Long-term outcome and evaluation of organ function in pediatric patients undergoing haploidentical and matched related hematopoietic cell transplantation for sickle cell disease

Abstract

HLA-matched related donor (MRD) hematopoietic stem cell transplantation (HSCT) is a well-established therapy for patients with sickle cell disease (SCD); however, experience using alternative donors, including haploidentical donors, in HSCT for SCD is limited. We report the long-term outcomes of 22 pediatric patients who underwent related donor HSCT for SCD at St. Jude Children's Research Hospital, either a myeloablative sibling MRD HSCT (n = 14) or reduced-intensity parental haploidentical donor HSCT (n = 8). The median patient age was 11.0 ± 3.9 years in the MRD graft recipients and 9.0 ± 5.0 years in the haploidentical donor graft recipients. The median follow-up was 9.0 ± 2.3 years, with an overall survival (OS) of 93% and a recurrence/graft failure rate of 0%, for the MRD cohort and 7.4 ± 2.4 years, with an OS of 75%, disease-free survival of 38%, and disease recurrence of 38%, for the haploidentical donor cohort. We report the long-term hematologic response and organ function in patients undergoing MRD or haploidentical donor HSCT for severe SCD. Our data demonstrate long-term hematologic improvements after HSCT with sustained engraftment, and confirm that HSCT offers long-term protection from common complications of SCD, including stroke, pulmonary hypertension, acute chest, and nephropathy, regardless of donor source.

Trial registration: ClinicalTrials.gov NCT00152113 NCT00186810.

Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Kaplan-Meier estimates of OS and DFS after MRD HSCT and haploidentical HSCT. OS and DFS were determined with events defined as death, graft rejection, or recurrence of SCD after MRD HSCT (A) or haploidentical HSCT (B). Tick marks represent surviving patients and indicate the duration of follow-up after transplantation. The percentages above each curve indicate the estimates of OS, DFS, and cumulative incidence of graft rejection or recurrence of disease for the entire cohort.

Figure 2

Disease response after MRD HSCT (solid lines) and haploidentical HSCT (dashed lines) for SCD. Mean ± SEM values are plotted over time after MRD HSCT and haploidentical HSCT for hemoglobin and hematocrit (A), hemoglobin fractions (B), reticulocyte index and percent (C), and iron and ferritin levels (D).

Figure 3

IQ, renal function, and cardiac function before and after HSCT. IQ (A), renal function (B), and cardiac function (C) were monitored before (solid symbols) and yearly after (open symbols) MRD (●, ○) and haploidentical (HAPLO) (■, □) HSCT. Mean ± SEM values are plotted over time after HSCT for CrCl (Bi) and shortening fraction (Ci), and median and SEM values for CrCl (Bii) and shortening fraction (Cii) before HSCT are compared with the values measured at the most recent evaluation.

Figure 4

Pulmonary function before and after HSCT. PFTs, including FVC (A), DLCO (B), FEV1 (C), and FEV1/FVC ratio (D), were monitored before (solid symbols) and yearly after (open symbols) HSCT. Mean ± SEM values are plotted over time after MRD (●, ○) and haploidentical (HAPLO) (■, □) HSCT for FVC (Ai) and DLCO (Bi). The median ± SEM values before HSCT or first available values (closed symbols) are compared with the most recent value (open symbol) for FVC (Aii), DLCO (Bii), FEV1 (Ci), and FEV1/FVC ratio (Cii).

Figure 5

Bone density before and after HSCT. Whole-body (A) and vertebral body (B) BMD (i) and BMD z-scores (ii) were monitored before (solid symbols) and after (open symbols) HSCT. Median ± SEM values for the MRD (●, ○) and haploidentical (HAPLO) (■, □) recipients are compared with those measured at the most recent evaluation.