Cancer Treatment Today » Immunology

Intravenous Gamma Globulin and/ or plasma excange for Gullain-Barre syndrome – pro

M Levin, MD — Wed, 26 Jun 2013 15:15:22 +0000

Guillain-Barr 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-Barr 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.

Both plasma exchange (PE) therapy and intravenous immune globulin (IVIG) have proven effective for Guillain-Barr syndrome (GBS). They are both thought to diminish autoantibody production and increase solubilization and removal of immune complexes. Both have been shown to shorten recovery time by as much as 50%. IVIG is easier to administer and has fewer complications than PE and is usually the initial treatment.

Randomized trials in severe disease show that IVIG started within 4 weeks from onset hastens recovery as much as plasma exchange. Combination therapy of both, does not improve outcomes or shortened illness duration over one or the other.

1. Shahar E. Current therapeutic options in severe Guillain-Barre syndrome. Neuropharmacol. Jan-Feb 2006;29(1):45-51

2.Bascic-Kes V, Kes P, Zavoreo I, Lisak M, Zadro L, Coric L, et al. Guidelines for the use of intravenous immunoglobulin in the treatment of neurologic diseases. Acta Clin Croat. Dec 2012;51(4):673-83.

3.[Best Evidence] Hughes RA, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain-Barr syndrome. Cochrane Database Syst Rev. Jun 16 2010;6:CD002063

For Lay version see here

For Rituxan for Gullain-barre see here

Remicade for Graft Versus Host Disease – pro

admin — Sat, 01 Sep 2012 22:41:53 +0000

Graft-versus-host disease (GVHD) is an illness that appears in pa tients after allogeneic bone marrow transplantation. Acute disease usually manifests in the first one or two months after transplantation. It targets epidermal cells in the skin, liver, and gastrointestinal tract. It is graded I through IV on the basis of the severity of the disease. Chronic GVHD usually occurs more than three months after allogeneic bone marrow transplantation. It is graded on the basis of the extent, rather than severity, of the disease.
Infliximab is a chimeric human-murine monoclonal antibody to TNF-. It binds to both soluble and transmembrane human TNF- and inhibits binding to TNF- receptors. Infliximab is currently indicated for the treatment of immunologic-based diseases (rheumatoid arthritis, moderately to severely active Crohn’s disease, and fistulizing Crohn’s disease), assuming patients have had inadequate responses to conventional therapy. It is not approved for the treatment of GVHD. There are case reports of its use for GVHD. Remicade has also been reported to cause GVHD. The 2012 guideline by Dignan et al in British Journal of Hematology does not recommend infliximab in second line (after failure of steroids) .

Dignan FL, Amrolia P, Clark A, Cornish J, Jackson G, Mahendra P, Scarisbrick JJ, Taylor PC, Shaw BE, Potter MN, on behalf of the Haemato-oncology Task Force of the British Committee [trunc]. Diagnosis and management of chronic graft-versus-host disease. Br J Haematol. 2012 Jul;158(1):46-61. [125 references]

Uptodate, Treatment of chronic graft-versus-host disease, 2015

Alousi AM, Weisdorf DJ, Logan BR, Bolaños-Meade J, Carter S, Difronzo N, et al. Etanercept, mycophenolate, denileukin, or pentostatin plus corticosteroids for acute graft-versus-host disease: a randomized phase 2 trial from the Blood and Marrow Transplant Clinical Trials Network. Blood. Jul 16 2009;114(3):511-7.

A phase I study has been completed: GVH 022P: Study Using Anti Tumor Necrosis Factor Antibody (Infliximab) for Treatment of Acute Graft Versus Host Disease
This study has been completed, NCT00228839. The major purpose of this study is to evaluate the way the body uses and absorbs (the pharmacokinetic profile) a drug called anti tumor necrosis factor antibody (infliximab) for the treatment of acute GVHD.

