Outcome of childhood acute Lymphoblastic leukemia in Egyptian children: A challenge for limited health resource countries

Figures & data

Table 1. Detailed protocol of treatment of different risk stratification of childhood ALL

Standard risk	High–risk standard arm	High-risk augmented arm
Consolidation SR (1 month)	Consolidation HR-SA (5 weeks)	Consolidation HR-AA (9 weeks)
IV VCR 1.5 mg/m^2 D0	PO 6 MP 60 mg/m^2 D0–27	IV CPM: 1000 mg/m^2 D0, 28
PO 6MP 75 mg/m^2/ D0–27	IV CPM: 1000 mg/m^2 D0, 14	IV or S.Q Ara-C 75 mg/m D1–4, 8–11, 29–32, 36–39
IT MTX (D7, 14, 21)	IV or SQ Ara-C 75 mg/m^2 D1–4, 8–11, 22–25	PO 6MP 60 mg/m^2 D0–13, 28–41
	IT MTX D0, 7, 14, 21	IV VCR 1.5 mg/m^2 D14, 21, 42, 49
	Testicular RTX (for testicular disease)	IM l-Aspar 6000 IU/m^2/thrice/week (6 doses × 2)
		IT MTX D0, 7, 14*, 21*
		Radiation therapy (CNS disease)
Interim maintenance SR (I and II) (2 months)	Interim maintenance HR-SA (2 months)	Interim maintenance I and II (2months) HR-AA
IT MTX D0, 28	PO MTX 15 mg/m^2 D7, 14, 21, 35	IV VCR 1.5 mg/m^2 D0, 20, 30, 40
IV VCR1.5 mg/m^2 D0, 28	PO 6 MP 60 mg/m^2 D0–14	IV MTX 100 mg/m^2 escalate by 50 mg/m^2/dose D0, 10, 20, 30, 40
PO Dex 6 mg/m^2 × 5 D0, 28	IT MTX D0	IM l-Aspar 15000 IU/M2.1 day after MTX D1, 11, 21, 31, 41
PO MP 75 mg/m^2 D0–49		IT MTX D0
PO MTX 20 mg/m^2 D0, 7, 14, 21, 35, 42, 49
Delayed intensification (SR)	Delayed intensification (HR-SA)	Delayed intensification (HR-AA)
IT MTX D0, 28	IV VCR 1.5 mg/m–D0, 7, 14	IV VCR 1.5 mg/m^2 D0, 7, 14, 42, 49
IV VCR 1.5/m^2 D0, 7, 14	IV Doxo 25 mg/m^2–D 0, 7, 14	IV Doxo 25 mg/m^2 D0, 7, 14
IV Doxo 25 mg/m^2 D0, 7, 14	PO Dexa 10 mg/m^2/d D0–7, D14–21	PO Dexa 10 mg/m^2 D0–21
PO Dex 10 mg/m^2 D0–6, 14–20	IM l-Aspar 6000 IU/m^2/thrice/week (6 doses)	IM l-Aspar 6000 IU/m^2/thrice/week D3 (6 doses) and 42 (6 doses)
IM l-Aspar 6000 IU/m^2 × 6 doses	IV CPM 1000 mg/m^2 D28	IV CPM 1000 mg/m^2 D28
IV CPM1000 mg/m^2 D28	PO 6TG 60 mg/m^2 × 14 D28–42	PO 6TG 60 mg/m^2 × 14 D28–41
PO MP 60 mg/m^2 D28–42	IV or S.Q ARA-C 75 mg/m^2 D29–32, 36–39	IV or S.Q ARA-C 75 mg/m^2 D29–32, 36–39
SQ, IV ARA-C 75 mg/m^2 D28–31, 35–38	IT MTX 0, 28, 35	IT MTX D0, 28

VCR, vincristine; DOX, doxorubicin; Dex, dexamethasone; 6MP, 6mercaptopureine; MTX, methotrexate; TG, thioguanine; CPM, cyclophosphamide.

*Without CNS disease.

