Difference between revisions of "Acquired thrombotic thrombocytopenic purpura"
Jump to navigation
Jump to search
Warner-admin (talk | contribs) m (Text replacement - "8 PubMed" to "8/ PubMed") |
Warner-admin (talk | contribs) m (Text replacement - "*<big>We have moved How I Treat articles to a dedicated page.</big>" to "*''We have moved How I Treat articles to a dedicated page.''") |
||
| (20 intermediate revisions by 2 users not shown) | |||
| Line 3: | Line 3: | ||
[[#top|Back to Top]] | [[#top|Back to Top]] | ||
</div> | </div> | ||
| − | {{#lst: | + | {{#lst:Editorial board transclusions|heme}} |
| + | *''We have moved [[How I Treat]] articles to a dedicated page.'' | ||
{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
|- | |- | ||
| Line 10: | Line 11: | ||
|} | |} | ||
{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
| − | |||
| − | |||
| − | |||
| − | |||
=Initial therapy= | =Initial therapy= | ||
==Caplacizumab & Plasma exchange {{#subobject:4c678d|Regimen=1}}== | ==Caplacizumab & Plasma exchange {{#subobject:4c678d|Regimen=1}}== | ||
| Line 19: | Line 16: | ||
===Regimen {{#subobject:9a4e05|Variant=1}}=== | ===Regimen {{#subobject:9a4e05|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
| − | ! style="width: | + | !style="width: 20%"|Study |
| − | ! style="width: | + | !style="width: 20%"|Dates of enrollment |
| − | ! style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
| − | ! style="width: | + | !style="width: 20%"|Comparator |
| + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://doi.org/10.1056/NEJMoa1505533 Peyvandi et al. 2016 (TITAN<sub>TTP</sub>)] | |[https://doi.org/10.1056/NEJMoa1505533 Peyvandi et al. 2016 (TITAN<sub>TTP</sub>)] | ||
| + | |2010-10 to 2014-01 | ||
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc) | | style="background-color:#1a9851" |Randomized Phase 2 (E-esc) | ||
|[[#Plasma_exchange|Plasma exchange]] | |[[#Plasma_exchange|Plasma exchange]] | ||
| − | | style="background-color:#1a9850" |Reduced time to response | + | | style="background-color:#1a9850" |Reduced time to response (primary endpoint) |
|- | |- | ||
|[https://doi.org/10.1056/NEJMoa1806311 Scully et al. 2019 (HERCULES)] | |[https://doi.org/10.1056/NEJMoa1806311 Scully et al. 2019 (HERCULES)] | ||
| + | |2015-11 to 2017-04 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
|[[#Plasma_exchange|Plasma exchange]] | |[[#Plasma_exchange|Plasma exchange]] | ||
| − | | style="background-color:#1a9850" |Shorter median time to platelet count normalization | + | | style="background-color:#1a9850" |Shorter median time to platelet count normalization (primary endpoint)<br><br>Lower composite outcome events (secondary endpoint) |
| − | Lower composite outcome events ( | ||
|- | |- | ||
|} | |} | ||
| Line 39: | Line 38: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Supportive therapy==== | ====Supportive therapy==== | ||
| − | *[[Caplacizumab (Cablivi)]] | + | *[[Caplacizumab (Cablivi)]] 10 mg IV once on day 1, then 10 mg SC once per day during plasma exchange and then for 30 additional days |
* Plasma exchange with discontinuation of plasma exchange five days after normalization of platelet count. | * Plasma exchange with discontinuation of plasma exchange five days after normalization of platelet count. | ||
</div></div> | </div></div> | ||
| + | |||
===References=== | ===References=== | ||
| − | # '''TITAN:''' Peyvandi F, Scully M, Kremer Hovinga JA, Cataland S, Knöbl P, Wu H, Artoni A, Westwood JP, Mansouri Taleghani M, Jilma B, Callewaert F, Ulrichts H, Duby C, Tersago D; TITAN Investigators. Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2016 Feb 11;374(6):511-522. [https://doi.org/10.1056/NEJMoa1505533 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26863353/ PubMed] NCT01151423 | + | # '''TITAN:''' Peyvandi F, Scully M, Kremer Hovinga JA, Cataland S, Knöbl P, Wu H, Artoni A, Westwood JP, Mansouri Taleghani M, Jilma B, Callewaert F, Ulrichts H, Duby C, Tersago D; TITAN Investigators. Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2016 Feb 11;374(6):511-522. [https://doi.org/10.1056/NEJMoa1505533 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26863353/ PubMed] [https://clinicaltrials.gov/study/NCT01151423 NCT01151423] |
