Frequency and dose of GO as well as treatment response in the 15 children with relapsed/refractory AML
| Patient no. . | Disease status before GO . | Pre-existing liver disease . | No. GO courses . | GO dose/course . | BM before GO (%)* . | BM blasts after GO . | Response . | GO toxicity (NCI-CTC criteria)† . | Further treatment . | Follow-up . |
|---|---|---|---|---|---|---|---|---|---|---|
| UPN 01 | Refractory relapse | No | 2 | 2 × 7.5 mg/m2 | 60 (94) | 1 | CRp | Grade 3 hypotension during infusion | MRD SCT | Alive 9 mo after SCT |
| UPN 02 | De novo refractory | No | 1 | 7.5 mg/m2 | 17 (98) | 0 | CRp | No | MRD SCT | Alive 6 mo after SCT |
| UPN 03 | Refractory relapse | No | 3 | 2 × 9 and 1 × 7.5 mg/m2 | 45 (97) | 5 | CRp | No | MUD SCT | Relapse, death from AML |
| UPN 04 | Refractory relapse | No | 1 | 7.5 mg/m2 | 78 (89) | 0 | CRp | No | MUD SCT with 8% blasts in the BM | Relapsed, still alive 4 mo after SCT |
| UPN 05 | De novo refractory | No | 2 | 2 × 9 mg/m2 | 90 (39) | 2 | CRp | Transient grade 3 hyperbilirubinaemia | MRD SCT | Death, septic shock |
| UPN 06 | Refractory relapse | No | 2 | 2 × 9 mg/m2 | 82 (80) | 0 | Response | No | Autologous SCT | Death, fungal sepsis |
| UPN 07 | Refractory relapse | No | 3 | 1 × 9 mg/m2 and 2 × 6 mg/m2‡ | 7 (65) | 0 | Response | No | None | Relapse, death from AML |
| UPN 08 | Second relapse | Yes2-153 | 1 | 7.5 mg/m2 | 25 (NA) | 4 | Response | Grade 4 liver toxicity: VOD | None | Relapse, death from AML |
| UPN 09 | De novo refractory | No | 2 | 1 × 4 and 1 × 6 mg/m2 | 18 (90%) | 23 | Stable | No | None | Death due to relapse and fungal infection |
| UPN 10 | Second relapse | No | 3 | 2 × 4 mg/m2 and 1 × 9 mg/m2 | 26 (95) | 32 | Stable | No | None | Death from AML |
| UPN 11 | Third relapse | No | 1 | 9 mg/m2 | 87 (47) | 83 | Stable | No | None | Death from AML |
| UPN 12 | Second relapse | No | 1 | 7.5 mg/m2 | 18 (84) | 54 | Progression | Grade 2 transaminase elevation | SCT and DLI for subsequent relapse | Alive with stable disease |
| UPN 13 | Refractory relapse | No | 2 | 2 × 9 mg/m2 | 61 (94) | 100 | Progression | No | None | Death from AML |
| UPN 14 | Refractory relapse | No | 1 | 4 mg/m2 | 60 (27) | 98 | Progression | No | None | Death from AML |
| UPN 15 | De novo refractory | No | 1 | 7.5 mg/m2 | 88 (97) | NA2-155 | Progression | Grade 4 liver toxicity due to AML infiltration of the liver2-155 | None | Death from AML |
| Patient no. . | Disease status before GO . | Pre-existing liver disease . | No. GO courses . | GO dose/course . | BM before GO (%)* . | BM blasts after GO . | Response . | GO toxicity (NCI-CTC criteria)† . | Further treatment . | Follow-up . |
|---|---|---|---|---|---|---|---|---|---|---|
| UPN 01 | Refractory relapse | No | 2 | 2 × 7.5 mg/m2 | 60 (94) | 1 | CRp | Grade 3 hypotension during infusion | MRD SCT | Alive 9 mo after SCT |
| UPN 02 | De novo refractory | No | 1 | 7.5 mg/m2 | 17 (98) | 0 | CRp | No | MRD SCT | Alive 6 mo after SCT |
| UPN 03 | Refractory relapse | No | 3 | 2 × 9 and 1 × 7.5 mg/m2 | 45 (97) | 5 | CRp | No | MUD SCT | Relapse, death from AML |
| UPN 04 | Refractory relapse | No | 1 | 7.5 mg/m2 | 78 (89) | 0 | CRp | No | MUD SCT with 8% blasts in the BM | Relapsed, still alive 4 mo after SCT |
| UPN 05 | De novo refractory | No | 2 | 2 × 9 mg/m2 | 90 (39) | 2 | CRp | Transient grade 3 hyperbilirubinaemia | MRD SCT | Death, septic shock |
| UPN 06 | Refractory relapse | No | 2 | 2 × 9 mg/m2 | 82 (80) | 0 | Response | No | Autologous SCT | Death, fungal sepsis |
| UPN 07 | Refractory relapse | No | 3 | 1 × 9 mg/m2 and 2 × 6 mg/m2‡ | 7 (65) | 0 | Response | No | None | Relapse, death from AML |
| UPN 08 | Second relapse | Yes2-153 | 1 | 7.5 mg/m2 | 25 (NA) | 4 | Response | Grade 4 liver toxicity: VOD | None | Relapse, death from AML |
| UPN 09 | De novo refractory | No | 2 | 1 × 4 and 1 × 6 mg/m2 | 18 (90%) | 23 | Stable | No | None | Death due to relapse and fungal infection |
| UPN 10 | Second relapse | No | 3 | 2 × 4 mg/m2 and 1 × 9 mg/m2 | 26 (95) | 32 | Stable | No | None | Death from AML |
| UPN 11 | Third relapse | No | 1 | 9 mg/m2 | 87 (47) | 83 | Stable | No | None | Death from AML |
| UPN 12 | Second relapse | No | 1 | 7.5 mg/m2 | 18 (84) | 54 | Progression | Grade 2 transaminase elevation | SCT and DLI for subsequent relapse | Alive with stable disease |
| UPN 13 | Refractory relapse | No | 2 | 2 × 9 mg/m2 | 61 (94) | 100 | Progression | No | None | Death from AML |
| UPN 14 | Refractory relapse | No | 1 | 4 mg/m2 | 60 (27) | 98 | Progression | No | None | Death from AML |
| UPN 15 | De novo refractory | No | 1 | 7.5 mg/m2 | 88 (97) | NA2-155 | Progression | Grade 4 liver toxicity due to AML infiltration of the liver2-155 | None | Death from AML |
BM indicates bone marrow; MRD, matched related donor, NA, not available; DLI, donor lymphocyte infusion.
The bone marrow blast percentage and in parentheses the percentage of leukemic cells with CD33 expression directly prior to GO treatment. CD33 percentages over 20% are considered positive.
All patients experienced NCI-CTC grade 3 to 4 hematologic toxicity, which is not mentioned here.
This patient was treated with GO at large time intervals for subsequent relapses. After the first course the blast percentage in the bone marrow dropped from 7% to 0% (see “Results”).
This patient was treated with a MUD-SCT complicated by VOD before treatment with GO and redeveloped VOD despite defibrotide prophylaxis (see “Results”).
This patient died at day 6 after GO treatment due to leukemic progression. Peripheral blood values were as follows: WBC 20 × 109/L with 95% blasts preceding GO, followed by a drop in WBC to 1.3 × 109/L (42% blasts) at day 3 after the first course of GO, after which the WBC rose to 11.1 × 109/L with 90% blasts at day 6 after GO. Death occurred due to liver failure caused by leukemic infiltration, as proven by liver biopsy, without any signs of VOD.