. Author manuscript; available in PMC: 2014 Feb 1.

Published in final edited form as: Pediatr Blood Cancer. 2012 Jun 12;60(2):185–195. doi: 10.1002/pbc.24228

Table I.

Summary of CNS-directed treatments

Trial	Year	Ref	CNS-directed therapy
A: TIT versus IT therapy
^*CCG-1952	1996	11	DITa × 1 + IT MTX × 1 R: TITa × 14 (f) or 18 (m) v IT MTX × 14 (f) or 18 (m)
B: Radiotherapy plus IT therapy versus extra IT therapy
a Radiotherapy v IT therapy
CCG-161	1978	12	IT MTX × 6 R: 18 Gy CRT v IT MTX × 8
CCG-105	1983	13	IT MTX × 6 R: 18 Gy CRT v IT MTX × 8 (f) or 14 (m)
INEN-P83	1983		IT MTX × 5 R: 18 Gy CRT v IT MTX × 12
CCG-1882	1989	14	IT MTX × 14 (f) or 18 (m) + IT AraC × 1 R: 18 Gy CRT v IT MTX × 7
b Radiotherapy (+ IT) v DIT or TIT therapy
^†SWOG 7623/AlinC12	1976	15	R: 24 Gy CRT + IT MTX × 5 v TITa × 22
LAL 7/78	1978	16	R: 24 Gy CRT + IT MTX × 6 v DITa × 10
INS 84	1984	17	TITa × 6 R: 18Gy CRT v TITa × 12
INEN-P85	1985		R: 18 Gy CRT + IT MTX × 5 v TITa × 17
c Radiotherapy + DIT v TIT therapy
^*DFCI ALL 95-001	1996	18	IT AraC × 1 + TITa × 2 R: 18Gy CRT + DITa × 6 v TITa × 12
C: Addition of IV methotrexate to long-term IT therapy or radiotherapy with IT therapy
a TIT therapy +/- IV methotrexate
SJCRH Total XIIIA	1991	19	TITa × 13 or 17 + 2 g/m²IV MTX × 9 or 10 R: ± 1 g/m² IV MTX × 1
^*POG 9005	1991	20	1 g/m² IV mp × 17–19 + TITA × 16 R: ± 1 g/m² IV MTX × 12
FRALLE 93 LR	1993	21	TITc × 16 R: ± 1·5 g/m² IV MTX × 6
FRALLE 93 IR	1993	21	TITc × 18 R: ± 8 g/m² IV MTX × 4
^*SJCRH Total XIIIB	1994	22	1 g/m² IV mp + TITa × 13 or 15 + 2 g/m² IV MTX × 10 R: ± 1 g/m² IV MTX × 1
b IT therapy +/- IV methotrexate
CCG-139	1984	23	IT MTX × 15 (f) or 20 (m) R: ± 0·5 g/m² IV MTX × 24 (f) or 33 (m)
DFCI 87001	1987	24	IT AraC × 1 + IT MTX × 10 (HR: + 18 Gy CRT) R: ± 4 g/m² IV MTX × 1
UKALLXI LWCC	1990	25	IT MTX × 16 R: ± 6–8 g/m² IV MTX × 3
c Radiotherapy with IT therapy +/- IV methotrexate
DFCI 81001	1981	26	18 or 28 Gy CSCRT + IT AraC × 1 + IT MTX × 8 R: ± 4 g/m²IV MTX × 1
^*POG 9404	1994	27	TITa × 11 + 18 Gy CRT R: ± 5 g/m² IV MTX × 4
D: IV methotrexate + IT therapy v TIT
^*POG8035/8036	1981	28	TITa × 6 R: 1 g/m² IV MTX × 17 + IT MTX × 4 v TITa × 17
E: Addition of IT therapy to radiotherapy plus short-term IT therapy
^†CALGB-7113	1971	29	24 Gy CRT + IT MTX × 12 R: ± IT MTX × 3
CCG-162	1978	30	18 Gy CRT + IT MTX × 6 R: ± IT MTX × 8
UKALLVII	1979	31	18 or 24 Gy CRT + IT MTX × 5 R: ± IT MTX × 8
F: Radiotherapy plus IT therapy v IV methotrexate plus IT therapy
CLB 7611	1976	32	IT MTX × 6 R: 24 Gy CRT v 0·5 g/m² IV MTX × 3
^†NCI 77-02	1980	33	R: 18–24 Gy CRT + IT MTX × 5 v 33·6 g/m² IV MTX × 10
ALL-BFM-81	1981	34	IT MTX × 6 R: 12–18 Gy CRT v 0·5 g/m² IV MTX × 4
Jena ALL VII 81	1981	35	IT MTX × 8 R: 18 Gy CRT v 0·5 g/m² IV MTX × 4
JCCLSG L-874	1987	36	DITb × 3 R: 18 Gy CRT v 2 g/m² IV MTX × 3 + DITb × 6
JCCLSG I-874	1987	36	(2 g/m² × 1 + 4·5 g/m² × 20) IV MTX + DITb × 1 R: 18 Gy CRT + DITb × 2 v 4·5 g/m² IV MTX × 3
