Imatinib-Induced Hypogammaglobulinemia in Children and Adolescents with Chronic Myeloid Leukemia

Totadri, Sidharth; Thipparapu, S.; Aggarwal, Ritu; Sharma, Madhulika; Naseem, Shano; Jain, Richa; Trehan, Amita; Malhotra, Pankaj; Varma, Neelam; Bansal, Deepak

doi:10.1080/08880018.2020.1759739

Cited by 8 publications

(10 citation statements)

References 15 publications

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“…Similar findings were reported in a pediatric cohort with CML (N = 30, mean age: 16.4 years, range: 9-23 years) where they were treated with imatinib at a median dose of 287.5 mg/m 2 (IQR: 267.3, 345.0) for a median duration of 6 years [15]. The IgG, IgA, and IgM plasma levels decreased in 9 (30%), 8 (27%), and 10 (33%) patients, respectively.…”

Section: Altered Humoral and Cellular Immune Functionsupporting

confidence: 84%

Chronic Myeloid Leukemia in Children: Immune Function and Vaccinations

Suttorp

Carrion

Hijiya

2021

JCM

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Children with CML need TKI treatment for many years, and the lack of knowledge about immune dysfunction with TKI has hindered routine immunizations. This review attempts to provide an overview of the effects of TKIs licensed for children (e.g., imatinib, dasatinib, and nilotinib) on immune function, as well as its implications on immunizations. We discuss surveillance strategies (e.g., immunoglobulin blood serum levels and hepatitis B reactivation) and immunizations. All inactivated vaccines (e.g., influenza, pneumococcal, and streptococcal) can be given during the treatment of CML in the chronic phase, although their efficacy may be lower. As shown in single cases of children and adults with CML, live vaccines (e.g., varicella, measles, mumps, rubella, and yellow fever) may be administered under defined circumstances with great precautions. We also highlight important aspects of COVID-19 in this patient population (e.g., the outcome of COVID-19 infection in adults with CML and in children with varying hemato-oncological diseases) and discuss the highly dynamic field of presently available different vaccination options. In conclusion, TKI treatment for CML causes humoral and cellular immune dysfunction, which is mild in most patients, and thus infectious complications are rare. Routine immunizations are important for health maintenance of children, but vaccinations for children with CML on TKI therapy should be carefully considered.

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Section: Altered Humoral and Cellular Immune Functionsupporting

confidence: 84%

Chronic Myeloid Leukemia in Children: Immune Function and Vaccinations

Suttorp

Carrion

Hijiya

2021

JCM

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“…Assessment of the following criteria is desirable when CML BCR-ABL1 is diagnosed: (a) for optimal monitoring of treatment response in individual patients: gender, age, height, bodyweight in correlation to the TKI dose administered [ 108 ], identification of mutations in the BCR-ABL1 kinase domain in patients with CML-AP and CML-BP, identification of the BCR-ABL1 breakpoint on a genomic (DNA) level [ 63 , 66 , 109 , 110 , 111 , 112 ], (b) to compare data on pediatric CML BCR-ABL1 internationally: a threphine biopsy (degree of fibrosis, nests of blasts), due to the rarity of pediatric CML all patients should be enrolled in trials and enrolled into the international pediatric CML registry [ 4 ], for comparison of BCR-ABL1 mRNA levels when assessing the treatment response, data derived from individual laboratories must be aligned to a reference method (International Standard, IS) applying laboratory-specific conversion factors [ 113 , 114 ], (c) to improve the scientific understanding of the disease: identification of genes and their products influencing TKI blood serum concentration and metabolism [ 108 , 115 ], assessment of acquired von Willebrand disease in cases with elevated platelets [ 73 , 81 ], vaccination status at diagnosis and maintenance of immunity under TKI treatment [ 116 , 117 , 118 ], identification of somatic or germline mutations and epigenetic modification in addition to BCR-ABL1 [ 55 , 57 , 66 , 112 , 119 , 120 , 121 , 122 ]. …”

