Successful Treatment of Diffuse Large B-Cell Non-Hodgkin Lymphoma with Modified CHOP (Cyclophosphamide/Doxorubicin/Vincristine/ Prednisone) Chemotherapy and Rituximab in a Patient with Nijmegen Syndrome

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive syndrome of chromosomal instability mainly characterized by microcephaly at birth, combined immunodeficiency and predisposition to malignancies. Due to a founder mutation in the underlying NBN gene (c.657_661del5) the disease is encountered most frequently among Slavic populations. The principal clinical manifestations of the syndrome are: microcephaly, present at birth and progressive with age, dysmorphic facial features, mild growth retardation, mild-to-moderate intellectual disability, and, in females, hypergonadotropic hypogonadism. Combined cellular and humoral immunodeficiency with recurrent sinopulmonary infections, a strong predisposition to develop malignancies (predominantly of lymphoid origin) and radiosensitivity are other integral manifestations of the syndrome. The NBN gene codes for nibrin which, as part of a DNA repair complex, plays a critical nuclear role wherever double-stranded DNA ends occur, either physiologically or as a result of mutagenic exposure. Laboratory findings include: (1) spontaneous chromosomal breakage in peripheral T lymphocytes with rearrangements preferentially involving chromosomes 7 and 14, (2) sensitivity to ionizing radiation or radiomimetics as demonstrated in vitro by cytogenetic methods or by colony survival assay, (3) radioresistant DNA synthesis, (4) biallelic hypomorphic mutations in the NBN gene, and (5) absence of full-length nibrin protein. Microcephaly and immunodeficiency are common to DNA ligase IV deficiency (LIG4 syndrome) and severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation due to NHEJ1 deficiency (NHEJ1 syndrome). In fact, NBS was most commonly confused with Fanconi anaemia and LIG4 syndrome. Genetic counselling should inform parents of an affected child of the 25% risk for further children to be affected. Prenatal molecular genetic diagnosis is possible if disease-causing mutations in both alleles of the NBN gene are known. No specific therapy is available for NBS, however, hematopoietic stem cell transplantation may be one option for some patients. Prognosis is generally poor due to the extremely high rate of malignancies.Zespół Nijmegen (Nijmegen breakage syndrome; NBS) jest rzadkim schorzeniem z wrodzoną niestabilnością chromosomową dziedziczącym się w sposób autosomalny recesywny, charakteryzującym się przede wszystkim wrodzonym małogłowiem, złożonymi niedoborami odporności i predyspozycją do rozwoju nowotworów.Choroba występuje najczęściej w populacjach słowiańskich, w których uwarunkowana jest mutacją założycielską w genie NBN (c.657_661del5). Do najważniejszych objawów zespołu zalicza się: małogłowie obecne od urodzenia i postępujące z wiekiem, charakterystyczne cechy dysmorfii twarzy, opóźnienie wzrastania, niepełnosprawność intelektualną w stopniu lekkim do umiarkowanego oraz hipogonadyzm hipogonadotropowy u dziewcząt. Na obraz choroby składają się także: niedobór odporności komórkowej i humoralnej, który jest przyczyną naw...

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“…The intensity of therapy is usually adapted to individual risk factors and tolerance [13,21,29,153]. …”

Section: Management Including Treatmentmentioning

confidence: 99%

Nijmegen breakage syndrome (NBS)

Chrzanowska

Gregorek

Dembowska‐Bagińska

et al. 2012

Orphanet J Rare Dis

214

185

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“…The presence of mechanical allodynia and hyperalgesia were assessed using a series of calibrated von Frey hairs (1,2,4,6,8,10,15,26,60, 100, 180, and 300 g; Stoelting, Wood Dale, IL), which were applied to the plantar surface of the hind paw with increasing force until the individual filament used just started to bend. The filament was applied for a period of 1-2 s and the procedure was repeated five times at 4-to 5-s intervals.…”

Section: Nociceptive Behavioral Testsmentioning

confidence: 99%

“…Antineoplastic drugs remain the most effective and commonly used molecules in human cancer chemotherapy [1][2][3]. However, their therapeutical effectiveness is seriously limited by a major dose-dependent side-effect, which is painful peripheral neuropathy [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Cellular and functional evidence for a protective action of neurosteroids against vincristine chemotherapy-induced painful neuropathy

Meyer

Patte‐Mensah

Taleb

et al. 2010

Cell. Mol. Life Sci.

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Painful neuropathy is a major side-effect limiting cancer chemotherapy. Therefore, novel strategies are required to suppress the neuropathic effects of anticancer drugs without altering their chemotherapeutic effectiveness. By combining biochemical, neuroanatomical/neurochemical, electrophysiological and behavioral methods, we demonstrated that progesterone-derived neurosteroids including 5alpha-dihydroprogesterone and 3alpha,5alpha-tetrahydroprogesterone suppressed neuropathic symptoms evoked in naive rats by vincristine. Neurosteroids counteracted vincristine-induced alterations in peripheral nerves including 2',3'-cyclic nucleotide 3'-phosphodiesterase, neurofilament-200 kDa and intraepidermal nerve fiber repression, nerve conduction velocity, and pain transmission abnormalities (allodynia/hyperalgesia). In skin-tumor rats generated with carcinosarcoma-cells, vincristine, which suppressed the skin tumor and restored normal blood concentration of vascular endothelial growth factor (VEGF), reproduced neuropathic side-effects. Administered alone, neurosteroids did not affect the tumor and VEGF level. Combined with vincristine, neurosteroids preserved vincristine anti-tumor action but counteracted vincristine-induced neural side-effects. Together, these results provide valuable insight into the cellular and functional mechanisms underlying anticancer drug-induced neuropathy and suggest a neurosteroid-based strategy to eradicate painful neuropathy.

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“…Rituximab plus a modified CHOP regimen also achieved remission in a 17‐year‐old male with Nijmegen breakage syndrome and secondary diffuse, large, B‐cell lymphoma. The patient has been in complete remission for 3 years after completing treatment 18. This was the first reported case of a patient with Nijmegen breakage syndrome being successfully treated with this regimen.…”

Section: Discussionmentioning

confidence: 89%

Rituximab as monotherapy and in addition to reduced CHOP in children with primary immunodeficiency and non‐Hodgkin lymphoma

Shabbat

Aharoni

Sarid

et al. 2009

Pediatric Blood & Cancer

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Children with primary immunodeficiency or chromosomal breakage syndromes are at increased risk of developing non-Hodgkin lymphomas; they cannot tolerate standard chemotherapy regimens. We report two children with diffuse, large, B-cell lymphoma; one had ataxia telangiectasia and one had common variable immunodeficiency. Both were given rituximab, 1 as monotherapy and 1 in combination with a reduced CHOP regimen. Complete remission was obtained in each patient. Use of rituximab as a first-line monotherapy or in conjunction with reduced chemotherapy should be considered to reduce cytotoxic effects.

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Successful Treatment of Diffuse Large B-Cell Non-Hodgkin Lymphoma with Modified CHOP (Cyclophosphamide/Doxorubicin/Vincristine/ Prednisone) Chemotherapy and Rituximab in a Patient with Nijmegen Syndrome

Cited by 8 publications

References 25 publications

Nijmegen breakage syndrome (NBS)

Nijmegen breakage syndrome (NBS)

Cellular and functional evidence for a protective action of neurosteroids against vincristine chemotherapy-induced painful neuropathy

Rituximab as monotherapy and in addition to reduced CHOP in children with primary immunodeficiency and non‐Hodgkin lymphoma

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