Safety of hematopoietic cell infusion in children with malignant and non‐malignant diseases

Abstract

HPC infusions have been associated with a variety of adverse events related to either patient or HPC product-related factors. Studies documenting infusion-related AEs in children are limited. We reviewed HPC infusion records in 354 children. Infusion-related adverse events were classified as follows: grade 0-absent, grade I-mild, grade II-moderate, grade III-severe, grade IV-life-threatening, and grade V-death. The percentage of patients with grade 0, I, and II-IV AEs was as follows: 0 = 67%, I = 23.4%, and II-V = 9.6% (one patient had fatal anaphylactic reaction to dimethyl sulfoxide). The incidence of grade II-IV hypertension was 7.1%. There was a higher incidence of AEs with infusion of allogeneic bone marrow versus allogeneic PBSCs (47.4% vs 25.3%, P = .001). Cryopreserved products had a lower incidence of infusion-associated AEs compared with fresh HPC products (24% vs 39.4%, P = .003). Allogeneic HPC infusion volume (>100 mL) was a significant risk factor for infusion-associated AEs (P < .001). Patients >10 years who received autologous HPC infusions had higher risk of AEs when compared to patients <10 years (P = .01). Our study demonstrated that despite a high incidence of infusion-associated hypertension, HPC infusion is relatively safe in children. Investigating strategies to optimize management of hypertension in the setting of HPC infusion is warranted.

Hematopoietic cell infusion‐related adverse events in pediatric/small recipients in a prospective/multicenter study

“…Although HCI-AEs were most frequently noted in BMT in a recent retrospective study of pediatric recipients, a vast majority of the HCI-AEs in their study was hypertension in BMT. 15 Consistent with this, the present study found hypertension was the most frequent HCI-AE, especially in BMT, in pediatric recipients and small adult recipients. However, our study also detected several HCI-AEs other than hypertension, which might have led to a comparable overall HCI-AE incidence in BMT compared with other sources.…”

“…Moreover, it has also been reported that gastrointestinal symptoms, including nausea and vomiting, were often observed in pediatric recipients who were infused with HSC products. 15,16 Although it might be conceivable that the fast infusion contributed to such symptoms, the rate of infusion in pediatric recipients with nausea and vomiting was very similar to those without the symptoms (not shown). Also, antiemetics were prophylactically used in some pediatric recipients, but the administration of antiemetics did not reduce the incidence of gastrointestinal symptoms in our limited data.…”

“…Recently, other retrospective studies have also reported high frequencies of hypertension and cardiopulmonary AEs due to HSC infusions. 14,15 Heneghan et al 15 also demonstrated a lower incidence of HCI-AEs due to cryopreserved products rather than those due to fresh products. These findings suggest that product volume and some DMSO-independent factors, such as plasma components, contribute to HCI-AEs.…”

“…It is unclear if product volume and component effects are more substantial in recipients with a small body, and if recipients' age-related factors alter susceptibility to HCI-AEs in pediatric recipients. However, there have been few retrospective studies from single centers for HCI-AEs in pediatric recipients, 15,16 and data on HCI-AEs in small and pediatric recipients are lacking.…”

“…Kazuhiko Ikeda , 1,2 Hitoshi Ohto, 1,2 Minami Yamada-Fujiwara, 1,3 Yoshiki Okuyama, 1,4 Shin-ichiro Fujiwara , 1,5 Kazuo Muroi, 1,6 Takehiko Mori, 7 Kinuyo Kasama, 8 Heiwa Kanamori, 1,9 Tohru Iseki, 1,10 Tokiko Nagamura-Inoue, 1,11 Kazuaki Kameda, 12 Junya Kanda, 13 Kazuhiro Nagai, 14 Nobuharu Fujii, 15 Takashi Ashida, 16 Asao Hirose, 17 Tsutomu Takahashi, 18 Keiji Minakawa, 2 and Ryuji Tanosaki 1 BACKGROUND: Hematopoietic cell infusion-related adverse events (HCI-AEs) in hematopoietic stem cell transplantations (HSCTs) have been largely attributed to toxicity of dimethyl sulfoxide (DMSO) for cryopreservation, but HSC products also contain various cells and plasma components. Our recent prospective study of 1125 HSCT recipients revealed the highest overall HCI-AE rate in bone marrow transplantation (BMT) using fresh/noncryopreserved products, although products of peripheral blood stem cell transplantation and cord blood transplantation (CBT) are generally cryopreserved with DMSO containing smaller plasma volumes.…”