scholarly journals Clinical Utility of Complex Assessment With Evoked Potentials in Acute Lymphoblastic Leukemia Survivors: Comparison of Various Treatment Protocols

2020 ◽  
Author(s):  
Slawomir Kroczka ◽  
Konrad Stepien ◽  
Izabela Witek-Motyl ◽  
Kinga Kwiecinska ◽  
Eryk Kapusta ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Evoked Potentials ◽  
Lymphoblastic Leukemia ◽  
Objective Assessment ◽  
Harmful Effect ◽  
Diagnostic Methods ◽  
Joint Analysis ◽  
Control Group ◽  
The Impact

Abstract Background: One of the largest success in a pediatric hematology is a prominent improvement of survival in acute lymphoblastic leukemia (ALL). Simultaneously, it encourages to focus on long-term effects of the treatment such as neurotoxicity. One of the few diagnostic methods that allow an objective assessment of sensory organization are evoked potentials (EP).Methods: We analyzed the group consisted of 167 ALL long-term survivors, aged 4.9-28.4 years, without auditory, visual and sensory deviations. Patients were treated with New York (NY, n=35), previous modified Berlin-Frankfurt-Münster (pBFM, n=47) and BFM95 (n=85) protocols. In order to assess the impact of radiotherapy on recorded EP, a joint analysis of NY and pBFM groups was performed. The control group consisted of 35 patients, aged 6-17 years. The analyzed patients underwent a complex assessment with visual EP (VEP), somatosensory EP (SEP) and brainstem auditory EP (BAEP) in accordance with current standards.Results: ALL treatment contributed to the shortening of wave I latency (1.59 vs 1.90, P=0.003) and prolongation of I-III (2.23 vs 2.04, P=0.004) and I-V (4.57 vs 4.24, P=0.002) interwave latencies in BAEP. A significant effect was also noticed in P100 (106.32 vs 101.57, P<0.001) and N135 (151.42 vs 138.22, P<0.001) latencies for VEP and N18 amplitude (3.24 vs 4.70, P=0.007) and P25 latency (21.32 vs 23.39, P<0.001) for SEP. The distribution of abnormalities between protocols was similar in BAEP (NY - 68.6%, pBFM - 61.7%, BFM95 - 69.4%, P=0.650), VEP (NY - 68.6%, pBFM - 42.5%, BFM95 - 58.3%, P=0.053) and significantly different for SEP (NY - 62.9%, pBFM - 36.2%, BFM95 - 53.0%, P=0.045). The harmful effect of radiotherapy was most clearly marked in numerous disturbances of SEP parameters.Conclusions: The presented analysis indicates a high frequency of subclinical abnormalities in EP regardless of the analyzed protocol. To our knowledge current study is the largest and one of the most complex research examining the role of EP in ALL patients. The obtained results indicate the possibility of using a single, objective and non-invasive measurement of EP in ALL survivors in order to stratify the risk of developing sensory abnormalities in adulthood.

scholarly journals Clinical utility of complex assessment with evoked potentials in acute lymphoblastic leukemia survivors: comparison of various treatment protocols

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Slawomir Kroczka ◽  
Konrad Stepien ◽  
Izabela Witek-Motyl ◽  
Kinga Kwiecinska ◽  
Eryk Kapusta ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Evoked Potentials ◽  
Lymphoblastic Leukemia ◽  
Objective Assessment ◽  
Harmful Effect ◽  
Diagnostic Methods ◽  
Joint Analysis ◽  
Control Group ◽  
The Impact

