Use of rituximab for refractory cytopenias associated with autoimmune lymphoproliferative syndrome (ALPS)

Rao, V. Koneti; Price, Susan; Perkins, Katie; Aldridge, Patricia; Tretler, Jean; Davis, Joie; Dale, Janet K.; Gill, Fred A.; Hartman, Kip R.; Stork, Linda C.; Gnarra, David J.; Krishnamurti, Lakshmanan; Newburger, Peter E.; Puck, Jennifer M.; Fleisher, Thomas A.

doi:10.1002/pbc.21965

Cited by 72 publications

(73 citation statements)

References 38 publications

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“…Anti-CD20 mAbs were used in 9 patients with autoimmune cytopenia. As reported previously, 24 efficacy in the treatment of AIHA was disappointing (no effect, n ϭ 3; partial improvement, n ϭ 3). Three patients with ITP achieved remission after rituximab, but 2 relapsed a few months later.…”

Section: Disease Managementmentioning

confidence: 84%

“…Anti-CD20 antibody therapy in ALPS patients does not appear to be-at least for AIHA-as effective as in patients without ALPS. 24 It is already known that ALPS is accompanied by an increased risk of lymphoma. 2,25,34 Thirteen cases of various lymphoid malignancies (mainly B-cell NHL and HL, including nodular lymphocytepredominant HL) were reported in 12 patients.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A survey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation

Neven

Magérus-Chatinet

Florkin

et al. 2011

Blood

154

135

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Section: Disease Managementmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

A survey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation

Neven

Magérus-Chatinet

Florkin

et al. 2011

Blood

154

135

View full text Add to dashboard Cite

“…In general, the ALPS phenotype and ALPS type III were enrolled in our studies more recently than the ALPS type Ia patients; therefore, the younger somatic patients in these groups were more likely to benefit from recent recommendations in management, emphasizing avoidance of splenectomy. 32,33 Patients with somatic FAS mutations who were originally classified as ALPS type III were all male and had a later age of onset of disease with the exception of two 1-year olds. This could be the result of the small number of patients studied, and evaluation of additional patients may yield a more balanced gender ratio, similar to the somatic type Ia patients originally classified as ALPS phenotype, with 3 males and 3 females.…”

Section: Somatic Fas Mutations In Alps 5167mentioning

confidence: 99%

Somatic FAS mutations are common in patients with genetically undefined autoimmune lymphoproliferative syndrome

Dowdell

Niemela

Price

et al. 2010

Blood

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138

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“…on April 8, 2019. by guest www.bloodjournal.org From been used by others as well as in 12 ALPS patients in our cohort. 71,72 In 7 of 9 patients with ALPS and thrombocytopenia, rituximab therapy led to median response duration of 21 months (range, 14-36 months). In contrast, none of the 3 children treated with rituximab for AIHA responded.…”

mentioning

confidence: 99%

How I treat autoimmune lymphoproliferative syndrome

Rao

Oliveira²

2011

Blood

Self Cite

165

153

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Autoimmune lymphoproliferative syndrome (ALPS) represents a failure of apoptotic mechanisms to maintain lymphocyte homeostasis, permitting accumulation of lymphoid mass and persistence of autoreactive cells that often manifest in childhood with chronic nonmalignant lymphadenopathy, hepatosplenomegaly, and recurring multilineage cytopenias. Cytopenias in these patients can be the result of splenic sequestration as well as autoimmune complications manifesting as autoimmune hemolytic anemia, immune-mediated thrombocytopenia, and autoimmune neutropenia. More than 300 families with hereditary ALPS have now been described; nearly 500 patients from these families have been studied and followed worldwide over the last 20 years by our colleagues and ourselves. Some of these patients with FAS mutations affecting the intracellular portion of the FAS protein also have an increased risk of B-cell lymphoma. The best approaches to diagnosis, followup, and management of ALPS, its associated cytopenias, and other complications resulting from infiltrative lymphoproliferation and autoimmunity are presented. This trial was registered at www.clinicaltrial.gov as #NCT00001350. (Blood. 2011;118(22): 5741-5751) IntroductionAutoimmunity results from failure of self-tolerance, which can be further divided into central and peripheral tolerance. Central tolerance is fostered by apoptosis through elimination of autoreactive lymphocytes in generative lymphoid organs (the bone marrow and thymus), whereas mechanisms of peripheral tolerance include anergy, deletion by apoptosis, and suppression by regulatory T cells to avoid autoimmunity and tissue damage. 1 Apoptosis, the intrinsic program of cell death, is triggered by receptor-ligand interactions at the cell surface (the extrinsic pathway) or by the activation of mitochondrial proteins (the intrinsic pathway), leading to processing and activation of caspases and their downstream targets. Lymphocyte apoptosis mediated by the cell surface receptor FAS plays a pivotal role in lymphocyte homeostasis. FAS (also termed CD95/APO1) is a member of the tumor necrosis factor receptor superfamily of proteins that directly trigger apoptosis to maintain lymphocyte homeostasis and peripheral immune tolerance and prevent autoimmunity. 2,3 It is a membrane-bound molecule that is highly expressed, not only on activated B and T lymphocytes but also present in other cells, such as hepatocytes. FAS is present on the cell surface as a preformed trimer. 4 Its binding with FAS ligand leads to conformational changes on the intracellular portion of FAS protein triggering rapid recruitment of the death domain of the adaptor protein FADD (Fas-associated death domain) to the homologous death domain in the cytoplasmic tail of FAS. This is followed by the recruitment of procaspases 8 or 10 through the interaction of their death-effecter domains with the amino termini of FADD. The resulting Fas/FADD/caspase complex is termed the death-inducing signaling complex that incites a further cascade of caspase activation culminati...

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Use of rituximab for refractory cytopenias associated with autoimmune lymphoproliferative syndrome (ALPS)

Cited by 72 publications

References 38 publications

A survey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation

A survey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation

Somatic FAS mutations are common in patients with genetically undefined autoimmune lymphoproliferative syndrome

How I treat autoimmune lymphoproliferative syndrome

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