A comparison of immune reconstitution and graft‐versus‐host disease following myeloablative conditioning versus reduced toxicity conditioning and umbilical cord blood transplantation in paediatric recipients

Abstract

Summary Immune reconstitution appears to be delayed following myeloablative conditioning (MAC) and umbilical cord blood transplantation (UCBT) in paediatric recipients. Although reduced toxicity conditioning (RTC) vs. MAC prior to allogeneic stem cell transplantation is associated with decreased transplant-related mortality, the effects of RTC vs. MAC prior to UCBT on immune reconstitution and risk of graft-versus-host disease (GVHD) are unknown. In 88 consecutive paediatric recipients of UCBT, we assessed immune cell recovery and immunoglobulin reconstitution at days +100, 180 and 365 and analysed risk factors associated with acute and chronic GVHD. Immune cell subset recovery, immunoglobulin reconstitution, and the incidence of opportunistic infections did not differ significantly between MAC vs. RTC groups. In a Cox model, MAC vs. RTC recipients had significantly higher risk of grade II-IV acute GVHD (Hazard Ratio [HR] 6.1, p=0.002) as did recipients of 4/6 vs. 5-6/6 HLA-matched UCBT (HR 3.1, p=0.03), who also had significantly increased risk of chronic GVHD (HR 18.5, p=0.04). In multivariate analyses, MAC vs. RTC was furthermore associated with significantly increased transplant-related (Odds Ratio 26.8, p=0.008) and overall mortality (HR=4.1, p=0.0001). The use of adoptive cellular immunotherapy to accelerate immune reconstitution and prevent and treat opportunistic infections and malignant relapse following UCBT warrants further investigation.

Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease

“…15,17 All patients and parents signed informed consent and assent (patients >7 years). This research study was approved by Columbia University Medical Center Institutional Review Board and is registered on www.clinicaltrials.gov as NCT00408447.…”

“…17 Seventeen patients received a BFA conditioning regimen consisting of BU (3.2-4 mg/kg/day i.v. divided b.i.d., days − 8 to − 5), fludarabine (30 mg/m 2 /day, days − 8 to − 3) and alemtuzumab (2 mg/m 2 day − 6, 6 mg/m 2 days − 5, − 4 and 20 mg/m 2 days − 3, − 2; 54 mg/m 2 total dose, days − 6 to − 2) as we have previously described.…”

“…15 BU pharmacokinetic studies were performed for all patients with a target steady state concentration (C ss ) of 600-900 ng/mL. 17,18 For patient 13, melphalan (70 mg/m 2 /day, days − 8 and − 7) was substituted for BU due to the development of respiratory distress with the first dose of BU.…”

Pediatric allo-SCT for malignant and non-malignant diseases: impact on health-related quality of life outcomes

“…1 Advanced techniques in tissue typing, better understanding of the immune system and biological response modifiers, and better supportive care, [2][3][4] along with the use of unrelated or mismatched-related donors and peripheral blood stem cells or umbilical cord blood stem cells have contributed to improved patient outcomes. [5][6][7][8] Furthermore, to improve survival [5][6][7][8] and reduce acute complications such as acute GVHD (aGVHD) and late effect including organ toxicity, there has been a shift from treating pediatric patients with myeloablative conditioning (MAC) to reduced-toxicity conditioning (RTC) followed by allo-SCT. 9 Although HSCT is well-established, markedly less attention has focused on the health-related quality of life (HRQOL) of pediatric recipients.…”

Safety of liposomal cytarabine CNS prophylaxis in children, adolescent and young adult hematopoietic stem cell transplant recipients with acute leukemia and non-Hodgkin lymphoma

“…Conditioning regimens were largely protocol driven and disease specific and consisted of both myeloablative conditioning (n = 19, 76%) and reduced toxicity conditioning (n = 5, 24%) selected according to the patient's disease status, organ function and performance status as we have previously described. [5][6][7] Fifteen patients received a TBI (1200 cGy)-containing conditioning regimen. Six patients received an additional CNS boost of up to 1200 cGy.…”