Cancer Treatment Today » Immune System

DLI for T cell leukemia and lymphoma – pro

M Levin, MD — Fri, 10 Jan 2014 16:27:04 +0000

Donor lymphocyte infusions are designed to awaken some degree of graft versus host reaction, which contains within it also the graft versus disease effect. It is a modality that can be used after allogeneic transplantation to treat relapse by “awakening” an immune response. . Almost all work on DLI was in B cell leukemias and lymphomas. How it affects T cell malignancies is not well studied and most of what is known was in Adult T-Cell leukami/Lymphoma. Many questions remain. For example, achieving hematologic remission with DLI is not an easy task, especially in patients with a high tumor burden and rapidly proliferating leukemic cells.. Cytoreductive therapy before DLI is thought to improve effectiveness of DLI. Unfortunately, which regimens to use for this cytoreduction has not been defined. How to induce and manage graft versus host reaction has not been defined. Even the very effectiveness of allogeneic transplantation in T-Cell Leukemias continues to be studied. To conclude, DLI remains experimental for T Cell malignancies due to lack of reliable information on how to do it and how effective it is.

Hidehiro Itonag et al, Treatment of relapsed adult T-cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation: the Nagasaki Transplant Group experience Blood January 3, 2013 vol. 121 no. 1 219-225

Gabriel IH. Graft versus lymphoma effect after early relapse following reduced-intensity sibling allogeneic stem cell transplantation for relapsed cytotoxic variant of mycosis fungoides. Bone Marrow Transplant 2007;40(4):401-403.

Herbert KE, . Graft-versus-lymphoma effect in refractory cutaneous T-cell lymphoma after reduced-intensity HLA-matched sibling allogeneic stem cell transplantation. Bone Marrow Transplant 2004;34(6):521-525.

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Topical cidofovir in immunocompromised patients – pro

M Levin, MD — Fri, 09 Nov 2012 13:10:59 +0000

VISTIDE (cidofovir) is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS). The FDA says: “THE SAFETY AND EFFICACY OF VISTIDE (cidofovir) HAVE NOT BEEN ESTABLISHED FOR TREATMENT OF OTHER CMV INFECTIONS (SUCH AS PNEUMONITIS OR GASTROENTERITIS), CONGENITAL OR NEONATAL CMV DISEASE, OR CMV DISEASE IN NON-HIV-INFECTED INDIVIDUALS.”

It is a nephrotoxoc drug and cannot be administered to people with kidney dysfunction, which, however, is common after stem cell transplantation or aggressive chemotherapy. Therefore, some attempt to reconstitute the IV formulation and use it topically. It is a water-soluble polar molecule and is predicted to be absorbable across the gastrointestinal tract following oral administration although. No oral formulations are currently available and bioavailability studies have been performed to a limited extent only in animals. It has been compounded in bases for topical use although topical formulations are prohibitively expensive (approximately $65 US per gram of extemporaneously compounded 3% cidofovir cream or it can be compounded as a 1% solution. There are case reprots of using these preparations for condyloma acumina, veruca vulgaris, laryngeal papillomatosis, Kaposi’s sarcoma, poxvirus infections and herpetic infections.

De Clercq and Holy demonstrated that topical cidofovir was effective against human herpesvirus types 1 and 2 and thymidine kinase deficient herpesvirus type 1 in mice. They demonstrated that its efficacy was superior to acyclovir. Snoeck et al reported successful the use of topical cidofovir in 2 patients, one with AIDS and the othe, a bone amrrow transplant patient, with resistant herpesvirus infections. Lateef et al used a topical preparation for a 4-year-old child with AIDS and a large facial ulcer secondary to herpesvirus type 1. Other case reprots were published by C.R.SIms in 2007, B. Muluneh in 2012

Lalezari et al reported a randomized, double blind, placebo controlled phase I/II clinical study of cidofovir gel in 30 patients with AIDS, all of whom had acyclovir-resistant herpes simplex infections. Eleven patients received 0.3% gel, nine patients received 1.0% gel and 10 were treated with placebo once a day for 5 days. Fifty percent of cidofovir patients had at least 50% improvement in infection in contrast with no improvement in the placebo patients. Thirty percent of the cidofovir treated patients had complete healing, compared with none of the placebo treated patients. The median time for negative viral cultures to be obtained from lesions in the cidofovir treated group was 2 days. Eighty seven per cent of CDV treated patients and no placebo treated patients developed negative viral cultures. Application site reactions occurred in 25 % of cidofovir-treated patients and in 20% of placebo-treated patients. Of the 6 patients treated with CDV who had complete healing, the response was sustained in 3.

