Autoimmune lymphoproliferative syndrome medical therapy: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 60: | Line 60: | ||
[[Category:Disease]] | [[Category:Disease]] | ||
[[Category:Hematology]] | [[Category:Hematology]] | ||
Revision as of 02:43, 6 July 2021
|
Autoimmune lymphoproliferative syndrome Microchapters |
|
Differentiating Autoimmune lymphoproliferative syndrome from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Autoimmune lymphoproliferative syndrome medical therapy On the Web |
|
American Roentgen Ray Society Images of Autoimmune lymphoproliferative syndrome medical therapy |
|
FDA on Autoimmune lymphoproliferative syndrome medical therapy |
|
CDC on Autoimmune lymphoproliferative syndrome medical therapy |
|
Autoimmune lymphoproliferative syndrome medical therapy in the news |
|
Blogs on Autoimmune lymphoproliferative syndrome medical therapy |
|
Directions to Hospitals Treating Autoimmune lymphoproliferative syndrome |
|
Risk calculators and risk factors for Autoimmune lymphoproliferative syndrome medical therapy |
Editor-In-Chief: David Teachey, MD [1]
Overview
Currently, there is no standard curable treatment for Autoimmune lymphoproliferative syndrome [[ALPS]]. Treatment of different features of ALPS as cytopenias, autoimmune syndromes as well as monitoring and treating the consequences as splenomegaly, lymphoma can be helpful.
Treatment
- Mostly commonly directed at autoimmune disease
- Maybe needed to treat bulky lymphoproliferation
- First line therapies
- Corticosteroids
- Very active but toxic with chronic use
- IVIgG
- Not as effective as in other immune cytopenia syndromes
- Corticosteroids
- Second line therapies
- Mycophenolate mofetil (cellcept)[1]
- Inactivates inosine monophosphate
- Active in most patients
- Most studied medicine in clinical trials
- Some patients have complete resolution of autoimmune disease
- Some patients have partial responses
- Some patients relapse
- Does not affect lymphoproliferation or reduce DNTs
- Well-tolerated: Side effects: Diarrhea, neutropenia
- Does not require therapeutic drug monitoring
- No drug-drug interactions
- Can cause hypogammaglobulinemia (transient) requiring IVIgG replacement
- Consider PCP prophylaxis but usually not needed
- Sirolimus (rapamycin, rapamune)
- mTOR (mammalian target of rapamycin) inhibitor[2]
- Active in most patients
- Second most studied agent in clinical trials
- Most patients have complete resolution of autoimmune disease (>90%)[3] [4]
- Most patients have complete resolution of lymphoproliferation, including lymphadenopathy and splenomegaly (>90%)
- Some patients have near complete response (disease flares with viral illness)
- A few patients have had partial responses (most commonly patient with non-cytopenia autoimmune disease)
- Most patients have elimination of peripheral blood DNTs
- mTOR/Akt/PI3K pathway may be activated in abnormal ALPS cells: mTOR inhibitors may be targeted therapy
- May not be as immune suppressive in normal lymphocytes as other agents. Some patients have had improvement in immune function with transition from cellcept to rapamycin[5]
- Not reported to cause hypogammaglobulinemia
- Hypothetically, may have lower risk of secondary cancers as opposed to other immune suppressants
- Always a risk with any agent in pre-cancerous syndrome as immune suppression can decreased tumor immunosurvellence
- mTOR inhibitors active against lymphomas, especially EBV+ lymphomas. Thus, THEORETICALLY could eliminate malignant clones.
- Requires therapeutic drug monitoring
- Goal serum trough 5-15ng/ml
- Drug-drug interactions
- Well tolerated: Side effects: mucositis, diarrhea, hyperlipidemia, delayed wound healing
- Consider PCP prophylaxis but usually not needed
- Other agents:
- Fansidar,[6] [7] mercaptopurine: More commonly used in Europe. Good ancedotal data
- Rituximab: AVOID. Can cause life long hypogammaglobulinemia[8]
- Splenectomy: AVOID. >30% risk of pneumococcal sepsis even with vaccination and antibiotic prophylaxis[9] [10]
- Mycophenolate mofetil (cellcept)[1]
References
- ↑ Rao VK, Dugan F, Dale JK, Davis J, Tretler J, Hurley JK; et al. (2005). "Use of mycophenolate mofetil for chronic, refractory immune cytopenias in children with autoimmune lymphoproliferative syndrome". Br J Haematol. 129 (4): 534–8. doi:10.1111/j.1365-2141.2005.05496.x. PMID 15877736.
- ↑ Teachey DT, Obzut DA, Axsom K, Choi JK, Goldsmith KC, Hall J; et al. (2006). "Rapamycin improves lymphoproliferative disease in murine autoimmune lymphoproliferative syndrome (ALPS)". Blood. 108 (6): 1965–71. doi:10.1182/blood-2006-01-010124. PMC 1895548. PMID 16757690.
- ↑ Teachey DT, Greiner R, Seif A, Attiyeh E, Bleesing J, Choi J; et al. (2009). "Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome". Br J Haematol. 145 (1): 101–6. doi:10.1111/j.1365-2141.2009.07595.x. PMC 2819393. PMID 19208097.
- ↑ Janić MD, Brasanac CD, Janković JS, Dokmanović BL, Krstovski RN, Kraguljac Kurtović JN (2009). "Rapid regression of lymphadenopathy upon rapamycin treatment in a child with autoimmune lymphoproliferative syndrome". Pediatr Blood Cancer. 53 (6): 1117–9. doi:10.1002/pbc.22151. PMID 19588524.
- ↑ Teachey DT (2011). "Autoimmune lymphoproliferative syndrome: new approaches to diagnosis and management". Clin Adv Hematol Oncol. 9 (3): 233–5. PMID 21475130.
- ↑ van der Werff Ten Bosch J, Schotte P, Ferster A, Azzi N, Boehler T, Laurey G; et al. (2002). "Reversion of autoimmune lymphoproliferative syndrome with an antimalarial drug: preliminary results of a clinical cohort study and molecular observations". Br J Haematol. 117 (1): 176–88. PMID 11918552.
- ↑ Rao VK, Dowdell KC, Dale JK, Dugan F, Pesnicak L, Bi LL; et al. (2007). "Pyrimethamine treatment does not ameliorate lymphoproliferation or autoimmune disease in MRL/lpr-/- mice or in patients with autoimmune lymphoproliferative syndrome". Am J Hematol. 82 (12): 1049–55. doi:10.1002/ajh.21007. PMID 17674358.
- ↑ Rao VK, Price S, Perkins K, Aldridge P, Tretler J, Davis J; et al. (2009). "Use of rituximab for refractory cytopenias associated with autoimmune lymphoproliferative syndrome (ALPS)". Pediatr Blood Cancer. 52 (7): 847–52. doi:10.1002/pbc.21965. PMC 2774763. PMID 19214977.
- ↑ Rao VK, Oliveira JB (2011). "How I treat autoimmune lymphoproliferative syndrome". Blood. doi:10.1182/blood-2011-07-325217. PMID 21885601.
- ↑ Neven B, Magerus-Chatinet A, Florkin B, Gobert D, Lambotte O, De Somer L; et al. (2011). "A survey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation". Blood. doi:10.1182/blood-2011-04-347641. PMID 21885602.