Section: Essential and Desirable Diagnostic Criteriamentioning

confidence: 99%

“…(c) to improve the scientific understanding of the disease: identification of genes and their products influencing TKI blood serum concentration and metabolism [ 108 , 115 ], assessment of acquired von Willebrand disease in cases with elevated platelets [ 73 , 81 ], vaccination status at diagnosis and maintenance of immunity under TKI treatment [ 116 , 117 , 118 ], identification of somatic or germline mutations and epigenetic modification in addition to BCR-ABL1 [ 55 , 57 , 66 , 112 , 119 , 120 , 121 , 122 ]. …”

Section: Essential and Desirable Diagnostic Criteriamentioning

confidence: 99%

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Definition, Epidemiology, Pathophysiology, and Essential Criteria for Diagnosis of Pediatric Chronic Myeloid Leukemia

Suttorp

Millot

Sembill

et al. 2021

Cancers

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Depending on the analytical tool applied, the hallmarks of chronic myeloid leukemia (CML) are the Philadelphia Chromosome and the resulting mRNA fusion transcript BCR-ABL1. With an incidence of 1 per 1 million of children this malignancy is very rare in the first 20 years of life. This article aims to; (i) define the disease based on the WHO nomenclature, the appropriate ICD 11 code and to unify the terminology, (ii) delineate features of epidemiology, etiology, and pathophysiology that are shared, but also differing between adult and pediatric patients with CML, iii) give a short summary on the diseases to be considered as a differential diagnosis of pediatric CML, (iv) to describe the morphological, histopathological and immunophenotypical findings of CML in pediatric patients, (v) illustrate rare but classical complications resulting from rheological problems observed at diagnosis, (vi) list essential and desirable diagnostic criteria, which hopefully in the future will help to unify the attempts when approaching this rare pediatric malignancy.

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“…The IgG, IgA, and IgM levels were reduced in nine (30%), eight (27%), and ten (33%) patients, respectively, and 5/30 (17%) patients had pan-hypogammaglobulinemia. In total, 14 (47%) patients had a deficiency of one or more serum immunoglobulins [91]. Ota et al [92] conducted a multicenter cooperative study to analyze the adverse events associated with TKIs used as initial treatment for CML in 450 patients, of whom eight were children and adolescents (six of the eight received imatinib) aged 0-19 years.…”

Section: Imatinibmentioning

confidence: 99%

Secondary Dysgammaglobulinemia in Children with Hematological Malignancies Treated with Targeted Therapies

Tragiannidis

Groll

2021

Pediatr Drugs

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Targeted therapies have emerged as innovative treatments for patients whose disease does not respond to conventional chemotherapy, and their use has widely expanded in the field of pediatric hematologic malignancies in the last decade. While they carry the promise of improved disease control and survival and are currently investigated in first-line treatment protocols for patients with poor prognostic markers, they are associated with a considerable incidence of specific toxicities, including cytokine-release syndrome, neurotoxicity, hepatotoxicity, nephrotoxicity, cardiotoxicity, endocrine adverse events, and infectious complications. Iatrogenic or secondary dysgammaglobulinemia is a main consequence of targeted therapies using monoclonal antibodies and other antibody-derived treatments that target specific antigens on lymphoid cells (blinatumomab, inotuzumab ozogamicin, rituximab), chimeric antigen receptor T cells, tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib) and, to a lesser extent, checkpoint inhibitors (pembrolizumab, nivolumab). This review discusses the diagnosis and incidence of secondary or iatrogenic dysgammaglobulinemia in children treated with targeted therapies for leukemias and lymphomas, and options for monitoring and treatment.

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Imatinib-Induced Hypogammaglobulinemia in Children and Adolescents with Chronic Myeloid Leukemia

Cited by 8 publications

References 15 publications

Chronic Myeloid Leukemia in Children: Immune Function and Vaccinations

Chronic Myeloid Leukemia in Children: Immune Function and Vaccinations

Definition, Epidemiology, Pathophysiology, and Essential Criteria for Diagnosis of Pediatric Chronic Myeloid Leukemia

Secondary Dysgammaglobulinemia in Children with Hematological Malignancies Treated with Targeted Therapies

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