A distinctive form of immune thrombocytopenia in a phase 2 study of alemtuzumab for the treatment of relapsing-remitting multiple sclerosis

Cuker, Adam; Coles, Alasdair; Sullivan, H.; Fox, Edward J.; Goldberg, Mark A.; Oyuela, Pedro; Purvis, Annie; Beardsley, Diana S.; Margolin, David

doi:10.1182/blood-2011-08-371138

Cited by 97 publications

(73 citation statements)

References 34 publications

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“…Gold, L-dopa, procainamide and sulphonamides have been associated with this type of reaction [16]. Recently, alemtuzumab, a humanized anti-CD52 monoclonal antibody was associated with the development of ITP in 6 (2.8%) of 216 patients with multiple sclerosis [34]. Thrombocytopenia developed between 19 and 39 months from first exposure and serological studies for anti-platelet antibodies were inconclusive.…”

Section: Drug-induced Autoantibody Formationmentioning

confidence: 99%

Approach to the Diagnosis and Management of Drug-Induced Immune Thrombocytopenia

Arnold

Nazi

Warkentin

et al. 2013

Transfusion Medicine Reviews

153

144

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Drug-induced immune thrombocytopenia (DITP) is a challenging clinical problem that is underrecognized, difficult to diagnose and associated with severe bleeding complications. DITP may be caused by classic drug-dependent platelet antibodies (eg, quinine); haptens (eg, penicillin); fibandependent antibodies (eg, tirofiban); monoclonal antibodies (eg, abciximab); autoantibody formation (eg, gold); and immune complex formation (eg, heparin). A thorough clinical history is essential in establishing the diagnosis of DITP and should include exposures to prescription medications, herbal preparations and even certain foods and beverages. Clinical and laboratory criteria have been established to determine the likelihood of a drug being the cause of thrombocytopenia, but these criteria can only be applied retrospectively. The most commonly implicated drugs include quinine, quinidine, trimethoprim/sulfamethoxazole and vancomycin. We propose a practical approach to the diagnosis of the patient with suspected DITP. Key features are: the presence of severe thrombocytopenia (platelet nadir <20 × 10 9 /L); bleeding complications; onset 5 to 10 days after first drug exposure, or within hours of subsequent exposures or after first exposure to fibans or abciximab; and exposure to drugs that have been previously implicated in DITP reactions. Treatment involves stopping the drug(s), administering platelet transfusions or other therapies if bleeding is present and counselling on future drug avoidance. The diagnosis can be confirmed by a positive drug re-challenge, which is often impractical, or by demonstrating drug-dependent platelet reactive antibodies in vitro. Current test methods, which are mostly flow cytometry-based, must show drug-dependence, immunoglobulin binding, platelet specificity and *

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Section: Drug-induced Autoantibody Formationmentioning

confidence: 99%

Approach to the Diagnosis and Management of Drug-Induced Immune Thrombocytopenia

Arnold

Nazi

Warkentin

et al. 2013

Transfusion Medicine Reviews

153

144

View full text Add to dashboard Cite

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“…The occurrence of secondary autoimmune diseases may be related to the use of lymphocyte-depleting antibodies administered during HSCT conditioning [64]. A retrospective registry review reports a 9 % incidence of secondary autoimmunity among patients who received ATG during HSCT conditioning, but secondary autoimmune disease occurred in only 4 % of patients who did not receive a lymphocyte-depleting agent [62].…”

