Progressive Increase Of Thymoglobulin Severe Infusion Reactions Used In The Conditioning Regimen Of Allogeneic Stem Cell Transplantation. Comparative Study Between 2004 and 2012

Thymoglobulin (ATG) infusion-related reactions in stem cell transplant (SCT) recipients are frequent. Minor reactions as fever and chills are the most usually observed. Severe and potentially life-threatening reactions are rare (>1/10.000 and <1/1000) and are associated with hypotension, oligoanuria, respiratory and heart impairment,

To analyze the adverse events observed during ATG infusion in patients undergoing SCT and treated with ATG for GVHD prophylaxis. The emergence of fever, chills, rash, pruritus, gastrointestinal symptoms, cephalea, peripheral edema, hypotension, oligoanuria, pulmonary edema, dyspnea, chest pain, arrhythmia and death during ATG infusion were collected. Premedication with corticosteroids, acetaminophen and antihistaminics, and the needs of additional treatment, oxygen support, diuretics and treatment discontinuations or switch were also analyzed.

Sixty-five patients received ATG since 2004 to June 2012. Patients were grouped into three periods: first (2004-2006, 13 patients), second (2007-2009, 25 patients) and third (2010-2012, 27 patients). In all periods total median dose of ATG was 7.5 mg/kg. Fourty-nine patients (75%) developed infusion-associated reaction, being higher into the third period (46%, 72%, 93%, p< 0.01). The incidence of minor reactions as fever (90%), chills (57%), and skin reaction (35%) was similar in the three periods. Moderate reactions as peripheral edema (0%, 11%, 61%, p <0.001) and gastrointestinal symptoms (0%, 13%, 52%, p <0.002) were higher into the third period. Fifteen patients (31%) developed serious reactions and the majority accounted into the last period (29%, 11%, 48%, p=0.04). Dyspnea (25%) and pulmonary edema accounted for 9% of patients and both were higher into the third period (14%, 6%, 44%, p= 0.02) and (0%, 0%,26%, p=0.02). Although we did not reach statistical differences (p = 0.09) there were more cases of hypothension (0%, 6%, 26%) and oligoanuria (0%, 0%, 17%) in the last period. One patient developed chest pain associated with arrhythmia in the third period. None patient died during or shortly after ATG infusion. The needs of additional treatment, specially steroids (29%, 33%, 64%, p=0.09), oxygen (0%, 0%, 57%, p = 0.002) and diuretics (0%,0%,83%, p =0.001) were mostly used in the last period.

Since 2010, the incidence of moderate and severe ATG infusion-associated reactions in patients undergoing SCT is significantly more frequent than previously and in our opinion these facts may be confirmed in other studies.

No relevant conflicts of interest to declare.