Cancer Treatment Today » Immune Thrombocytopenic Purpure

Intravenous gammaglobulin for ITP – pro

M Levin, MD — Thu, 30 Aug 2012 18:05:01 +0000

Lay Summary: IVIG is standard for ITP but represents a “holding action” rather than a cure.

IVIG is approved by the FDA for use in the treatment of the following diseases: Kawasaki disease, dermato/polymyositis, idiopathic thrombocytopenic purpura (ITP), Guillain-Barre syndrome, polyneuropathy, some viral diseases, and some forms of immune deficiency. The place of IVIG in the treatment of ITP is not well clarified. It does not modify the disease as do steroids and splenectomy, but only gains a temporary rise in platelet counts, until definitive therapy can be planned or accomplished. In addition, a number of alternatives exist, including: Anti-RhoD, vincristine, Rituximab, danazol, high dose pulse steroids and even chemotherapy. IVIG is accordingly best used as a temporary measure, to prepare the patient for spenectomy or while discussions of other treatments take place. It is also occasionally used to wait and see if a spontaneous remission of the ITP occurrs; however, this use is less supported by the literature.
Based on the literature, CMS advises the following:IVIG is indicated for chronic ITP only when all of the following conditions are met:

Prior treatment with corticosteroids and splenectomy;
Duration of illness less than 6 months;
Age of 10 years or older;
No concurrent illness/disease explaining thrombocytopenia; and
Platelet counts persistently at or below 20,000/ml.

The Australian guideline sets the plt. level at 30K and adds preoperative use and use in preagnant women as well as for severe bleeding and other indications.

Anderson D, Ali K, Blanchette V, et al. Guidelines on the use of intravenous immune globulin for hematologic conditions. Transfus Med Rev. 2007;21(2 Suppl 1):S9-56.

George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ, Blanchette VS, Bussel JB, Cines DB, Kelton JG, Lichtin AE, McMillan R, Okerbloom JA, Regan DH, Warrier I: Idiopathic thrombocytopenic purpura: A practice guideline developed by explicit methods for the American Society of Hematology. Blood 88:3, 1996

Download 2011 ITP Pocket Guide[1]

Cines DB, Blanchette VS: Immune thrombocytopenic purpura. N Engl J Med 2002 Mar 28; 346(13): 995-1008

Kahn MJ, McCrae KR: Splenectomy in Immune Thrombocytopenic Purpura: Recent Controversies and Long-term Outcomes. Curr Hematol Rep 2004 Sep; 3(5): 317-23

McMillan R, Durette C: Long-term outcomes in adults with chronic ITP after splenectomy failure. Blood 2004 Aug 15; 104(4): 956-60

Australian Guideline(2007)

http://www.nba.gov.au/ivig/pdf/criteria-qrg.pdf

Alan H. Lazarus^{* Mechanism of action of IVIG in ITP}2002 Blackwell Science Ltd Vox Sanguinis Volume 83, Issue Supplement s1, pages 53–55, August 2002

Cindy Neunert et al, The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. April 21, 2011; Blood: 117 (16)

Rituximab for ITP – pro

M Levin, MD — Thu, 30 Aug 2012 18:03:31 +0000

Although the record does not clearly support ITP, it is a reasonable diagnosis in the context of other CBC values. In three large cohorts of adults who had failed multiple therapeutic modalities, patients were treated with the regimen of anti-CD20 used to treat B-cell lymphoma—375 mg/m2 weekly for 4 weeks. Approximately 50% of patients had a partial or complete response, and about 33% had durable remissions. Rituximab for other than first line has been recommended in a recent treatment review in a major journal and is being increasingly used. Medicare lists it as reimbursable.

A recent critical review states: “While these studies clearly document the therapeutic efficacy of rituximab in chronic, refractory ITP in both adults and children, we still do not know which ITP patients should receive rituximab therapy. …further trials are definitively needed in order to determine the place of rituximab in the treatment of ITP.” However, it is generally accepted that some patients can benefit from Rituxan and obtain long term remissions of their disease.

NICEmade no firm recommendatiosn based on the evidence that is reported in this summary for adults includes a systematic review and meta-analysis, 2 that have been published since the systematic review, and a retrospective cohort study comparing rituximab with splenectomy. Also included in the evidence summary is a systematic review of studies in children and young people.