| − | # '''HERCULES:''' Scully M, Cataland SR, Peyvandi F, Coppo P, Knöbl P, Kremer Hovinga JA, Metjian A, de la Rubia J, Pavenski K, Callewaert F, Biswas D, De Winter H, Zeldin RK; HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019 Jan 24;380(4):335-346. Epub 2019 Jan 9. [https://doi.org/10.1056/NEJMoa1806311 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30625070/ PubMed] NCT02553317 | + | # '''HERCULES:''' Scully M, Cataland SR, Peyvandi F, Coppo P, Knöbl P, Kremer Hovinga JA, Metjian A, de la Rubia J, Pavenski K, Callewaert F, Biswas D, De Winter H, Zeldin RK; HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019 Jan 24;380(4):335-346. Epub 2019 Jan 9. [https://doi.org/10.1056/NEJMoa1806311 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30625070/ PubMed] [https://clinicaltrials.gov/study/NCT02553317 NCT02553317] |
| + | |||
==Plasma exchange {{#subobject:4b548d|Regimen=1}}== | ==Plasma exchange {{#subobject:4b548d|Regimen=1}}== | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:0e1e05|Variant=1}}=== | ===Regimen {{#subobject:0e1e05|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
| − | ! style="width: | + | !style="width: 20%"|Study |
| − | ! style="width: | + | !style="width: 20%"|Dates of enrollment |
| − | ! style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
| − | ! style="width: | + | !style="width: 20%"|Comparator |
| + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
|[https://doi.org/10.1056/NEJM199108083250604 Rock et al. 1991] | |[https://doi.org/10.1056/NEJM199108083250604 Rock et al. 1991] | ||
| + | |1982-1989 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
| − | |[[# | + | |[[#Plasma_infusion_888|Plasma infusion]] |
| style="background-color:#91cf60" |Seems to have superior OS | | style="background-color:#91cf60" |Seems to have superior OS | ||
|- | |- | ||
| Line 64: | Line 67: | ||
*Total plasma exchange as follows (minimum of 7 treatments in first 9 hospital days): | *Total plasma exchange as follows (minimum of 7 treatments in first 9 hospital days): | ||
**Treatments 1 to 3: Exchange of 1.5 times the predicted plasma volume | **Treatments 1 to 3: Exchange of 1.5 times the predicted plasma volume | ||
| − | ** | + | **Treatment 4 onwards: Exchange of 1.0 times the predicted plasma volume |
====Supportive therapy==== | ====Supportive therapy==== | ||
*[[Dipyridamole (Persantine)]] 400 mg (route not specified) once per day for at least two weeks | *[[Dipyridamole (Persantine)]] 400 mg (route not specified) once per day for at least two weeks | ||
| Line 71: | Line 74: | ||
===References=== | ===References=== | ||
# Rock GA, Shumak KH, Buskard NA, Blanchette VS, Kelton JG, Nair RC, Spasoff RA; Canadian Apheresis Study Group. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. N Engl J Med. 1991 Aug 8;325(6):393-7. [https://doi.org/10.1056/NEJM199108083250604 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2062330/ PubMed] | # Rock GA, Shumak KH, Buskard NA, Blanchette VS, Kelton JG, Nair RC, Spasoff RA; Canadian Apheresis Study Group. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. N Engl J Med. 1991 Aug 8;325(6):393-7. [https://doi.org/10.1056/NEJM199108083250604 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2062330/ PubMed] | ||
| − | # '''TITAN:''' Peyvandi F, Scully M, Kremer Hovinga JA, Cataland S, Knöbl P, Wu H, Artoni A, Westwood JP, Mansouri Taleghani M, Jilma B, Callewaert F, Ulrichts H, Duby C, Tersago D; TITAN Investigators. Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2016 Feb 11;374(6):511-522. [https://doi.org/10.1056/NEJMoa1505533 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26863353/ PubMed] NCT01151423 | + | # '''TITAN:''' Peyvandi F, Scully M, Kremer Hovinga JA, Cataland S, Knöbl P, Wu H, Artoni A, Westwood JP, Mansouri Taleghani M, Jilma B, Callewaert F, Ulrichts H, Duby C, Tersago D; TITAN Investigators. Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2016 Feb 11;374(6):511-522. [https://doi.org/10.1056/NEJMoa1505533 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26863353/ PubMed] [https://clinicaltrials.gov/study/NCT01151423 NCT01151423] |
