Cycle-level toxicity data
| Variable . | HDMTX-P (n = 445 cycles), % . | HDMTX-T (n = 269 cycles), % . | Overall (n = 714 cycles), % . |
|---|---|---|---|
| Cycles delayed ≥7 d due to toxicity | 11 (3) | 12 (6) | 23 (4) |
| Preceded by HDMTX | 7 (64) | 12 (100) | 19 (83) |
| Median delay, days (range) | 7 (7-14) | 8 (7-33) | 8 (7-33) |
| Reason for delay | (n = 11) | (n = 12) | (n = 23) |
| Myelosuppression | 5 (45) | 1 (8) | 6 (26) |
| Infection/NF | 4 (36) | 6 (50) | 10 (43) |
| Mucositis | 1 (9) | 1 (8) | 2 (9) |
| AKI | 1 (9) | 1 (8) | 2 (9) |
| Other | 0 (0) | 3 (25) | 3 (13) |
| Cycles with doxorubicin and/or cyclophosphamide dose reductions* | 4 (1) | 5 (2) | 9 (1) |
| Preceded by HDMTX | 1 (25) | 3 (60) | 4 (44) |
| Cycles with HDMTX dose reductions | 4 (1) | 8 (3) | 12 (2) |
| Preceded by HDMTX | 3 (75) | 3 (38) | 6 (50) |
| Doxorubicin RDI, median (range) | 1.00 (0.45-1.00) | ||
| ≥0.70 | 79 (98) | — | — |
| ≥0.90 | 73 (90) | ||
| Cyclophosphamide RDI, median (range) | 1.00 (0.47-1.00) | ||
| ≥0.70 | 79 (98) | — | — |
| ≥0.90 | 73 (90) | ||
| NF | 27 (6) | 24 (9) | 51 (7) |
| NF preceded by HDMTX-containing cycle | 19 (70) | 24 (100) | 43 (84) |
| AKI† | |||
| Any grade | 42 (17) | 50 (21) | 92 (19) |
| Grade 1 (>ULN - 1.5 × ULN) | 14 (6) | 11 (5) | 25 (5) |
| Grade 2 (>1.5 - 3.0 ULN) | 25 (10) | 30 (15) | 55 (11) |
| Grade 3 (>3.0 - 6.0 ULN) | 3 (1) | 7 (3) | 10 (2) |
| Grade 4 (> 6.0 ULN) | 0 | 2 (1) | 2 (< 1) |
| Glucarpidase administration† | 3 (1) | 5 (2) | 8 (2) |
| ALT/AST increase, grade ≥3† | 5 (2) | 6 (2) | 11 (2) |
| Bilirubin increase, grade ≥3† | 0 (0) | 1 (0.4) | 1 (0.2) |
| Mucositis, grade ≥3 | 7 (2) | 10 (4) | 17 (2) |
| Variable . | HDMTX-P (n = 445 cycles), % . | HDMTX-T (n = 269 cycles), % . | Overall (n = 714 cycles), % . |
|---|---|---|---|
| Cycles delayed ≥7 d due to toxicity | 11 (3) | 12 (6) | 23 (4) |
| Preceded by HDMTX | 7 (64) | 12 (100) | 19 (83) |
| Median delay, days (range) | 7 (7-14) | 8 (7-33) | 8 (7-33) |
| Reason for delay | (n = 11) | (n = 12) | (n = 23) |
| Myelosuppression | 5 (45) | 1 (8) | 6 (26) |
| Infection/NF | 4 (36) | 6 (50) | 10 (43) |
| Mucositis | 1 (9) | 1 (8) | 2 (9) |
| AKI | 1 (9) | 1 (8) | 2 (9) |
| Other | 0 (0) | 3 (25) | 3 (13) |
| Cycles with doxorubicin and/or cyclophosphamide dose reductions* | 4 (1) | 5 (2) | 9 (1) |
| Preceded by HDMTX | 1 (25) | 3 (60) | 4 (44) |
| Cycles with HDMTX dose reductions | 4 (1) | 8 (3) | 12 (2) |
| Preceded by HDMTX | 3 (75) | 3 (38) | 6 (50) |
| Doxorubicin RDI, median (range) | 1.00 (0.45-1.00) | ||
| ≥0.70 | 79 (98) | — | — |
| ≥0.90 | 73 (90) | ||
| Cyclophosphamide RDI, median (range) | 1.00 (0.47-1.00) | ||
| ≥0.70 | 79 (98) | — | — |
| ≥0.90 | 73 (90) | ||
| NF | 27 (6) | 24 (9) | 51 (7) |
| NF preceded by HDMTX-containing cycle | 19 (70) | 24 (100) | 43 (84) |
| AKI† | |||
| Any grade | 42 (17) | 50 (21) | 92 (19) |
| Grade 1 (>ULN - 1.5 × ULN) | 14 (6) | 11 (5) | 25 (5) |
| Grade 2 (>1.5 - 3.0 ULN) | 25 (10) | 30 (15) | 55 (11) |
| Grade 3 (>3.0 - 6.0 ULN) | 3 (1) | 7 (3) | 10 (2) |
| Grade 4 (> 6.0 ULN) | 0 | 2 (1) | 2 (< 1) |
| Glucarpidase administration† | 3 (1) | 5 (2) | 8 (2) |
| ALT/AST increase, grade ≥3† | 5 (2) | 6 (2) | 11 (2) |
| Bilirubin increase, grade ≥3† | 0 (0) | 1 (0.4) | 1 (0.2) |
| Mucositis, grade ≥3 | 7 (2) | 10 (4) | 17 (2) |