G Kobbe et al, Treatment of severe steroid refractory acute graft-versus-host disease with infliximab, a chimeric human/mouse antiTNF antibody July (1) 2001, Volume 28, Number 1, Pages 47-49

Marshall J, Blackhouse G, Goeree R, et al. Infliximab for the treatment of Crohn’s disease: a systematic review and cost-utility analysis. Technology Report No. 24. Ottawa, ON: Canadian Coordinating Office for Health Technology Assessment (CCOHTA); 2002.

Stem Cell transplant for Scleroderma – pro

M Levin, MD — Thu, 30 Aug 2012 18:35:32 +0000

Lay Summary: Stem cell transplantation in the hope of modifying disease activity in scleroderma is under active clinical investigational.

Immunosuppressive agents such as cyclophosphamide have long been used to treat autoimmune disease, but the dose is often limited by bone marrow suppression. More than ten years ago several groups considered adopting the oncological approach of myeloablative therapy followed by haematological ‘rescue’ using either autologous or allogeneic hematopoietic stem cells to treat severe, therapy-resistant autoimmune disease. The concept was supported by animal model data, suggesting tolerance induction in a rat arthritis model and cases of patients receiving an hematopoietic stem cell transplantation (HSCT) for conventional indications and in whom a coincidental autoimmune disease was improved or eradicated.

After several international meetings, consensus guidelines were developed and the first published case of a patient receiving an HSCT as treatment for an autoimmune disease alone was published in October 1996. Since then, over 1000 patients have been transplanted for autoimmune disease, the majority within the context of phase I/II trials and more recently within phase III prospective randomized studies.

The recent phase 3 Autologous Stem Cell Transplantation International Scleroderma (ASTIS) open-label, parallel-group trial included 29 clinical centers in 10 countries. During a median follow-up of 5.8 years, there were a total of 53 events: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, more events occurred in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, the HSCT group experienced 14 events (17.7%) vs 14 events (18.2%) in the control group. At 4 years, a total of 15 events (19%) had occurred in the HSCT group vs 20 events (26%) in the control group. At 4 years, time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% confidence interval, 0.16 – 0.74) and 0.34 (95% confidence interval, 0.16 – 0.74) at 2 years. Transplant was more effective than cyclophosphamide alone. It was reported in JAMA. 2014;311:2485-2487, with an supportive editorial on pp. 2490-2498 and there is a recently supportive NEJM article referenced below.

Autologous stem cell transplantation is well supported and has become standard in poorly responding scleroderma cases.

Sullivan KM, Goldmuntz EA, Keyes-Elstein L, et al. Myeloablative autologous stem-cell transplantation for severe scleroderma. N Engl J Med 2018;378:35-47

Nash RA, McSweeney PA, Crofford LJ, et al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the U.S. multicenter pilot study. Blood 2007; 23 April

van Laar JM, Farge D, Sont JK, et al. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA 2014;311:2490-2498.

van Laar JM, Tyndall A. Adult stem cells in the treatment of autoimmune diseases. Rheumatology (Oxford) 2006; 45:1187-1193.

Alan Tyndall; Daniel E. Furst Adult Stem Cell Treatment of Scleroderma Curr Opin Rheumatol. 2007;19(6):604-610

http://www.fhcrc.org/science/clinical/ltfu/physician/physician.pdf, 2011

Jacob M. van Laar Kamran Naraghi Alan Tyndall, Haematopoietic stem cell transplantation for poor-prognosis systemic sclerosis. Rheumatology (Oxford) (2015) 54 (12): 2126-2133.

Beclomethasone for graft versus host disease – pro

M Levin, MD — Thu, 30 Aug 2012 18:31:01 +0000

The pathological and clinical findings of gastrointestinal (GI) graft-versus-host disease (GVHD) are similar to those of inflammatory bowel disease. Three previous studies had shown the safety and efficacy of the topical BDP for GI GVHD. It is possibe that it would function similarly for GVHD. Several small pahse IIs tudies suggest that it suppresses allogeneic immune responses in the gut without causing significant immunosuppression.

This therapy is under study: Compassionate Use of Beclomethasone in Treating Patients With Graft-Versus-Host Disease of the Gastrointestinal Tract, NCT00055666.