Sacks et al described the successful use of cidofovir topical gel in otherwise healthy patients with recurrent genital herpes infection. Ninety-six patients were randomized in a double blind, placebo controlled trial. All patients were confirmed by viral culture or serology as having recurrent genital herpes simplex. Treatment consisted of a single application of cidofovir gel 1%, 3%, 5% or placebo within 12 hours of an outbreak. All patients treated with cidofovir showed a decrease both in median time for cultures to become negative and in the number of days to complete healing. Sacks et al concluded that topical cidofovir gel was well tolerated and possessed significant antiviral activity.

In conclusion, there a a number of case reports and series that support this drug, as well as two Phase II studies, one randomized. 1%, 3% and 5% solutions have shown activity.
Edward J. Zabawski, Review of Topical and Intralesional Cidofovir
Jr.Dermatology Online Journal 6(1): 3, 2000

De Clercq E. Therapeutic potential of Cidofovir (HPMPC, Vistide) for the treatment of DNA virus (i.e. herpes-, papova-, pox- and adenovirus) infections. Verh K Acad Geneeskd Belg 1996;58(1):19-47; discussion 47-9.

Snoeck R, Andrei G, Gerard M, Silverman A, Hedderman A, Balzarini J, Sadzot-Delvaux C, Tricot G, Clumeck N, De Clercq E. Successful treatment of progressive mucocutaneous infection due to acyclovir- and foscarnet-resistant herpes simplex virus with (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC). Clin Infect Dis 1994;18(4):570-8.

Lateef F, Don PC, Kaufmann M, White SM, Weinberg JM. Treatment of acyclovir-resistant, foscarnet-unresponsive HSV infection with topical cidofovir in a child with AIDS [letter; comment] Arch Dermatol 1998;134(9):1169-70.

Lalezari J, Schacker T, Feinberg J, Gathe J, Lee S, Cheung T, Kramer F, Kessler H, Corey L, Drew WL, Boggs J, McGuire B, Jaffe HS, Safrin S. A randomized, double-blind, placebo-controlled trial of cidofovir gel for the treatment of acyclovir-unresponsive mucocutaneous herpes simplex virus infection in patients with AIDS. J Infect Dis 1997;176(4):892-8.

Sacks SL, Shafran SD, Diaz-Mitoma F, Trottier S, Sibbald RG, Hughes A, Safrin S, Rudy J, McGuire B, Jaffe HS. A multicenter phase I/II dose escalation study of single-dose cidofovir gel for treatment of recurrent genital herpes. Antimicrob Agents Chemother 1998;42(11):2996-9.

Sims CR, Thompson K, Chemaly RF, Shpall EJ, Champlin RE, Safdar A. Oral topical cidofovir: novel route of drug delivery in a severely immunosuppressed patient with refractory multidrug-resistant herpes simplex virus infection.Transpl Infect Dis. 2007 Sep;9(3):256-9.

B. Muluneh et al, Successful clerance of acyclovir resistant, foscarnet refractory herpes virus lesions with topical cidifivit in allogneic hematoppoietic stem cell transplant patient, J Oncol Pharm Pract, published online 24 May 2012

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Leukine for Melanoma – pro

M Levin, MD — Mon, 06 Aug 2012 16:29:54 +0000

Lay Summary: Leukine is being explored for treating melanoma. A phase II trial and a phase III trial were recently reported.

Leukine (granulocyte macrophage colony stimulating factor, GM-CSF, Sargramostim), which is approved for marketing for hematopoietic reconstitution and reversal of chemo induced neutropenia, also has activity as a macrophage activator. It has been reported that Leukine stimulates peripheral blood monocytes in vitro to become cytotoxic for human melanoma cells. It has further been shown in clinical trials that in vivo administration of Leukine at low doses also results in monocyte activation as shown by enhanced cytotoxicity. Finally, Leukine causes release of an angiogenesis inhibitor by the macrophages. Because of these effects, interest was aroused in its use for melanoma.

