Primary immunosuppressive TNI-based conditioning regimens in pediatric patients treated with haploidentical hematopoietic cell transplantation

D Wegener,F Heinzelmann,P Lang,F Paulsen,N Weidner,M Döring,U Holzer,D Zips,M Ebinger

doi:10.1007/s00066-021-01840-y

Abstract

PurposeThis retrospective analysis aims to address the toxicity and efficacy of a modified total nodal irradiation (TNI)-based conditioning regimen before haploidentical hematopoietic cell transplantation (HCT) in pediatric patients.Materials and methodsPatient data including long-term follow-up were evaluated of 7 pediatric patients with malignant (n = 2) and non-malignant diseases (n = 5) who were treated by a primary TNI-based conditioning regimen. TNI was performed using anterior/posterior opposing fields. All patients received 7 Gy single-dose TNI combined with systemic agents followed by an infusion of peripheral blood stem cells (n = 7). All children had haploidentical family donors.ResultsEngraftment was reached in 6/7 children after a median time of 9.5 days; 1 child had primary graft failure but was successfully reconditioned shortly thereafter. After an average follow-up time of 103.5 months (range 8.8–138.5 months), event-free (EFS) and overall survival (OS) rates were 71.4% and 85.7%, respectively. One child with a non-malignant disease died 8.8 months after transplantation due to a relapse and a multiple organ failure. Follow-up data was available for 5/6 long-term survivors with a median follow-up (FU) of 106.2 months (range 54.5–138.5 months). Hypothyroidism and deficiency of sexual hormones was present in 3/5 patients each. Mean forced expiratory volume in 1 s (FEV1) after TNI was 71%; mean vital capacity (VC) was 78%. Growth failure (< 10th percentile) occurred in 2/5 patients (height) and 1/5 patient (weight). No secondary malignancies were reported.ConclusionIn this group of patients, a primary single-dose 7 Gy TNI-based conditioning regimen before HCT in pediatric patients allowed sustained engraftment combined with a tolerable toxicity profile leading to long-term OS/EFS. Late toxicity after a median FU of over 9 years includes growth failure, manageable hormonal deficiencies, and acceptable decrease in lung function.

Highlights

Haploidentical hematopoietic cell transplantation (HCT) is a potentially curative treatment for several life-threatening malignant and benign hematological diseases [1]
Long-term outcome and toxicity data are scarce in this high-risk population [5, 6] and a variety of total nodal irradiation (TNI) regimes are in use [7, 8]
An analysis of 7 pediatric patients treated by a 7-Gy single-dose TNI conditioning regimen before primary HCT for various benign or malignant diseases (Tables 1 and 2) was performed

Summary

Introduction

Haploidentical hematopoietic cell transplantation (HCT) is a potentially curative treatment for several life-threatening malignant and benign hematological diseases [1]. The effect of non-myeloablative modified total nodal irradiation (TNI) to achieve immunosuppression and the feasibility and favorable outcome of TNI-based (re-)conditioning regimes have been described previously for both malignant and nonmalignant diseases [2,3,4]. Long-term outcome and toxicity data are scarce in this high-risk population [5, 6] and a variety of TNI regimes are in use [7, 8]. This retrospective analysis aims to address the efficacy and toxicity of a 7 Gy single-dose TNI-based conditioning regimen before HCT on pediatric patients with various lifethreatening diseases

Methods

Results

Discussion

Conclusion