Pediatr Blood Cancer 2015;62:2018–2020
BRIEF REPORT Treatment of EBV-Associated Nodular Sclerosing Hodgkin Lymphoma in a Patient With Ataxia Telangiectasia With Brentuximab Vedotin and Reduced COPP Plus Rituximab Michael T. Meister, MD,* Sandra Voss, Patientswith ataxia telangiectasia (AT)withmalignancies facepoor prognosisdueto increasedtreatment-relatedtoxicity.Here,wereporta 14-year-old male with AT and Hodgkin lymphoma (HL) who received brentuximab vedotin and reduced COPP plus rituximab
Key words:
and Dirk Schwabe,
MD
courses. This treatment resulted in complete remission and showed no severe toxicity. Pediatr Blood Cancer 2015;62:2018–2020. © 2015 Wiley Periodicals, Inc.
ataxia telangiectasia; brentuximab vedotin; Hodgkin lymphoma
INTRODUCTION Ataxia telangiectasia (AT) is a rare autosomal recessive multisystem disorder characterized by progressive cerebellar dysfunction like ataxia or kinetic tremor, movement disorders, oculocutaneous telangiectasias, combined cellular and humoral immunodeficiency with recurrent sinopulmonary infections and an increased rate of malignancies, especially lymphomas and leukemias.[1] The ataxia telangiectasia mutated (ATM) gene located on chromosome 11q2–23 encodes for a serin/threonin protein kinase that plays a major role in DNA repair. A deficient ATM results in a hypersensitivity of DNA to ionizing radiation and DNA-damaging chemotherapeutics.[2] Diagnosis is based on clinical presentation and elevated levels of alpha-fetoprotein (AFP) in the patient’s blood.[3] There is no curative therapy. The expectancy of life is decreased and most patients with AT die from severe infections or malignant diseases. Hodgkin lymphoma (HL) is a less often occurring malignancy in children with AT.[4] In these patients, it is almost always associated with Epstein–Barr virus infection (EBV).[5] Children with HL without AT face excellent prognosis with an estimated 5 years survival rates over 90%. Therapy consists of chemotherapy and irradiation based on risk stratification.[6] In contrast, children with AT face dismal prognosis with a median survival of 3 months with or without treatment.[4,7] Brentuximab vedotin is an antibody-drug conjugate composed of an anti-CD30 antibody linked to a microtubule-disrupting agent monomethyl auristatin E (MMAE) which leads to apoptosis after internalization. There are different phase I/II trials ongoing which are evaluating the potential role of brentuximab vedotin in monoor combination treatment of pediatric Hodgkin lymphoma (ClinicalTrials.gov Identifier: NCT01780662, NCT01492088, NCT01920932).
CASE DESCRIPTION We report a 14-year-old male who was diagnosed for AT in early childhood. He suffered from two respiratory tract infections on average per year and showed progressive neurological symptoms with kinetic tremor, ataxia which left him wheelchair-bound and coordinative dysfunction with stuttering. In a routine checkup, cervical lymphadenopathy in the left jaw angle was detected. In addition, the patient suffered from thoracic pain. An MRI scan of C
MD,
2015 Wiley Periodicals, Inc. DOI 10.1002/pbc.25621 Published online 24 June 2015 in Wiley Online Library (wileyonlinelibrary.com).