A trial of therapy in the adjuvant setting was favourable. The median survival was prolonged over three-fold in patients who received Leukine to 34.3 months compared to matched historical controls (median survival 10.2 months). The observed 2-year survival was 64% in the study patients vs. 15% in the controls, (p < 0.001). Toxicity was minimal, the major side effect being mild fatigue; there were no reports of Grade 4 toxicity or serious adverse events.

An interim analysis of another trial was presented at the 6th International Conference on Admuvant Therapy of Melanoma in Stockholm in 2006 and 5th International Conference on Adjuvant Therapy of Melanoma in Athens in March, 2004. It supports the results of the earlier trial and suggests that Leukine improves survival in this patient population. Results from the Phase II study (ASCO 2010 abstract #20027) show that 60 percent of the 45 high-risk patients enrolled in the trial experienced disease-free survival and 64 percent of patients achieved overall survival at 21 months. The recent study used a year of Leukine and IL2 and then a year of Leukine. NCCN has not yet incorporated this information into its guidelines. Because there have recenlty been unfavorable trials of interferon, Luekine is being used more often than in the past.

In addition, one of the cooperative study groups, the Eastern Cooperative Oncology Group, has initiated a Phase III prospective randomized trial to further evaluate this therapy (E4697). Accrual of 800 patients has been completed. In 2010, a phase III study by Lawson et al, reported that adjuvant GM-CSF improves DFS of patients with completely resected high-risk melanoma with minimal toxicity. OS improvement is less and does not achieve statistical significance. This study included completely resected disease and mucosal melanoma and the results were at one year; a three year report is being prepared for publication.

Spitler, LE, Grossbard, ML, Ernstoff MS, et al: Adjuvant therapy of Stage III and IV malignant melanoma using granulocyte-macrophage colony-stimulating factor. J Clin Oncol 18:1614-1621, 2000

http://clinicaltrials.mayo.edu/clinicaltrialdetails.cfm?trial_id=100307

nccn.org, melanoma

Ravaud A, Delaunay M, Chevreau C, Coulon V, Debled M, Bret-Dibat C, Courbon F, Gualde N, Nguyen Bui B Granulocyte-macrophage colony-stimulating factor alone or with dacarbazine in metastatic melanoma: a randomized phase II trial.
2001-11-16, Br J Cancer., 85(10):1467-71.

Immunological effects and clinical outcomes in patients with high-risk melanoma given adjuvant therapy with granulocyte-macrophage colony stimulating factor (GM-CSF, sargramostim)
◦Lead investigator: Lynn Spitler, Northern California melanoma Center, Saint Mary’s Medical Center, San Francisco, CA
◦Abstract e20004, ASCO 2010

Followup of Resected Gastric Cancer – pro

M Levin, MD — Mon, 06 Aug 2012 16:26:53 +0000

Patients with early gastric cancer have an excellent prognosis after appropriate treatment, with a high survival rate and a low rate of recurrence.There are no guidelines as to how to follow gastric cancer. A recent review concluded: ” Early detection of asymptomatic gastric cancer recurrence did not improve overall survival of patients with recurrence after curative resection. Until development of more effective treatment for this disease, close follow-up may offer no survival benefit. ” After 5 years, it is usually assumed that a cancer is cured and the proposed intensive re-evalaution in not supported by credible literature.It is still unclear whether intensive follow-up after surgery produces significant benefits in patients with gastric cancer. A previous retrospective study concluded that follow-ups were not useful.There have been no data to suggest that chemotherapeutic agents are useful in the treatment of recurrent gastric cancer detected during follow-up.

C. Kunisaki, H. Akiyama, M. Nomura, G. Matsuda, Y. Otsuka, H. Ono, Y. Nagahori, H. Hosoi, M. Takahashi, F. Kito, et al.
Significance of Long-Term Follow-Up of Early Gastric Cancer
Ann. Surg. Oncol., March 1, 2006; 13(3): 363 – 369.

