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Article: Integrins and the Metastasis-like Dissemination of Acute Lymphoblastic Leukemia to the Central Nervous System.

Modvig, Signe / Jeyakumar, Jenani / Marquart, Hanne Vibeke / Christensen, Claus

2023 Volume 15, Issue 9

Abstract: Acute lymphoblastic leukemia (ALL) disseminates with high prevalence to the central nervous system (CNS) in a process resembling aspects of the CNS surveillance of normal immune cells as well as aspects of brain metastasis from solid cancers. Importantly, ...

Abstract	Acute lymphoblastic leukemia (ALL) disseminates with high prevalence to the central nervous system (CNS) in a process resembling aspects of the CNS surveillance of normal immune cells as well as aspects of brain metastasis from solid cancers. Importantly, inside the CNS, the ALL blasts are typically confined within the cerebrospinal fluid (CSF)-filled cavities of the subarachnoid space, which they use as a sanctuary protected from both chemotherapy and immune cells. At present, high cumulative doses of intrathecal chemotherapy are administered to patients, but this is associated with neurotoxicity and CNS relapse still occurs. Thus, it is imperative to identify markers and novel therapy targets specific to CNS ALL. Integrins represent a family of adhesion molecules involved in cell-cell and cell-matrix interactions, implicated in the adhesion and migration of metastatic cancer cells, normal immune cells, and leukemic blasts. The ability of integrins to also facilitate cell-adhesion mediated drug resistance, combined with recent discoveries of integrin-dependent routes of leukemic cells into the CNS, have sparked a renewed interest in integrins as markers and therapeutic targets in CNS leukemia. Here, we review the roles of integrins in CNS surveillance by normal lymphocytes, dissemination to the CNS by ALL cells, and brain metastasis from solid cancers. Furthermore, we discuss whether ALL dissemination to the CNS abides by known hallmarks of metastasis, and the potential roles of integrins in this context.
Language	English
Publishing date	2023-04-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15092504
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Article ; Online: Flow Cytometric Detection of Malignant Blasts in Cerebrospinal Fluid: A Biomarker of Central Nervous System Involvement in Childhood Acute Lymphoblastic Leukemia.

Thastrup, Maria / Marquart, Hanne Vibeke / Schmiegelow, Kjeld

Biomolecules

2022 Volume 12, Issue 6

Abstract: Despite the excellent prognosis for children and adolescents with acute lymphoblastic lymphoma (ALL), the involvement of the central nervous system (CNS) represents a major therapeutic challenge. Patients who develop CNS relapse have a very poor ... ...

Abstract	Despite the excellent prognosis for children and adolescents with acute lymphoblastic lymphoma (ALL), the involvement of the central nervous system (CNS) represents a major therapeutic challenge. Patients who develop CNS relapse have a very poor prognosis, and since current methods cannot reliably identify patients with CNS involvement or patients at high risk of CNS relapse, all children with ALL receive CNS-directed treatment. The current golden standard for detecting CNS involvement is the assessment of cytomorphology on cytospin slides of cerebrospinal fluid (CSF). This technique is inadequate due to low sensitivity and reproducibility. Flow cytometric analysis of CSF represent a novel, highly specific and sensitive technique for the detection of leukemic cells in the CNS. In prospective studies, CSF flow cytometry demonstrated two to three times higher rates of CNS involvement at diagnosis of childhood ALL than conventional cytospin, and especially demonstrated superior sensitivity in detecting low-level CNS disease. CNS involvement determined via flow cytometry has been linked to a higher risk of CNS relapse and poor outcomes in several studies. In this review, we discuss the central analytical concepts of CSF flow cytometry and summarize the current evidence supporting the use of flow cytometric detection of malignant blasts as a biomarker of CNS involvement in childhood ALL.
MeSH term(s)	Acute Disease ; Adolescent ; Biomarkers ; Central Nervous System/pathology ; Child ; Flow Cytometry/methods ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Prospective Studies ; Recurrence ; Reproducibility of Results
Chemical Substances	Biomarkers
Language	English
Publishing date	2022-06-09
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12060813
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Article: Flow Sorting, Whole Genome Amplification and Next-Generation Sequencing as Combined Tools to Study Heterogeneous Acute Lymphoblastic Leukemia.

Fardoos, Rabiah / Christensen, Claus / Øbro, Nina Friesgaard / Overgaard, Ulrik Malthe / Als-Nielsen, Bodil / Madsen, Hans Ole / Marquart, Hanne Vibeke

Diagnostics (Basel, Switzerland)

2023 Volume 13, Issue 21

Abstract: Next-generation sequencing (NGS) methods have been introduced for immunoglobulin (IG)/T-cell receptor (TR) gene rearrangement analysis in acute lymphoblastic leukemia (ALL) and lymphoma (LBL). These methods likely constitute faster and more sensitive ... ...

