Autoimmune Thrombocytopenia After Treatment With Campath 1h in a Patient With Chronic Lymphocytic Leukaemia

Otton, SH; Dl, Turner; Frewin, Rebecca; Sv, Davies; Jeffs, Simon A.

doi:10.1046/j.1365-2141.1999.01576.x

Cited by 28 publications

(11 citation statements)

References 4 publications

(4 reference statements)

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“…If antigen binding on clonal B cells is important, this is not because of direct antibody production, but immune response to the antigen should be mediated by other cells in the microenvironment, and this is the case of T cells. Given that the course of CLL is typically characterized by profound immunosuppression, with T-cell function impairment and altered immune surveillance, both the microenvironment and cell-to-cell interactions are likely to be implicated in the emergence of nonneoplastic autoreactive B and T cells (12,39,(41)(42)(43)(44). Murine and human studies on autoimmune hemolytic anemia have shown that autoreactive T-helper (T H ) cells are critical for the induction of the autoimmune phenomena (21).…”

Section: Discussionmentioning

confidence: 99%

Immune Thrombocytopenia in Patients with Chronic Lymphocytic Leukemia Is Associated with Stereotyped B-cell Receptors

Visco

Maura

Tuana

et al. 2012

Clinical Cancer Research

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Purpose: To assess biologic features related to the development of immune thrombocytopenia (ITP) in patients with chronic lymphocytic leukemia (CLL).Experimental Design: We retrospectively analyzed 463 patients with CLL with available immunoglobulin heavy-chain variable (IGHV) gene status and B-cell receptor (BCR) configuration [heavy-chain complementary-determining region 3 (HCDR3)], of whom thirty-six developed ITP, according to previously defined criteria. Most of them had available cytogenetic analysis.Results: We observed a significant association between ITP occurrence and IGHV unmutated gene status (P < 0.0001), unfavorable cytogenetic lesions (P ¼ 0.005), and stereotyped HCDR3 (P ¼ 0.006). The more frequent stereotyped HCDR3 subsets were #1 (IGHV1-5-7/IGHD6-19/IGHJ4; 16 of 16 unmutated) and #7 (IGHV1-69 or IGHV3-30/IGHD3-3/IGHJ6; 13 of 13 unmutated), both being significantly more represented among patients developing ITP (P ¼ 0.003 and P ¼ 0.001, respectively). Moreover, restricting the analysis to unmutated patients, subset #7 confirmed its independent significant association with the occurrence of ITP (P ¼ 0.013). Both unmutated IGHV mutational status, del(11)(q23) and stereotyped BCR were significantly associated with shorter time to ITP development (P < 0.0001, P ¼ 0.02, and P ¼ 0.005, respectively) than other patients.Conclusion: Our data suggest that patients with CLL and peculiar BCR conformations are at higher risk of developing secondary ITP and that stereotyped BCR may be involved in the pathogenesis of this complication.

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Section: Discussionmentioning

confidence: 99%

Immune Thrombocytopenia in Patients with Chronic Lymphocytic Leukemia Is Associated with Stereotyped B-cell Receptors

Visco

Maura

Tuana

et al. 2012

Clinical Cancer Research

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“…Few cases of severe thrombocytopenia arising as a complication of alemtuzumab therapy for disorders other than MS have been published [20][21][22][23] despite its approval for the treatment of CLL a decade ago and its growing off-label use in a variety of settings such as hematopoietic and solid organ transplantation. Several reports even document the effective use of alemtuzumab for the treatment of ITP and other autoimmune cytopenias.…”

Section: Discussionmentioning

confidence: 99%

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

Cuker

Coles

Sullivan³

et al. 2011

Blood

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“…52 There have been 2 reports of fatal refractory ITP after treatment of chronic lymphocytic leukemia with alemtuzumab. 53,54 In 3 cases, ITP (one case fatal) occurred during a clinical trial of alemtuzumab for MS. 55 As with the published reports, we have found the autoimmune cytopenias developing after alemtuzumab and auto-HSCT to be generally severe and refractory to steroid therapy alone. All our patients required multiple agents to treat the cytopenias, and demonstrated a response to rituximab, which appears to be an effective agent in refractory cases.…”

Section: Discussionmentioning

confidence: 99%

Development of a secondary autoimmune disorder after hematopoietic stem cell transplantation for autoimmune diseases: role of conditioning regimen used

Loh¹,

Oyama²,

Statkute³

et al. 2006

Blood

134

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Patients undergoing autologous hematopoietic stem cell transplantation (auto-HSCT) for autoimmune disease may have an added propensity to develop a second autoimmune disorder, given the genetic predisposition to autoimmunity. Therefore, we undertook a retrospective analysis of all patients who have undergone auto-HSCT for an autoimmune disease in our institution to determine the occurrence of a second autoimmune disorder and possible risk factors. In all, 155 patients underwent auto-HSCT for various autoimmune diseases; of those patients, 6 manifested a distinct secondary autoimmune disease at a median of 8.5 months (range, 2-30 months) after auto-HSCT. There were 2 patients with systemic lupus erythematosus, conditioned with a regimen containing antithymocyte globulin (ATG), who developed factor VIII inhibitors with severe bleeding. There were 4 patients (2 with multiple sclerosis, one each with lupus and systemic sclerosis) who received an alemtuzumab-containing conditioning regimen who developed autoimmune cytopenias. Among the 155 patients, the frequency of secondary autoimmune complications was 16.0% with alemtuzumab (4/25), 1.9% for ATG (2/102), and 0% for conditioning regimens without lympho-depleting antibodies (0/28)-a difference that was found to be significantly higher with alemtuzumab exposure (P ‫؍‬ .011). In contrast, sex, type of ATG used, and CD34-selection of peripheral blood stem cells were not found to be significantly associated with development of a secondary autoimmune disorder. (Blood. 2007;109:2643-2648)

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Autoimmune Thrombocytopenia After Treatment With Campath 1h in a Patient With Chronic Lymphocytic Leukaemia

Cited by 28 publications

References 4 publications

Immune Thrombocytopenia in Patients with Chronic Lymphocytic Leukemia Is Associated with Stereotyped B-cell Receptors

Immune Thrombocytopenia in Patients with Chronic Lymphocytic Leukemia Is Associated with Stereotyped B-cell Receptors

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

Development of a secondary autoimmune disorder after hematopoietic stem cell transplantation for autoimmune diseases: role of conditioning regimen used

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