Yasuhiro Kodera, MD, Seiji Ito, MD, Yoshitaka Yamamura, MD, Yoshinari Mochizuki, MD, Michitaka Fujiwara, MD, Kenji Hibi, MD, Katsuki Ito, MD, Seiji Akiyama, MD and Akimasa Nakao, Follow-Up Surveillance for Recurrence After Curative Gastric Cancer Surgery Lacks Survival Benefit Annals of Surgical Oncology 10:898-902 (2003)

Kodera Y, Ito S, Yamamura Y, et al. A follow-up surveillance for recurrence after curative gastric cancer surgery lacks survival benefit. Ann Surg Oncol 2003; 10:898–902.[

PET for FUO – pro

M Levin, MD — Mon, 06 Aug 2012 16:25:31 +0000

The best way to approach this situation is as PET being done for fever of unknown origin. There is little evidence of recurrent lymphoma. The bone marrow has 2% of cells that may be monoclonal and no Fever of unknown origin (FUO) is among the most difficult medical puzzles to solve.PET appears to have a very high negative predictive value in ruling out inflammatory causes of fever.If positive, PET can direct attention to rareas of fartehr workup but does jnot reliably distinguish infetious, malaignant and inflammatory causes of fever.The limited data of prospective studies indicate that 18F-FDG PET has the potential to play a central role as a second-line procedure in the management of patients with FUO. In these studies, the PET scan contributed to the final diagnosis in 25% – 69% of the patients. In the category of infectious diseases, a diagnosis of focal abdominal, thoracic, or soft-tissue infection, as well as chronic osteomyelitis, can be made with a high degree of certainty. Negative findings on 18F-FDG PET essentially rule out orthopedic prosthetic infections. In patients with noninfectious inflammatory diseases, 18F-FDG PET is of importance in the diagnosis of large-vessel vasculitis and seems to be useful in the visualization of other diseases, such as inflammatory bowel disease, sarcoidosis, and painless subacute thyroiditis. In patients with tumor fever, diseases commonly detected by 18F-FDG PET include Hodgkin’s disease and aggressive non-Hodgkin’s lymphoma but also colorectal cancer and sarcoma. 18F-FDG PET has the potential to replace other imaging techniques in the evaluation of patients with FUO. Compared with labeled white blood cells, 18F-FDG PET allows diagnosis of a wider spectrum of diseases. Compared with 67Ga-citrate scanning, 18F-FDG PET seems to be more sensitive.

Lorenzen J, Buchert R, Bohuslavizki KH. Value of FDG PET in patients with fever of unknown origin. Nucl Med Commun 2001;22:779-83.

Knockaert DC, Vanderschueren S, Blockmans D. Fever of unknown origin in adults: 40 years on. J Intern Med 2003;253:263-75.

MELLER Johannes ; SAHLMANN Carsten-Oliver ; SCHEEL Alexander Konrad 18F-FDG PET and PET/CT in fever of unknown origin The Journal of nuclear medicine 2007, vol. 48, no1, pp. 35-45

Rituxan for Gullain-Barre Syndrome – pro

M Levin, MD — Mon, 06 Aug 2012 16:23:42 +0000

Guillain-Barré syndrome is a disorder in which the body’s immune system attacks part of the peripheral nervous system. Symptoms include varying degrees of weakness or tingling sensations in the legs. Sometimes, the weakness and abnormal sensations spread to the arms and upper body and progress to paralysis. There is no known cure for Guillain-Barré syndrome, but therapies can lessen the severity of the illness and accelerate the recovery in most patients. Currently, plasmapheresis and high-dose immunoglobulin therapy are most often used.

GB syndrome can occurr is association with various conditions, as a paraneopastic syndrome or secondary to a viral infection. Rituximab has also been reported to be associated with causing GB, probably through its anti-immune effect. There are also reports of rituximab association with improvement in GB. Review of the literature finds only case report level evidence to support rituximab for GB. The plan states: “Experimental means any treatment where the stated proposed treatment has no supporting literature for safety or efficacy in human trials”. Since this is the case for rituximab for GB, it should be considered investigational.

