Ann Boekstegers, Germany

Dr von Hauner childrens hospital Immunology

Presenter of 1 Presentation

Poster Display Malignancy and PID

DIAGNOSIS AND TREATMENT OF T-ALL AND B-NHL IN TWO SISTERS WITH NIJMEGEN BREAKAGE SYNDROME WITH CHEMOTHERAPY AND ALLOGENEIC STEM CELL TRANSPLANTATION

Lecture Time
10:13 - 10:14
Room
Poster Area
Date
20.09.2019, Friday
Session Time
10:00 - 17:00
Board Number
14
Presentation Topic
Malignancy and PID

Abstract

Background and Aims

Nijmegen breakage syndrome (NBS) is a syndromic disorder of DNA repair resulting in microcephaly, growth retardation, immunodeficiency, and cancer predisposition.

Methods

We performed clinical, immunological, and genetic analysis.

Results

Two sisters of 7 and 16 years presented to us with failure to thrive, microcephaly, bird-like face, and chronic lung disease. Immunological work-up revealed hypogammaglobulinemia, low switched-memory B cells, and loss of T-cell naivety. Additionally, the younger sister had T-cell acute lymphoblastic leukaemia treated with conventional chemotherapy three years ago. We found the known Slavic homozygous NBN nonsense variants (c.657_661del5) confirming NBS. PCP prophylaxis and immunoglobulin replacement were started. Two months later, the index patient developed aggressive, diffuse large B-cell lymphoma stage III with infiltration of the kidneys, liver, spleen, pancreas and thyroid gland. Modified chemotherapy according to the B-NHL 2013 protocol was initiated and led to partial remission. Due to the high relapse risk and to cure the associated immunodeficiency, the patient and her family opted for allogeneic hematopoietic stem cell transplantation (HSCT). After reduced intensity conditioning, the patient underwent allogeneic HSCT from an HLA compatible (9/10) matched unrelated donor. Her post-transplant course was complicated by transient kidney dysfunction and the development of acute GvHD °IV involving skin (°II) and gut (°IV). After intensive treatment with methylprednisolone, infliximab and ruxolitinib the patient’s condition stabilized.

Conclusions

NBS is associated with a very high risk of variable hematopoietic malignancies. Apart from conventional treatment individualized allogeneic HSCT approaches are feasible and can correct the immunodeficiency and reduce the risk of recurring hematopoietic malignancies.

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