Cancer Treatment Today » Immunology

Rituxan for PTLD -pro

M Levin, MD — Thu, 25 Apr 2013 18:23:26 +0000

Post-transplant lymphoproliferative disease (PTLD) remains a major complication after solid organ and allogeneic stem cell transplantation. It is usually related to outgrowth of lymphocytes infected with Epstein-Barr virus (EBV). Following titers and an individualized treatment plan including decreased immunosuppression and other agents should be chosen based on the severity and extent of disease.

Some classify PTLD into three groups(1): Early lesion (ie, plasmacytic hyperplasia and infectious mononucleosis-like PTLD), Polymorphic PTLD and Monomorphic PTLD Monomorphic PTLD. Rituxan appears to have some role in the management of this condition. Several studies show that it reduces both the titers and severity of PTLD. It can be given by itself of with low dose chemotherapy(2).

The strategy of following titers and giving prophylactic Rituxan has not been formally studied. Most published studies have dealt with treating patients who already have PTLD.

1.Swerdlow SH, Campo E, Harris NL, et al. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, IARC Press, Lyon 2008.

2.Gross TG, Orjuela MA, Perkins SL, Park JR, Lynch JC, Cairo MS, Smith LM, Hayashi RJ.Low-dose chemotherapy and rituximab for posttransplant lymphoproliferative disease (PTLD): a Children’s Oncology Group Report. Am J Transplant. 2012 Nov;12(11):3069-75.

3.Jain AB, Marcos A, Pokharna R, Shapiro R, Fontes PA, Marsh W, Mohanka R, Fung JJ.Rituximab (chimeric anti-CD20 antibody) for posttransplant lymphoproliferative disorder after solid organ transplantation in adults: long-term experience from a single center. Transplantation. 2005 Dec 27;80(12):1692-8.

5..N. Milpied et al, Humanized anti-CD20 monoclonal antibody (Rituximab) in post transplant B-lymphoproliferative disorder: A retrospective analysis on 32 patients Medicine, Annals of Oncology
Volume 11, Issue suppl 1, Pp. S113-S116.

For Lay version see here

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

ImmuKnow Immune Cell Function Assay – pro

M Levin, MD — Tue, 19 Jun 2012 17:33:21 +0000

In April 2002, the FDA approved the Cylex Immune Cell Function Assay (Cylex Inc., Columbia, MD) for the detection of cell mediated immune response in populations undergoing immunosuppressive therapy for organ transplant. FDA clearance of tests does not include specific indications. The test calculates the concentration of ATP (ng/ml) from a calibration curve and compared to ATP level ranges to characterize the cellular immune function of the sample. A variety of studies since 2009 have reached conflicting and contradictory conclusions regarding the utility of this test in liver, heart and kidney transplantation. Some showed no efficacy and others had promising but inconclusive results and recommend farther study. The American Society of Transplantation (AST) does not mention the use of the Cylex Immune Cell Function assay in its recommendations for the screening, monitoring and reporting of infections complications in the evaluation of recipients of organ transplantation (AST, 2006). Chon and Brennan (2009) commented that there is no consensus on the utility of the Immuknow assay in renal transplant rejection other than in the research setting. Martinu et al (2009) commented that “the data in lung transplantation are scarce and not very promising to date”, and that “the ImmuKnow assay does not seem to have the potential to differentiate between infection and rejection in lung transplant recipients and, until more data becomes available, should not be used clinically in this patient population.”

More recent studies continue to exhibit the same pattern. Torio et al (2011) stated that the Cylex ImmuKnow assay provides a rapid assessment of global immune function in immunocompromised patients by measuring the global immune responses of CD4 T cells from a whole-blood sample. The authors concluded that these findings confirmed that the ImmuKnow assay identified transplant patients at risk for infection. It may provide information to guide immunosuppressive therapy, but the assay did not seem to have the potential to differentiate subjects experiencing rejection.

De Paolis et al (2011) concluded that this preliminary analysis showed a beneficial capacity of this assay to represent the global depression of the immune system. They did not confirm the predictive value of higher IK values for an increased risk of an acute rejection episode.

Huskey et al (2011) retrospectively analyzed 1,330 ImmuKnow assay values in 583 renal transplant recipients at a single center from 2004 to 2009 and correlated these values with episodes of opportunistic infections (OI) and acute rejection (AR) in the subsequent 90 days. The authors concluded that these findings fail to show an association between single time point ImmuKnow assay values and the subsequent development of an adverse event in the subsequent 90 days. The optimal use of the ImmuKnow assay in kidney transplantation has yet to be determined. A number of other studies reached similar conclusions.

This test is not currently recommended by any guidelines and should be considered investigational at this time.

Clinical / Medical References:

Chon WJ, Brennan DC. Investigational methods in the diagnosis of acute renal allograft rejection. UpToDate [online serial]. Waltham, MA: UpToDate; October 2009.
Martinu T, Chen DF, Palmer SM. Acute rejection and humoral sensitization in lung transplant recipients. Proc Am Thorac Soc. 2009;6(1):54-65.
Torío A, Fernández E, Montes-Ares O, et al. Lack of association of immune cell function test with rejection in kidney transplantation. Transplant Proc. 2011;43(6):2168-2170.
De Paolis P, Favarò A, Piola A, et al. “Immuknow” to measurement of cell-mediated immunity in renal transplant recipients undergoing short-term evaluation. Transplant Proc. 2011;43(4):1013-1016.
Huskey J, Gralla J, Wiseman AC. Single time point immune function assay (ImmuKnow) testing does not aid in the prediction of future opportunistic infections or acute rejection. Clin J Am Soc Nephrol. 2011;6(2):423-429.

Read the Layperson version here.