Hodgkinʼs Disease in Pediatric Patients with Naturally Occurring Immunodeficiency

Robison, Leslie L.; Stoker, Valerie; Frizzerà, Glauco; Heinitz, Karen; Meadows, Anna T.; Filipovich, Alexandra H.

doi:10.1097/00043426-198722000-00019

Cited by 37 publications

(11 citation statements)

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“…Although over half of these tumors occurred in patients with Ataxia-Telangiectasia (AT) (30%) and common variable immunodeficiency (24%), about 25% were seen in patients with the WAS and SCID. 7-9 A recent analysis of data reported to the Australasian Society of Clinical Immunology and Allergy PID Registry showed that while there was a 1.6-fold excess relative risk of cancer observed for PID patients, the standardized incidence ratio (SIR) was 5.36-8.82 for non-Hodgkin lymphoma, leukemia and stomach cancer. The SIRs for all cancers were significantly increased in patients with CVID and AT.…”

Section: Discussionmentioning

confidence: 99%

Malignancies after Hematopoietic Cell Transplantation for Primary Immune Deficiencies: A Report from the Center for International Blood and Marrow Transplant Research

Kamani

Kumar

Hassebroek³

et al. 2011

Biology of Blood and Marrow Transplantation

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We describe the incidence of malignancy in patients with primary immunodeficiency disorders (PIDD) following hematopoietic cell transplantation (HCT). From the Center for International Blood and Marrow Transplant Research, 2266 PIDD patients who had undergone allogeneic HCT between 1968 and 2003 were identified. Patient, disease and transplant factors for development of malignancy were examined and pathology reports for reported malignancies reviewed independently by a pathologist for confirmation. The incidence of malignancy was highest for Wiskott-Aldrich syndrome (3.3%) with an overall incidence of 2.3% for PIDD. Post-HCT malignancy was confirmed for 52 of 63 reported cases. Forty-five of 52 patients developed a lymphoproliferative disorder (PTLD) at a median of 3 months post-HCT. Of these, 26 had received T-cell depleted (TCD) bone marrow. Three patients who developed myelodysplastic syndrome had received TCD marrow and total body irradiation. Three patients developed a solid tumor. Patients with PIDD are at a relatively low risk of developing malignancies post-HCT compared to their historical risk of cancer. The most frequent malignancy or lymphoproliferative disorder was early-onset PTLD. As in other HCT recipients, TCD appears to correlate with PTLD development. Our results lend support to the hypothesis that immune reconstitution in PIDD following HCT leads to a decrease in cancer risk.

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Section: Discussionmentioning

confidence: 99%

Malignancies after Hematopoietic Cell Transplantation for Primary Immune Deficiencies: A Report from the Center for International Blood and Marrow Transplant Research

Kamani

Kumar

Hassebroek³

et al. 2011

Biology of Blood and Marrow Transplantation

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“…A pediatric Hodgkin lymphoma case-control study comparing 20 HL cases (50% A-T, 45% immunoglobulin defects) from the ICR to 100 cases of HL in children without known immunodeficiency from the Late Effects Study Group confirmed that Hodgkin lymphoma occurs in A-T patients at a significantly younger age (mean 7.8 years) than in the general pediatric population (mean 11.5 years) [14]. In our literature review examining cases of HL in A-T (Table 1), the average age at diagnosis was 9.6 years old (range 3-25, median 8.8 years).…”

Section: Hodgkin Lymphoma In A-t and A Review Of The Literaturementioning

confidence: 93%

“…All subtypes of HL have been reported in A-T; however, a review of the ICR shows that 42% of A-T patients show the mixed-cellularity subtype of HL and 33% of A-T patients have the lymphocyte depleted subtype [14]. These subtypes of HL are infrequently seen in developed countries, have an increased association with HIV, and are both highly associated with EBV [15].…”

Section: Hodgkin Lymphoma In A-t and A Review Of The Literaturementioning

confidence: 99%

“…A-T patients have an increased risk of developing cancer, and Hodgkin lymphoma accounts for 10% of all malignancies seen in these patients [13]. A-T patients present with Hodgkin lymphoma at a younger age than the general pediatric population, and usually at an advanced stage of disease [14]. The diagnosis of malignancy may precede the diagnosis of A-T or follow it.…”

Section: Introductionmentioning

confidence: 99%

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Hodgkin lymphoma in a young child contributing to a diagnosis of ataxia telangiectasia: review of the literature