Abstract Background One of the greatest success of pediatric hematology is a prominent improvement of survival in acute lymphoblastic leukemia (ALL). Therefore, special attention needs to be paid to long-term side effects of the treatment such as neurotoxicity. One of the few diagnostic methods that allow an objective assessment of sensory systems are evoked potentials (EP). Methods The analyzed group consisted of 167 ALL long-term survivors, aged 4.9–28.4 years, without auditory, visual and sensory deviations. Patients were treated with New York (NY, n = 35), previous modified Berlin-Frankfurt-Münster (pBFM, n = 47) and BFM95 (n = 85) protocols. In order to assess the impact of radiotherapy on recorded EP, a joint analysis of NY and pBFM groups was performed. The control group consisted of 35 patients, aged 6–17 years. The analyzed patients underwent a complex assessment with visual EP (VEP), somatosensory EP (SEP) and brainstem auditory EP (BAEP) in accordance with current standards. Results ALL treatment contributed to the shortening of wave I latency (1.59 vs 1.90, P = 0.003) and prolongation of I-III (2.23 vs 2.04, P = 0.004) and I-V (4.57 vs 4.24, P = 0.002) interwave latencies of BAEP. A significant effect was also noticed in P100 (106.32 vs 101.57, P < 0.001) and N135 (151.42 vs 138.22, P < 0.001) latencies of VEP and N18 amplitude (3.24 vs 4.70, P = 0.007) and P25 latency (21.32 vs 23.39, P < 0.001) of SEP. The distribution of abnormalities between protocols was similar in BAEP (NY - 68.6%, pBFM - 61.7%, BFM95–69.4%, P = 0.650), VEP (NY - 68.6%, pBFM - 42.5%, BFM95–58.3%, P = 0.053) and significantly different for SEP (NY - 62.9%, pBFM - 36.2%, BFM95–53.0%, P = 0.045). The harmful effect of radiotherapy was most clearly marked in numerous disturbances of SEP parameters. Conclusions The presented analysis indicates a high frequency of subclinical abnormalities in EP regardless of the analyzed protocol. To our knowledge current study is the largest and one of the most complex research examining the role of EP in ALL patients. The obtained results indicate the possibility of using a single, objective and non-invasive measurement of EP in ALL survivors in order to stratify the risk of developing sensory abnormalities in adulthood.

scholarly journals Polyneuropathy in Acute Lymphoblastic Leukemia Long-Term Survivors: Clinical and Electrophysiological Characteristics With the Impact of Radiotherapy

2021 ◽  
Vol 8 ◽  
Author(s):  
Slawomir Kroczka ◽  
Konrad Stepien ◽  
Izabela Witek-Motyl ◽  
Tomasz Klekawka ◽  
Eryk Kapusta ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Negative Influence ◽  
Joint Analysis ◽  
Childhood All ◽  
Oncological Treatment ◽  
Complex Disorders ◽  
The Impact

Introduction: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer with one of the highest survival rates. Long-term complications that occur after intensive oncological treatment often impair normal daily functioning. However, existing data on peripheral nervous system condition in ALL survivors remain conflicting.Materials and Methods: The study group consisted of 215 ALL survivors. Patients were treated with New York (NY, n = 45), previous modified Berlin–Frankfurt–Münster (pBFM, n = 64), and BFM95 (n = 106) protocols. Time elapsed between the end of the treatment and the control examination varied from 0.3 to 20.9 years. The analyzed patients underwent a neurophysiological analysis with electroneurography (ENG) of motor (median and peroneal) and sensory (median and sural) nerves as well as electromyography (EMG) of tibialis anterior, vastus lateralis, and interosseous I muscles. To estimate the influence of radiotherapy on recorded neurophysiological responses, a joint analysis of NY, and pBFM groups was performed.Results: Clinical symptoms of polyneuropathy were noted among 102 (47.4%) children during the ALL therapy and in 111 (51.6%) during follow-up. At the time of treatment, polyneuropathy was diagnosed in 57.8% participants from NY group, 35.9%—pBFM and 50.0%—BFM95 (p = 0.145). A significantly higher incidence of polyneuropathy was observed during a follow-up in the NY group (68.9%; p &lt; 0.001 vs. pBFM, p = 0.002 vs. BFM95). The most frequent abnormality within all the protocols was demyelination (NY: 44.4%, pBFM: 59.4%, BFM95: 41.5%), in contrast to the least frequently registered isolated axonal changes. The negative influence of oncological treatment on neurophysiological parameters in ALL survivors was observed. Complex disorders of motor nerves, sensory nerves, and motor unit potentials were registered. Motor-sensory neuropathy was the most frequently found pathology in all analyzed protocols. The harmful effect of radiotherapy was also observed in EMG results.Conclusions: Detailed neurophysiological analysis in long-term childhood ALL survivors has shown generalized abnormalities in registered parameters. To our knowledge, the current study is the largest and one of the most comprehensive ones among those examining disturbances in ENG and EMG in this group of patients. Moreover, we are the first ones to demonstrate the negative influence of radiotherapy on peripheral nerve conduction parameters.