Table 2. Presenting clinical and laboratory data of included ALL patients

Age (years)
Range	2–15
Mean (SD)	5.9 (3.3)
Age groups, N (%)
<10 years	46 (88.5)
≥10 years	6 (11.5)
Sex, N (%)
Male	32 (61.5)
Female	20 (38.5)
Clinical presentation, N (%)
Enlarged lymph nodes	17 (32.7)
Hepatomegaly	37 (71.2)
Splenomegaly	35 (67.3)
CNS disease	3 (5.8)
Hemoglobin (g/dl)
Range	3.6–8.0
Mean (SD)	6.1 (1.5)
WBCs (×10^3/dl)
Range	1.0–530.0
Mean (SD)	19.9 (31.6)
WBCs risk groups N (%)
<10 × 10^3/dl	19 (36.5)
≥10 – <50 × 10^3/dl	17 (32.7)
≥50 × 10^3/dl	16 (30.8)
Platelets (×10^3/dl)
Range	20–121
Mean (SD)	61.0 (34.1)
Immunophenotype, N (%)
T-cell	14 (26.9)
Precursor-B	38 (73.1)

Table 3. Clinical and laboratory data of ALL patients at presentation according to their immunophenotype

Observations	T-cell	Precursor-B	P value
Age (years)
<10	10 (21.4)	36 (78.6)	0.041
≥10	4 (66.7)	2 (33.3)
Mean (SD)	7.8 (4.6)	5.1 (2.2)
Sex
Male	10 (31.3)	22 (68.8)
Female	4 (20.0)	16 (80.0)	NS
Enlarged lymph nodes, N (%)	4 (28.6)	13 (34.2)	NS
Enlarged liver	10 (71.4)	27 (71.1)	NS
Enlarged spleen	10 (71.4)	25 (68.8)	NS
CNS leukemia	1 (7.4)	2 (5.3)	NS
Hemoglobin (g/dl)
Mean (SD)	8.3 (2.0)	6.0 (1.9)	0.001
WBCs (×10^3/dl)
Mean (SD)	143.3 (135.2)	20.4 (27.6)	0.005
Min–Max	16.6–530.0	1.0–135.0
Neutrophils (×10^3/dl), mean (SD)	17.2 (23.8)	6.4 (8.7)	NS
Platelets (×10^3/dl), mean (SD)	98.7 (93.4)	65.6 (55.5)	NS
Standard risk	–	25 (69.4)
High-risk standard arm	10 (71.4)	6 (16.7)	<0.001
High-risk augmented arm	4 (28.6)	5 (13.9)

Figure 1. OS function from diagnosis (till death) among ALL patients adopting modified CCG-based protocol.

Figure 2. OS function from diagnosis (till death) among ALL patients adopting different arms of CCG.

Table 4. Serious adverse events/relapse data of the studied group

Patient ID	Protocolreceived	Event type	Phase oftherapy	Outcome	Cause of death
Serious adverse events
2	HR SA	Sepsis	Maintenance	Died in CR1	Septic shock
3	HR SA	Hand and CNS thrombosis	Maintenance	Died in CR1	CNS thrombosis
6	SR	CNS thrombosis	Induction	Alive Convulsions	NA
13	HR AA	Intracranial hemorrhage	Induction	No neurological sequelae	Hepatic encephalopathy
		Liver cell failure HCV related	Maintenance	Died in CR1
23	HR AA	CNS infection	Induction	Resolved-alive	NA
25	HR SA	Sepsis, diarrhea, hypokalemia	Induction	Died in CR1	Septic shock
Relapse data
27	SR	BM, testicular	Off chemo	Died	Relapse and bronchopneumonia
34	SR	Testicular	IM 1	Alive	NA
35	SR	BM	Off chemo	Alive	NA
45	HR SA	BM	Maintenance	Died	Relapse and bleeding
46	HR SA	BM	Maintenance	Died	Relapse and fungal pneumonia
48	HR AA	Extra medullary	IM 2	Alive	NA