2010

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“…1 The heterozygous carriers of the ATM gene, who are clinically normal, have an increased susceptibility to cancer, [2][3][4] particularly breast cancer, [4][5][6] and patients with AT are at high risk of malignancies such as leukemia and malignant lymphoma, including Hodgkin disease (HD). 2,[7][8][9][10] Although most cases of HD occur sporadically, there may be inheritable factors involved in the development of HD, [11][12][13][14][15] and a subset of HD is associated with an increased incidence of secondary malignancies, especially in patients who were younger at the time of treatment. [16][17][18][19] Survivors of HD, like AT carriers, are at increased risk of radiation-induced breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of polymorphic variations of the ataxia telangiectasia mutated (ATM) gene in childhood Hodgkin disease

Takagi

Tsuchida²,

Oguchi³

et al. 2004

Blood

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There are conflicting reports about the involvement of single nucleotide polymorphisms (SNPs) of the ataxia telangiectasia mutated (ATM) gene with cancer, and the consequences of these SNPs for ATM function remain unclear. We therefore sought to identify SNPs of the ATM gene in pediatric Hodgkin disease (HD) and to analyze ATM function in cells from patients with these SNPs. We have identified SNPs of the ATM gene in 5 of 14 children (S1455R, n ‫؍‬ 1; H1380Y, n ‫؍‬ 1; N1650S, n ‫؍‬ 2; and I709I, n ‫؍‬ 1). One patient had nonsense-associated altered splicing of the ATM gene. Lymphoblastoid cell lines expressing the S1455R and N1650S exhibited defective ATM-mediated p53 phosphorylation and Chk2 activation; cells expressing the H1380Y exhibited defective c-Abl activation after X-irradiation. Expression of the N1650S in ATM-null fibroblasts conferred only partial hyperradiosensitivity. Furthermore, the introduction of N1650S ATM into U2OS cells, which express wild-type ATM, showed reduced p53-Ser15 phosphorylation, suggesting a dominant-negative effect of the N1650S over the wild-type ATM protein. We conclude that the rare polymorphic variants of the ATM gene that we identified in children with HD encode functionally abnormal proteins, and we discuss the possible genetic risk factors for childhood HD. IntroductionIt is estimated that 0.5% to 1% of the general population are heterozygous carriers of mutations in the ataxia telangiectasia mutated (ATM) gene that is responsible for ataxia telangiectasia (AT), an autosomal recessive, multisystem disorder associated with progressive cerebellar ataxia, bulbar telangiectasia, immunologic deficiency, chromosomal instability, radiation sensitivity, and predisposition to lymphoreticular cancers. 1 The heterozygous carriers of the ATM gene, who are clinically normal, have an increased susceptibility to cancer, 2-4 particularly breast cancer, 4-6 and patients with AT are at high risk of malignancies such as leukemia and malignant lymphoma, including Hodgkin disease (HD). 2,7-10 Although most cases of HD occur sporadically, there may be inheritable factors involved in the development of HD, [11][12][13][14][15] and a subset of HD is associated with an increased incidence of secondary malignancies, especially in patients who were younger at the time of treatment. [16][17][18][19] Survivors of HD, like AT carriers, are at increased risk of radiation-induced breast cancer. 18,20,21 The 13-kb transcript of the ATM gene encodes a 350-kDa protein kinase whose carboxy-terminal region exhibits homology to the catalytic domain of phosphoinositide-3-kinases 22,23 and that plays key roles in intracellular signaling, cell-cycle control, and DNA repair and recombination. 24 In response to DNA damage, increased ATM protein kinase activity mediates the activation and stabilization of p53 and results in cell-cycle arrest. p53 is stabilized by ATM-mediated phosphorylation at Ser15 25,26 and Ser20. The ATM-dependent phosphorylation of p53 at Ser20 is mediated by the checkpoint kinases Cds1/Chk2...

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Hodgkinʼs Disease in Pediatric Patients with Naturally Occurring Immunodeficiency

Cited by 37 publications

References 0 publications

Malignancies after Hematopoietic Cell Transplantation for Primary Immune Deficiencies: A Report from the Center for International Blood and Marrow Transplant Research

Malignancies after Hematopoietic Cell Transplantation for Primary Immune Deficiencies: A Report from the Center for International Blood and Marrow Transplant Research

Hodgkin lymphoma in a young child contributing to a diagnosis of ataxia telangiectasia: review of the literature

Identification and characterization of polymorphic variations of the ataxia telangiectasia mutated (ATM) gene in childhood Hodgkin disease

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