G.McDonald, M.Bouvier, D.Hockenbery, J.Stern, T.Gooley, A.Farrand, C.Murakami, D.Levine
Oral beclomethasone dipropionate for treatment of intestinal graft-versus-host disease: A randomized, controlled trial Gastroenterology, Volume 115, Issue 1, Pages 28-35

Y Miura et al, Oral beclomethasone dipropionate as an initial treatment of gastrointestinal acute graft-versus-host disease after reduced-intensity cord blood transplantation Bone Marrow Transplantation (2006) 38, 577–579.

Pet/CT or CT scanning for malignancy in dermatomyositis – pro

M Levin, MD — Thu, 30 Aug 2012 18:21:54 +0000

Dermatomyositis is an autoimmune disease that has a characteristic skin eruptionand may be autoimmune; it is sometimes associated with malignancy. Because this is a rare disease, not much is known about this association and there are no guidelines to my knowledge, but experts often recommend CT scanning to exclude coexistent malignancy. A link between malignancy and DM is well established. Numerous case series and population-based studies have confirmed this association, although estimation of malignancy incidence among DM patients varies from 15% to 27%.

Few studies have investigated specific imaging modalities for DM malignancy screening. A role for screening with CT chest/abdomen/pelvis was shown in a retrospective analysis of 33 DM patients, 13 of which were found to have malignancies (15). However, routine screening failed to identify four malignancies and screening not supported by physical exam (PE) and/or symptoms was positive in only 13% of cases. On the other hand, several recent cohort studies have found that CT scans were the most common test that detected an underlying malignancy when DM patients underwent malignancy screening.

A single prospective study compared whole-body [18F] fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) to “conventional” malignancy screening among DM patients. In this study, conventional screening included CT thorax/abdomen, mammography, gynecological examination, pelvic ultrasound, and tumor marker analysis [CA125, CA19.9, carcinoembryonic antigen, prostate-specific antigen (PSA)]. Nine of 55 patients were diagnosed with malignancy. Notably, FDG-PET/CT and conventional screening had similar overall positive and NPVs for malignancy among DM patients (92.7%).

A recent review concludes that a routine search for underlying malignancy is not justified in dermatomyositis patients. Kanna et al srite: ” We believe one of the most important steps to this, as emphasized by the HVCTF-ACP in their framework, is to identify the subset of DM patients in whom malignancy screening has high value. To optimize the risk: benefit ratio of any screening test, it is well-known that it is important to define a high-risk subgroup. As only a minority will ever develop malignancy (15–27%) identifying the subset of DM patients who warrant malignancy screening appears to be a feasible goal. Additional work to be done includes collecting data to, (I) minimize malignancy overdiagnosis in DM patients, (II) identify the prevalence of false-positive malignancy diagnoses in DM patients, (III) assess patient morbidity/mortality associated with malignancy screening, and (IV) calculate the cost-effectiveness of malignancy screening.

As summarized above, research has already laid the groundwork necessary for more focused projects that may eventually establish high-value malignancy screening guidelines within the setting of DM. For example, although malignancy risk may persist years after DM diagnosis, it has reproducibly been found to be highest within the first 12 months, supporting this is likely the time period that will be associated with an optimal risk: benefit ratio and the highest screening value (10,13). Furthermore, the clinical and laboratory factors that have been shown to predict or protect against underlying malignancy should be more meticulously explored to determine which, if any, can truly be used to further increase/decrease the level of clinical suspicion for underlying malignancies.”

Khanna U, Galimberti F, Li Y, Fernandez AP. Dermatomyositis and malignancy: should all patients with dermatomyositis undergo malignancy screening?. Ann Transl Med. 2021;9(5):432. doi:10.21037/atm-20-5215

Agnès Sparsa, Eric Liozon, François Herrmann, Kim Ly, Valérie Lebrun, Pascale Soria, Véronique Loustaud-Ratti, Marie-Laure Bouyssou-Gauthier, Serge Boulinguez, Christophe Bédane, Marie-Odile Jauberteau, Elisabeth Vidal, and Jean-Marie Bonnetblanc
Routine vs Extensive Malignancy Search for Adult Dermatomyositis and Polymyositis: A Study of 40 Patients
Arch Dermatol, Jul 2002; 138: 885 – 890.

