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Original Article

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Korean J Hematol 2012; 47(1):

Published online March 31, 2012

https://doi.org/10.5045/kjh.2012.47.1.44

© The Korean Society of Hematology

Factors influencing lymphocyte reconstitution after allogeneic hematopoietic stem cell transplantation in children

Keun Wook Bae, Bo Eun Kim, Kyung Nam Koh, Ho Joon Im, and Jong Jin Seo*

Author Info. +

Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.

Correspondence to : Correspondence to Jong Jin Seo, M.D., Ph.D. Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Pungnap-dong, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-3383, Fax: +82-2-473-3725, jjseo@amc.seoul.kr

Received: December 9, 2011; Revised: March 4, 2012; Accepted: March 7, 2012

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Background

Immune reconstitution (IR) after hematopoietic stem cell transplantation (HSCT) reduces transplantation-related complications such as infection and improves HSCT outcomes.

Methods

We retrospectively analyzed IR of lymphocyte subpopulations in 38 pediatric patients for hematologic malignant diseases after allogeneic HSCT from April 2006 to July 2008. T-cell-, B-cell-, and natural killer (NK) cell-associated antigens were assayed in peripheral blood by flow cytometry analysis of 5 lymphocyte subsets, CD3+, CD3+/CD4+, CD4+/CD8+, CD16+/CD56+, and CD19+, before and 3 and 12 months after transplantation.

Results

Reconstitutions of CD16+/CD56+ and CD3+/CD8+ lymphocytes were achieved rapidly, whereas that of CD3+/CD19+ lymphocytes occurred later. Age was not related to reconstitution of any lymphocyte subset. Total body irradiation (TBI) and anti-thymocyte globulin (ATG) administration were related to delayed reconstitution of total lymphocytes and CD3+ lymphocytes, respectively. Reconstitutions of CD3+/CD4+ lymphocytes and CD3+/CD8+ lymphocytes were significantly delayed in patients who received umbilical cord blood stem cells. In patients with chronic graft-versus-host disease (cGVHD), recovery of the total lymphocyte count and CD19+ lymphocytes at 3 months post-transplant were significantly delayed. However, acute GVHD (aGVHD) and cytomegalovirus (CMV) reactivation did not influence the IR of any lymphocyte subset. Further, delayed reconstitution of lymphocyte subsets did not correspond to inferior survival outcomes in this study.

Conclusion

We observed that some lymphocyte reconstitutions after HSCT were influenced by the stem cell source and preparative regimens. However, delayed CD19+ lymphocyte reconstitution may be associated with cGVHD.

Keywords Immune reconstitution, Hematopoietic stem cell transplantation, Children, Lymphocyte subset

Article

Original Article

Korean J Hematol 2012; 47(1): 44-52

Published online March 31, 2012 https://doi.org/10.5045/kjh.2012.47.1.44

Copyright © The Korean Society of Hematology.

Factors influencing lymphocyte reconstitution after allogeneic hematopoietic stem cell transplantation in children

Keun Wook Bae, Bo Eun Kim, Kyung Nam Koh, Ho Joon Im, and Jong Jin Seo*

Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.

Correspondence to: Correspondence to Jong Jin Seo, M.D., Ph.D. Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Pungnap-dong, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-3383, Fax: +82-2-473-3725, jjseo@amc.seoul.kr

Received: December 9, 2011; Revised: March 4, 2012; Accepted: March 7, 2012

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Immune reconstitution (IR) after hematopoietic stem cell transplantation (HSCT) reduces transplantation-related complications such as infection and improves HSCT outcomes.

Methods

We retrospectively analyzed IR of lymphocyte subpopulations in 38 pediatric patients for hematologic malignant diseases after allogeneic HSCT from April 2006 to July 2008. T-cell-, B-cell-, and natural killer (NK) cell-associated antigens were assayed in peripheral blood by flow cytometry analysis of 5 lymphocyte subsets, CD3+, CD3+/CD4+, CD4+/CD8+, CD16+/CD56+, and CD19+, before and 3 and 12 months after transplantation.

Results

Reconstitutions of CD16+/CD56+ and CD3+/CD8+ lymphocytes were achieved rapidly, whereas that of CD3+/CD19+ lymphocytes occurred later. Age was not related to reconstitution of any lymphocyte subset. Total body irradiation (TBI) and anti-thymocyte globulin (ATG) administration were related to delayed reconstitution of total lymphocytes and CD3+ lymphocytes, respectively. Reconstitutions of CD3+/CD4+ lymphocytes and CD3+/CD8+ lymphocytes were significantly delayed in patients who received umbilical cord blood stem cells. In patients with chronic graft-versus-host disease (cGVHD), recovery of the total lymphocyte count and CD19+ lymphocytes at 3 months post-transplant were significantly delayed. However, acute GVHD (aGVHD) and cytomegalovirus (CMV) reactivation did not influence the IR of any lymphocyte subset. Further, delayed reconstitution of lymphocyte subsets did not correspond to inferior survival outcomes in this study.

Conclusion

We observed that some lymphocyte reconstitutions after HSCT were influenced by the stem cell source and preparative regimens. However, delayed CD19+ lymphocyte reconstitution may be associated with cGVHD.

Keywords: Immune reconstitution, Hematopoietic stem cell transplantation, Children, Lymphocyte subset

Fig 1.

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Figure 1.

Patients included in the study.

Blood Research 2012; 47: 44-52https://doi.org/10.5045/kjh.2012.47.1.44

Table 1 . Patient characteristics..

Abbreviations: ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CML, chronic myeloid leukemia; MDS, myelodysplastic syndrome; HLA, human leukocyte antigen; TBI, total body irradiation; ATG, anti-thymocyte globulin..

Table 2 . Summary of HSCT procedures and outcomes..

a)Limited or extensive..

Abbreviations: HSCT, hematopoietic stem cell transplantation; AW, alive and well; DOD, died of disease; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CML, chronic myeloid leukemia; MDS, myelodysplastic syndrome; BMT, bone marrow transplantation; PBSCT, peripheral blood stem cell transplantation; CBT, cord blood stem cell transplantation; BU, busulfan; CY, cyclophosphamide; TBI, total body irradiation; FLU, fludarabine; ATG, anti-thymocyte globulin; CSA, cyclosporin A; MTX, methotrexate; MMF, mycophenolate mofetil; MPD, methyl prednisolone; IPS, idiopathic pneumonia syndrome; ARDS, acute respiratory distress syndrome..

Table 3 . Summary of lymphocyte reconstitution in all patients..

Abbreviation: SDS, standard deviation score; this was calculated on the bases of the reference values from Kim et al. (2001) [23]..

Table 4 . HSCT characteristics and complications affecting lymphocyte reconstitution..

All data are presented as (N patients with reconstitution of lymphocyte subset of the corresponding column)/(N patients with the condition of the corresponding row)..

Abbreviation: NS, not significant; statistically significant results are shown in boxes; BM, bone marrow; PBSC, peripheral blood stem cell; UCB, umbilical cord blood stem cell..
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