Thrombotic Thrombocytopenic Purpura Complicating Chronic Myelogenous Leukemia Treated with Interferon-α

Rachmani, Rita; Avigdor, Abraham; Youkla, Mona; Raanani, Pia; Zilber, Moshe; Ravid, Mordchai; Ben‐Bassat, Isaac

doi:10.1159/000040905

Cited by 28 publications

(10 citation statements)

References 9 publications

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“…Both immune phenomena could be attributed either to the hematological disease or to IFN therapy. Rachmani et al [25]described 2 patients with CML who developed TTP following treatment with IFN. In 1 patient, a lymphoblastic transformation was diagnosed concomitantly.…”

Section: Hematological Disordersmentioning

confidence: 99%

Immune-Mediated Complications during Interferon Therapy in Hematological Patients

2002

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Interferon (IFN), a leukocyte-derived cytokine, has been used to treat several hematological malignancies. The most common adverse effects of IFN are flu-like symptoms. Autoimmune side effects are infrequent but may be hazardous and irreversible. These may occur in several ways: autoantibodies may either appear during the treatment or existing titers may rise, subclinical autoimmune phenomena may become clinically manifest or autoimmune diseases may appear de novo. The main categories of IFN immune-mediated side effects are: thyroid, hematological, connective tissue, renal and miscellaneous disorders. The most common ones are thyroid disorders, which manifest either as hypo- or hyperthyroidism. Patients with pre-existing autoantibodies are more susceptible to the exacerbation of thyroid autoimmunity, probably since IFN enhances the levels of autoimmunity. Hematological disorders include autoimmune anemia and thrombocytopenia and thrombotic thrombocytopenic purpura. The immunological derangement of autoimmune hemolytic anemia manifests as enhanced destruction of antibody-coated red blood cells and induction of autoreactive B cells secreting these antibodies. Although autoimmune thrombocytopenia is rare, a sharp reduction in the platelet counts, beyond that expected from the antiproliferative effects of IFN, should raise this possibility. Thrombotic thrombocytopenic purpura has recently been included among the autoimmune disorders. Sporadic cases have been reported in association with IFN treatment. The clinical spectrum of IFN-induced connective tissue disorders ranges from typical systemic lupus erythematosus to seropositive or seronegative rheumatoid arthritis. Some authors also reported on the development of Behçet’s disease in chronic myeloid leukemia patients treated with IFN. The underlying reason for the skin hyperreactivity in Behçet’s disease and the effect of IFN treatment in these patients may be altered neutrophil activity in both disorders. Several series evaluated the incidence of Raynaud’s phenomenon in patients treated with IFN for hematological disorders. Some of them reported on a rather high incidence of nailfold capillary microscopy abnormalities with or without Raynaud’s phenomenon. Whether IFN-induced Raynaud’s phenomenon is immune-mediated or directly caused vasospasm, is still unknown although the occurrence of several autoantibodies suggests an immune mechanism. Adverse effects of IFN therapy on the kidney include proteinuria and rarely nephrotic syndrome or acute and chronic renal failure. The mechanism of renal injury is unclear although an immune mechanism is suggested. Sporadic cases of other immune-mediated side effects have been published. These include dermatological adverse effects manifesting as psoriasis, pemphigus and vitiligo, and also rare cases of sarcoidosis, hepatitis, colitis or cryoglobulinemia. In conclusion, patients treated with IFN should be monitored for symptoms of autoimmunity. Patients with previous autoimmune phenomena should be treated, if possible, with alterna...

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Section: Hematological Disordersmentioning

confidence: 99%

Immune-Mediated Complications during Interferon Therapy in Hematological Patients

2002

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“…However, IFN may have a variety of toxic effects, and sporadic cases of TTP occurring during treatment with IFN for CML have been reported for a total of 30 cases (table 1)[6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21]. The 31 cases summarized by us showed poor prognosis: 7 of the total cases or 2 of the 12 cases which had undergone PE could reach normal creatinine levels.…”

Section: Discussionmentioning

confidence: 99%

“…Thrombotic thrombocytopenic purpura (TTP) is recognized as a rare side effect using IFN [3, 4], which occurs as the result of vascular or immunological events [5, 6]. Although TTP cases, treated with IFN for CML, have been reported sporadically during the past 10 years [6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21], the precise relationship between CML, IFN therapy and TTP remains to be clarified. …”

Section: Introductionmentioning

confidence: 99%

Von Willebrand Factor-Cleaving Protease Activity Remains at the Intermediate Level in Thrombotic Thrombocytopenic Purpura

Sugimoto

Saigo

Shin³

et al. 2005

Acta Haematol

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A 59-year-old woman, diagnosed with chronic myelogenous leukemia (chronic phase) and treated with interferon-α for 13 years, developed renal failure. Renal biopsy showed thrombotic thrombocytopenic purpura, but intensive therapy including plasma exchange and steroid administration was not effective. The activity of von Willebrand factor-cleaving protease was detectable at the intermediate level (15–46%) during the clinical course, suggesting that this case was not compatible with the previously reported pattern of idiopathic or drug-induced thrombotic thrombocytopenic purpura, but with the pattern associated with malignant disease or immunological disorders. Further studies to determine the effects of interferon-α on endothelial cells in chronic myelogenous leukemia patients are needed.

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“…Recently, 7 cases of TTP have been encountered in patients with CML treated with IFN-α. In 4 of these, the patients received IFN-α and HU [8, 9, 10]; in 2 other cases, TTP occurred during the blastic phase of the disease [11, 12]. Shammas et al [14]described a case of TTP in a patient with CML treated by HU.…”

Section: Discussionmentioning

confidence: 99%

“…Autoimmune disorders have also been reported, such as hemolytic anemia, thrombocytopenic purpura, hepatitis, thyroiditis and systemic lupus erythematosus [6, 7]. Thrombotic thrombocytopenic purpura (TTP) is infrequent with IFN-α, and only a few cases have been reported [8, 9, 10, 11, 12]. In our case, we suspect a clear relationship between TTP and IFN-α, and we discuss the role of IFN-α in the pathogenesis of this disease.…”

Section: Introductionmentioning

confidence: 99%

Thrombotic Thrombocytopenic Purpura during Interferon Alpha Treatment for Chronic Myelogenous Leukemia

Lacotte¹,

Thierry²,

Delwail³

et al. 1999

Acta Haematol

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Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome have recently been observed in patients undergoing interferon alpha (IFN-α) therapy. However, the relationship between disease and therapy has not been established, essentially because of concomitant treatment or previous bone marrow transplantation. We present a case of TTP developing during IFN-α therapy for chronic myelogenous leukemia. In this case, IFN-α seems to be the only etiological agent.

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Thrombotic Thrombocytopenic Purpura Complicating Chronic Myelogenous Leukemia Treated with Interferon-α

Cited by 28 publications

References 9 publications

Immune-Mediated Complications during Interferon Therapy in Hematological Patients

Immune-Mediated Complications during Interferon Therapy in Hematological Patients

Von Willebrand Factor-Cleaving Protease Activity Remains at the Intermediate Level in Thrombotic Thrombocytopenic Purpura

Thrombotic Thrombocytopenic Purpura during Interferon Alpha Treatment for Chronic Myelogenous Leukemia

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