Survival Impact of Early Post-Transplant Toxicities in Pediatric and Adolescent Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Malignant and Nonmalignant Diseases: Recognizing Risks and Optimizing Outcomes

Abstract

In pediatric and adolescent patients undergoing allogeneic hematopoietic cell transplantation, treatment-related toxicities remain a clinical challenge. A paucity of data investigates the risks for and survival impact of treatment-related toxicities in this population. Here the authors assess the relative toxicity of myeloablative, reduced-toxicity, and reduced-intensity conditioning regimens; identify patient-related predictors of post-transplant toxicities; and investigate the impact of early post-transplant toxicities on transplant-related mortality (TRM). In this retrospective study, 164 patients (aged 1 to 22 years) underwent allogeneic stem cell transplantation after busulfan-based conditioning for malignant and nonmalignant diseases between 2000 and 2014. The number of grades III to IV toxicities between days 0 and +30 was calculated for each patient. TRM was calculated to 2 years. Median patient age was 9 years, and median number of toxicities was 3 (range, 0 to 17). The 100-person day incidence of post-transplant toxicities in myeloablative conditioning was not different from the incidence in reduced-toxicity conditioning (13.88 versus 13.59, P = .812). Reduced intensity was less toxic than both myeloablative and reduced toxicity (13.75 versus 8.41, P <.001). Age ≥ 12 years (.276 with SE = .138, P =.045) and unrelated donor transplant (.318 with SE = 0.113, P = .005) were risk factors for ≥3 toxicities. Having ≥3 toxicities or a performance score < 90 conferred higher risk of TRM (P = .021). In pediatric and adolescent patients undergoing hematopoietic cell transplantation, reduced-toxicity conditioning was not significantly less toxic than myeloablative conditioning. Additionally, the number of post-transplant toxicities correlated with the risk of mortality. Further investigations to confirm our findings are warranted.

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

“…In HSCT, the phase of hematopoietic cell infusion (HCI) is a time when acute regimen-related toxicities often occur. 2,3 In addition, HCI itself can lead to adverse events (AEs), such as flushing, nausea and vomiting, malodor, hypotension, hypertension, allergic reactions, arrhythmia, encephalopathy, and respiratory distress. [4][5][6][7][8][9][10] AEs associated with blood transfusion, which is usually component-based therapy, have been widely and routinely surveyed.…”

“…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.…”

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

“…Conditioning regimens were disease‐specific and protocol‐driven in accordance with institutional and cooperative group studies. Details of conditioning regimens used for both autoHCT and alloHCT have been previously published by our group . In brief, myeloablative conditioning regimen consisted of either TBI [12 Gray] + 1‐2 high‐dose alkylators or busulfan (12.8‐16 mg/kg) + 1 high‐dose alkylators .…”

“…RIC regimens contained busulfan (6.4‐8 mg/kg) or melphalan (140 mg/m 2 ) + fludarabine. Serotherapy consisted of alemtuzumab (54 mg/m 2 ) or ATG (8 mg/kg) …”

Risk Factors for Transplant Outcomes in Children and Adolescents with Non-Malignant Diseases Following Allogeneic Hematopoietic Stem Cell Transplantation

“…The results an analysis by Burroughs et al of patients with non-malignant diseases indicate that RTC conditioning is effective and improves survival due to its lower toxicity [25]. However, Al Mulla et al showed that reduced-toxicity conditioning was not significantly less toxic than myeloablative in pediatric and adolescent patients undergoing allogeneic HCT [26]. In our study, pediatric TRM score had no effect on TRM and OS, probably because the type of non-malignant disease was not included in the TRM stratification, and according to our analysis, the underlying disease affected survival after HCT.…”