scholarly journals L-Asparaginase Toxicity in the Treatment of Children and Adolescents with Acute Lymphoblastic Leukemia

2021 ◽  
Vol 10 (19) ◽  
pp. 4419
Author(s):  
Madalina-Petronela Schmidt ◽  
Anca-Viorica Ivanov ◽  
Daniel Coriu ◽  
Ingrith-Crenguta Miron
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Children And Adolescents ◽  
Lymphoblastic Leukemia ◽  
Event Free Survival ◽  
Long Term Outcomes ◽  
Term Survival ◽  
Free Survival ◽  
The Impact

Asparaginase is a basic component of chemotherapy in pediatric acute lymphoblastic leukemia (ALL) and has played a crucial role in improving the long-term survival of this disease. The objectives of this retrospective study were to elucidate the toxicity profile associated with asparaginase in children and adolescents with ALL, to analyze the impact of each type of toxicity on long-term outcomes, and to identify risk factors. We analyzed the medical charts of 165 patients diagnosed with ALL at Sf. Maria Iasi Children’s Hospital from 2010 to 2019 and treated according to a chemotherapeutic protocol containing asparaginase. The median duration of follow-up was 5 years (0.1–11.5 years). Groups of patients with specific types of toxicity were compared to groups of patients without toxicity. We found the following incidence of asparaginase-associated toxicity: 24.1% clinical hypersensitivity, 19.4% hepatotoxicity, 6.7% hypertriglyceridemia, 4.2% hyperglycemia, 3.7% osteonecrosis, 3% pancreatitis, 2.4% thrombosis, and 1.2% cerebral thrombosis. Overall, 82 patients (49.7%) had at least one type of toxicity related to asparaginase. No type of toxicity had a significant impact on overall survival or event-free survival. Being older than 14 years was associated with a higher risk of osteonecrosis (p = 0.015) and hypertriglyceridemia (p = 0.043) and a lower risk of clinical hypersensitivity (p = 0.04). Asparaginase-related toxicity is common and has a varied profile, and its early detection is important for realizing efficient and appropriate management.

Visual-Evoked Potentials in Long-Term Survivors of Acute Lymphoblastic Leukemia in Childhood

1996 ◽  
Vol 27 (04) ◽  
pp. 194-196 ◽  
Author(s):  
M. Überall ◽  
H. Hertzberg ◽  
W. Meier ◽  
T. Langer ◽  
J. Beck ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Evoked Potentials ◽  
Visual Evoked Potentials ◽  
Lymphoblastic Leukemia ◽  
Long Term Survivors ◽  
Visual Evoked

scholarly journals Long-Term Efficacy of Methylphenidate in Enhancing Attention Regulation, Social Skills, and Academic Abilities of Childhood Cancer Survivors

2010 ◽  
Vol 28 (29) ◽  
pp. 4465-4472 ◽  
Author(s):  
Heather M. Conklin ◽  
Wilburn E. Reddick ◽  
Jason Ashford ◽  
Susan Ogg ◽  
Scott C. Howard ◽  
...  
Keyword(s):  
Social Skills ◽  
Acute Lymphoblastic Leukemia ◽  
Cancer Survivors ◽  
Behavioral Problems ◽  
Lymphoblastic Leukemia ◽  
Cancer Control ◽  
Childhood Cancer Survivors ◽  
Control Group ◽  
Parent Ratings

