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Immunological reactions induced by bendamustine


Bendamustine is being recently used as treatment of chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma. There are just a few reported cases of adverse reactions to bendamustine so far, none of them with an allergological study.


Patient 1

A 61-year old woman, diagnosed with B-cell CLL (B-CLL) received bendamustine, tolerating the first cycle. Three weeks later, 8 hours after the 1st dose of the 2nd cycle, she suffered throat discomfort, pruritus, hives, general erythema and facial swelling; which disappeared within 24 hours after treatment.

Patient 2

A 61-year old man, diagnosed with B-CLL. Four years ago, he adequately tolerated bendamustine. One week after the first and well tolerated cycle, he received the second, and within 8-10 hours after the dose he developed a maculopapular exanthema, edema in arms and legs, along with desquamation of hands and feet, without residual lesions. Symptoms disappeared within the first two weeks.

Patient 3

A 63-year old man, diagnosed with B-CLL. Three hours after the infusion of the first and second cycles of bendamustine, he had a generalized tremor and fever of 39℃. The symptoms ceased with acetaminophen 650mg. One month later, 3 hours after the 3rd cycle of bendamustine, he had generalized tremor and erythema, dizziness and body temperature of 39℃. Hypotension, paroxysmal atrial fibrillation and a mild renal failure were verified. The symptoms disappeared with acetaminophen 1gr and an adequate hydration.


We performed skin-prick-test (SPT) at 1 mg/ml and intradermal testing (IDT) at 0.001, 0.01, 0.1 and 1mg/ml, with immediate and delayed lectures (24h and 72h). As negative controls two B-CLL patients underwent SPT and IDT with negative results.

Patient 1

SPT was negative. IDT at 0.1 and 1mg/ml were positive at 24h, being negative 72h later. The rest of the tests were negative.

Patient 2

He had a negative SPT. The 24h lectures of the IDT were positive at 0.01, 0.1 and 1mg/ml, remaining positive 72h later. The rest of the tests were negative.

Patient 3

The SPT and IDT, both immediate and delayed lectures, were negative.


We report the first two cases of hypersensitivity to bendamustine with a positive result in the allergological study carried out, which demonstrated a delayed cutaneous hypersensitivity to bendamustine. We also report the first case of drug fever induced by bendamustine in clinical use, showing neither a type I nor a IV hypersensitivity mechanism to bendamustine.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Sanchez-Gonzalez, MJ., Barbarroja-Escudero, J., Antolin-Amerigo, D. et al. Immunological reactions induced by bendamustine. Clin Transl Allergy 4 (Suppl 3), P56 (2014).

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