Scheinfeld N. A review of the cutaneous paraneoplastic associations and metastatic presentations of ovarian carcinoma. Clin Exp Dermatol.2008 Jan;33(1):10-5. Epub 2007 Nov 3. (s)

Daclizumab for Graft Versus Host disease – pro

M Levin, MD — Thu, 30 Aug 2012 18:20:31 +0000

Daclizumab (trade name Zenapax) is a therapeutic humanized monoclonal antibody to the alpha subunit of the IL-2 receptor of T cells. It is used to prevent rejection in organ transplantation, especially in kidney transplants.Daclizumab reduces the incidence and severity of acute rejection in kidney transplantation without increasing the incidence of opportunistic infections.
This drug has been used to treat graft vs. Host Disease (GVHD) in stem cell as well as other types of transplants but most evidence is in the form of case reports and series.

It was studied in a clinical study: Methylprednisolone With or Without Daclizumab in Treating Patients With Acute Graft-Versus-Host Disease, NCT00053976 . This was a randomized phase III trial to compare the effectiveness of methylprednisolone with or without daclizumab in treating patients who have acute graft-versus-host disease following donor bone marrow transplantation. The study was halted after a planned interim analysis showed a significantly worse 100-day survival in the group receiving corticosteroids plus daclizumab (77% vs 94%; P = .02). Overall survival at 1 year was also inferior in the combination arm (29% vs 60%; P = .002). Both relapse- and GVHD-related mortality contributed to the increased mortality in the combination group. It concluded: “The combination of corticosteroids and daclizumab should not be used as initial therapy of acute GVHD.”

D T Teachey et al, Daclizumab for children with corticosteroid refractory graft-versus-host disease
Bone Marrow Transplantation (2006) 37, 95–99 2005

C H Hui et al, Daclizumab has poor efficacy in steroid-refractory severe acute graft-versus-host disease: a single centre experience with 12 allograft patientsBone Marrow Transplantation (2008) 41, 409–410;2007

Srinivasan, R, Chakrabarti, S, Walsh, T, et al. Improved survival in steroid-refractory acute graft versus host disease after non-myeloablative allogeneic transplantation using a daclizumab-based strategy with comprehensive infection prophylaxis. Br J Haematol 2004; 124:777.

Stephanie J. Lee, David Zahrieh, Edward Agura, Margaret L. MacMillan, Richard T. Maziarz, Philip L. McCarthy, Jr, Vincent T. Ho, Corey Cutler, Edwin P. Alyea, Joseph H. Antin, and Robert J. Soiffer
Effect of up-front daclizumab when combined with steroids for the treatment of acute graft-versus-host disease: results of a randomized trial Blood 104: 1559-1564;

Stem cell transplantation for CIDP – pro

M Levin, MD — Thu, 30 Aug 2012 18:19:11 +0000

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is an acquired immune-mediated inflammatory disorder of the peripheral nervous system. The pathologic hallmark of the disease is loss of the myelin sheath (the fatty covering that protects nerve fibers) of the peripheral nerves.
First line treatment for CIDP includes corticosteroids (e.g. prednisone), plasmapheresis (plasma exchange) and intravenous immunoglobulin (IVIg) which may be prescribed alone or in combination with an immunosuppressant drug. IVIG and plasmapheresis have proven benefit in randomized, double-blind, placebo-controlled trials. A nubmer of case reprots, series and some phase II studies establish that amny patients with this condition respond with amelioration of symptoms or with a remission after a high dose therapy regimen with autologous stem cell transplantation.

