| | Patient | Age [year] | Underlying disease | Therapy prior to CNS relapse | Time of CNS relapse [months after diagnosis] | Symptoms at CNS relapse | Diagnosis of CNS relapse | Concomitant anti leukemic treatment for CNS relapse [d]¥ | BCR-ABL mutation detected | Duration of nilotinib monotherapy [d] | Best response in CSF | Duration of nilotinib administration (mono + concomitant therapy) | Type of relapse/progression |
| | 1 | 38 | CML-BC | AlloSCT, DLIs, imatinib, and dasatinib | 132 | Headache, vertigo, and facial palsy | Clinical signs and symptoms, csf cytology, csf immunophenotyping, csf BCR-ABL qPCR, and decrease in csf donor chimerism | Intrathecal triple therapy*[d−100, d−98, d−95, d−91],
INNO406 360 mg tid, [d−66 to d−53],
Donor lymphocytes [d−28, d−23, d−14, d−7, d0, d+7, d+14, d+25],
2000 mg/m2 Cytarabin i.v. [d−35 to d−34] | V299L | 406 | CR with MRD positivity | 431 | Systemic (intracerebral chloromas) |
| | 2 | 19 | c-ALL | GMALL-protocol, alloSCT, and dasatinib | 17 | Headache and anisocoria | Clinical signs and symptoms, csf cytology, csf BCR-ABL qPCR, and decrease in csf donor chimerism | Intrathecal triple therapy* [d+10, d+29, d+52, d+78],
375 mg/m2 rituximab i.v. [d+30, d+38, d+53]
2 mg vincristine i.v. [d+29, d+56, d+78]
4 mg dexamethasone bid. [d+52 to d+83] | T315I | NA£ | SD | 99 | Systemic (bone marrow) |
| | 3 | 49 | c-ALL | GMALL-protocol, alloSCT, and dasatinib | 28 | Facial palsy headache | Clinical signs and symptoms, csf BCR-ABL qPCR, and positive csf cytology on 2nd relapse | Intrathecal triple therapy* [d+848, d+851, d+855, d+858, d+864, d+871, d+878, d+892, d+1310, d+1421, d+1531, d+1544, d+1547, d+1551]
Rituximab 20 mg i.th [d+1320, d+1334, d+1341, d+1356, d+1369, d+1382, d+1554, d+1560, d+1567, d+1618, d+1671, d+1740] | T315I, F317L | 847 | MRD negativity | 1786 | Systemic (peritoneum) |
| | 4 | 15 | c-ALL | ALL-BFM2000, alloSCT. DLI, Ifn, GM-CSF, imatinib, and ALLRez2002 | 80 | Headache, vomiting, and seizures | Clinical signs and symptoms, csf BCR-ABL, and BM BCR-ABL | Dasatinib [d−60–182]
Radiotherapy [d−32–45]
Intrathecal triple therapy€ [d−60] | None | NA£ | MRD negativity | 650+ | In remission |
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PR = partial response, SD = stable disease, CR = complete remission, NA = Not applicable, c-ALL = common ALL, DLI = donor lymphocyte infusion, Ifn = Interferon; GMALL-Protocol: Polychemotherapy induction, consolidation and postremision protocol of the german ALL study group for adults; BFM2000: Polychemotherapy induction, consolidation and postremision protocol of the german ALL study group for pediatric patients; i.v.: intravenous; i.th = intrathecal,
¥relative to start of nilotinib treatment; *consisting of 15 mg MTX, 40 mg Cytarabin and 4 mg dexamethasone; €consisting of 12 mg MTX, 30 mg Cytarabin and 10 mg prednisone at 4-week intervals for one year and 6-week intervals after one year; £nilotinib applied with periodic concomitant anti-leukemic treatment.
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