P	Transplant group(n = 55)	Non-transplant group(n = 143)	P
Gender, n (%)			0.176			0.307
Male	77 (53.8)	27 (43.5)		31 (56.4)	69 (48.3)
Female	66 (46.2)	35 (56.5)		24 (43.6)	74 (51.7)
Age(years), mean (range)	39(14-73)	41 (14-73)	0.467	31 (14-59)	42 (14-73)	<0.001
WBC count (×10^9/L)	89.93 (1.50-504.64)	78.17 (1.10-974.82)	0.515	77.86 (1.10-470.84)	89.48 (1.50-974.82)	0.552
HB (g/L)	91 (32-160)	90 (43-161)	0.921	87 (32-160)	91 (38-161)	0.335
PLT count (×10^9/L)	59 (1-356)	52 (3-329)	0.525	58 (4-248)	57 (1-356)	0.937
Chromosome type, n (%)			0.208			0.888
Ph+ only	40 (28.0)	12 (19.4)		12 (21.8)	39 (27.3)
Ph+ plus additional changes	30 (21.0)	21 (33.9)		14 (25.5)	35 (24.5)
Normal karyotype	44 (30.8)	19 (30.6)		18 (32.7)	43 (30.1)
Unknown	29 (20.2)	10 (16.1)		11 (20.0)	26 (18.2)
BCR-ABL1, n (%)			0.244			0.675
P190	59 (41.3)	24 (38.7)		21 (38.2)	58 (40.6)
P210	31 (21.7)	20 (32.3)		16 (29.1)	33 (23.1)
Unknown	53 (37.0)	18 (29.0)		18 (32.7)	52 (36.4)
TKIs received			0.315			0.822
First-generation	106 (74.1)	50 (80.7)		42 (76.4)	107 (74.8)
Second-generation	37 (25.9)	12 (19.3)		14 (25.4)	35 (24.5)
Year of initial diagnosis			0.128			<0.001
2010-2015	50 (35.0 )	27 (43.5)		15 (27.3)	60 (42.0)
2015-2020	93 (65.0)	35 (56.5)		40 (72.7)	83 (58.0)

Table 3. Response at the end-of-induction.

	All patients(n = 205)	Standard chemotherapy group(n = 143)	Reduced-dose chemotherapy group(n = 62)	P
Hematologic CR, n (%)	175 (85.4)	120 (83.9)	55 (88.7)	0.375
MMR, n/tested (%)	79/139 (56.8)	56/100 (56.0)	23/39 (58.9)	0.750
MCR, n/tested (%)	30/139 (21.6)	22/100 (22.0)	8/39 (20.5)	0.891
Early mortality, n (%)	7 (3.4)	5 (3.5)	2 (3.2)	0.922

Figure 1. Simon–Makuch plotsfor overall survival (A) and disease-free survival (B) in all Ph-positive ALL.

Figure 2. Cumulative incidence curves for relapse and non-relapse mortality(NRM) in all Ph-positive ALL.

Figure 3. Forest plot summarizing the multivariable model for OS in all Ph-positive ALL.

Data availability statement:

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. All data and materials support the published claims and comply with field standards. All the content has not been published elsewhere, nor is it under consideration for publication anywhere else.