Toothaker TB, Brannagan TH (2007). “Chronic inflammatory demyelinating polyneuropathies: current treatment strategies”. Curr Neurol Neurosci Rep 7 (1): 63–70

S. Renaud, P. Fuhr, J. Halter, A. Gratwohl, A. Steck(2007) Autologous stem cell transplantation in therapy resistant chronic inflammatory demyelinating disease (CIDP) A phase II study. Call for patients
Clinical Neurophysiology, Volume 118, Issue 2, Pages e4-e5

Oyama, Y., Sufit, R., Loh, Y., Statkute, L., Yaung, K., Quigley, K., Gonda, E., Spahovic, D., Bronesky, D., Burt, R. K.
NONMYELOABLATIVE AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR REFRACTORY CIDP
Neurology 2007 69: 1802-1803

Brannagan, T.H., III, Pradhan, A., Heiman-Patterson, T., Winkelman, A.C., Styler, M.J., Topolsky, D.L., Crilley, P.A., Schwartzman, R.J., Brodsky, I., Gladstone, D.E.
High-dose cyclophosphamide without stem-cell rescue for refractory CIDP
Neurology 2002 58: 1856-1858

H. W Axelson, G. Oberg, and H. Askmark
Successful repeated treatment with high dose cyclophosphamide and autologous blood stem cell transplantation in CIDP
BMJ Case Reports, February 2, 2009; 2009

Lehmann, Helmar C., Meyer zu Horste, Gerd, Kieseier, Bernd C., Hartung, Hans-Peter
Review: Pathogenesis and treatment of immune-mediated neuropathies
Therapeutic Advances in Neurological Disorders 2009 2: 261-281

Treatment of Langherhan’s Hystiocytosis and Revlimid – pro

M Levin, MD — Fri, 24 Aug 2012 17:13:30 +0000

Histiocytosis is a rare disease that involves hystiocytes. The disease can range from limited involvement that spontaneously regresses to progressive multiorgan involvement that can be chronic and debilitating. In some cases, the disease can be life-threatening. It is approximated that histiocytosis affects 1 in 200,000 children born each year in the United States. The disease us rare and not much is known securely about how to treat it. Because of its rarity, prospective studies are not possible.

In 2009, a guideline was published by the Hystiocytosis Soceity It recommends an initial 6-week course of therapy with vinblastine and prednisone for all patients with MS-LCH regardless of risk organ involvement.It is also recommended that all patients who have complete disease resolution (NED)
after 6-12 weeks of initial therapy continue with maintenance therapy. Maintenance therapy consists of pulses of vinblastine and prednisone every 3 weeks and daily continuous 6-mercaptopurine (6MP) for a total treatment duration of 12 months. Currently, there is insufficient evidence to support an optimal course of treatment for use with patients suffering from severe progressive MS-LCH who do not respond to standard therapy. Recently, promising results have been reported for patients treated with a combined regimen of 2-chlorodeoxyadenosine (2-CdA, Cladribin, Leustatin) and cytarabine (Ara-C) (12); as well as stem cell transplantation after reduced intensity conditioning regimen (RIC-SCT). However, the results generated by both reports are based on limited observations and must be validated by the prospective clinical trials.

As far as Revlmid, Strurz reported a case of successful treatment with this agent, and there is another case report and a case series of 4 cases:

Uppuluri R, Ramachandrakurup S, Balaji R, Subburaj D, Bakane A, Raj R.Successful Treatment of Refractory Langerhans Cell Histiocytosis of the Choroid Plexus in a Child With Pulse Dexamethasone and Lenalidomide.J Pediatr Hematol Oncol. 2017 Mar;39(2):e74-e78.

R Uppuluri et al.Excellent Remission Rates With Limited Toxicity in Relapsed/Refractory Langerhans Cell Histiocytosis With Pulse Dexamethasone and Lenalidomide in Children
Pediatr Blood Cancer 64 (1), 110-112. 2016 Aug 24.

Both, and the case report by Sztutz bring us to six cases in the literature,which is not sufficient to establish a SOC.

and a study is ongoing: A Study of Lenalidomide for Adult Histiocyte Disorders, NCT02523040.