the thorax revealed bilateral hilar, bilateral mediastinal, and left axillary lymphomas. A sample of the cervical lymphoma was collected and led to the diagnosis of an EBV-associated nodularsclerosing Hodgkin lymphoma with expression of high levels of CD30 and low levels of CD20. The following staging examinations revealed supraclavicular lymphomas, further cervical lymphomas, as well as a suspect splenic lesion. Blood examinations showed a mild anemia (hemoglobin 12.1 g/dl) as well as slightly elevated liver enzymes with sonographical signs of a steatosis hepatis. Serum levels of uric acid and lactate dehydrogenase (LDH) were not elevated. At diagnosis, the serum level of AFP was elevated at 141.8 ng/ml (range
BRIEF REPORT Treatment of EBV-Associated Nodular Sclerosing Hodgkin Lymphoma in a Patient With Ataxia Telangiectasia With Brentuximab Vedotin and Reduced COPP Plus Rituximab Michael T. Meister, MD,* Sandra Voss, Patientswith ataxia telangiectasia (AT)withmalignancies facepoor prognosisdueto increasedtreatment-relatedtoxicity.Here,wereporta 14-year-old male with AT and Hodgkin lymphoma (HL) who received brentuximab vedotin and reduced COPP plus rituximab
Key words:
and Dirk Schwabe,
MD
courses. This treatment resulted in complete remission and showed no severe toxicity. Pediatr Blood Cancer 2015;62:2018–2020. © 2015 Wiley Periodicals, Inc.
ataxia telangiectasia; brentuximab vedotin; Hodgkin lymphoma
INTRODUCTION Ataxia telangiectasia (AT) is a rare autosomal recessive multisystem disorder characterized by progressive cerebellar dysfunction like ataxia or kinetic tremor, movement disorders, oculocutaneous telangiectasias, combined cellular and humoral immunodeficiency with recurrent sinopulmonary infections and an increased rate of malignancies, especially lymphomas and leukemias.[1] The ataxia telangiectasia mutated (ATM) gene located on chromosome 11q2–23 encodes for a serin/threonin protein kinase that plays a major role in DNA repair. A deficient ATM results in a hypersensitivity of DNA to ionizing radiation and DNA-damaging chemotherapeutics.[2] Diagnosis is based on clinical presentation and elevated levels of alpha-fetoprotein (AFP) in the patient’s blood.[3] There is no curative therapy. The expectancy of life is decreased and most patients with AT die from severe infections or malignant diseases. Hodgkin lymphoma (HL) is a less often occurring malignancy in children with AT.[4] In these patients, it is almost always associated with Epstein–Barr virus infection (EBV).[5] Children with HL without AT face excellent prognosis with an estimated 5 years survival rates over 90%. Therapy consists of chemotherapy and irradiation based on risk stratification.[6] In contrast, children with AT face dismal prognosis with a median survival of 3 months with or without treatment.[4,7] Brentuximab vedotin is an antibody-drug conjugate composed of an anti-CD30 antibody linked to a microtubule-disrupting agent monomethyl auristatin E (MMAE) which leads to apoptosis after internalization. There are different phase I/II trials ongoing which are evaluating the potential role of brentuximab vedotin in monoor combination treatment of pediatric Hodgkin lymphoma (ClinicalTrials.gov Identifier: NCT01780662, NCT01492088, NCT01920932).
CASE DESCRIPTION We report a 14-year-old male who was diagnosed for AT in early childhood. He suffered from two respiratory tract infections on average per year and showed progressive neurological symptoms with kinetic tremor, ataxia which left him wheelchair-bound and coordinative dysfunction with stuttering. In a routine checkup, cervical lymphadenopathy in the left jaw angle was detected. In addition, the patient suffered from thoracic pain. An MRI scan of C
MD,
2015 Wiley Periodicals, Inc. DOI 10.1002/pbc.25621 Published online 24 June 2015 in Wiley Online Library (wileyonlinelibrary.com).
the thorax revealed bilateral hilar, bilateral mediastinal, and left axillary lymphomas. A sample of the cervical lymphoma was collected and led to the diagnosis of an EBV-associated nodularsclerosing Hodgkin lymphoma with expression of high levels of CD30 and low levels of CD20. The following staging examinations revealed supraclavicular lymphomas, further cervical lymphomas, as well as a suspect splenic lesion. Blood examinations showed a mild anemia (hemoglobin 12.1 g/dl) as well as slightly elevated liver enzymes with sonographical signs of a steatosis hepatis. Serum levels of uric acid and lactate dehydrogenase (LDH) were not elevated. At diagnosis, the serum level of AFP was elevated at 141.8 ng/ml (range