Abstract	Next-generation sequencing (NGS) methods have been introduced for immunoglobulin (IG)/T-cell receptor (TR) gene rearrangement analysis in acute lymphoblastic leukemia (ALL) and lymphoma (LBL). These methods likely constitute faster and more sensitive approaches to analyze heterogenous cases of ALL/LBL, yet it is not known whether gene rearrangements constituting low percentages of the total sequence reads represent minor subpopulations of malignant cells or background IG/TR gene rearrangements in normal B-and T-cells. In a comparison of eight cases of B-cell precursor ALL (BCP-ALL) using both the EuroClonality NGS method and the IdentiClone multiplex-PCR/gene-scanning method, the NGS method identified between 29% and 139% more markers than the gene-scanning method, depending on whether the NGS data analysis used a threshold of 5% or 1%, respectively. As an alternative to using low thresholds, we show that IG/TR gene rearrangements in subpopulations of cancer cells can be discriminated from background IG/TR gene rearrangements in normal B-and T-cells through a combination of flow cytometry cell sorting and multiple displacement amplification (MDA)-based whole genome amplification (WGA) prior to the NGS. Using this approach to investigate the clonal evolution in a BCP-ALL patient with double relapse, clonal TR rearrangements were found in sorted leukemic cells at the time of second relapse that could be identified at the time of diagnosis, below 1% of the total sequence reads. These data emphasize that caution should be exerted when interpreting rare sequences in NGS experiments and show the advantage of employing the flow sorting of malignant cell populations in NGS clonality assessments.
Language	English
Publishing date	2023-10-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics13213306
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Article ; Online: Widespread alterations in systemic immune profile are linked to lung function heterogeneity and airway microbes in cystic fibrosis.

Rossi, Elio / Lausen, Mads / Øbro, Nina Friesgaard / Colque, Antonella / Nielsen, Bibi Uhre / Møller, Rikke / de Gier, Camilla / Hald, Annemette / Skov, Marianne / Pressler, Tacjana / Molin, Søren / Ostrowski, Sisse Rye / Marquart, Hanne Vibeke / Johansen, Helle Krogh

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

2024

Abstract: Background: Excessive inflammation and recurrent airway infections characterize people with cystic fibrosis (pwCF), a disease with highly heterogeneous clinical outcomes. How the overall immune response is affected in pwCF, its relationships with the ... ...

Abstract	Background: Excessive inflammation and recurrent airway infections characterize people with cystic fibrosis (pwCF), a disease with highly heterogeneous clinical outcomes. How the overall immune response is affected in pwCF, its relationships with the lung microbiome, and the source of clinical heterogeneity have not been fully elucidated. Methods: Peripheral blood and sputum samples were collected from 28 pwCF and an age-matched control group. Systemic immune cell subsets and surface markers were quantified using multiparameter flow cytometry. Lung microbiome composition was reconstructed using metatranscriptomics on sputum samples, and microbial taxa were correlated to circulating immune cells and surface markers expression. Results: In pwCF, we found a specific systemic immune profile characterized by widespread hyperactivation and altered frequencies of several subsets. These included substantial changes in B-cell subsets, enrichment of CD35 Conclusion: The CF-specific immune signature, involving hyperactivation, immune dysregulation with alteration in Treg homeostasis, and impaired B-cell function, is a potential source of lung function heterogeneity. The activity of specific microbes contributes to disrupting the balance of the immune response. Our data provide a unique foundation for identifying novel markers and immunomodulatory targets to develop the future of cystic fibrosis treatment and management.
Language	English
Publishing date	2024-05-02
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2084724-5
ISSN	1873-5010 ; 1569-1993
ISSN (online)	1873-5010
ISSN	1569-1993
DOI	10.1016/j.jcf.2024.04.015
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Zs.A 6028: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
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Article: Integrin-Mediated Adhesion and Chemoresistance of Acute Lymphoblastic Leukemia Cells Residing in the Bone Marrow or the Central Nervous System.

Scharff, Bibi Fatima Syed Shah / Modvig, Signe / Marquart, Hanne Vibeke / Christensen, Claus

Frontiers in oncology

2020 Volume 10, Page(s) 775

Abstract: Acute Lymphoblastic Leukemia (ALL) is the most common cancer in childhood. Despite a significantly improved prognosis over the last decade with a 5-years survival rate of ~90%, treatment-related morbidity remains substantial and relapse occurs in 10-15% ... ...

