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  1. Article: Antibody-Drug Conjugates for the Treatment of Acute Pediatric Leukemia.

    Stokke, Jamie L / Bhojwani, Deepa

    Journal of clinical medicine

    2021  Volume 10, Issue 16

    Abstract: The clinical development of antibody-drug conjugates (ADCs) has gained momentum in recent years and these agents are gradually moving into frontline regimens for pediatric acute leukemias. ADCs consist of a monoclonal antibody attached to a cytotoxic ... ...

    Abstract The clinical development of antibody-drug conjugates (ADCs) has gained momentum in recent years and these agents are gradually moving into frontline regimens for pediatric acute leukemias. ADCs consist of a monoclonal antibody attached to a cytotoxic payload by a cleavable linker. This structure allows for highly cytotoxic agents to be directly delivered to leukemia cells leading to cell death and avoids excessive off-tumor toxicity. Near universal expression on B-cell acute lymphoblastic leukemia (ALL) blasts and the ability of rapid internalization has rendered CD22 an ideal target for ADC in B-ALL. Inotuzumab ozogamicin, the anti-CD22 antibody linked to calicheamicin led to complete remission rates of 60-80% in patients with relapsed/refractory B-ALL. In acute myeloid leukemia (AML), the CD33 targeting gemtuzumab ozogamicin has demonstrated modest improvements in survival and is the only ADC currently licensed in the United States for pediatric patients with de novo AML. Several other ADCs have been developed and tested clinically for leukemia but have achieved limited success to date. The search for additional leukemia-specific targets and optimization of ADC structure and specificity are ongoing efforts to improve their therapeutic window. This review provides a comprehensive overview of ADCs in acute leukemias, with a focus on pediatric ALL and AML.
    Language English
    Publishing date 2021-08-13
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm10163556
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  2. Article ; Online: IKZF1

    Kovach, Alexandra E / Wengyn, Maximilian / Vu, My H / Doan, Andrew / Raca, Gordana / Bhojwani, Deepa

    Pediatric blood & cancer

    2024  , Page(s) e30996

    Abstract: Background: Compared to other ethnicities, Hispanics/Latinos (H/L) have a high incidence of acute lymphoblastic leukemia (ALL), enrichment of unfavorable ALL genetic subtypes, and worse outcomes, even after correcting for socioeconomic factors. We ... ...

    Abstract Background: Compared to other ethnicities, Hispanics/Latinos (H/L) have a high incidence of acute lymphoblastic leukemia (ALL), enrichment of unfavorable ALL genetic subtypes, and worse outcomes, even after correcting for socioeconomic factors. We previously demonstrated increased incidence of the high-risk genetic drivers IKZF1 deletion and IGH::CRLF2 rearrangement in H/L compared to non-H/L children with B-ALL. Here in an expanded pediatric cohort, we sought to identify novel genetic drivers and secondary genetic alterations in B-ALL associated with H/L ethnicity.
    Procedure: Comprehensive clinicopathologic data from patients with B-ALL treated from 2016 to 2020 were analyzed. Subtype was determined from karyotype, fluorescence in situ hybridization (FISH), chromosome microarray (CMA), and our next-generation sequencing (NGS) panel (OncoKids). Non-driver genetic variants were also examined. p-Values less than .05 (Fisher's exact test) were considered significant.
    Results: Among patients with B-ALL at diagnosis (n = 273), H/L patients (189, 69.2%) were older (p = .018), more likely to present with CNS2 or CNS3 disease (p = .004), and NCI high-risk ALL (p = .014) compared to non-H/L patients. Higher incidence of IGH::CRLF2 rearrangement (B-ALL, BCR::ABL1-like, unfavorable; p = .016) and lower incidence of ETV6::RUNX1 rearrangement (favorable, p = .02) were also associated with H/L ethnicity. Among secondary (non-subtype-defining) genetic variants, B-ALL in H/L was associated with IKFZ1 deletion alone (p = .001) or with IGH::CRLF2 rearrangement (p = .003). The IKZF1
    Conclusions: Our study shows enrichment of high-risk genetic variants in H/L B-ALL and raises consideration for novel therapeutic targets.
    Language English
    Publishing date 2024-04-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2131448-2
    ISSN 1545-5017 ; 1545-5009
    ISSN (online) 1545-5017
    ISSN 1545-5009
    DOI 10.1002/pbc.30996
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    Zs.A 1131: Show issues Location:
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  3. Article ; Online: Managing therapy-associated neurotoxicity in children with ALL.