LANGERHANS CELL HISTIOCYTOSIS Histiocyte Society Evaluation and Treatment Guidelines April 2009

Szturz P, Adam Z, Rehák Z, Koukalová R, Slaisová R, Stehlíková O, Chovancová J, Klabusay M, Krej?í M, Pour L, Hájek R, Mayer J. Lenalidomide proved effective in multisystem Langerhans cell histiocytosis. Acta Oncol. 2012 Mar;51(3):412-5. doi: 10.3109/0284186X.2011.631581. .

Histiocyte Society 26th Annual Meeting Abstracts, Boston, Massachusetts
Article first published online: 4 FEB 2011
Pediatric Blood & Cancer Volume 56, Issue 4, pages 689–703, April 2011

Bernard F, Thomas C, Bertrand Y, Munzer M, Landman Parker J, Ouache M,
et al. Multi-centre pilot study of 2-chlorodeoxyadenosine and cytosine arabinoside
combined chemotherapy in refractory Langerhans cell histiocytosis with
haematological dysfunction. Eur J Cancer 2005;41(17):2682-9.

Steiner M, Matthes-Martin S, Attarbaschi A, Minkov M, Grois N, Unger E, et al. Improved outcome of treatment-resistant high-risk Langerhans cell histiocytosis after allogeneic stem cell transplantation with reduced-intensity conditioning. Bone Marrow Transplant 2005;36(3):215-25.

MEK may be helpful, but results are very preliminary at this time. See https://www.investorvillage.com/smbd.asp?mb=1086&mn=16747&pt=msg&mid=17850518

Read the Layperson version here.

Photopheresis for graft versus host disease – pro

M Levin, MD — Fri, 24 Aug 2012 01:11:20 +0000

The use of photopheresis or Extra Corporeal Perfusion (ECP) as a treatment of graft-versus-host disease (GVHD) after a prior allogeneic stem cell transplant is based on the fact that GVHD is similar to autoimmune disease in that it too is an immunologically mediated disease. Chronic GVHD typically presents with more diverse symptomatology resembling autoimmune diseases such as progressive systemic sclerosis, systemic lupus erythematosus, or rheumatoid arthritis. It may affect the mouth, eyes, respiratory tract, musculoskeletal system, peripheral nerves, as well as the skin, liver, or gut – the usual sites of acute GVHD.

A 2001 BlueCross BlueShield Association Technology Evaluation Center (TEC) Assessment, which offered the following observations and conclusions:

For acute GVHD or chronic GVHD in previously untreated patients, or in those responding to conventional therapy, there were no studies that met selection criteria and reported results of extracorporeal photopheresis, alone or in combination with other therapies. Therefore, it was not possible to draw conclusions concerning the effects of this therapy on health outcomes in previously untreated or responsive patients.
In acute GVHD, a phase II study by Greinix et al. involving 38 patients reported complete remission in 86%, 55%, and 30% of patients with grades 2, 3, and 4 agvhd respectively. The best results were obtained in 82%, 61%, and 61% of patients with skin, liver, and gut agvhd respectively.
Studies focusing on patients with chronic GVHD unresponsive to other therapies reported resolution or marked improvement of lesions in about 50% of patients. The one phase II study by Flowers et al. reported on a multicentre prospective phase II randomized study in 23 transplant centres in North and South America, Europe, and Australia. The 95 enrolled patients were randomized either to ECP plus standard therapy or to standard therapy alone. The conclusion reached was that ECP had a steroid-sparing effect in the treatment of chronic GVHD.
Three studies reported outcomes for 38 patients with acute GVHD that was refractory to standard treatment with steroids and other immunosuppressive drugs. Patients with Grade IV disease were generally unresponsive to photopheresis. While a single study of 21 patients reported responses in a majority of patients with Grade III disease, the small number of patients in this study was not sufficient to permit conclusions concerning the outcomes of photopheresis for treatment-refractory acute GVHD. SInce then there ahd been a nubmer of otehr reprots but no studies. A 2008 workshop convcded: “The evidence for the efficacy of ECP has been appraised by a combined British Photodermatology Group and U.K. Skin Lymphoma Group workshop on the basis of evidence published up to the end of 2001 and on the consensus of best practice. There is fair evidence for the use of ECP in erythrodermic CTCL and steroid-refractory GVHD, but randomized controlled studies are needed.” National Institute for Health and Clinical Excellence in the UK endorsed the use of ECP for CTCL and because of the complexity of treatment supported its use in specialized centres and also suggested the need for expansion of this service.

