Contributions
Abstract: EP348
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Clinical
Background
In pediatric acute leukemias, balance of treatment results and toxic events has been addressed by the Ponte di Legno Toxicity Working Group (PdLTWG), stressing the need of correct reporting. Acute neurological adverse events (ANAE) on the central nervous system during chemotherapy for Acute Lymphoblastic Leukemia (ALL) are frequent (5,4%), but definitions of clinical and radiological criteria are challenging.
Aims
We collected the ANAE recorded during chemotherapy treatment in children enrolled in ALL AIEOP (Associazione Italiana di Emato-Oncologia Pediatrica) protocols to evaluate their incidence, clinical and radiological characteristics and severity.
Methods
Among patients enrolled in ALL AIEOP protocols, 115 ANAE were reported by 27 Centres from 2009 to 2018. Demographic, hematological and treatment data were obtained from the AIEOP Web database. These CNS ANAE were analyzed: seizures, Posterior Reversible leukoEncephalopathy Syndrome (PRES), Methotrexate Stroke-Like-Syndrome (MTX SLS), depressed level of consciousness (DLC). Vascular, infectious and peripheral ANAE were excluded. When available, MRI performed within 7 days from the NAE and follow-up images were evaluated centrally by two pediatric neuroradiologists blinded to clinical data.
Results
One hundred fifteen ANAE were reported in 113 children. The clinical diagnosis was decided by the reporting center and confirmed centrally, based on reporting details.
The most frequently reported event was PRES (42 patients), which occurred mostly (one third) in high risk leukemia patients and mostly during induction and delayed intensification. Seizures were reported in 25 patients, mostly during induction phase. MTX-SLS occurred in 14 patients, predominantly older ones (median 11 y); almost all these events occurred during consolidation or delayed intensification. ANAE were severe (CTCAE ≥3) in 64% of patients but long-term outcomes were rarely reported (9%). One patient died (0.8%). Stopping or reducing chemotherapy occurred in 36% of patients.
MRI images from 67 events were available for centralized analysis. MRI was unremarkable in 22 cases, mostly patients presenting with seizures (n=17). Abnormal MRI (n=37) outlined three main radiological patterns: PRES (32%); MTX-SLS (22%); non-specific leukopathy (9%). Central evaluation confirmed PRES in 18/19 cases, 1 case was considered MTX-SLS; diagnosis changed from DLC to PRES in 1 case. MTX-SLS were confirmed in 9/13 cases; 4 more cases of MTX-SLS were found, changing the diagnosis from PRES (1 case) and seizure (3 cases). Leukopathy was identified in patients with seizures (n=2), DLC (n=2) and MTX-SLS (n=1). On follow-up scans, 43% of the patients displayed radiological sequelae: cortico-subcortical atrophic changes, leukopathy and in one case hippocampal sclerosis. Sequelae were statistically related (p<0,05) with holo-hemispheric watershed pattern in PRES and with FLAIR hyperintensity in MTX-SLS; their clinical meaning requires further observation.
Conclusion
This study confirms the need for accurate reporting and centralized clinical and radiological review of ANAE, to allow modulations of chemotherapy on evidence criteria.
Keyword(s): Acute lymphoblastic leukemia, Chemotherapy toxicity
Abstract: EP348
Type: E-Poster Presentation
Session title: Acute lymphoblastic leukemia - Clinical
Background
In pediatric acute leukemias, balance of treatment results and toxic events has been addressed by the Ponte di Legno Toxicity Working Group (PdLTWG), stressing the need of correct reporting. Acute neurological adverse events (ANAE) on the central nervous system during chemotherapy for Acute Lymphoblastic Leukemia (ALL) are frequent (5,4%), but definitions of clinical and radiological criteria are challenging.
Aims
We collected the ANAE recorded during chemotherapy treatment in children enrolled in ALL AIEOP (Associazione Italiana di Emato-Oncologia Pediatrica) protocols to evaluate their incidence, clinical and radiological characteristics and severity.
Methods
Among patients enrolled in ALL AIEOP protocols, 115 ANAE were reported by 27 Centres from 2009 to 2018. Demographic, hematological and treatment data were obtained from the AIEOP Web database. These CNS ANAE were analyzed: seizures, Posterior Reversible leukoEncephalopathy Syndrome (PRES), Methotrexate Stroke-Like-Syndrome (MTX SLS), depressed level of consciousness (DLC). Vascular, infectious and peripheral ANAE were excluded. When available, MRI performed within 7 days from the NAE and follow-up images were evaluated centrally by two pediatric neuroradiologists blinded to clinical data.
Results
One hundred fifteen ANAE were reported in 113 children. The clinical diagnosis was decided by the reporting center and confirmed centrally, based on reporting details.
The most frequently reported event was PRES (42 patients), which occurred mostly (one third) in high risk leukemia patients and mostly during induction and delayed intensification. Seizures were reported in 25 patients, mostly during induction phase. MTX-SLS occurred in 14 patients, predominantly older ones (median 11 y); almost all these events occurred during consolidation or delayed intensification. ANAE were severe (CTCAE ≥3) in 64% of patients but long-term outcomes were rarely reported (9%). One patient died (0.8%). Stopping or reducing chemotherapy occurred in 36% of patients.
MRI images from 67 events were available for centralized analysis. MRI was unremarkable in 22 cases, mostly patients presenting with seizures (n=17). Abnormal MRI (n=37) outlined three main radiological patterns: PRES (32%); MTX-SLS (22%); non-specific leukopathy (9%). Central evaluation confirmed PRES in 18/19 cases, 1 case was considered MTX-SLS; diagnosis changed from DLC to PRES in 1 case. MTX-SLS were confirmed in 9/13 cases; 4 more cases of MTX-SLS were found, changing the diagnosis from PRES (1 case) and seizure (3 cases). Leukopathy was identified in patients with seizures (n=2), DLC (n=2) and MTX-SLS (n=1). On follow-up scans, 43% of the patients displayed radiological sequelae: cortico-subcortical atrophic changes, leukopathy and in one case hippocampal sclerosis. Sequelae were statistically related (p<0,05) with holo-hemispheric watershed pattern in PRES and with FLAIR hyperintensity in MTX-SLS; their clinical meaning requires further observation.
Conclusion
This study confirms the need for accurate reporting and centralized clinical and radiological review of ANAE, to allow modulations of chemotherapy on evidence criteria.
Keyword(s): Acute lymphoblastic leukemia, Chemotherapy toxicity