| − | # '''HERCULES:''' Scully M, Cataland SR, Peyvandi F, Coppo P, Knöbl P, Kremer Hovinga JA, Metjian A, de la Rubia J, Pavenski K, Callewaert F, Biswas D, De Winter H, Zeldin RK; HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019 Jan 24;380(4):335-346. Epub 2019 Jan 9. [https://doi.org/10.1056/NEJMoa1806311 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30625070/ PubMed] NCT02553317 | + | # '''HERCULES:''' Scully M, Cataland SR, Peyvandi F, Coppo P, Knöbl P, Kremer Hovinga JA, Metjian A, de la Rubia J, Pavenski K, Callewaert F, Biswas D, De Winter H, Zeldin RK; HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019 Jan 24;380(4):335-346. Epub 2019 Jan 9. [https://doi.org/10.1056/NEJMoa1806311 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30625070/ PubMed] [https://clinicaltrials.gov/study/NCT02553317 NCT02553317] |
=Maintenance/Preemptive treatment= | =Maintenance/Preemptive treatment= | ||
==Rituximab monotherapy {{#subobject:4cadec|Regimen=1}}== | ==Rituximab monotherapy {{#subobject:4cadec|Regimen=1}}== | ||
| Line 81: | Line 84: | ||
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
| − | |[ | + | |[https://doi.org/10.1182/blood-2014-01-550244 Hie et al. 2014] |
| style="background-color:#91cf61" |Registry | | style="background-color:#91cf61" |Registry | ||
|- | |- | ||
| Line 91: | Line 94: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
| − | # '''Retrospective:''' Hie M, Gay J, Galicier L, Provôt F, Presne C, Poullin P, Bonmarchand G, Wynckel A, Benhamou Y, Vanhille P, Servais A, Bordessoule D, Coindre JP, Hamidou M, Vernant JP, Veyradier A, Coppo P; French Thrombotic Microangiopathies Reference Centre. Preemptive rituximab infusions after remission efficiently prevent relapses in acquired thrombotic thrombocytopenic purpura. Blood. 2014 Jul 10;124(2):204-10. Epub 2014 May 28. [ | + | # '''Retrospective:''' Hie M, Gay J, Galicier L, Provôt F, Presne C, Poullin P, Bonmarchand G, Wynckel A, Benhamou Y, Vanhille P, Servais A, Bordessoule D, Coindre JP, Hamidou M, Vernant JP, Veyradier A, Coppo P; French Thrombotic Microangiopathies Reference Centre. Preemptive rituximab infusions after remission efficiently prevent relapses in acquired thrombotic thrombocytopenic purpura. Blood. 2014 Jul 10;124(2):204-10. Epub 2014 May 28. [https://doi.org/10.1182/blood-2014-01-550244 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24869941/ PubMed] |
| − | ## '''Update:''' Jestin M, Benhamou Y, Schelpe AS, Roose E, Provôt F, Galicier L, Hié M, Presne C, Poullin P, Wynckel A, Saheb S, Deligny C, Servais A, Girault S, Delmas Y, Kanouni T, Lautrette A, Chauveau D, Mousson C, Perez P, Halimi JM, Charvet-Rumpler A, Hamidou M, Cathébras P, Vanhoorelbeke K, Veyradier A, Coppo P; French Thrombotic Microangiopathies Reference Center. Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic thrombocytopenic purpura. Blood. 2018 Nov 15;132(20):2143-2153. Epub 2018 Sep 10. [ | + | ## '''Update:''' Jestin M, Benhamou Y, Schelpe AS, Roose E, Provôt F, Galicier L, Hié M, Presne C, Poullin P, Wynckel A, Saheb S, Deligny C, Servais A, Girault S, Delmas Y, Kanouni T, Lautrette A, Chauveau D, Mousson C, Perez P, Halimi JM, Charvet-Rumpler A, Hamidou M, Cathébras P, Vanhoorelbeke K, Veyradier A, Coppo P; French Thrombotic Microangiopathies Reference Center. Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic thrombocytopenic purpura. Blood. 2018 Nov 15;132(20):2143-2153. Epub 2018 Sep 10. [https://doi.org/10.1182/blood-2018-04-840090 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30201758/ PubMed] |
=Relapsed or refractory= | =Relapsed or refractory= | ||
''These treatments are usually used in addition to therapeutic plasma exchange, not in its place. There are also many treatments reported at the case report or case series level; the reader is guided to the 2015 Blood article, [http://www.bloodjournal.org/content/125/25/3860.long "How I treat refractory thrombotic thrombocytopenic purpura"] for further details.'' | ''These treatments are usually used in addition to therapeutic plasma exchange, not in its place. There are also many treatments reported at the case report or case series level; the reader is guided to the 2015 Blood article, [http://www.bloodjournal.org/content/125/25/3860.long "How I treat refractory thrombotic thrombocytopenic purpura"] for further details.'' | ||
| Line 99: | Line 102: | ||
