Basiliximab as Treatment for Steroid-Refractory Acute Graft-versus-Host Disease in Pediatric Patients after Haploidentical Hematopoietic Stem Cell Transplantation

Abstract

Basiliximab has been used successfully as a second-line treatment for steroid-refractory (SR) acute graft-versushost disease (aGVHD) in adult patients after haploidentical hematopoietic stem cell transplant (haplo-HSCT) but has not been studied separately in the pediatric setting. We retrospectively reviewed 100 pediatric patients after haplo-HSCT receiving basiliximab for grades II (57%), III (27%), and IV (16%) SR aGVHD between January 2015 and December 2017. The median number of basiliximab doses was 4 (range, 2 to 9). The day 28 overall response rate was 85%, with complete response in 74% of patients, partial response in 11% of patients, and no response in 15% of patients. The day 28 overall response rates were 94.6% in skin SR aGVHD, 81.6% in gut SR aGVHD, and 66.7% in liver SR aGVHD. Infectious complications included bacterial infection (11%), presumed or documented fungal infections (7%), cytomegalovirus viremia (53%), Epstein-Barr virus viremia (11%), human herpesvirus-6 viremia (7%), and herpes simplex virus viremia (1%). The 3-year overall survival, disease-free survival, nonrelapse mortality, and relapse rates between responders and nonresponders were 81.3% versus 46.7% (P < .001), 79.0% versus 46.7% (P = .001), 6.1% versus 33.3% (P < .001), and 14.9% versus 20.0% (P = .46), respectively. We conclude that basiliximab is an effective second-line agent for pediatric patients with SR aGVHD after haplo-HSCT, particularly for skin SR aGVHD.

The incidence, risk factors, and outcomes of acute graft‐vs‐host disease in pediatric T‐cell‐replete haploidentical hematopoietic stem cell transplantation

“…Myeloid and platelet engraftment were defined according to previous reports 5,13 . Hematopoietic chimerism was evaluated by PCR amplification of STRs for all patients using peripheral blood samples and buccal mucosa and by FISH for sex‐mismatched pairs using BM samples.…”

“…7,12 The standard initial therapy for aGVHD is corticosteroids; only approximately 50% of patients demonstrate responses. 13,14 The standard second-line agent for the treatment of SR-aGVHD is not clear, and no consensus has been reached, including in pediatric patients. 15,16 aGVHD in pediatric TCR haplo-HSCT without PT-Cy has been reported in previous studies.…”

“…In recent years, several studies analyzed various risk factors for aGVHD, and the most consistently reported risk factors significantly associated with an increased risk of grades II‐IV aGVHD were recipient HLA mismatching with the donor, alloimmunization of the donor, the use of a female donor for male recipients, and older patient age 7,12 . The standard initial therapy for aGVHD is corticosteroids; only approximately 50% of patients demonstrate responses 13,14 . The standard second‐line agent for the treatment of SR‐aGVHD is not clear, and no consensus has been reached, including in pediatric patients 15,16 …”

Treatment and unmet needs in steroid-refractory acute graft-versus-host disease

“…Infections occurred in 65% of patients in this study; 48% of patients were alive after a mean follow-up of 2 years. Several subsequent studies also showed high ORRs (82-92%), including in pediatric patients; however,~50-70% of patients experienced GVHD recurrence, and rates of infectious complications were high [21,[57][58][59]. Kaplan-Meier-estimated probabilities were 48% for 3-year event-free survival and 20% for 5-year OS [21,57].…”

Invasive Fungal Diseases in Children with Hematological Malignancies Treated with Therapies That Target Cell Surface Antigens: Monoclonal Antibodies, Immune Checkpoint Inhibitors and CAR T-Cell Therapies

“…Approved biosimilars of rituximab (Reditux ® , Rixathon ® , Ruxience ® and others) seem to have similar infection rates with rituximab, even though data for IFDs are currently lacking [50]. 90 Y-ibritumomab tiuxetan, as stated above, is associated with more severe leukopenia, possibly due to radiation effects on cells surrounding CD20+ targets. Nevertheless, the spectrum of infections is similar to that of rituximab [41].…”