Section: Lesson 9: the Reconstituted Immune System Retains A Predispomentioning

confidence: 99%

Hematopoietic Stem Cell Therapy for Multiple Sclerosis: Top 10 Lessons Learned

Atkins

Freedman

2013

Neurotherapeutics

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Reports from more than 600 hematopoietic stem cell transplants (HSCT) have appeared in the medical literature for the last 1 and one-half decades. The patient's own stem cells are harvested and stored temporarily while high doses of chemotherapy and biologics are used to destroy the auto-destructive immune system. The immune system is regenerated from the infused autologous hematopoietic stem cells. Increasing clinical experience has refined patient selection criteria and management in the peri-transplant period leading to a reduction in treatment-related complications. HSCT, when used to treat patients with aggressive highly active multiple sclerosis, can reduce or eliminate ongoing clinical relapses, halt further progression, and reduce the burden of disability in some patients, in the absence of chronic treatment with disease-modifying agents. The top 10 lessons learned from the growing experience using HSCT for the treatment of multiple sclerosis are discussed.Keywords Hematopoietic stem cell transplantation . Multiple sclerosis . Autoimmunity . Immune ablation There are published reports of more than 600 bone marrowbased transplants performed primarily for the treatment of multiple sclerosis (MS). This review will focus on why and how the hematopoietic stem cell transplantation (HSCT) procedure is used and discuss some of the lessons that can be gleaned from the experience of using HSCT to treat MS.MS is an organ-specific autoimmune disease that results in exclusive central nervous system (CNS) demyelination and axonal damage. Early on, multifocal localized pockets of inflammation lead to transient neurologic dysfunction manifesting as a series of relapses followed by remissions, usually with complete recovery owing to adequate CNS repair. However, as the damage accumulates, repair becomes inadequate and leads to incomplete resolution of disability, culminating in a neurodegenerative process amid a sea of smoldering and changing inflammation. This is probably the underlying state for the clinical stage of secondary progressive MS (SP-MS), a phase characterized by relentless and progressive accumulation of neurological disability with dwindling evidence of discrete relapses [1].Targeting inflammation with interferon-β, glatiramer acetate, natalizumab, fingolimod, and other immune-modulating agents reduces the frequency of relapses, but the impact on delaying the onset, preventing or slowing the tempo of SP-MS remains uncertain [2][3][4]. Several other drugs are in late stage clinical trials and may provide new alternatives for some patients with relapsing-remitting MS (RR-MS). However, despite these therapeutic advances, a subset of patients seem refractory and rapidly develop severe neurological impairment, whereas other patients may have a slower progression of illness that ultimately results in marked functional disabilities. Only a single agent, mitoxantrone, has been shown to temporarily halt or slow the tempo of SP-MS [5,6], but even then, this occurs only in SP-MS patients who have highly act...

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“…Of the alemtuzumab-associated cases, 2/108 (1.9%) occurred in the 12 mg/day group and 4/108 (3.7%) occurred in the 24 mg/day group [3].…”

Section: Low-dose Alemtuzumab-associated Immune Thrombocytopenia In Cmentioning

confidence: 94%

“…Gianluigi Reda, 1 Francesco Maura, 2 Giuseppe Gritti, 3 Anna Gregorini, 2 Francesca Binda, 2 Francesca Guidotti, 2 Alfonso Piciocchi, 4 Carlo Visco, 5 Francesco Rodeghiero, 5 and Agostino Cortelezzi 2 *…”

Section: Low-dose Alemtuzumab-associated Immune Thrombocytopenia In Cunclassified

“…In particular, ITP has been reported in about 2-5% of CLL population [1,2]. Recently, Cuker et al reported the occurrence of ITP in 6/216 patients with relapsing-remitting multiple sclerosis in a phase 2 clinical trial of annual alemtuzumab [3]. Alemtuzumab is an anti-CD52 monoclonal antibody used in CLL both as first-line treatment and in relapsed/refractory patients [4,5].…”

Section: Low-dose Alemtuzumab-associated Immune Thrombocytopenia In Cmentioning

confidence: 99%

See 1 more Smart Citation

Low‐dose alemtuzumab‐associated immune thrombocytopenia in chronic lymphocytic leukemia

et al. 2012

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A distinctive form of immune thrombocytopenia in a phase 2 study of alemtuzumab for the treatment of relapsing-remitting multiple sclerosis

Cited by 97 publications

References 34 publications

Approach to the Diagnosis and Management of Drug-Induced Immune Thrombocytopenia

Approach to the Diagnosis and Management of Drug-Induced Immune Thrombocytopenia

Hematopoietic Stem Cell Therapy for Multiple Sclerosis: Top 10 Lessons Learned

Low‐dose alemtuzumab‐associated immune thrombocytopenia in chronic lymphocytic leukemia

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