===Regimen variant #1, "High-dose" {{#subobject:0ea120|Variant=1}}=== | ===Regimen variant #1, "High-dose" {{#subobject:0ea120|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
| − | ! style="width: | + | !style="width: 20%"|Study |
| − | ! style="width: | + | !style="width: 20%"|Dates of enrollment |
| − | ! style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
| − | ! style="width: | + | !style="width: 20%"|Comparator |
| + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
| − | |[ | + | |[https://doi.org/10.1007/s00277-009-0877-5 Balduini et al. 2009] |
| + | |2000-2006 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
|[[#Methylprednisolone_monotherapy|Methylprednisolone]]; standard-dose | |[[#Methylprednisolone_monotherapy|Methylprednisolone]]; standard-dose | ||
| Line 112: | Line 117: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunosuppressive therapy==== | ====Immunosuppressive therapy==== | ||
| − | *[[Methylprednisolone (Solumedrol)]] | + | *[[Methylprednisolone (Solumedrol)]] 10 mg/kg/day IV on days 1 to 3, then 2.5 mg/kg/day IV on days 4 to 23 |
| − | + | '''23-day course''' | |
| − | |||
</div></div><br> | </div></div><br> | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, "Standard-dose" {{#subobject:84ebef|Variant=1}}=== | ===Regimen variant #2, "Standard-dose" {{#subobject:84ebef|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
| − | ! style="width: | + | !style="width: 20%"|Study |
| − | ! style="width: | + | !style="width: 20%"|Dates of enrollment |
| − | ! style="width: | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
| − | ! style="width: | + | !style="width: 20%"|Comparator |
| + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
| − | |[ | + | |[https://doi.org/10.1007/s00277-009-0877-5 Balduini et al. 2009] |
| + | |2000-2006 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Methylprednisolone_monotherapy|Methylprednisolone]]; high-dose | |[[#Methylprednisolone_monotherapy|Methylprednisolone]]; high-dose | ||
| Line 132: | Line 138: | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunosuppressive therapy==== | ====Immunosuppressive therapy==== | ||
| − | *[[Methylprednisolone (Solumedrol)]] | + | *[[Methylprednisolone (Solumedrol)]] 1 mg/kg/day IV on days 1 to 3, then 2.5 mg/kg/day IV on days 4 to 23 |
| − | + | '''23-day course''' | |
| − | |||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
| − | # Balduini CL, Gugliotta L, Luppi M, Laurenti L, Klersy C, Pieresca C, Quintini G, Iuliano F, Re R, Spedini P, Vianelli N, Zaccaria A, Pogliani EM, Musso R, Bobbio Pallavicini E, Quarta G, Galieni P, Fragasso A, Casella G, Noris P, Ascari E; Italian TTP Study Group. High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study. Ann Hematol. 2010 Jun;89(6):591-6. Epub 2009 Dec 23. [ | + | # Balduini CL, Gugliotta L, Luppi M, Laurenti L, Klersy C, Pieresca C, Quintini G, Iuliano F, Re R, Spedini P, Vianelli N, Zaccaria A, Pogliani EM, Musso R, Bobbio Pallavicini E, Quarta G, Galieni P, Fragasso A, Casella G, Noris P, Ascari E; Italian TTP Study Group. High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study. Ann Hematol. 2010 Jun;89(6):591-6. Epub 2009 Dec 23. [https://doi.org/10.1007/s00277-009-0877-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20033409/ PubMed] |
| + | |||
==Rituximab monotherapy {{#subobject:4cadec|Regimen=1}}== | ==Rituximab monotherapy {{#subobject:4cadec|Regimen=1}}== | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1 {{#subobject:8bca2c|Variant=1}}=== | ===Regimen variant #1 {{#subobject:8bca2c|Variant=1}}=== | ||
| − | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
| − | ! style="width: | + | !style="width: 33%"|Study |
| − | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
| + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1016/j.transci.2010.09.018 de la Rubia et al. 2010] | |[https://doi.org/10.1016/j.transci.2010.09.018 de la Rubia et al. 2010] | ||
| − | | style="background-color:# | + | | |
| + | | style="background-color:#ffffbe" |Retrospective | ||
|- | |- | ||
|[https://doi.org/10.1111/bjh.13408 Clark et al. 2015] | |[https://doi.org/10.1111/bjh.13408 Clark et al. 2015] | ||
| + | |2008-11-20 to 2012-12-28 | ||
| style="background-color:#91cf61" |Phase 2 | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
