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Dendritic and T Cell Subsets Correlate with the Development and Site of Acute GVHD Following Unrelated Cord Blood Transplantation. A Multivariate Analysis of Host, Graft, and Day+50 Immune Profile.

Publication ,  Conference
Szabolcs, P; Park, K-D; Marti, L; Lee, Y-A; Reese, M; Sanders, L; Niedzwiecki, D; Kurtzberg, J
Published in: Blood
November 16, 2004

HLA-mismatched unrelated umbilical cord blood transplantation (uUCBT) is a suitable option for those who lack HLA-matched sibling donors. Although UCB T cells mount significantly less cytotoxicity and cytokine response than adult T cells uUCBT can lead to significant aGVHD. We hypothesized that select features of T cell and dendritic cell (DC) reconstitution will correlate with the development of aGVHD. Here we report on 106 prospectively studied pediatric patients, all full donor chimera. Methods: On day +50 we determined by 4-color surface and ic. FACS the reconstitution of T cell subsets, lymphoid, and myeloid DC, and measured their homeostatic proliferation, activation state, and inducible cytokine secretion to correlate with the risk for developing aGVHD. Logistic regression models were created on variables with a univariate P value <0.05 by Wilcoxon rank-sum test. Results: Mean age of patients was 6.4 years, 65 patients are alive with a mean time of 36 months follow-up (61%). Survival is lower (26%) in patients who developed aGVHD at grade III–IV (n=21), versus those with grade 0–II (73%, n=85, p<0.0001), while it is not different (p=0.5) for those with grade II–IV (n=52) versus 0–I (n=54). More patients with aGVHD grade III–IV experienced de novo opportunistic infection (OI) impacting their survival (p=0.0001), while death due to OI was similar for those with grII–IV GVHD vs 0–I. Non-infectious death was similar regardless of GVHD grade. Among potential confounding factors (Table I) younger age/smaller body size were associated with grade II–IV aGVHD while gender, CMV status, graft content did not. Younger children were less likely to have malignancy/receive TBI. HLA mismatch at 2–3 HLA alleles was the only confounder significantly related to developing gr III–IV aGVHD (p=0.008). Table I presents immune parameters correlating with grade II–IV aGVHD. Several variables correlating with grIII–IV GVHD in univariate analysis (e.g activated/DR+CD4 T cells) lost significance in the multivariable model when OI was added. Still higher % and absolute numbers of CD4+ T cells secreting IL-2 and TNF remained significant. Additionally, fewer CD123+ DC in the circulation (0.7/μl) correlated with gr III–IV aGVHD in contrast with grade 0–II (2.5/μl, p=0.009). More T cells were in cell cycle of those with grIII–IV GVHD (27% Ki-67+ cells vs 16%, p=0.04). In patients with grII–IV skin GVHD T cells expressing the skin homing molecule CLA appeared (2% vs 0%, p=0.05). Conclusion; HLA-mismatch at >1Ag and select patterns of T cell subset and DC reconstitution may identify those at risk for GVHD.UNIVARIATE AND MULTIVARIATE ANALYSIS OF DAY+50 IMMUNE PROFILE AND THE RISK FOR DEVELOPING GRADE II–IV ACUTE GVHDVARIABLE Median Values for patients with GVHD Median Values for patients without GVHD Rank Sum Test p-value Logistic regression p-value Confounders tested; age, gender, weight, CMV serology, HLA mismatch, malignancy, TBI, presence of OI, infused total cell dose/kg, CD34+ progenitor/kg, CD3+ T cell dose/kg % TNF secreting T cells 18% 2% 0.0001 0.001 %CD8+ T cells secreting TNF 5.8% 0.6% 0.008 ≤ 0.03 %CD4+ T cells secreting TNF 22% 4% 0.0002 ≤ 0.02 % IL-2 secreting T cells 17% 8% 0.0009 ≤ 0.005 %CD4+ T cells secreting IL-2 31% 14% 0.007 ≤ 0.017

Duke Scholars

Published In

Blood

DOI

EISSN

1528-0020

ISSN

0006-4971

Publication Date

November 16, 2004

Volume

104

Issue

11

Start / End Page

981 / 981

Publisher

American Society of Hematology

Related Subject Headings

  • Immunology
  • 3213 Paediatrics
  • 3201 Cardiovascular medicine and haematology
  • 3101 Biochemistry and cell biology
  • 1114 Paediatrics and Reproductive Medicine
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology
 

Citation

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Szabolcs, P., Park, K.-D., Marti, L., Lee, Y.-A., Reese, M., Sanders, L., … Kurtzberg, J. (2004). Dendritic and T Cell Subsets Correlate with the Development and Site of Acute GVHD Following Unrelated Cord Blood Transplantation. A Multivariate Analysis of Host, Graft, and Day+50 Immune Profile. In Blood (Vol. 104, pp. 981–981). American Society of Hematology. https://doi.org/10.1182/blood.v104.11.981.981
Szabolcs, Paul, Kyung-Duk Park, Luciana Marti, Young-Ah Lee, Melissa Reese, Linda Sanders, Donna Niedzwiecki, and Joanne Kurtzberg. “Dendritic and T Cell Subsets Correlate with the Development and Site of Acute GVHD Following Unrelated Cord Blood Transplantation. A Multivariate Analysis of Host, Graft, and Day+50 Immune Profile.” In Blood, 104:981–981. American Society of Hematology, 2004. https://doi.org/10.1182/blood.v104.11.981.981.
Szabolcs, Paul, et al. “Dendritic and T Cell Subsets Correlate with the Development and Site of Acute GVHD Following Unrelated Cord Blood Transplantation. A Multivariate Analysis of Host, Graft, and Day+50 Immune Profile.Blood, vol. 104, no. 11, American Society of Hematology, 2004, pp. 981–981. Crossref, doi:10.1182/blood.v104.11.981.981.
Szabolcs P, Park K-D, Marti L, Lee Y-A, Reese M, Sanders L, Niedzwiecki D, Kurtzberg J. Dendritic and T Cell Subsets Correlate with the Development and Site of Acute GVHD Following Unrelated Cord Blood Transplantation. A Multivariate Analysis of Host, Graft, and Day+50 Immune Profile. Blood. American Society of Hematology; 2004. p. 981–981.

Published In

Blood

DOI

EISSN

1528-0020

ISSN

0006-4971

Publication Date

November 16, 2004

Volume

104

Issue

11

Start / End Page

981 / 981

Publisher

American Society of Hematology

Related Subject Headings

  • Immunology
  • 3213 Paediatrics
  • 3201 Cardiovascular medicine and haematology
  • 3101 Biochemistry and cell biology
  • 1114 Paediatrics and Reproductive Medicine
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology