Preexisting conditions in pediatric ALL patients: Spectrum, frequency and clinical impact

Schütte, Peter; Möricke, Anja; Zimmermann, Martin; Bleckmann, Kirsten; Reismüller, Bettina; Attarbaschi, Andishe; Mann, Georg; Bodmer, Nicole; Niggli, Felix; Schrappe, Martin; Stanulla, Martin; Kratz, Christian P.

doi:10.1016/j.ejmg.2015.12.008

Cited by 24 publications

(14 citation statements)

References 15 publications

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“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Primary immunodeficiencies (PID) such as DNA repair defects (Nijmegen breakage syndrome, Ataxia telangiectasia, Bloom syndrome or constitutional mismatch repair deficiency), severe combined immunodeficiencies (SCID), common variable immunodeficiencies (CVID), and immune-osseous dysplasias (Di George syndrome or cartilage hair hypoplasia) have an extraordinary risk of developing leukemia and lymphoma. [5][6][7][8][9][10][11][12][13][14][15][16][17]20,21 Although these patients seem to have an inferior prognosis and an increased risk of treatment-related toxicity and death compared to patients with lymphoid malignancies without a PID, curative therapies including allogeneic stem cell transplantation (allo-SCT) have been repeatedly reported. 5,6,10,11,15,16,22 Systematic data on the spectrum of common and rare pre-existing conditions associated with NHL in children and adolescents are scarce with respect to the type of the pre-existing conditions and the clinical characteristics and outcome of the associated NHL subtypes.…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7][8][9][10][11][12][13][14][15][16][17]20,21 Although these patients seem to have an inferior prognosis and an increased risk of treatment-related toxicity and death compared to patients with lymphoid malignancies without a PID, curative therapies including allogeneic stem cell transplantation (allo-SCT) have been repeatedly reported. 5,6,10,11,15,16,22 Systematic data on the spectrum of common and rare pre-existing conditions associated with NHL in children and adolescents are scarce with respect to the type of the pre-existing conditions and the clinical characteristics and outcome of the associated NHL subtypes. Thus, the two largest childhood NHL consortia, the European Intergroup for Childhood NHL (EICNHL) and the international Berlin-Frankfurt-Münster (i-BFM) Study Group (SG), designed a retrospective multinational study to collect data on unselected types of pre-existing conditions among children and adolescents with NHL.…”

Section: Introductionmentioning

confidence: 99%

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Non-Hodgkin lymphoma and pre-existing conditions: spectrum, clinical characteristics and outcome in 213 children and adolescents

et al. 2016

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C hildren and adolescents with pre-existing conditions such as DNA repair defects or other primary immunodeficiencies have an increased risk of non-Hodgkin lymphoma. However, largescale data on patients with non-Hodgkin lymphoma and their entire spectrum of pre-existing conditions are scarce. A retrospective multinational study was conducted by means of questionnaires sent out to the national study groups or centers, by the two largest consortia in childhood non-Hodgkin lymphoma, the European Intergroup for Childhood non-Hodgkin Lymphoma, and the international BerlinFrankfurt-Münster Study Group. The study identified 213 patients with non-Hodgkin lymphoma and a pre-existing condition. Four subcategories were established: a) cancer predisposition syndromes (n=124, 58%); b) primary immunodeficiencies not further specified (n=27, 13%); c) genetic diseases with no increased cancer risk (n=40, 19%); and d) non-classifiable conditions (n=22, 10%). Seventy-nine of 124 (64%) cancer predispositions were reported in groups with more than 20 patients: ataxia telangiectasia (n=32), Nijmegen breakage syndrome (n=26), constitutional mis-

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Non-Hodgkin lymphoma and pre-existing conditions: spectrum, clinical characteristics and outcome in 213 children and adolescents

et al. 2016

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“…Additionally, other types of malignancies, such as carcinoma, that occur later in life than hematologic malignancies but much earlier than in the general population, as well as sarcoma, medulloblastoma, or neuroblastoma, were observed, especially in patients with NBS, Bloom syndrome, and CMMRD (Table II). 1,[48][49][50][51][52] The recently reported association of profound CID, monoclonal lymphoproliferative disease, and increased chemosensitivity in a patient with familial tumor predisposition and mutated RAD52 fits this picture. 53 Until now, no malignancies have been reported in patients with radiosensitive SCID caused by mutations in PRKDC or MRE11, probably because DNA-dependent protein kinase, catalytic subunit-deficient human subjects have no T-and B-cell development at all (reviewed by de Miranda et al 47 ), and MRE11 deficiency might be partially compensated by other components of the NBN/RAD50/MRE11 complex.…”

Section: The Immunologic and Biological Perspective: Categories Of Pimentioning

confidence: 79%

Intrinsic and extrinsic causes of malignancies in patients with primary immunodeficiency disorders

Hauck

Voss

Urban

et al. 2018

Journal of Allergy and Clinical Immunology

102

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Malignancies occur with a higher incidence rate and manifest earlier in life in patients with primary immunodeficiency disorders (PIDs) than in the general population. However, no universal mechanism of malignancy predisposition in patients with PIDs has been determined. Despite strong support for the physiologic role of tumor immunosurveillance and the increasing success of strategies in immunologic tumor therapy, which include checkpoint inhibition, mAbs, and engineered T-cell antigen receptors, the incidence and pattern of malignancies in patients with PIDs do not reflect an increased tumor immune escape per se. In contrast, malignancies appear to be restricted to either (1) tissue types bearing the same molecular defect that underlies the PID, such as syndromes of DNA repair deficiency or immune cell-specific maturation or functional defects that suggest a cell-intrinsic oncogenic basis, or (2) other tissues when they are infected by transforming viruses or chronically inflamed, pointing toward extrinsic causes for transformation that are potentially facilitated by but not predominantly caused by a lack of immunosurveillance. Based on recent studies of pre-existing conditions in patients with malignancies and on malignancies in large PID cohorts, we conclude that a large part of tumor predisposition in patients with PIDs is derived from the same molecular defect as the immunodeficiency itself. The presented concept elucidates diverse pathomechanisms and risks of malignancies in patients with PIDs in light of current tumor immune therapies.

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“…Furthermore, β-thalassemia patients not requiring RBC transfusions also develop hematological malignancies, including ALL, indicating that the simultaneous occurrence of these diseases may be coincidental (12,19). Of note, evidence indicates an association between T-cell ALL and preexisting ataxia-telangiectasia (AT), reflecting a non-random mechanism of leukemogenesis (14,20). In this regard, ATM gene truncating mutations were 12.9 times more frequent in childhood T-cell ALL compared with the normal population (P=0.004) (21).…”

Section: Discussionmentioning

confidence: 99%

A strategy for the clinical remission of acute lymphoblastic leukemia elicited by treatment of β‑thalassemia major: A case report

et al. 2017

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Abstract. Acute lymphoblastic leukemia (ALL) has been suggested as a long-term complication in patients with β-thalassemia major (β-TM). A 12-months-old male patient was diagnosed with β-TM. The patient required a blood transfusion weekly for 2 years. At the age of 4 years, a splenectomy was performed due to massive splenomegaly and frequent transfusion requirements. The histopathological analysis of the spleen revealed extensive hemosiderosis. ALL-L1 with the T immunophenotype and without central nervous system (CNS) involvement was diagnosed when the patient was 5 years old, and treated with anti-leukemic combination chemotherapy and CNS radiotherapy. The patient completed 24 months of treatment and has been in complete remission for 7 years, without long-term adverse events.

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Preexisting conditions in pediatric ALL patients: Spectrum, frequency and clinical impact

Cited by 24 publications

References 15 publications

Non-Hodgkin lymphoma and pre-existing conditions: spectrum, clinical characteristics and outcome in 213 children and adolescents

Non-Hodgkin lymphoma and pre-existing conditions: spectrum, clinical characteristics and outcome in 213 children and adolescents

Intrinsic and extrinsic causes of malignancies in patients with primary immunodeficiency disorders

A strategy for the clinical remission of acute lymphoblastic leukemia elicited by treatment of β‑thalassemia major: A case report

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