The authors of “Rapid reconstitution of regulatory T-cell subsets is associated with reduced rates of acute graft-versus-host disease and absence of viremia after cord blood transplantation in children with reduced-intensity conditioning using alemtuzumab” would like to clarify the following:
The analytical conclusions remain valid, even after recognizing a few honest errors as detailed below, primarily listing the subjects’ ages in Table 1. Although it may have been assumed by some, we never stated that samples were obtained on all patients at all time points. Most patients were coming for transplant from out of state, and therefore we did not have the opportunity to collect samples at all time points. Nonetheless, all the available data was presented in the manuscript, and no data was omitted. Again, because the analytical conclusions were based on all the available data, the analytical conclusions remain valid, even after recognizing a few errors as detailed below. We are happy to clarify within an erratum, the explanation why the conclusions and stat analyses remain valid and unchanged, even after this review. We intend to provide additional clarification for the Methods section and for Figure legends below. In Figure legends 2 and 4C, we used the term “all patients” to refer to samples available on all patients, before breaking them up into subgroups based on the presence or absence of graft versus host disease and viral infections.
Patients, Materials and Methods (pages 150-151 in Cytotherapy 2020;22 published version):
- 1Patient Ages:
- aThere were errors in 3 patients’ ages with the correct age listed here: Pt #1: 7m, Pt # 9: 8m; Pt 14: 6m. The corrected Table 1 is attached.Table 1Characteristics of patients
Pt group Pt Code Age At BMT Gender Diagnosis HLA match aGvHD Viremia UCB TNC N°/kg UCB CD34+ N°/kg w/o Gr I-II aGvHD or viremia (n=6) 1 7m M Krabbe Disease 6/6; 8/8 N N 7.6E+07 1.7E+05 2 7m F Krabbe Disease 5/6; 6/8 N N 1.0E+08 4.3E+05 3 1y7m M Krabbe Disease 6/6; 8/8 N N 7.6E+07 1.9E+05 4 1y F Bare Lymphocyte syndrome 4/6; 5/8 N N 8.6E+07 3.3E+05 5 1y F Bare Lymphocyte syndrome 4/6; 5/8 N N 8.6E+07 3.3E+05 6 9y2m M XLP2 4/6; 4/8 N N 5.3E+07 3.1E+05 w/ Gr I-II a GvHD & viremia (n=8) 7 2y5m F Krabbe Disease 5/6; 7/8 aGvHD, Gr I, skin EBV 2.2E+08 6.8E+05 8 8m M Gaucher Disease 4/6; 6/8 aGvHD, Gr I, skin CMV 2.3E+08 7.9E+05 9 8m F Hurler's Syndrome 5/6; 6/8 aGvHD, Gr I, skin Adeno 1.2E+08 2.5E+05 10 7y2m M MLD 6/6; 8/8 aGvHD, Gr II, skin CMV, Adeno, HHV-6 5.5E+07 2.6E+05 11 15y F CID 6/6; 6/8 aGvHD, Gr II, skin CMV, EBV, HHV-6 4.4E+07 1.8E+05 12 8m M MLD 6/6; 5/8 cGvHD, Gr II, skin CMV, EBV, Adeno 1.5E+08 4.7E+05 13 5y F MLD 5/6; 7/8 aGvHD, Gr II, skin Adeno, HHV-6 1.6E+08 7.7E+05 14 6m M Krabbe Disease 6/6; 7/8 aGvHD, Gr II, skin CMV, EBV 1.9E+08 9.2E+05 w/Gr I-II aGvHD alone (n=3) 15 7m M Krabbe Disease 6/6; 7/8 aGvHD, Gr I, skin N 1.7E+08 4.7E+05 16 11m F Osteopetrosis 6/6; 8/8 aGvHD, Gr I, skin N 1.1E+08 5.5E+05 17 6m F Gaucher Disease 4/6; 5/8 aGvHD, Gr II, skin N 2.5E+08 5.6E+05 w/viremia alone (n=4) 18 6y5m F MLD 5/6; 7/8 N Adeno 5.7E+07 2.5E+05 19 16y10m M XLP2 5/6; 6/8 N EBV 2.3E+07 1.1E+05 20 7y5m M Krabbe Disease 6/6; 7/8 N EBV 2.5E+07 1.4E+05 21 9y11m M MLD 5/6; 6/8 N EBV 4.8E+07 1.5E+05 Gr = grade.
- bDue to the errors in the patients’ ages, the median age for the entire cohort of 21 patients changes now to “1 year old” on page 150, line 2 (or the line 212 in the version of “article in press) under the paragraph of “Patients” in the section of “Patients, Materials, and Methods”.
- cThese errors in age did not impact the statistical result (we still do not find any correlation) when analyzed for association between patient age and Treg recovery as described on page 152, line 9 as published (or line 422 in the “article in press” version) in the paragraph of “Treg reconstitution is accelerated in comparison with the recovery of other T-cell subsets” in “Results” and Suppl. Figure 2.
- a
- 2Patients:
- aTwenty-one pediatric patients (age range from 6 months to 17 years old; median: 1 year old) with non-malignant diseases (>80% with inborn errors of metabolism) (Table 1) were transplanted with single unit cord blood on identical chemotherapy-based regimen. Eight patients were transplanted following informed consent on treatment plans before clinical trial registration in Fall 2013 (NCT01962415). Collection of blood samples at every time point was not feasible. Nevertheless, all data generated was analyzed and presented in the manuscript.
- bWe do not have records uploading the last sentence present in the published version of Cytotherapy; 2020;22: page 150. It is not present in the proofs that we reviewed in the “article in press” version. Nevertheless, the currently published last sentence in Methods could be revised as “Patient guardians have signed informed consent forms (ICF) for laboratory research studies with adherence to the tenets of the Declaration of Helsinki”. The ICF of one subject cannot be located but there are references by other individuals in electronic medical records that the guardian consented while another subject's parents signed ICF for another university's research form that permits sharing samples.
- a
- 3Statistical analysis page 151):
Please add: “F-test was applied for the comparison between Treg RI and the RI for CD3+T-cells, CD4+Tcon, CD8+Tcon, sjTREC, TCRβ SCS”. Wilcoxon matched-pairs signed-rank test was used for the comparison of the RI between memory Treg and naïve Treg.
Results section:
1) Please replace “all patients” in the legends of Fig 2 and Fig 4C to “all participating patients”
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Published online: July 11, 2022
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© 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.
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- Rapid reconstitution of regulatory T-cell subsets is associated with reduced rates of acute graft-versus-host disease and absence of viremia after cord blood transplantation in children with reduced-intensity conditioning using alemtuzumabCytotherapyVol. 22Issue 3
- PreviewForkhead box P3 (FOXP3)+ regulatory T cell (Treg) reconstitution after unrelated donor umbilical cord blood transplantation in chemotherapy-naïve children is incompletely characterized. We studied 21 children with nonmalignant diseases receiving an identical alemtuzumab-containing regimen. We hypothesized that Treg recovery may be perturbed in patients not only by acute graft-versus-host disease (aGVHD) but also by viremia. Tregs and their memory and naïve subsets were serially monitored for proliferation and apoptosis along with conventional T cells (Tcon).
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