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Original Article

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Korean J Hematol 2010; 45(3):

Published online September 30, 2010

https://doi.org/10.5045/kjh.2010.45.3.164

© The Korean Society of Hematology

Early central nervous system complications after allogeneic hematopoietic stem cell transplantation in children

Kyung Nam Koh, Meerim Park, Bo Eun Kim, Ho Joon Im*, and Jong Jin Seo

Author Info. +

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

Correspondence to : Correspondence to Ho Joon Im, M.D., Ph.D. Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, 388-1, Pungnap 2-dong, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-3371, Fax: +82-2-473-3725, hojim@amc.seoul.kr

Received: May 10, 2010; Revised: August 4, 2010; Accepted: September 2, 2010

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

Central nervous system (CNS) complications after allogeneic hematopoietic stem cell transplantation (HSCT) have not been well characterized in the pediatric population.

Methods

We retrospectively analyzed data of 202 consecutive children who underwent allogeneic HSCT (60 from matched related donors, 9 from mismatched related donors, and 133 from unrelated donors) at Asan Medical Center between 1998 and 2009.

Results

Twenty-seven children (13.5%) developed CNS complications within 6 months after HSCT. Calcineurin inhibitor (CNI)-associated neurotoxicity was the most common CNS complication (n=16), followed by CNS infection (n=2), cerebrovascular events (n=2), thrombotic microangiopathy-associated events (n=2), metabolic encephalopathy (n=2), irradiation/chemotherapy injury (n=1), and encephalopathy/myelopathy of unknown causes (n=2). Univariate analysis showed that a transplant from an alternative donor and the occurrence of acute graft-versus-host disease (GVHD) (>grade 2) were associated with a significantly increased risk of CNS complications. In the multivariate analysis, acute GVHD >grade 2 was identified as an independent risk factor for early CNS complications. The 5-year overall survival rate was significantly lower in patients with CNS complications (52.1% vs. 64.9%, P=0.014), whereas CNI-associated neurotoxicity did not affect the survival outcome.

Conclusion

CNS complications are frequent among children undergoing HSCT, contributing to early death after transplant. More attention should be paid to the development of CNS complications for recipients of alternative donor transplants and patients with severe acute GVHD who are at increased risk for CNS complications.

Keywords Allogeneic, Hematopoietic stem cell transplantation, Neurological complication, Cyclosporine, Children

Article

Original Article

Korean J Hematol 2010; 45(3): 164-170

Published online September 30, 2010 https://doi.org/10.5045/kjh.2010.45.3.164

Copyright © The Korean Society of Hematology.

Early central nervous system complications after allogeneic hematopoietic stem cell transplantation in children

Kyung Nam Koh, Meerim Park, Bo Eun Kim, Ho Joon Im*, and Jong Jin Seo

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

Correspondence to: Correspondence to Ho Joon Im, M.D., Ph.D. Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, 388-1, Pungnap 2-dong, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-3371, Fax: +82-2-473-3725, hojim@amc.seoul.kr

Received: May 10, 2010; Revised: August 4, 2010; Accepted: September 2, 2010

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

Central nervous system (CNS) complications after allogeneic hematopoietic stem cell transplantation (HSCT) have not been well characterized in the pediatric population.

Methods

We retrospectively analyzed data of 202 consecutive children who underwent allogeneic HSCT (60 from matched related donors, 9 from mismatched related donors, and 133 from unrelated donors) at Asan Medical Center between 1998 and 2009.

Results

Twenty-seven children (13.5%) developed CNS complications within 6 months after HSCT. Calcineurin inhibitor (CNI)-associated neurotoxicity was the most common CNS complication (n=16), followed by CNS infection (n=2), cerebrovascular events (n=2), thrombotic microangiopathy-associated events (n=2), metabolic encephalopathy (n=2), irradiation/chemotherapy injury (n=1), and encephalopathy/myelopathy of unknown causes (n=2). Univariate analysis showed that a transplant from an alternative donor and the occurrence of acute graft-versus-host disease (GVHD) (>grade 2) were associated with a significantly increased risk of CNS complications. In the multivariate analysis, acute GVHD >grade 2 was identified as an independent risk factor for early CNS complications. The 5-year overall survival rate was significantly lower in patients with CNS complications (52.1% vs. 64.9%, P=0.014), whereas CNI-associated neurotoxicity did not affect the survival outcome.

Conclusion

CNS complications are frequent among children undergoing HSCT, contributing to early death after transplant. More attention should be paid to the development of CNS complications for recipients of alternative donor transplants and patients with severe acute GVHD who are at increased risk for CNS complications.

Keywords: Allogeneic, Hematopoietic stem cell transplantation, Neurological complication, Cyclosporine, Children

Fig 1.

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Figure 1.

The cumulative incidence of central nervous system complications according to different types of donor within 6 months posttransplant. CI, confidence interval; HSCT, hematopoietic stem cell transplantation.

Blood Research 2010; 45: 164-170https://doi.org/10.5045/kjh.2010.45.3.164

Fig 2.

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Figure 2.

Kaplan-Meier plots of overall survival in patients with and without CNS complications (A) and CNI neurotoxicity (B) within 6 months posttransplant. CNS, central nervous system; CNI, calcineurin inhibitor; HSCT: hematopoietic stem cell transplantation.

Blood Research 2010; 45: 164-170https://doi.org/10.5045/kjh.2010.45.3.164

Table 1 . Patient characteristics and risk factors for development of central nervous system complications within 6 months after hematopoietic stem cell transplant..

a)Other BMF included pure red cell anemia and Kostmann syndrome, b)Immunodeficiency included chronic granulomatous disease, severe combined immunodeficiency, Omenn syndrome, and Wiskott-Aldrich syndrome, c)Storage disease included Krabbe disease and adrenoleukodystrophy..

Abbreviations: CNS, central nervous system; AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia; BAL, biphenotypic acute leukemia; CML, chronic myelogenous leukemia; JMML, juvenile myelomonocytic leukemia; MDS, myelodysplastic syndrome; HLH, hemophagocytic lymphohistiocytosis; SAA, severe aplastic anemia; BMF, bone marrow failure; TBI, total body irradiation; ATG, antithymocyte globulin; MTX, methotrexate; MMF, mycophenolate mofetil; GVHD, graft-versus-host disease; NA, not applicable..

Table 2 . Number and type of central nervous systemcomplications according to the type of donor..

Abbreviations: CNI, calcineurin inhibitor; TMA, thrombotic microangiopathy; RT, radiotherapy..

Table 3 . Multivariate regression analysis for central nervous system complications within 6 months after hematopoietic stem cell transplant..

Abbreviations: GVHD, graft-versus-host disease; CI, confidence interval..
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