Abstract	Acute Lymphoblastic Leukemia (ALL) is the most common cancer in childhood. Despite a significantly improved prognosis over the last decade with a 5-years survival rate of ~90%, treatment-related morbidity remains substantial and relapse occurs in 10-15% of patients (1). The most common site of relapse is the bone marrow, but early colonization and subsequent reoccurrence of the disease in the central nervous system (CNS) also occurs. Integrins are a family of cell surface molecules with a longstanding history in cancer cell adherence, migration and metastasis. In chronic lymphoblastic leukemia (CLL), the VLA-4 integrin has been acknowledged as a prognostic marker and mounting evidence indicates that this and other integrins may also play a role in acute leukemia, including ALL. Importantly, integrins engage in anti-apoptotic signaling when binding extracellular molecules that are enriched in the bone marrow and CNS microenvironments. Here, we review the current evidence for a role of integrins in the adherence of ALL cells within the bone marrow and their colonization of the CNS, with particular emphasis on mechanisms adding to cancer cell survival and chemoresistance.
Language	English
Publishing date	2020-05-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2020.00775
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Article ; Online: Granulocyte Colony-Stimulating Factor Effectively Mobilizes TCR γδ and NK Cells Providing an Allograft Potentially Enhanced for the Graft-Versus-Leukemia Effect for Allogeneic Stem Cell Transplantation.

Minculescu, Lia / Sengelov, Henrik / Marquart, Hanne Vibeke / Ryder, Lars Peter / Fischer-Nielsen, Anne / Haastrup, Eva

Frontiers in immunology

2021 Volume 12, Page(s) 625165

Abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) is a potential cure for patients with hematological malignancies but substantial risks of recurrence of the malignant disease remain. TCR γδ and NK cells are perceived as potent innate effector ... ...

Abstract	Allogeneic hematopoietic stem cell transplantation (HSCT) is a potential cure for patients with hematological malignancies but substantial risks of recurrence of the malignant disease remain. TCR γδ and NK cells are perceived as potent innate effector cells in HSCT and have been associated with post-transplant protection from relapse in clinical studies. Immunocompetent cells from the donor are crucial for patient outcomes and peripheral blood stem cells (PBSC) are being increasingly applied as graft source. G-CSF is the preferential mobilizing agent in healthy donors for PBSC grafts, yet effects of G-CSF on TCR γδ and NK cells are scarcely uncovered and could influence the graft composition and potency of these cells. Therefore, we analyzed T and NK cell subsets and activation markers in peripheral blood samples of 49 donors before and after G-CSF mobilization and-for a subset of donors-also in the corresponding graft samples using multicolor flowcytometry with staining for CD3, CD4, CD8, TCRαβ, TCRγδ, Vδ1, Vδ2, HLA-DR, CD45RA, CD197, CD45RO, HLA-DR, CD16, CD56, and CD314. We found that TCR γδ cells were mobilized and harvested with an efficiency corresponding that of TCR αβ cells. For TCR γδ as well as for TCR αβ cells, G-CSF preferentially mobilized naïve and terminally differentiated effector (TEMRA) cells over memory cells. In the TCR γδ cell compartment, G-CSF preferentially mobilized cells of the nonVδ2 types and increased the fraction of HLA-DR positive TCR γδ cells. For NK cells, mobilization by G-CSF was increased compared to that of T cells, yet NK cells appeared to be less efficiently harvested than T cells. In the NK cell compartment, G-CSF-stimulation preserved the proportion of CD56dim NK effector cells which have been associated with relapse protection. The expression of the activating receptor NKG2D implied in anti-leukemic responses, was significantly increased in both CD56dim and CD56bright NK cells after G-CSF stimulation. These results indicate differentiated mobilization and altering properties of G-CSF which could improve the effects of donor TCR γδ and NK cells in the processes of graft-versus-leukemia for relapse prevention after HSCT.
MeSH term(s)	CD56 Antigen/metabolism ; Cell Differentiation/drug effects ; Filgrastim/adverse effects ; Filgrastim/therapeutic use ; Flow Cytometry ; Graft vs Leukemia Effect ; Hematopoietic Stem Cell Mobilization/adverse effects ; Humans ; Immunophenotyping ; Killer Cells, Natural/drug effects ; Killer Cells, Natural/immunology ; Killer Cells, Natural/metabolism ; Killer Cells, Natural/transplantation ; Lymphocyte Activation/drug effects ; NK Cell Lectin-Like Receptor Subfamily K/metabolism ; Peripheral Blood Stem Cell Transplantation/adverse effects ; Phenotype ; Receptors, Antigen, T-Cell, gamma-delta/immunology ; Receptors, Antigen, T-Cell, gamma-delta/metabolism ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; T-Lymphocytes/transplantation ; Tissue Donors ; Transplantation, Homologous ; Treatment Outcome
Chemical Substances	CD56 Antigen ; KLRK1 protein, human ; NCAM1 protein, human ; NK Cell Lectin-Like Receptor Subfamily K ; Receptors, Antigen, T-Cell, gamma-delta ; Filgrastim (PVI5M0M1GW)
Language	English
Publishing date	2021-03-10
Publishing country	Switzerland
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.625165
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Article ; Online: Improved Innate Immune Function in Patients with Chronic Lymphocytic Leukemia Treated with Targeted Therapy in Clinical Trials.