NICE, Immune (idiopathic) thrombocytopenic purpura: rituximab. Evidence summary [ESUOM35] Published date: October 2014

Carson, K et al, “Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project.” Blood. 2009 May 14;113 (20):4834-40

Donald M. Arnold, MD, MSc; Francesco Dentali, MD; Mark A. Crowther, MD, MSc; Ralph M. Meyer, MD; Richard J. Cook, PhD; Christopher Sigouin, MSc; Graeme A. Fraser, MD; Wendy Lim, MD, MSc; and John G. Kelton, MD Systematic Review: Efficacy and Safety of Rituximab for Adults with Idiopathic Thrombocytopenic Purpura Ann INtern Med 2 January 2007 | Volume 146 Issue 1 | Pages 25-33

Stas et al, Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura Blood, 15 August 2001, Vol. 98, No. 4, pp. 952-957

Idiopathic Thrombocytopenic Purpura (ITP) and Anti-CD20 Monoclonal Antibody: A Case Report.
Clinical and Applied Thrombosis/Hemostasis, October 1, 2006; 12(4): 489 – 492

S. Berentsen Rituximab for the treatment of autoimmune cytopenias
Haematologica, December 1, 2007; 92(12): 1589 – 1596.

M. Ruggeri, S. Fortuna, and F. Rodeghiero
Heterogeneity of terminology and clinical definitions in adult idiopathic thrombocytopenic purpura: a critical appraisal from a systematic review of the literature
Haematologica, January 1, 2008; 93(1): 98 – 103.

ASH Education Book December 6, 2013 vol. 2013 no. 1 276-282 .

Arnold DM, Heddle NM, Carruthers J et al. (2012) A pilot randomized trial of adjuvant rituximab or placebo for nonsplenectomized patients with immune thrombocytopenia. Blood 119: 1356−62. doi 10.1182/blood-2011-08-374777

Auger S, Duny Y, Rossi JF et al. (2012) Rituximab before splenectomy in adults with primary idiopathic thrombocytopenic purpura: a meta-analysis. British Journal of Haematology 158: 386−98. doi: 10.1111/j.1365-2141.2012.09169.x

Gudbrandsdottir S, Birgens HS, Fredericksen H et al. (2013) Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia. Blood 121: 1976−81. doi: 10.1182/blood-2012-09-455691

Liang Y, Zhang L, Gao J et al. (2012) Rituximab for children with immune thrombocytopenia: a systematic review. PLoS ONE 7: doi: 10.1371/journal.pone.0036698

Moulis G, Sailler L, Sommet A et al. (2013) Rituximab versus splenectomy in persistent or chronic adult primary immune thrombocytopenia: an adjusted comparison of mortality and morbidity. American Journal of Haematology 89: 41−6. doi: 10.1002/ajh.23580

WinRho for Immune Thrombocytopenic Purpura (ITP) – pro

M Levin, MD — Thu, 30 Aug 2012 18:02:05 +0000

Immune (or idiopathic) thrombocytopenic purpura (ITP) is commonly encountered by the practicing hematologist. Clinical management decisions have traditionally been guided by individual training and past experience. Input from the literature has been more from observational reports of case series than from scientific results of hypothesis-driven research. Practice guidelines and several surveys of clinical hematology practice have highlighted important questions in the field, and in the past 5 to 10 years both clinical and laboratory investigations have produced valuable new information, especially about options in refractory disease. Unfortunately, the last comprehensive guideline have been published a decade ago.

Generally, the standard of practice for patients who cannot maintain an adequate platelet count on tapering steroids is to undergo splenectomy. In 60% to 70% of patients this restores a normal platelet count for at least 5 to 10 years. It allows those patients who respond to this procedure to avoid both the risks of low platelet counts and the toxicity of daily steroids. However, although both the site of platelet destruction and the response to intravenous immunoglobulin (IVIG) have been suggested to predict response to splenectomy, there is no universally acknowledged way to predict which patients will respond. SOme patients do not respond and otehrs relapse, sometimes due to a regrowth of accessory spleen tissue. WHen clearly identifeid, an accessory spleen should be removed, if spenectomy reviously resulted in a remission. However, the decision to repeat what is now an open splenectomy is fraught with uncertainty. Patients are often reluctant to be exposed to the inherent risks of surgery and the small but significant risk of overwhelming sepsis after splenectomy without a guarantee of success. It is acceptable to proceed with other therapies at that point. Anti-RhD is one such option.

IV anti-D is a safe and effective treatment in approximately two thirds of Rh+, nonsplenectomized adults with ITP and can be used as a steroid-sparing agent. There is no reason to believe that anti-D is curative or that it affected the natural history of the ITP in these adults. Rather, it appeared to give patients time to improve on their own.

George JN, Woolf SH, Raskob GE, et al. Idiopathic Thrombocytopenic Purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood. 1996;88:3–40.

Cines DB, Bussel JB. How I treat idiopathic thrombocytopenic purpura (ITP). Blood. 2004;106:2244–2251.

Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med. 2002;346:995–1008

Cooper N, Woloski BMR, Fodero EM, Novoa M, Leber M, Bussel JB. Does treatment with intermittent infusions of IV anti-D allow a proportion of adults with recently diagnosed immune thrombocytopenic purpura (ITP) to avoid splenectomy? Blood. 2002;99: 1922

Nplate vs splenectomy – pro

M Levin, MD — Thu, 30 Aug 2012 17:50:07 +0000

Adult Immune (Idiopathic) Thrombocytopenic Purpura (ITP) is a chronic and potentially serious autoimmune disorder characterized by low platelet counts in the blood. In it, platelets are destroyed by the patient’s own immune system. ITP has historically been considered a disease of platelet destruction; however, recent data also suggest that the most prominent defect is the body’s inability to compensate for platelet destruction by increasing production. Newer approaches to treating ITP fous on increasing platelet production. The U.S. Food and Drug Administration has approved Nplate (romiplostim) in August 2008. This drug is the first product that directly stimulates the bone marrow to produce needed platelets in patients with a rare blood disorder that can lead to serious bleeding. Nplate revealed a number of adverse reactions, from bone-marrow abnormalities to dangerous blood clots. A Risk Evaluation and Mitigation Strategy (REMS) has been developed to address the risks of Nplate therapy. Under the Food and Drug Administration Amendments Act of 2007, FDA has determined that a REMS is necessary for the benefits of Nplate to outweigh the risks of the product. The REMS will include a Medication Guide for patients and requires that all prescribers and patients enroll in a special program to track the long term safety of Nplate therapy.

Where a splenectomy was not performed, a recent study presented at the 14th congress of the European Hematology Association from a study comparing romiplostim (Nplate®) to the medical standard of care (SOC) in non-splenectomised patients with chronic immune thrombocytopenic purpura (ITP).

The study involved 234 adults with chronic ITP, who were treated with either romiplostim (n=157) or medical SOC (n=77); the latter was prescribed by the investigator according to standard institutional practices or therapeutic guidelines; the only treatments not allowed were investigational agents or other thrombopoietic agents. A total of 13 (8%) patients who received romiplostim and 27 (35%) of those in the SOC group underwent splenectomy or discontinued the study prior to reporting a splenectomy. Furthermore, 12% and 27% experienced treatment failure (platelet counts ≤20,000 platelets/microL for four consecutive weeks, a major bleeding event, and/or a change in therapy due to intolerable side effects or bleeding symptoms) or discontinued the study, respectively.

Whether to use splenectomy always before Nplate remains an issue of debate. Perdomo notes and discusses this uncertianty;l however, splenectomy remains a less costly treatment that is as likely to produce equivalent therapeutic or diagnostic results

Perdomo J. Role of romiplostim in splenectomized and nonsplenectomized patients with immune thrombocytopenia. Immunotargets Ther. 2016;5:1-7. Published 2016 Feb 22. doi:10.2147/ITT.S80648

http://www.fda.gov/cder/foi/label/2008/125268lbl.pdf – Prescribing information

J. N. George, Management of Immune Thrombocytopenia — Something Old, Something New. November 11, 2010
N Engl J Med 2010; 363:1959-1961

IV gammaglobulin for ITP before epidural anesthesisa – pro

M Levin, MD — Thu, 30 Aug 2012 17:47:33 +0000

The Cut-off platelet cound is not known. Older literature says: one hundred thousand.

While IVIG has some role in presurgical situations, plt. ct of sixty eight is probably not sufficient for the proposed surgery and would be justified. A recent review says: “Normally, spinal or epidural anesthesia is considered safe if the platelet count is over 80,000/µl. However, the consistently low platelet counts in ITP seem to be less problematic than rapidly falling values due to other diseases, because this is often accompanied by platelet dysfunction or coagulopathy. In several studies neuraxial anesthesia was successfully performed with platelet counts between 50,000 and 80,000/µl. Nevertheless, the minimum safe platelet count for neuraxial blockade remains undefined in these patients.”

Englbrecht JS, Pogatzki-Zahn EM, Zahn P.Spinal and epidural anesthesia in patients with hemorrhagic diathesis : Decisions on the brink of minimum evidenceAnaesthesist. 2011 Jul 31

Cyclosporin for ITP – pro

M Levin, MD — Sat, 23 Jun 2012 01:39:23 +0000

There are patients with refractory autoimmune thrombocytopenia do not respond to standard therapy with high-dose corticosteroids, WinRHO, Rituxan, IVGG, and splenectomy. Cyclosporin is useful for some patients who occasionally respond to it. There are many published case reports of its effectiveness. It is recommended for refractory cases in standard reviews.

Since very few pateints are this refractory, prospective studies are not possible but cyclosporine is widely accepted, including being mentioned in compenida for off-label use for Evan’s syndrome which is a combination of immune thrombocytopenia and hemolytic anemia.

D B. Cines and J. B. Bussel
How I treat idiopathic thrombocytopenic purpura (ITP)
Blood, October 1, 2005; 106(7): 2244 – 2251.

Kappers-Klunne MC, van’t Veer MB. Cyclosporin A for the treatment of patients with chronic idiopathic thrombocytopenia purpura refractory to corticosteroids or splenectomy. Br J Haematol. 2001;114: 121-125

Bourgeois E, Caulier MT, Delarozee C, et al. Long-term follow-up of chronic autoimmune thrombocytopenic purpura refractory to splenectomy: a prospective analysis. Br J Haematol. 2003;120:1079-1088