Tagraxofusp and anti-CD123 in blastic plasmacytoid dendritic cell neoplasm: a new hope.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy, characterized by poor prognosis if treated with conventional therapy. Allogenic hematologic stem cell transplant can improve survival and can be curative, but it is available in a small percentage of patients given that the median age at diagnosis is 70 years. In this scenario it is assumed that only the development of precision medicine-driven therapy will change BPDCN patient prognosis. CD123 (the α-subunit of interleukin (IL)-3 receptor) is over-expressed on BPDCN cells surface and seems to be the ideal marker to develop antibody-based therapies. Tagraxofusp (Elzonris®), a recombinant immunotoxin consisting of human interleukin-3 fused to a truncated diphtheria toxin, has been approved by FDA in December 2018 for the treatment of BPDCN in adult and pediatric patients. tagraxofusp has shown promising clinical activity, with a high overall response rate and quite manageable safety profile even in elderly patients. It seems to improve overall survival too, but comparative trials are necessary to confirm this. Adverse events are commonly reported and the most important are transaminitis, thrombocytopenia and capillary leak syndrome (CLS). Therefore, to prevent the onset of severe CLS is recommended to reserve tagraxofusp for patients with preserved hepatic and cardiac functions, and to strictly observe serum albumin level. Further studies are required to resolve many several unanswered questions about tagraxofusp. In this review, we will resume and discuss pharmacological characteristic of tagraxofusp, results of clinical trials leading to its approval by FDA in 2018 and future perspectives about its use in BPDCN and other hematological malignancies.

Systemic capillary leak syndrome in a patient receiving adjuvant oxaliplatin for locally advanced colon cancer.

Colorectal cancer is the third most common cancer diagnosed in the USA each year. Oxaliplatin, a platinum-based chemotherapy agent, is part of the standard adjuvant chemotherapy regimen FOLFOX (oxaliplatin with 5-fluorouracil [5-FU] and leucovorin [LV]) for the treatment of stage III and some high-risk stage II colorectal cancers. Although oxaliplatin is generally well tolerated, certain side effects such as nausea, vomiting, and peripheral neuropathy are common. We report a case of oxaliplatin-induced capillary-leak syndrome in a 63-year-old man undergoing his 12th and final cycle of FOLFOX for stage III colorectal cancer. To our knowledge, this is the first case of systemic capillary leak syndrome (SCLS) reported in association with oxaliplatin. Currently, there is no prevention for SCLS. Documenting future cases of SCLS attributed to oxaliplatin is vital, as SCLS is associated with significant morbidity and mortality and no standard treatments beyond supportive care measures exist. Early recognition and diagnosis are therefore essential to improving patient outcomes.

Intraperitoneal photodynamic therapy causes a capillary-leak syndrome.

BACKGROUND: In patients undergoing intraperitoneal (IP) photodynamic therapy (PDT), the combination of aggressive surgical debulking and light therapy causes an apparent systemic capillary-leak syndrome that necessitates significant intensive care unit (ICU) management after surgery. METHODS: From May 1997 to May 2001, 65 patients underwent surgical debulking and PDT as part of an ongoing phase II trial for disseminated IP cancer. Perioperative data were reviewed retrospectively, and statistical analyses were performed to determine whether any identifiable factors were associated with the need for mechanical ventilation for longer than 1 day and with the occurrence of postoperative complications. RESULTS: Forty-three women and 22 men (mean age, 49 years) were treated. Operative time averaged 9.8 hours, and mean estimated blood loss was 1450 mL. The mean crystalloid requirement for the first 48 hours after surgery was 29.3 L, and 49 patients required blood products. Twenty-four patients were intubated for longer than 24 hours, with a mean of 8.3 days for those intubated longer than 1 day. The median ICU stay was 4 days. Overall, 110 complications developed in 45 (69%) of the 65 patients. Significant complications included 6 patients with acute respiratory distress syndrome, 28 patients with infectious complications, and 4 patients with anastomotic complications. Statistical analyses revealed that surgery-related factors were significantly associated with these complication outcomes. CONCLUSIONS: Patients who undergo surgical debulking and IP PDT develop a significant capillary-leak syndrome after surgery that necessitates massive volume resuscitation, careful ICU monitoring, and, frequently, prolonged ventilatory support.