Lethal vascular leak syndrome after denileukin diftitox administration to a patient with cutaneous gamma/delta T‐cell lymphoma and occult cirrhosis

Abstract

Denileukin diftitox (Ontak) is an immunotoxin used in the treatment of cutaneous T-cell lymphomas. Vascular leak syndrome is a known complication of this therapy, although the syndrome is most often self-limited. We report the case of a patient with cutaneous gamma/delta (cd) T-cell lymphoma and previous undiagnosed liver disease treated with denileukin diftitox. Just 4 days after initiating drug therapy, the patient developed profound vascular leak syndrome characterized by a rapid fall in his previously normal serum albumin to levels below the limit of detection. The patient then quickly deteriorated into rhabdomyolysis and eventual death. To our knowledge, this is the first report of a death directly related to denileukin diftitox therapy. The purpose of this case is to increase awareness and improve management of patients who are treated with denileukin diftitox with resulting vascular leak syndrome leading to hypoalbuminemia. Am. J. Hematol. 83:593-600, 2008. V

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

“…Of note, Dd should not be administered in a facility ill equipped to provide cardiopulmonary resuscitation. Severe and persistent transaminitis, thyrotoxicosis, loss of visual acuity or color vision, and rhabdomyolysis have been reported but are uncommon [240,[246][247][248]. Investigations combining Dd with conventional chemotherapeutic agents are ongoing.…”

Management of the Cutaneous Peripheral T-Cell Lymphomas

“…34 Local radiation therapy followed by denileukin diftitox was also successful in inducing remission in a single case report. 35 However, 1 case of fatal vascular leak syndrome in a patient with CGD-TCL was attributed to treatment with denileukin diftitox, 36 although it is not clear whether the underlying diagnosis predisposed to it. Unique sites of extracutaneous involvement have also been reported, including testicular, ocular adnexal, and central nervous system involvement.…”

“…60,61 Finally, as mentioned above, denileukin diftitox has been used in the treatment of PCGN-CTL as well. 35,36 Other novel therapies are being developed for PTCL, MF, and SS but have not yet been evaluated in these subtypes. For instance, in the studies evaluating pralatrexate, PCGD-TCL, cutaneous CD8 + TCL, and PCSM-TCL were not excluded, but none was enrolled.…”

Update on treatment of cutaneous T-cell lymphoma

“…More rarely visual changes and hypersensitivity skin rashes may occur [31 ,32 ]. A report [33 ] of lethal VLS has been reported in a patient with cutaneous gamma/delta T-cell lymphoma with occult liver disease. Transient thyroidosis followed by hypothyroidism has been observed, thus monitoring of thyroid function tests is advised [31 ,34].…”