GCMTLA	1988	37	TITb × 6 R: 12–18 Gy CRT v 0·5 g/m² IV MTX × 4 + TITb × 6
^†TCCSG L89-12	1989	38	TITa × 4 + DITa × 3 R: 18 Gy CRT v 3 g/m² IV MTX
UKALLXI HWCC	1990	25	IT MTX × 7 or 9 R: 24 Gy CRT v 6–8 g/m² IV MTX × 3 + IT MTX × 8 or 9
^†TCCSG L92-13 HR	1992	38	DITb × 4 + TITa × 3 R: 18 Gy CRT + DITb × 1 v 3 g/m² IV MTX × 2
^*MRC ALL97	1997	39	IT MTX × 7 or 9 R: 24 Gy CRT v 6–8 g/m² IV MTX × 3 + IT MTX × 8 or 9
G: Higher dose of IV methotrexate
^*POG 9405	1994	40	TITa × 22 R: 2·5 g/m² IV MTX × 12 v 1 g/m² IV MTX × 12
^*POG 9406	1994	40	TITa × 18 + 1 g/m² IV mp × 6 R: 2·5 g/m² IV MTX × 6 v 1 g/m² IV MTX × 6
H: Higher doses of radiotherapy
UKALL V	1976	41	IT MTX × 5 R: 24 Gy v 21 Gy CRT
UKALLVI(i)	1978	42	IT MTX × 8 or IT MTX × 6 + IT AraC × 2 + 0·5 g/m² IV MTX × 3 R: 24 Gy v 21 Gy CRT
UKALLVI(ii)	1978	42	IT MTX × 8 or IT MTX × 6 + IT AraC × 2 + 0·5 g/m² IV MTX × 3 R: 24 Gy v 18 Gy CRT
UKALLVII	1979	31	IT MTX × 5 R: 24 Gy v 18 Gy CRT
GBTLI-80	1980	43	IT MTX × 13 R: 24 Gy v 18 Gy CRT
TCCSG L81-10	1981	44	DITa × 5 R: 24 Gy v 18 Gy CRT
ALL-BFM-83	1983	34	IT MTX × 8 + 0·5 g/m² IV MTX × 4 R: 18 Gy v 12 Gy CRT
I: Addition of radiotherapy
a Addition to IT
^†POG CNS2	1970	45	IT MTX × 20 R: ± 24 Gy CRT
^†CLB 7111	1971	46	IT MTX × 6 R: ± 24 Gy CRT
^†SWOG 690/691/Alinc9	1971	47	TITa × 10 R: ± 18–24 Gy CRT
^†DFCI-SFCC	1972	48	IT MTX × 9 R: ± 24 Gy CRT
^†CLB 7411	1974	49	IT MTX × 6 R: ± 24 Gy CRT
CCG-101	1974	50	IT MTX × 6 R: ± 24 Gy CRT
^*CCG-123	1983	51	IT AraC × 1 + IT MTX × 6 R: ± 18Gy CRT
b Addition to IV with IT
EORTC 58832	1983	52	2·5 g/m² IV MTX × 4 + IT MTX × 7 R: ± 16–20 Gy CRT
J: Higher dose of IV methotrexate v more IT or DIT therapy
FRALLE 87	1987	53	DITc × 5 R: 8 g/m² IV MTX × 4 v 3 g/m² IV MTX × 4 + DITc × 5
FRALLE 89	1989	21	IT MTX × 5 R: 8 g/m²IV MTX × 4 v 3 g/m²IV MTX × 4 + IT MTX × 5
K: Addition of IV methotrexate plus IT, DIT or TIT therapy to radiotherapy plus IT or TIT therapy and/or IV methotrexate
Jena ALLVII 81	1981	35	12 or 18 Gy CRT + IT MTX × 8 R: ± 0·5 g/m² IV MTX × 4 + IT MTX × 4
TCCSG L84-11 SR	1984	38	18 Gy CRT + TITa × 5 + 0·5 g/m² IV MTX × 4 + IT MTX × 4 R: ± 0·5 g/m² IV MTX × 3 + DITb × 6
TCCSG L84-11 HR	1984	38	24 Gy CRT + TITa × 5 + 0·5g/m² IV MTX × 12 + DITb × 12 R: ± 0·5 g/m² IV MTX × 3 + TITa × 6
Other comparisons without data
^†ALGB 6801	1968	54	R: IT MTX × 15
^†GATLA-70	1970	55	R: ± 24 Gy CRT + IT MTX × 5
^†NCI 72-1	1971	56	24 Gy CRT R: IT AraC × 38 v IT MTX × 35
^†NCI-84-C-153A	1984		R: 33·6 g/m² IV MTX × 10 v IT MTX × 8

^†

Data not available;

Not in previous paper; AraC, cytosine arabinoside; CRT, cranial irradiation; CSCRT, craniospinal irradiation; DITa, IT MTX + IT AraC; DITb, IT MTX + IT Hc; DITc, IT MTX + IT P; Dx, dexamethasone; f, female; Hc, hydrocortisone; IT, intrathecal; m, male; mp, mercaptopurine; MTX, methotrexate; P, prednisone; R, randomization; TITa, IT MTX + IT AraC + IT Hc; TITb, IT MTX + IT AraC + IT Dx; TITc, IT MTX + IT AraC + IT P.