A 2012 guideline(Dinghan et al) recommends it as second line treatment.

Greinix HT, Knobler RM, Worel N. The effect of intensified extracorporeal photochemotherapy on long-term survival in patients with severe acute graft-versus-host disease. Haematologica. 2006;91:405–8.

Scarisbrick JJ, Taylor P, Holtick U, et al. U.K. consensus statement on the use of extracorporeal photopheresis for treatment of cutaneous T-cell lymphoma and chronic graft-versus-host disease. Br J Dermatol. 2008;158:659–678.

J. Klassen, The role of photopheresis in the treatment of graft-versus-host disease Curr Oncol. 2010 April; 17(2): 55–58.

Halle P, Paillard C, D’Incan M et al. Successful extracorporeal photochemotherapy for chronic graft-versus-host disease in pediatric patients. J Hematother Stem Cell Res 2002;11(3):501-12

Salvaneschi L, Perotti C, Zecca M et al. Extracorporeal photochemotherapy for treatment of acute and chronic GVHD in childhood. Transfusion 2001;41(10):1299-305

Flowers ME, Apperley JF, van Besien K. A multi-center prospective phase 2 randomized study of extracorporeal photopheresis for treatment of chronic graft-versus-host disease. Blood. 2008;112:2667–74. [Erratum in: Blood 2009;113:4478]

Clinical Summary:
71 year-old man s/p reduced intensisty allogeneic transplant from sister after AML diagnosed and induced in May 2010. He developed Graft vs Host Disease and was treated with tacrolimus but now received photopheresis.

IMC-A12 – pro

M Levin, MD — Mon, 20 Aug 2012 20:08:44 +0000

IMC-A12 (ImClone Systems Incorporated), a fully human monoclonal IgG1 antibody that binds with high affinity to the IGF-IR, inhibits ligand-dependent receptor activation and downstream signaling. IMC-A12 also mediates robust internalization and degradation of the IGF-IR. In human tumor xenograft models, IGF-IR blockade by IMC-A12 results in rapid and profound growth inhibition of cancers of the breast, lung, colon, and pancreas, and many other neoplasms. Although promising single-agent activity has been observed, the most impressive effects of targeting the IGF-IR with IMC-A12 have been noted when this agent was combined with cytotoxic agents or other targeted therapeutics. So far, only a few preliminary human studies had been published, including in Ewing sarcoma. This drug may also have applications in autoimmunde disorders. It remains an experimental drug.

Eric K. Rowinsky et al, IMC-A12, a Human IgG1 Monoclonal Antibody to the Insulin-Like Growth Factor I Receptor Clin Cancer Res September 15, 2007 13; 5549s

Suman Malempati, Brenda Weigel, Ashish M. Ingle, Charlotte H. Ahern, Julie M. Carroll, Charles T. Roberts, Joel M. Reid, Stephen Schmechel, Stephan D. Voss, Steven Y. Cho, Helen X. Chen, Mark D. Krailo, Peter C. Adamson, and Susan M. Blane Phase I/II Trial and Pharmacokinetic Study of Cixutumumab in Pediatric Patients With Refractory Solid Tumors and Ewing Sarcoma: A Report From the Children’s Oncology Group JCO Jan 20, 2012:256-262

Terry J. Smith Insulin-Like Growth Factor-I Regulation of Immune Function: A Potential Therapeutic Target in Autoimmune Diseases? Pharmacological Reviews June 2010 vol. 62 no. 2 199-236

Read the Layperson version here.