Svanberg Teglgaard, Rebecca / Marquart, Hanne Vibeke / Hartling, Hans Jakob / Bay, Jakob Thaning / da Cunha-Bang, Caspar / Brieghel, Christian / Faitová, Tereza / Enggaard, Lisbeth / Kater, Arnon P / Levin, Mark-David / Kersting, Sabina / Ostrowski, Sisse Rye / Niemann, Carsten U

Clinical cancer research : an official journal of the American Association for Cancer Research

2024 Volume 30, Issue 9, Page(s) 1959–1971

Abstract: Purpose: Patients with chronic lymphocytic leukemia (CLL) have increased risk of severe infections. Although adaptive immune dysfunction is well described, clinical tools for identifying patients at risk are lacking, warranting investigation of ... ...

Abstract	Purpose: Patients with chronic lymphocytic leukemia (CLL) have increased risk of severe infections. Although adaptive immune dysfunction is well described, clinical tools for identifying patients at risk are lacking, warranting investigation of additional immune components. In contrast to chemotherapy, targeted agents could spare or even improve innate immune function. Therefore, we investigated innate immune phenotypes and function in patients with CLL before and during targeted treatment. Experimental design: Baseline and consecutive blood samples were collected from patients with CLL treated with acalabrutinib (n = 17) or ibrutinib+venetoclax (n = 18) in clinical trials. Innate immune function was assessed by TruCulture, a whole-blood ligand-stimulation assay quantifying cytokine release in response to standardized stimuli. Innate immune phenotypes were characterized by flow cytometry. As a proxy for infections, we mapped antimicrobial use before and during treatment. Results: At baseline, patients with CLL displayed impaired stimulated cytokine responses to the endotoxin lipopolysaccharide (LPS) along with deactivated monocytes, enrichment of myeloid-derived suppressor cells and metamyelocytes, and elevated (unstimulated) proinflammatory cytokines. Two/three cycles of acalabrutinib or ibrutinib normalized LPS-stimulated responses, in parallel with decreased duration of infections. Innate immune profiles and elevated proinflammatory cytokines further normalized during longer-term acalabrutinib or ibrutinib+venetoclax, paralleled by decreased infection frequency. Conclusions: Innate immune impairment and infection susceptibility in patients with CLL were restored in parallel during targeted therapy. Thus, targeted treatment may reduce the risk of infections in CLL, as currently under investigation in the PreVent-ACaLL phase 2 trial of acalabrutinib+venetoclax for high-risk CLL (NCT03868722).
MeSH term(s)	Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell/immunology ; Immunity, Innate/drug effects ; Aged ; Male ; Female ; Middle Aged ; Cytokines/metabolism ; Adenine/analogs & derivatives ; Adenine/therapeutic use ; Piperidines/therapeutic use ; Pyrazines/therapeutic use ; Molecular Targeted Therapy ; Benzamides/therapeutic use ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects
Chemical Substances	acalabrutinib (I42748ELQW) ; Cytokines ; Adenine (JAC85A2161) ; Piperidines ; Pyrazines ; ibrutinib (1X70OSD4VX) ; Benzamides
Language	English
Publishing date	2024-02-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-23-2522
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Article ; Online: Minimal residual disease monitoring cannot fully replace bone marrow morphology in assessing disease status in pediatric acute lymphoblastic leukemia.

Rathe, Mathias / Preiss, Birgitte / Marquart, Hanne Vibeke / Schmiegelow, Kjeld / Wehner, Peder Skov

APMIS : acta pathologica, microbiologica, et immunologica Scandinavica

2020 Volume 128, Issue 5, Page(s) 414–419

Abstract: Minimal residual disease (MRD) monitoring has a strong prognostic value in childhood lymphoblastic leukemia (ALL) and is currently utilized in all major pediatric ALL protocols. MRD monitoring is done by multiparameter flow cytometry, IG/TCR quantitative ...