Ostronoff F, Perales MA, Stubblefield MD, Hsu KC.Rituximab-responsive Guillain-Barré syndrome following allogeneic hematopoietic SCT.Bone Marrow Transplant. 2008 Jul;42(1):71-2.

Carmona, Alberto1; Alonso, Juan; Heras, Manuel; Navarrete, AgustínGuillain-Barre syndrome in a patient with diffuse large B-cell lymphoma, and rituximab maintenance therapy. An association beyound anecdotal evidence? Clinical and Translational Oncology, Volume 8, Number 10, October 2006 , pp. 764-766(3)

Terenghi F, Ardolino G, Nobile-Orazio EGuillain-Barré syndrome after combined CHOP and rituximab therapy in non-Hodgkin lymphoma.Peripher Nerv Syst. 2007 Jun;12(2):142-3.

Rituxan: Prevention of Post-transplant Lymphoproliferative Disorders – pro

M Levin, MD — Mon, 06 Aug 2012 16:18:50 +0000

Anti-CD20 (Rituximab) is a humanised monoclonocal antibody directed against the specific CD20 antigens found on B lymphocytes plasma membrane. It has been approved by the FDA for the treatment of lymphoma and post-transplant lymphoproliferative diseases. The rationale for using Rituxan for treating EBV infections is that it can destroy B cells and thus “dampen” T-cell response caused by immune dysregulation. After bone marrow transplantation (BMT) using T-cell-depleted marrow from an unrelated donor or HLA-mismatched related donor, the risk of developing lymphoproliferative disease associated with the Epstein-Barr virus (EBV) ranges from 1% to 25%. Although this medicine has been approved by the Food and Drug Administration to treat patients with other types of lymphomas, and has been used to treat a small number of patients with EBV lymphomas and other types of B-cell leukemias, it has not been approved to try and prevent EBV-lymphomas. Use of Rituximab to try to prevent EBV-lymphomas is therefore experimental. Results of a recent study are awaited: Rituximab (Rituxan) for the Prevention of EBV-LPD Epstein Barr Virus (EBV) Lymphoproliferative Disorder Post T Cell Depleted Unrelated and HLA Mis-Matched Related HSCT,NCT00648037 Ingrid Kuehnle, M. Helen Huls, Zhensheng Liu, Micah Semmelmann, Robert A. Krance, Malcolm K. Brenner, Cliona M. Rooney, and Helen E. Heslop CD20 monoclonal antibody (rituximab) for therapy of Epstein-Barr virus lymphoma after hemopoietic stem-cell transplantation Blood 95: 1502-1505.

Gruhn B; Meerbach A; Häfer R; Zell R; Wutzler P; Zintl F
Pre-emptive therapy with rituximab for prevention of Epstein-Barr virus-associated lymphoproliferative disease after hematopoietic stem cell transplantation. Bone marrow transplantation 2003;31(11):1023-5.

Chronic Lyme Disease Treatment – pro

M Levin, MD — Mon, 06 Aug 2012 16:14:14 +0000

Treatment of Lyme disease is the subject of much controversy and has been subjected to legal action.
The most controversial issue is empiric treatment of patients with symptoms that remain after a one month course of antibiotics. Many patients continue to complain of various hard to characterize symptoms and some physicians advocate continued antibiotic treatment and report that it helps. The Infectious Diseases Society of America IDSA) issued guidelines that do not recommend continued treatment after a month of therapy. In response, a group of physicans who treat Lyme Disease set up a Lyme Disease Association that issued a competing set of guidelines that includes chronic Lyme disease treatment and also took the IDSA to court. They also supported the passage of a bill in Connecticute. H.B. 6200 contains language that will protect CT licensed Lyme treating physicians from prosecution by the State of Connecticut Medical Examining Board solely on the basis of a clinical diagnosis and /or for treatment of long-term Lyme disease. The bill provides the definition for Lyme disease which includes , “the presence in a patient of signs and symptoms compatible with acute infection with Borrelia burgdorferi; or with late stage or persistent or chronic infection with Borrelia burgdorferi, or with complications related to such an infection.” The Connecticut Attorney General investigated the IDSA.

