Interferon-α

Reactions 760 - 17 Jul 1999 S Interferon-α Thrombotic microangiopathy and renal failure: 3 case reports Two patients developed thrombotic microangiopathy and 1 developed renal failure after long-term treatment with interferon-α for chronic myelogenous leukaemia. The first patient, a 49-year-old man, received interferon-α 10 MU/day and hydroxycarbamide [hydroxyurea]. Five years after the original diagnosis, cytarabine was added to his treatment regimen when he developed thrombocytosis. 67 months after he started interferon-α therapy, he developed severe refractory anaemia and began corticosteroid treatment for presumed interferon-induced immune haemolysis. The following serum values were recorded: platelet count 32 × 10 9 /L; total bilirubin 2.1 with indirect bilirubin 2 mg/dl; lactate dehydrogenase 6957 IU/L; BUN 35 mg/dl and creatinine 1.6 mg/dl. A peripheral blood smear showed moderate schistocytosis. Haemolytic uraemic syndrome was diagnosed and the patient started daily plasmapheresis. He then developed nonoliguric renal failure and started daily haemodialysis. However, the following month, his leukaemia worsened and he developed multiorgan failure and died of the complications. The second patient, a 24-year-old woman, received interferon-α 9 MU/day and cytarabine. 36 months later, she developed exertional dyspnoea and cardiomegaly. She was treated for cardiomyopathy with corticosteroids, digoxin and furosemide. Interferon-α therapy was stopped, but 1 month later, she developed severe hypertension. The woman’s platelet count was 20 × 10 9 /L, her haemoglobin level was 11.9 g/dl, her WBC count was 10 × 10 9 /L, her BUN level was 48 mg/dl, her creatinine level was 1.8 mg/dl and her lactate dehydrogenase level was 4300 IU/L. A peripheral blood smear was positive for schistocytes. Urinalysis showed 50–100 red blood cells with no casts. Renal failure secondary to haemolytic uraemic syndrome with malignant hypertension was diagnosed. The patient received daily plasmapheresis, but when her renal function worsened, she required haemodialysis. Her platelet count, lactic dehydrogenase and bilirubin levels eventually normalised. However, at 3 months’ follow-up, she was still dependent on haemodialysis. The third patient, a 36-year-old man, initially received interferon-α 2 MU/m 2 /day, increasing to 5 MU/m 2 /day. Interferon-γ was given concomitantly for the first 3 years of treatment and was restarted after a further 3 years. After about 8 years’ treatment with interferon-α, he presented with fatigue and hypertension and was found to have renal failure, marked anaemia and congestive heart failure. Laboratory tests showed the following: WBC count 10.9 × 10 9 /L; platelet count 282 × 10 9 /L; red blood cell poikilocytosis and anisocytosis, lactate dehydrogenase 259 U/L; serum haptoglobin level 144 mg/dl and urinalysis positive for protein and occasional casts. Interferon therapy was stopped and the patient began haemodialysis and antihypertensive therapy. His renal function stabilised after approximately 18 months of peritoneal dialysis. At follow-up, 4 years after he first developed renal failure, he did not require haemodialysis. Author comment: ‘This rare but definite complication of rIFN [interferon]-α therapy should be recognized early when clinical and laboratory findings are suggestive, so that rIFN-α therapy can be discontinued immediately and appropriate therapeutic measures can be initiated.’ Ravandi-Kashani F, et al. Thrombotic microangiopathy associated with interferon therapy for patients with chronic myelogenous leukemia: coincidence of true side effect? Cancer 85: 2583-2588, 15 Jun 1999 - USA 800778718 1 Reactions 17 Jul 1999 No. 760 0114-9954/10/0760-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved

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Transcript of Interferon-α

Reactions 760 - 17 Jul 1999

SInterferon-αThrombotic microangiopathy and renal failure:3 case reports

Two patients developed thrombotic microangiopathy and 1developed renal failure after long-term treatment withinterferon-α for chronic myelogenous leukaemia.

The first patient, a 49-year-old man, received interferon-α10 MU/day and hydroxycarbamide [hydroxyurea]. Five yearsafter the original diagnosis, cytarabine was added to histreatment regimen when he developed thrombocytosis. 67months after he started interferon-α therapy, he developedsevere refractory anaemia and began corticosteroid treatmentfor presumed interferon-induced immune haemolysis.

The following serum values were recorded: platelet count32 × 109/L; total bilirubin 2.1 with indirect bilirubin 2 mg/dl;lactate dehydrogenase 6957 IU/L; BUN 35 mg/dl andcreatinine 1.6 mg/dl.

A peripheral blood smear showed moderate schistocytosis.Haemolytic uraemic syndrome was diagnosed and the patientstarted daily plasmapheresis. He then developed nonoliguricrenal failure and started daily haemodialysis. However, thefollowing month, his leukaemia worsened and he developedmultiorgan failure and died of the complications.

The second patient, a 24-year-old woman, receivedinterferon-α 9 MU/day and cytarabine. 36 months later, shedeveloped exertional dyspnoea and cardiomegaly. She wastreated for cardiomyopathy with corticosteroids, digoxin andfurosemide. Interferon-α therapy was stopped, but 1 monthlater, she developed severe hypertension.

The woman’s platelet count was 20 × 109/L, herhaemoglobin level was 11.9 g/dl, her WBC count was 10 ×109/L, her BUN level was 48 mg/dl, her creatinine level was 1.8mg/dl and her lactate dehydrogenase level was 4300 IU/L. Aperipheral blood smear was positive for schistocytes.Urinalysis showed 50–100 red blood cells with no casts.

Renal failure secondary to haemolytic uraemic syndromewith malignant hypertension was diagnosed. The patientreceived daily plasmapheresis, but when her renal functionworsened, she required haemodialysis. Her platelet count,lactic dehydrogenase and bilirubin levels eventuallynormalised. However, at 3 months’ follow-up, she was stilldependent on haemodialysis.

The third patient, a 36-year-old man, initially receivedinterferon-α 2 MU/m2/day, increasing to 5 MU/m2/day.Interferon-γ was given concomitantly for the first 3 years oftreatment and was restarted after a further 3 years. After about8 years’ treatment with interferon-α, he presented with fatigueand hypertension and was found to have renal failure, markedanaemia and congestive heart failure.

Laboratory tests showed the following: WBC count 10.9 ×109/L; platelet count 282 × 109/L; red blood cell poikilocytosisand anisocytosis, lactate dehydrogenase 259 U/L; serumhaptoglobin level 144 mg/dl and urinalysis positive for proteinand occasional casts.

Interferon therapy was stopped and the patient beganhaemodialysis and antihypertensive therapy. His renalfunction stabilised after approximately 18 months ofperitoneal dialysis. At follow-up, 4 years after he firstdeveloped renal failure, he did not require haemodialysis.

Author comment: ‘This rare but definite complication ofrIFN [interferon]-α therapy should be recognized early whenclinical and laboratory findings are suggestive, so that rIFN-αtherapy can be discontinued immediately and appropriatetherapeutic measures can be initiated.’Ravandi-Kashani F, et al. Thrombotic microangiopathy associated with interferontherapy for patients with chronic myelogenous leukemia: coincidence of true sideeffect? Cancer 85: 2583-2588, 15 Jun 1999 - USA 800778718