Abstract	Minimal residual disease (MRD) monitoring has a strong prognostic value in childhood lymphoblastic leukemia (ALL) and is currently utilized in all major pediatric ALL protocols. MRD monitoring is done by multiparameter flow cytometry, IG/TCR quantitative PCR or reverse transcriptase quantitative PCR of leukemic fusion transcripts providing a reliable measurement of treatment response. However, occasionally bone marrow (BM) aspirates may not yield representative material or be misinterpreted due to treatment-induced changes in MRD marker profile, undetected subclones at diagnosis, contamination with peripheral blood or cell adhesion and stroma cell interactions posing a risk for underestimating MRD levels and misclassifying resistant disease that may be detected by traditional BM morphology methods, immunohistochemistry, karyotyping and FISH. We present four cases with high MRD levels where MRD monitoring failed to provide the correct stratification information. Through these cases, we discuss the continued need to consider all available information including BM smears, touch imprints and trephine biopsy preparations not only at diagnosis but throughout remission monitoring in pediatric ALL.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bone Marrow/pathology ; Child ; Child, Preschool ; Female ; Flow Cytometry ; Humans ; Immunophenotyping ; Male ; Neoplasm Recurrence, Local/diagnosis ; Neoplasm, Residual/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Remission Induction
Language	English
Publishing date	2020-03-25
Publishing country	Denmark
Document type	Case Reports
ZDB-ID	93340-5
ISSN	1600-0463 ; 0903-4641
ISSN (online)	1600-0463
ISSN	0903-4641
DOI	10.1111/apm.13037
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Ud II Zs.73: Show issues

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Article ; Online: Fatal JC-virus Granular Cerebellar Neuronopathy in a Patient Diagnosed with ALPS and Hypogammaglobulinemia.

Helweg-Larsen, Jannik / Rasmussen, Morten / Marquart, Hanne Vibeke / Kondziella, Daniel / Marvig, Rasmus L / Rosenstierne, Maiken Worsøe / Bay, Jakob Thaning / Ryder, Lars Peter / Gjerdrum, Lise Mette Rahbek / Bangsgaard, Regitze / Gideon, Peter / Sellebjerg, Finn Thorup / Fomsgaard, Anders

Journal of clinical immunology

2022 Volume 42, Issue 4, Page(s) 869–872

MeSH term(s)	Agammaglobulinemia/diagnosis ; Cerebellum ; Humans ; JC Virus/genetics ; Leukoencephalopathy, Progressive Multifocal/diagnosis
Language	English
Publishing date	2022-02-17
Publishing country	Netherlands
Document type	Letter
ZDB-ID	779361-3
ISSN	1573-2592 ; 0271-9142
ISSN (online)	1573-2592
ISSN	0271-9142
DOI	10.1007/s10875-022-01227-3
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Article ; Online: Does minimal central nervous system involvement in childhood acute lymphoblastic leukemia increase the risk for central nervous system toxicity?

Anastasopoulou, Stavroula / Harila-Saari, Arja / Als-Nielsen, Bodil / Eriksson, Mats Anders / Heyman, Mats / Johannsdottir, Inga Maria / Marquart, Hanne Vibeke / Niinimäki, Riitta / Pronk, Cornelis Jan / Schmiegelow, Kjeld / Vaitkeviciene, Goda / Thastrup, Maria / Ranta, Susanna

Pediatric blood & cancer

2022 Volume 69, Issue 7, Page(s) e29745

Abstract: Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) implicates enhanced intrathecal chemotherapy, which is related to CNS toxicity. Whether CNS involvement alone contributes to CNS toxicity remains unclear. We studied ...

Abstract	Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) implicates enhanced intrathecal chemotherapy, which is related to CNS toxicity. Whether CNS involvement alone contributes to CNS toxicity remains unclear. We studied the occurrence of all CNS toxicities, seizures, and posterior reversible encephalopathy syndrome (PRES) in children with ALL without enhanced intrathecal chemotherapy with CNS involvement (n = 64) or without CNS involvement (n = 256) by flow cytometry. CNS involvement increased the risk for all CNS toxicities, seizures, and PRES in univariate analysis and, after adjusting for induction therapy, for seizures (hazard ratio [HR] = 3.33; 95% confidence interval [CI]: 1.26-8.82; p = 0.016) and PRES (HR = 4.85; 95% CI: 1.71-13.75; p = 0.003).
MeSH term(s)	Central Nervous System ; Central Nervous System Neoplasms/drug therapy ; Child ; Flow Cytometry ; Humans ; Posterior Leukoencephalopathy Syndrome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Seizures
Language	English
Publishing date	2022-04-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.29745
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