Purpose Methylphenidate (MPH) ameliorates attention problems experienced by some cancer survivors in the short term, but its long-term efficacy is unproven. Patients and Methods This study investigates the long-term effectiveness of maintenance doses of MPH in survivors of childhood brain tumors (n = 35) and acute lymphoblastic leukemia (n = 33) participating in a 12-month MPH trial. Measures of attention (Conners' Continuous Performance Test [CPT], Conners' Rating Scales [CRS]), academic abilities (Wechsler Individual Achievement Test [WIAT]), social skills (Social Skills Rating System [SSRS]), and behavioral problems (Child Behavior Checklist [CBCL]) were administered at premedication baseline and at the end of the MPH trial while on medication. A cancer control group composed of patients who were not administered MPH (brain tumor = 31 and acute lymphoblastic leukemia = 23) was assessed on the same measures 2 months apart. Results For the MPH group, repeated measures analysis of variance revealed significant improvement in performance on a measure of sustained attention (CPT indices, P < .05); parent, teacher, and self-report ratings of attention (CRS indices, P < .05), and parent ratings of social skills or behavioral problems (SSRS and CBCL indices; P < .05). In contrast, the cancer control group only showed improvement on parent ratings of attention (Conners' Parent Rating Scale indices; P < .05) and social skills (SSRS and CBCL indices; P < .05). There was no significant improvement on the academic measure (WIAT) in either group. Conclusion Attention and behavioral benefits of MPH for childhood cancer survivors are maintained across settings over the course of a year. Although academic gains were not identified, MPH may offer benefits in academic areas not assessed.

scholarly journals Zoledronic Acid Reduces Osteonecrosis and Anti-Leukemic Efficacy in Murine Models of Acute Lymphoblastic Leukemia Therapy

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4029-4029
Author(s):  
Laura Janke ◽  
Jieun Kim ◽  
David Jenkins ◽  
Monique A Payton ◽  
Mary V Relling ◽  
...  
Keyword(s):  
Drinking Water ◽  
Acute Lymphoblastic Leukemia ◽  
Zoledronic Acid ◽  
Bone Density ◽  
Lymphoblastic Leukemia ◽  
Acid Group ◽  
Control Group ◽  
Increased Risk ◽  
The Impact ◽  
Acid Administration

Abstract Background: Osteonecrosis and osteopenia frequently complicate acute lymphoblastic leukemia (ALL) therapy. Interventions which reduce these bony toxicities without impairing the anti-leukemic efficacy of therapy are lacking. Case reports suggest that bisphosphonates may reduce the pain associated with osteonecrosis; however, it is unclear if they are effective in preventing or reducing the progression of osteonecrosis or modifying bone density loss during therapy. Their impact on the anti-leukemic efficacy of therapy is also unknown. Methods: We tested the efficacy of the bisphosphonate zoledronic acid (ZA) in the murine model of osteonecrosis. Four-week-old Balb/c mice were treated with dexamethasone (2mg/L in drinking water) and PEGylated-asparaginase [1200IU/kg intraperitoneal (IP) weekly] for 6 weeks. To test whether ZA could prevent osteonecrosis, mice received ZA 100ug/kg IP weekly starting with therapy initiation (early zoledronic acid group, receiving 6 total doses). To test whether ZA could prevent the progression of osteonecrosis, ZA administration was delayed until the fourth week of therapy (late zoledronic acid group, receiving 2 total doses) after osteonecrosis processes have already begun. All mice were humanly euthanized at 10 weeks post-natal. At the end of the 6 week therapy, osteonecrosis was assessed histologically at the distal femur, while bone density and quality measurements were obtained from the proximal tibia using the Siemeons Inveon uCT system. To test the impact of zoledronic acid on the anti-leukemic efficacy of therapy, nine-week-old B6 mice were injected with 2000 Arf-/- Bcr/Abl+ syngeneic acute lymphoblastic leukemia cells. Mice received three weeks of therapy identical to the osteonecrosis studies (including zoledronic acid randomization), except dexamethasone was increased to 4mg/L in the drinking water. Mice were sacrificed when moribund and leukemia as cause of death was confirmed by peripheral white blood cell count and spleen weight. Results: Osteonecrosis was reduced in the early zoledronic acid group compared to the control group (12/69 limbs vs. 25/72 limbs, p=0.03). The incidence of osteonecrosis in the late zoledronic acid group (19/56 limbs) was identical to that in the control group (p=1). Both zoledronic acid interventions increased the cortical thickness of the tibia [median 0.12mm in therapy treated controls; 0.18mm in early zoledronic acid group (p=<0.001 vs. control); 0.15mm in late zoledronic acid group (p=<0.001 vs. control)]. Thinner cortical wall thickness was associated with an increased risk of osteonecrosis in univariate analysis (p=0.03) but not in multivariate analysis including treatment arm (p=0.32). Epiphyseal arteriopathy, the preceding vascular lesion in osteonecrosis, was less common in early zoledronic acid mice vs. controls (15/60 vs. 28/51, p=0.002). Late zoledronic acid administration resulted in a similar rate of arteriopathy (22/47) compared to controls (p=0.55). There was no difference in the incidence of asparaginase plasma concentrations <1u/mL (p=0.25) or in plasma dexamethasone levels (p=0.67) in mice receiving ZA vs. control treated mice. Because early zoledronic acid administration reduced the rate of osteonecrosis and improved bone density, we tested its effect on the anti-leukemic efficacy of therapy. Mice that received zoledronic acid and chemotherapy had a shorter survival than mice receiving chemotherapy alone (mean 36 vs. 41.6 days, log-rank p=0.046, Figure 1). Conclusion: Zoledronic acid administration early in acute lymphoblastic leukemia therapy reduces osteonecrosis and osteopenia. Zoledronic acid is ineffective in reducing osteonecrosis when given later in therapy. However, the use of zoledronic acid impairs the combined anti-leukemic efficacy of dexamethasone and asparaginase. Further studies are underway to understand this relationship. Figure 1. Figure 1. Disclosures Relling: Shire Pharmaceuticals: Research Funding.