    Bhojwani, Deepa / Bansal, Ravi / Wayne, Alan S

    Hematology. American Society of Hematology. Education Program

    2021  Volume 2021, Issue 1, Page(s) 376–383

    Abstract: Several chemotherapeutic agents and novel immunotherapies provide excellent control of systemic and central nervous system (CNS) leukemia but can be highly neurotoxic. The manifestations of subacute methotrexate neurotoxicity are diverse and require ... ...

    Abstract Several chemotherapeutic agents and novel immunotherapies provide excellent control of systemic and central nervous system (CNS) leukemia but can be highly neurotoxic. The manifestations of subacute methotrexate neurotoxicity are diverse and require vigilant management; nonetheless, symptoms are transient in almost all patients. As methotrexate is a crucial drug to prevent CNS relapse, it is important to aim to resume it after full neurologic recovery. Most children tolerate methotrexate rechallenge without significant delays or prophylactic medications. Neurotoxicity is more frequent with newer immunotherapies such as CD19- chimeric antigen receptor T (CAR T) cells and blinatumomab. A uniform grading system for immune effector cell-associated neurotoxicity syndrome (ICANS) and algorithms for management based on severity have been developed. Low-grade ICANS usually resolves within a few days with supportive measures, but severe ICANS requires multispecialty care in the intensive care unit for life-threatening seizures and cerebral edema. Pharmacologic interventions include anticonvulsants for seizure control and glucocorticoids to reduce neuroinflammation. Anticytokine therapies targeted to the pathophysiology of ICANS are in development. By using illustrative patient cases, we discuss the management of neurotoxicity from methotrexate, CAR T cells, and blinatumomab in this review.
    MeSH term(s) Adolescent ; Antibodies, Bispecific/adverse effects ; Antibodies, Bispecific/therapeutic use ; Anticonvulsants/therapeutic use ; Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Central Nervous System Neoplasms/drug therapy ; Disease Management ; Female ; Glucocorticoids/therapeutic use ; Humans ; Immunotherapy, Adoptive/adverse effects ; Leukemia/drug therapy ; Male ; Methotrexate/adverse effects ; Methotrexate/therapeutic use ; Neurotoxicity Syndromes/etiology ; Neurotoxicity Syndromes/therapy
    Chemical Substances Antibodies, Bispecific ; Anticonvulsants ; Antineoplastic Agents ; Glucocorticoids ; blinatumomab (4FR53SIF3A) ; Methotrexate (YL5FZ2Y5U1)
    Language English
    Publishing date 2021-12-18
    Publishing country United States
    Document type Case Reports ; Journal Article ; Review
    ZDB-ID 2084287-9
    ISSN 1520-4383 ; 1520-4391
    ISSN (online) 1520-4383
    ISSN 1520-4391
    DOI 10.1182/hematology.2021000269
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  4. Article ; Online: Developing Therapy for Every Kid With Cancer - Summary of a Scientific Session at the 2023 ASCPT Meeting.

    Moore, Jason N / Campagne, Olivia / Bhojwani, Deepa / Crowe, Dean / Stewart, Clinton F

    Clinical pharmacology and therapeutics

    2023  Volume 115, Issue 2, Page(s) 185–187

    MeSH term(s) Humans ; Neoplasms/drug therapy
    Language English
    Publishing date 2023-11-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 123793-7
    ISSN 1532-6535 ; 0009-9236
    ISSN (online) 1532-6535
    ISSN 0009-9236
    DOI 10.1002/cpt.3101
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  5. Article ; Online: Hispanic ethnicity and the rs4880 variant in SOD2 are associated with elevated liver enzymes and bilirubin levels in children receiving asparaginase-containing chemotherapy for acute lymphoblastic leukemia.

    Wu, Sharon / Wang, Mengxi / Alqahtani, Amani / Lou, Mimi / Stock, Wendy / Bhojwani, Deepa / Alachkar, Houda

    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

    2022  Volume 150, Page(s) 113000

    Abstract: Asparaginase is an integral component of acute lymphoblastic leukemia (ALL) ...