| − | |||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Immunosuppressive therapy==== | ====Immunosuppressive therapy==== | ||
| − | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once | + | *[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1 |
====Supportive therapy==== | ====Supportive therapy==== | ||
| − | *[[Prednisone (Sterapred)]] 50 mg PO once | + | *[[Prednisone (Sterapred)]] 50 mg PO once on day 1, given prior to rituximab |
| − | *[[Diphenhydramine (Benadryl)]] 50 mg PO once | + | *[[Diphenhydramine (Benadryl)]] 50 mg PO once on day 1, given prior to rituximab |
| − | *[[Acetaminophen (Tylenol)]] 325 mg PO once | + | *[[Acetaminophen (Tylenol)]] 325 mg PO once on day 1, given prior to rituximab |
| − | '''4-week course''' | + | '''7-day cycle for 4 cycles (4-week course)''' |
</div></div><br> | </div></div><br> | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2 {{#subobject:a31c78|Variant=1}}=== | ===Regimen variant #2 {{#subobject:a31c78|Variant=1}}=== | ||
| − | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
| − | ! style="width: | + | !style="width: 33%"|Study |
| − | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
| + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1097/ccm.0b013e31822e9d66 Froissart et al. 2012] | |[https://doi.org/10.1097/ccm.0b013e31822e9d66 Froissart et al. 2012] | ||
| + | |2005-10 to 2008-05 | ||
| style="background-color:#91cf61" |Non-randomized | | style="background-color:#91cf61" |Non-randomized | ||
|- | |- | ||
| Line 178: | Line 188: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
| − | # de la Rubia J, Moscardó F, Gómez MJ, Guardia R, Rodríguez P, Sebrango A, Zamora C, Debén G, Goterris R, López R, Peña F, Pujol M, Vidaller A, Del Río-Garma J, Sanz MA; Grupo Español de Aféresis. Efficacy and safety of rituximab in adult patients with idiopathic relapsing or refractory thrombotic thrombocytopenic purpura: results of a Spanish multicenter study. Transfus Apher Sci. 2010 Dec;43(3):299-303. Epub 2010 Oct 12. [https://doi.org/10.1016/j.transci.2010.09.018 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20934383/ PubMed] | + | # '''Retrospective:''' de la Rubia J, Moscardó F, Gómez MJ, Guardia R, Rodríguez P, Sebrango A, Zamora C, Debén G, Goterris R, López R, Peña F, Pujol M, Vidaller A, Del Río-Garma J, Sanz MA; Grupo Español de Aféresis. Efficacy and safety of rituximab in adult patients with idiopathic relapsing or refractory thrombotic thrombocytopenic purpura: results of a Spanish multicenter study. Transfus Apher Sci. 2010 Dec;43(3):299-303. Epub 2010 Oct 12. [https://doi.org/10.1016/j.transci.2010.09.018 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20934383/ PubMed] |
# Froissart A, Buffet M, Veyradier A, Poullin P, Provôt F, Malot S, Schwarzinger M, Galicier L, Vanhille P, Vernant JP, Bordessoule D, Guidet B, Azoulay E, Mariotte E, Rondeau E, Mira JP, Wynckel A, Clabault K, Choukroun G, Presne C, Pourrat J, Hamidou M, Coppo P; French Thrombotic Microangiopathies Reference Center. Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange: experience of the French Thrombotic Microangiopathies Reference Center. Crit Care Med. 2012 Jan;40(1):104-11. [https://doi.org/10.1097/ccm.0b013e31822e9d66 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21926591/ PubMed] | # Froissart A, Buffet M, Veyradier A, Poullin P, Provôt F, Malot S, Schwarzinger M, Galicier L, Vanhille P, Vernant JP, Bordessoule D, Guidet B, Azoulay E, Mariotte E, Rondeau E, Mira JP, Wynckel A, Clabault K, Choukroun G, Presne C, Pourrat J, Hamidou M, Coppo P; French Thrombotic Microangiopathies Reference Center. Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange: experience of the French Thrombotic Microangiopathies Reference Center. Crit Care Med. 2012 Jan;40(1):104-11. [https://doi.org/10.1097/ccm.0b013e31822e9d66 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21926591/ PubMed] | ||
# '''Review:''' Lim W, Vesely SK, George JN. The role of rituximab in the management of patients with acquired thrombotic thrombocytopenic purpura. Blood. 2015 Mar 5;125(10):1526-31. Epub 2015 Jan 8. Review. [http://www.bloodjournal.org/content/125/10/1526.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351502/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25573992/ PubMed] | # '''Review:''' Lim W, Vesely SK, George JN. The role of rituximab in the management of patients with acquired thrombotic thrombocytopenic purpura. Blood. 