Genetic Signature of Acute Lymphoblastic Leukemia and Netherton Syndrome Co-incidence—First Report in the Literature

Skoczeń, Szymon; Stępień, Konrad; Młynarski, Wojciech; Centkowski, Piotr; Kwiecińska, Kinga; Korostyński, Michał; Piechota, Marcin; Wyrobek, Elżbieta; Moryl-Bujakowska, A; Strojny, Wojciech; Rej, Magdalena; Kowalczyk, Jerzy; Balwierz, Walentyna

doi:10.3389/fonc.2019.01477

Cited by 14 publications

(11 citation statements)

References 41 publications

(42 reference statements)

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“…Moreover, the reliability of these scales has been already undermined in the literature ( 22 – 24 ). Third, genetic methods, especially whole-exome sequencing, which are increasingly used to determine the individual predisposition to neurotoxicity development, have not been used ( 5 , 25 , 26 ).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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 < 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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…Currently, there is no research in the literature that could confirm this initial hypothesis. For this reason, longer observations also involving genetic methods useful in the pediatric population [ 24 , 25 ] are necessary.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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.

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“…For the future studies, the existence of common genetic background with specific molecular alterations brings opportunity for addition of molecular targeted therapies in patients usually resistant to conventional therapies ( 13 , 14 ).…”

Section: Discussion Of the Underlying Pathophysiology And Significancmentioning

confidence: 99%

Disseminated Juvenile Xanthogranuloma and Hemophagocytic Lymphohistiocytosis Developed During Treatment of Acute Lymphoblastic Leukemia: Case Report

et al. 2020

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The association between acute lymphoblastic leukemia (ALL), non-Langerhans cell histiocytosis (non-LCH), and hemophagocytic lymphohistiocytosis (HLH), to the best of our knowledge, has not been published to date. Juvenile xanthogranuloma (JXG), as a type of non-LCH, is usually a benign disease limited to the skin. Systemic involvement is rarely reported. The present case report describes a 15-year-old boy diagnosed with disseminated JXG involving skin and bone marrow concurrent with severe symptoms of HLH during ALL therapy. Examination of immunoglobulin heavy chain genes in B-cell precursor leukemic blasts and histiocytes in the skin and bone marrow revealed identical rearrangements, confirming clonal relationship between both diseases. Implementation of corticosteroids, vinblastine, etoposide, cyclosporine, and tocilizumab resulted in partial skin lesion resolution with no improvement of bone marrow function; therefore, hematopoietic stem cell transplantation (HSCT) was eventually performed. The patient's hematological and general status has improved gradually; however, remarkable recovery of skin lesions was observed after empirical antitubercular therapy. Mycobacterium spp. infection should be considered as a possible secondary HLH trigger. Triple association of ALL, non-LCH, and HLH highlights heterogeneity of histiocytic disorders and possible common origin of dendritic and lymphoid cells.

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Genetic Signature of Acute Lymphoblastic Leukemia and Netherton Syndrome Co-incidence—First Report in the Literature

Cited by 14 publications

References 41 publications

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

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

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

Disseminated Juvenile Xanthogranuloma and Hemophagocytic Lymphohistiocytosis Developed During Treatment of Acute Lymphoblastic Leukemia: Case Report

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