    Abstract Asparaginase is an integral component of acute lymphoblastic leukemia (ALL)
    MeSH term(s) Adult ; Asparaginase/adverse effects ; Bilirubin/therapeutic use ; Chemical and Drug Induced Liver Injury/etiology ; Chemical and Drug Induced Liver Injury/genetics ; Child ; Drug-Related Side Effects and Adverse Reactions ; Ethnicity ; Genotype ; Humans ; Liver Diseases ; Polymorphism, Single Nucleotide ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Prospective Studies ; Superoxide Dismutase/genetics ; Superoxide Dismutase/therapeutic use ; Transaminases
    Chemical Substances Superoxide Dismutase (EC 1.15.1.1) ; superoxide dismutase 2 (EC 1.15.1.1) ; Transaminases (EC 2.6.1.-) ; Asparaginase (EC 3.5.1.1) ; Bilirubin (RFM9X3LJ49)
    Language English
    Publishing date 2022-04-29
    Publishing country France
    Document type Journal Article
    ZDB-ID 392415-4
    ISSN 1950-6007 ; 0753-3322 ; 0300-0893
    ISSN (online) 1950-6007
    ISSN 0753-3322 ; 0300-0893
    DOI 10.1016/j.biopha.2022.113000
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    Ud II Zs.198: Show issues Location:
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  6. Article ; Online: Asparaginase toxicity in Hispanic adult and pediatric patients with acute lymphoblastic leukemia: current understanding.

    Alqahtani, Amani / Alhousari, Diala / Ali, Amir / Yaghmour, George / Orgel, Etan / Curran, Emily / Stock, Wendy / Bhojwani, Deepa / Alachkar, Houda

    Expert opinion on drug metabolism & toxicology

    2023  Volume 19, Issue 6, Page(s) 357–366

    Abstract: Introduction: Asparaginase is essential to chemotherapy regimens for acute lymphoblastic leukemia (ALL). Survival of patients with ALL has improved since incorporating asparaginase into chemotherapy backbones. Hispanic patients have a higher incidence ... ...

    Abstract Introduction: Asparaginase is essential to chemotherapy regimens for acute lymphoblastic leukemia (ALL). Survival of patients with ALL has improved since incorporating asparaginase into chemotherapy backbones. Hispanic patients have a higher incidence of ALL than other ethnicities and suffer inferior outcomes. The inferior outcome of Hispanics is due to several factors, including the increased incidence of high-risk genetic subtypes and susceptibility to treatment-related toxicity.
    Areas covered: We summarize the current knowledge of asparaginase-related toxicity by comparing their incidence between Hispanic and non-Hispanic patients. These toxicities include hypersensitivity, hepatotoxicity, pancreatitis, thrombosis, and hypertriglyceridemia. The PubMed database and Google Scholar were used to search for this review from October 2022 to June 2023.
    Expert opinion: Except for hepatotoxicity and hypertriglyceridemia secondary to asparaginase-based treatments, which may develop more frequently among Hispanic patients with ALL, other toxicities were comparable between Hispanic and non-Hispanic patients. Nevertheless, studies with larger cohorts and more accurate capturing of Hispanic ethnicity should be conducted to fill the gaps in the current knowledge.
    MeSH term(s) Humans ; Child ; Adult ; Asparaginase/adverse effects ; Antineoplastic Agents/adverse effects ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Hypertriglyceridemia/drug therapy ; Chemical and Drug Induced Liver Injury/drug therapy
    Chemical Substances Asparaginase (EC 3.5.1.1) ; Antineoplastic Agents
    Language English
    Publishing date 2023-07-10
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2214462-6
    ISSN 1744-7607 ; 1742-5255
    ISSN (online) 1744-7607
    ISSN 1742-5255
    DOI 10.1080/17425255.2023.2233412
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    Zs.A 6264: Show issues Location:
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  7. Article ; Online: Children's Oncology Group blueprint for research: Acute lymphoblastic leukemia.

    Raetz, Elizabeth A / Bhojwani, Deepa / Devidas, Meenakshi / Gore, Lia / Rabin, Karen R / Tasian, Sarah K / Teachey, David T / Loh, Mignon L

    Pediatric blood & cancer

    2023  Volume 70 Suppl 6, Page(s) e30585

    Abstract: Cure rates for acute lymphoblastic leukemia (ALL), the most common childhood cancer have steadily improved over the past five decades. This is due to intensifying systemic therapy, recognizing and treating the central nervous system as a sanctuary site, ... ...