Attorney General Richard Blumenthal announced that his antitrust investigation has uncovered serious flaws in the Infectious Diseases Society of America’s (IDSA) process for writing its 2006 Lyme disease guidelines and the IDSA has agreed to reassess them with the assistance of an outside arbiter.

The IDSA guidelines have sweeping and significant impacts on Lyme disease medical care. They are commonly applied by insurance companies in restricting coverage for long-term antibiotic treatment or other medical care and also strongly influence physician treatment decisions.

Insurance companies have denied coverage for long-term antibiotic treatment relying on these guidelines as justification. The guidelines are also widely cited for conclusions that chronic Lyme disease is nonexistent.

The attorney Gneral of the state of CT, wrote: “This agreement vindicates my investigation — finding undisclosed financial interests and forcing a reassessment of IDSA guidelines,” IDSA has reached an agreement with Attorney General’s Office by calling for creation of a review panel to thoroughly scrutinize the 2006 Lyme disease guidelines and update or revise them if necessary. The panel — comprised of individuals without conflicts of interest — will comprehensively review medical and scientific evidence and hold a scientific hearing to provide a forum for additional evidence. It will then determine whether each recommendation in the 2006 Lyme disease guidelines is justified by the evidence or needs revision or updating.

Where does this leave us at this point in time? My recommendation is that until the legal process and the IDSA review is completed, the existing IDSA guideline continue to be considered authoritative and long term continuous treatment for Lyme disase be considered experimental and unproven and medically necessary.

Evidence-based guidelines for the management of Lyme disease. Expert Rev Anti Infect Ther 2004;2(1 Suppl):S1-13. [66 references]

Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, Krause PJ, Bakken JS, Strle F, Stanek G, Bockenstedt L, Fish D, Dumler JS, Nadelman RB. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2006 Nov 1;43(9):1089-134.

Tamiflu for Prophylaxis – pro

M Levin, MD — Mon, 06 Aug 2012 16:12:49 +0000

Most guidelines for pre-exposure prophylaxis of influenza in patients with cancer and on chemotherapy suffice with recommending vaccination. Some mention antiviral prophylaxis.

Patients with active malignant disease are at higher risk for upper respiratory tract infection due to influenza, parainfluenza or respiratory syncycial virus (RSV). Although response to vaccination with the attenuated influenza vaccine in patients on chemotherapy is highly variable, ranging from 24–75%, immunoprophylaxis with the influenza vaccine is recommended for patients with active malignant disease or chemotherapy. The same applies to patients with lymphoproliferative disease or multiple myeloma. In areas and seasons where influenza is endemic, chemoprophylaxis with neuraminidase inhibitors like tamiflu can be considered simultaneously to vaccination in exposed patients with a high risk of influenza complications.

The CDS writes that the duration of pre-exposure chemoprophylaxis based depends on the duration of community influenza activity. Regimens as long as 28 days for zanamivir, and 42 days for oseltamivir, have been well tolerated, but no published data are available regarding use of regimens lasting >6 weeks. The drug must be taken each day for the duration of influenza activity in the community.

M. Sandherr et al, Antiviral prophylaxis in patients with haematological malignancies and solid tumours: Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Oncology (DGHO) Annals of Oncology 17: 1051–1059, 2006

Alastair Smith et al, Guidelines on the diagnosis and management of multiple myeloma 2005 British Journal of Haematology Volume 132, Issue 4, pages 410–451, February 2006

National Institute for Health and Clinical Excellence (NICE). Oseltamivir, amantadine (review) and zanamivir for the prophylaxis of influenza. London (UK): National Institute for Health and Clinical Excellence (NICE); 2008 Sep. 37 p. (Technology appraisal guidance; no. 158).

http://www.cdc.gov/flu/professionals/antivirals/antiviral-agents-flu.htm, 2012

Booy R, Lindley RI, Dwyer DE, Yin JK, Heron LG, Moffatt CR, Chiu CK, Rosewell AE, Dean AS, Dobbins T, Philp DJ, Gao Z, Macintyre CR. Treating and preventing influenza in aged care facilities: a cluster randomised controlled trial. PLoS One. 2012;7(10):e46509.

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