Comparison of Long-Term Neurocognitive Outcomes in Young Children With Acute Lymphoblastic Leukemia Treated With Cranial Radiation or High-Dose or Very High-Dose Intravenous Methotrexate

2006 ◽  
Vol 24 (24) ◽  
pp. 3858-3864 ◽  
Author(s):  
Brenda J. Spiegler ◽  
Kimberly Kennedy ◽  
Ronnen Maze ◽  
Mark L. Greenberg ◽  
Sheila Weitzman ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Young Children ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Attention And Memory ◽  
Cranial Radiation ◽  
Neurocognitive Outcomes ◽  
The Impact ◽  
Very High

Purpose Cranial radiation therapy (CRT) is associated with neurocognitive morbidity in survivors of childhood acute lymphoblastic leukemia (ALL). For most patients, CRT has been replaced with intensified systemic and intrathecal chemotherapy, often including methotrexate (MTX). The impact of chemotherapy-only protocols on neurocognitive outcomes is unclear, and the importance of systemic MTX dose has not been established. Patients and Methods Seventy nine of 120 eligible children diagnosed with high-risk ALL between the ages of 1.0 and 4.9 years participated in this retrospective cohort study. All patients were treated on a uniform chemotherapy protocol with one of three modalities of CNS prophylaxis, depending on their treatment era. In addition to intrathecal therapy, CNS-directed therapy consisted of CRT (18 Gy in 10 fractions) in 25 patients, high-dose intravenous (IV) MTX (8 g/m2 × 3 doses) in 32 patients and very high-dose IV MTX (33.6 g/m2 x 3 doses) in 22 patients. Participants completed tests of intelligence, academic achievement, attention, and memory. Results Neurocognitive assessment was conducted at least 5 years after diagnosis (mean, 10.5 years, standard deviation, 2.7 years). No difference was detected on any neurocognitive measure between children treated with high-dose or very high-dose IV MTX. The combined MTX groups scored near the population mean on 17/18 measures. Children treated with CRT performed more poorly than the MTX group on most measures. Conclusion Treatment strategies for young children with ALL that avoid CRT are associated with good long-term neurocognitive outcomes. In this cohort, the dose of IV MTX did not influence these outcomes.

Sign in / Sign up

Export Citation Format

Share Document