    Abstract Cure rates for acute lymphoblastic leukemia (ALL), the most common childhood cancer have steadily improved over the past five decades. This is due to intensifying systemic therapy, recognizing and treating the central nervous system as a sanctuary site, and implementing modern risk stratification to deliver varying intensities of therapy based on age, presenting white blood count, sentinel somatic genetics, and therapy response. Recently, numerous Children's Oncology Group trials have demonstrated the lack of benefit of intensifying traditional chemotherapy, providing evidence that new approaches are needed to cure the patients for whom cure has been elusive. Distinguishing those who require intensive or novel therapeutic approaches from others who will be cured with minimal therapy is key for future trials. Incorporating new genomic biomarkers and more sensitive measures of minimal/measurable residual disease provide opportunities to achieve these goals.
    MeSH term(s) Humans ; Child ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Central Nervous System ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Treatment Outcome
    Language English
    Publishing date 2023-07-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2131448-2
    ISSN 1545-5017 ; 1545-5009
    ISSN (online) 1545-5017
    ISSN 1545-5009
    DOI 10.1002/pbc.30585
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    Zs.A 1131: Show issues Location:
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  8. Article ; Online: B-cell acute lymphoblastic leukemia and juvenile xanthogranuloma in a patient with

    Newman, Haley / MacFarland, Suzanne P / Brodeur, Garrett M / Olson, Timothy / Bhojwani, Deepa / Stokke, Jamie / Kovach, Alexandra E / Clark, Mary Egan / Luo, Minjie / Li, Marilyn / Shah, Amish / Hunger, Stephen P

    Haematologica

    2024  Volume 109, Issue 5, Page(s) 1624–1627

    MeSH term(s) Female ; Humans ; ETS Translocation Variant 6 Protein ; Genetic Predisposition to Disease ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/complications ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Proto-Oncogene Proteins c-ets/genetics ; Repressor Proteins/genetics ; Thrombocytopenia/genetics ; Thrombocytopenia/diagnosis ; Thrombocytopenia/etiology ; Thrombocytopenia/pathology ; Xanthogranuloma, Juvenile/genetics ; Xanthogranuloma, Juvenile/diagnosis ; Xanthogranuloma, Juvenile/complications ; Xanthogranuloma, Juvenile/pathology ; Child ; Adolescent
    Chemical Substances ETS Translocation Variant 6 Protein ; Proto-Oncogene Proteins c-ets ; Repressor Proteins
    Language English
    Publishing date 2024-05-01
    Publishing country Italy
    Document type Case Reports ; Research Support, Non-U.S. Gov't
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2023.284151
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  9. Article ; Online: Development of second genetically distinct T-lymphoblastic leukemia in a pediatric patient.

    Hultquist, Haley / Rodriguez, Alyssa / Ferreira, Juanita E / Placek, Alexandra / Miller, Karin P / Wood, Brent L / Bhojwani, Deepa / Kapoor, Neena / Raca, Gordana / Gaynon, Paul / Kovach, Alexandra E

    Pediatric blood & cancer

    2024  , Page(s) e31050

    Language English
    Publishing date 2024-05-12
    Publishing country United States
    Document type Letter
    ZDB-ID 2131448-2
    ISSN 1545-5017 ; 1545-5009
    ISSN (online) 1545-5017
    ISSN 1545-5009
    DOI 10.1002/pbc.31050
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  10. Article ; Online: Characterization of PAX5 intragenic tandem multiplication in pediatric B-lymphoblastic leukemia by optical genome mapping.

    Jean, Jeffrey / Kovach, Alexandra E / Doan, Andrew / Oberley, Matthew / Ji, Jianling / Schmidt, Ryan J / Biegel, Jaclyn A / Bhojwani, Deepa / Raca, Gordana

    Blood advances

    2022  Volume 6, Issue 11, Page(s) 3343–3346

    MeSH term(s) Child ; Chromosome Mapping ; Humans ; Lymphoma, Non-Hodgkin ; PAX5 Transcription Factor/genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics
    Chemical Substances PAX5 Transcription Factor ; PAX5 protein, human
    Language English
    Publishing date 2022-03-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2021006328
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