2015 Mar 5;125(10):1526-31. Epub 2015 Jan 8. Review. [http://www.bloodjournal.org/content/125/10/1526.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351502/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25573992/ PubMed] | ||
| − | # Clark WF, Rock G, Barth D, Arnold DM, Webert KE, Yenson PR, Kelton JG, Li L, Foley SR; members of the Canadian Apheresis Group. A phase-II sequential case-series study of all patients presenting to four plasma exchange centres with presumed relapsed/refractory thrombotic thrombocytopenic purpura treated with rituximab. Br J Haematol. 2015 Jul;170(2):208-17. Epub 2015 Apr 8. [https://doi.org/10.1111/bjh.13408 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25855259 PubMed] | + | # Clark WF, Rock G, Barth D, Arnold DM, Webert KE, Yenson PR, Kelton JG, Li L, Foley SR; members of the Canadian Apheresis Group. A phase-II sequential case-series study of all patients presenting to four plasma exchange centres with presumed relapsed/refractory thrombotic thrombocytopenic purpura treated with rituximab. Br J Haematol. 2015 Jul;170(2):208-17. Epub 2015 Apr 8. [https://doi.org/10.1111/bjh.13408 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25855259/ PubMed] |
==Vincristine monotherapy {{#subobject:583bc2|Regimen=1}}== | ==Vincristine monotherapy {{#subobject:583bc2|Regimen=1}}== | ||
<div class="toccolours" style="background-color:#eeeeee"> | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:8892fc|Variant=1}}=== | ===Regimen {{#subobject:8892fc|Variant=1}}=== | ||
| − | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
| − | ! style="width: | + | !style="width: 33%"|Study |
| − | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
| + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1007/s002770050549 Ferrara et al. 1999] | |[https://doi.org/10.1007/s002770050549 Ferrara et al. 1999] | ||
| − | | style="background-color:#ffffbe" |Pilot, | + | |NR |
| + | | style="background-color:#ffffbe" |Pilot, fewer than 20 patients | ||
|- | |- | ||
|} | |} | ||
| Line 199: | Line 211: | ||
===References=== | ===References=== | ||
# Ferrara F, Copia C, Annunziata M, Spasiano A, Di Grazia C, Palmieri S, Prossomariti L, Mele G. Vincristine as salvage treatment for refractory thrombotic thrombocytopenic purpura. Ann Hematol. 1999 Nov;78(11):521-3. [https://doi.org/10.1007/s002770050549 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10602896/ PubMed] | # Ferrara F, Copia C, Annunziata M, Spasiano A, Di Grazia C, Palmieri S, Prossomariti L, Mele G. Vincristine as salvage treatment for refractory thrombotic thrombocytopenic purpura. Ann Hematol. 1999 Nov;78(11):521-3. [https://doi.org/10.1007/s002770050549 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10602896/ PubMed] | ||
| − | [[Category: | + | [[Category:Acquired thrombotic thrombocytopenic purpura regimens]] |
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Autoimmune hematologic conditions]] | [[Category:Autoimmune hematologic conditions]] | ||
[[Category:Cytopenias]] | [[Category:Cytopenias]] | ||
[[Category:Thrombotic disorders]] | [[Category:Thrombotic disorders]] | ||
Latest revision as of 11:37, 15 May 2024
| Section editor | |
|---|---|
 |
Benjamin Tillman, MD Vanderbilt University Nashville, TN, USA |
- We have moved How I Treat articles to a dedicated page.
5 regimens on this page
7 variants on this page
|
Initial therapy
Caplacizumab & Plasma exchange
Regimen
| Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Peyvandi et al. 2016 (TITANTTP) | 2010-10 to 2014-01 | Randomized Phase 2 (E-esc) | Plasma exchange | Reduced time to response (primary endpoint) |
| Scully et al. 2019 (HERCULES) | 2015-11 to 2017-04 | Phase 3 (E-esc) | Plasma exchange | Shorter median time to platelet count normalization (primary endpoint) Lower composite outcome events (secondary endpoint) |
Note: there is another trial named TITAN, in NSCLC.
Supportive therapy
- Caplacizumab (Cablivi) 10 mg IV once on day 1, then 10 mg SC once per day during plasma exchange and then for 30 additional days
- Plasma exchange with discontinuation of plasma exchange five days after normalization of platelet count.
References
- TITAN: Peyvandi F, Scully M, Kremer Hovinga JA, Cataland S, Knöbl P, Wu H, Artoni A, Westwood JP, Mansouri Taleghani M, Jilma B, Callewaert F, Ulrichts H, Duby C, Tersago D; TITAN Investigators. Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2016 Feb 11;374(6):511-522. link to original article PubMed NCT01151423
- HERCULES: Scully M, Cataland SR, Peyvandi F, Coppo P, Knöbl P, Kremer Hovinga JA, Metjian A, de la Rubia J, Pavenski K, Callewaert F, Biswas D, De Winter H, Zeldin RK; HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019 Jan 24;380(4):335-346. Epub 2019 Jan 9. link to original article contains dosing details in abstract PubMed NCT02553317
Plasma exchange
Regimen
| Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Rock et al. 1991 | 1982-1989 | Phase 3 (E-esc) | Plasma infusion | Seems to have superior OS |
Supportive therapy
- Total plasma exchange as follows (minimum of 7 treatments in first 9 hospital days):
- Treatments 1 to 3: Exchange of 1.5 times the predicted plasma volume
- Treatment 4 onwards: Exchange of 1.0 times the predicted plasma volume
Supportive therapy
- Dipyridamole (Persantine) 400 mg (route not specified) once per day for at least two weeks
- Aspirin 325 mg PO once per day for at least two weeks
References
- Rock GA, Shumak KH, Buskard NA, Blanchette VS, Kelton JG, Nair RC, Spasoff RA; Canadian Apheresis Study Group. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. N Engl J Med. 1991 Aug 8;325(6):393-7. link to original article contains dosing details in manuscript PubMed
- TITAN: Peyvandi F, Scully M, Kremer Hovinga JA, Cataland S, Knöbl P, Wu H, Artoni A, Westwood JP, Mansouri Taleghani M, Jilma B, Callewaert F, Ulrichts H, Duby C, Tersago D; TITAN Investigators. Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2016 Feb 11;374(6):511-522. link to original article PubMed NCT01151423
- HERCULES: Scully M, Cataland SR, Peyvandi F, Coppo P, Knöbl P, Kremer Hovinga JA, Metjian A, de la Rubia J, Pavenski K, Callewaert F, Biswas D, De Winter H, Zeldin RK; HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med. 2019 Jan 24;380(4):335-346. Epub 2019 Jan 9. link to original article PubMed NCT02553317
Maintenance/Preemptive treatment
Rituximab monotherapy
Regimen
| Study | Evidence |
|---|---|
| Hie et al. 2014 | Registry |
Note: this prospective registry trial left precise dosing details to physician discretion.
Immunosuppressive therapy
References
- Retrospective: Hie M, Gay J, Galicier L, Provôt F, Presne C, Poullin P, Bonmarchand G, Wynckel A, Benhamou Y, Vanhille P, Servais A, Bordessoule D, Coindre JP, Hamidou M, Vernant JP, Veyradier A, Coppo P; French Thrombotic Microangiopathies Reference Centre. Preemptive rituximab infusions after remission efficiently prevent relapses in acquired thrombotic thrombocytopenic purpura. Blood. 2014 Jul 10;124(2):204-10. Epub 2014 May 28. link to original article PubMed
- Update: Jestin M, Benhamou Y, Schelpe AS, Roose E, Provôt F, Galicier L, Hié M, Presne C, Poullin P, Wynckel A, Saheb S, Deligny C, Servais A, Girault S, Delmas Y, Kanouni T, Lautrette A, Chauveau D, Mousson C, Perez P, Halimi JM, Charvet-Rumpler A, Hamidou M, Cathébras P, Vanhoorelbeke K, Veyradier A, Coppo P; French Thrombotic Microangiopathies Reference Center. Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic thrombocytopenic purpura. Blood. 2018 Nov 15;132(20):2143-2153. Epub 2018 Sep 10. link to original article PubMed
Relapsed or refractory
These treatments are usually used in addition to therapeutic plasma exchange, not in its place. There are also many treatments reported at the case report or case series level; the reader is guided to the 2015 Blood article, "How I treat refractory thrombotic thrombocytopenic purpura" for further details.
Methylprednisolone monotherapy
Regimen variant #1, "High-dose"
| Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Balduini et al. 2009 | 2000-2006 | Phase 3 (E-esc) | Methylprednisolone; standard-dose | Might have superior CR rate |
Immunosuppressive therapy
- Methylprednisolone (Solumedrol) 10 mg/kg/day IV on days 1 to 3, then 2.5 mg/kg/day IV on days 4 to 23
23-day course
Regimen variant #2, "Standard-dose"
| Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|---|
| Balduini et al. 2009 | 2000-2006 | Phase 3 (C) | Methylprednisolone; high-dose | Might have inferior CR rate |
Immunosuppressive therapy
- Methylprednisolone (Solumedrol) 1 mg/kg/day IV on days 1 to 3, then 2.5 mg/kg/day IV on days 4 to 23
23-day course
References
- Balduini CL, Gugliotta L, Luppi M, Laurenti L, Klersy C, Pieresca C, Quintini G, Iuliano F, Re R, Spedini P, Vianelli N, Zaccaria A, Pogliani EM, Musso R, Bobbio Pallavicini E, Quarta G, Galieni P, Fragasso A, Casella G, Noris P, Ascari E; Italian TTP Study Group. High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study. Ann Hematol. 2010 Jun;89(6):591-6. Epub 2009 Dec 23. link to original article contains dosing details in abstract PubMed
Rituximab monotherapy
Regimen variant #1
| Study | Dates of enrollment | Evidence |
|---|---|---|
| de la Rubia et al. 2010 | Retrospective | |
| Clark et al. 2015 | 2008-11-20 to 2012-12-28 | Phase 2 |
Immunosuppressive therapy
- Rituximab (Rituxan) 375 mg/m2 IV once on day 1
Supportive therapy
- Prednisone (Sterapred) 50 mg PO once on day 1, given prior to rituximab
- Diphenhydramine (Benadryl) 50 mg PO once on day 1, given prior to rituximab
- Acetaminophen (Tylenol) 325 mg PO once on day 1, given prior to rituximab
7-day cycle for 4 cycles (4-week course)
Regimen variant #2
| Study | Dates of enrollment | Evidence |
|---|---|---|
| Froissart et al. 2012 | 2005-10 to 2008-05 | Non-randomized |
Immunosuppressive therapy
- Rituximab (Rituxan) (dose not specified) IV for 4 doses (timing not specified)
15-day course
References
- Retrospective: de la Rubia J, Moscardó F, Gómez MJ, Guardia R, Rodríguez P, Sebrango A, Zamora C, Debén G, Goterris R, López R, Peña F, Pujol M, Vidaller A, Del Río-Garma J, Sanz MA; Grupo Español de Aféresis. Efficacy and safety of rituximab in adult patients with idiopathic relapsing or refractory thrombotic thrombocytopenic purpura: results of a Spanish multicenter study. Transfus Apher Sci. 2010 Dec;43(3):299-303. Epub 2010 Oct 12. link to original article contains dosing details in abstract PubMed
- Froissart A, Buffet M, Veyradier A, Poullin P, Provôt F, Malot S, Schwarzinger M, Galicier L, Vanhille P, Vernant JP, Bordessoule D, Guidet B, Azoulay E, Mariotte E, Rondeau E, Mira JP, Wynckel A, Clabault K, Choukroun G, Presne C, Pourrat J, Hamidou M, Coppo P; French Thrombotic Microangiopathies Reference Center. Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange: experience of the French Thrombotic Microangiopathies Reference Center. Crit Care Med. 2012 Jan;40(1):104-11. link to original article PubMed
- Review: Lim W, Vesely SK, George JN. The role of rituximab in the management of patients with acquired thrombotic thrombocytopenic purpura. Blood. 2015 Mar 5;125(10):1526-31. Epub 2015 Jan 8. Review. link to original article link to PMC article PubMed
- Clark WF, Rock G, Barth D, Arnold DM, Webert KE, Yenson PR, Kelton JG, Li L, Foley SR; members of the Canadian Apheresis Group. A phase-II sequential case-series study of all patients presenting to four plasma exchange centres with presumed relapsed/refractory thrombotic thrombocytopenic purpura treated with rituximab. Br J Haematol. 2015 Jul;170(2):208-17. Epub 2015 Apr 8. link to original article contains dosing details in manuscript PubMed
Vincristine monotherapy
Regimen
| Study | Dates of enrollment | Evidence |
|---|---|---|
| Ferrara et al. 1999 | NR | Pilot, fewer than 20 patients |
Chemotherapy
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1, then 1 mg IV once per day on days 4 & 7
References
- Ferrara F, Copia C, Annunziata M, Spasiano A, Di Grazia C, Palmieri S, Prossomariti L, Mele G. Vincristine as salvage treatment for refractory thrombotic thrombocytopenic purpura. Ann Hematol. 1999 Nov;78(11):521-3. link to original article contains dosing details in abstract PubMed