The effectiveness of tacrolimus and minidose methotrexate in the prevention of acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation in children: a single-center study in Korea

Seong Shik Park; So Eun Jun; Young Tak Lim

doi:10.5045/kjh.2012.47.2.113

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Original Article

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Korean J Hematol 2012; 47(2):

Published online June 26, 2012

https://doi.org/10.5045/kjh.2012.47.2.113

The effectiveness of tacrolimus and minidose methotrexate in the prevention of acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation in children: a single-center study in Korea

Seong Shik Park, So Eun Jun, and Young Tak Lim^*

Author Info. +

Department of Pediatrics, Pusan National University College of Medicine, Busan, Korea.

Correspondence to : Correspondence to Young Tak Lim, M.D., Ph.D. Department of Pediatrics, Pusan National University College of Medicine, 1-10, Ami-dong, Seo-gu, Busan 602-739, Korea. Tel: +82-51-240-7298, Fax: +82-51-248-6205, limyt@pusan.ac.kr

Received: February 6, 2012; Revised: March 19, 2012; Accepted: May 16, 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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Abstract

Background

Knowledge of the roles of tacrolimus and minidose methotrexate (MTX) in the prevention of acute graft-versus-host disease (aGVHD) in pediatric allogeneic hematopoietic stem cell transplantation (HSCT) is limited. We retrospectively evaluated the engraftment status, incidence of aGVHD and chronic GVHD (cGVHD), and toxicities of tacrolimus and minidose MTX in aGVHD prophylaxis in children undergoing allogeneic HSCT.

Methods

Seventeen children, who underwent allogeneic HSCT and received tacrolimus and minidose MTX as GVHD prophylaxis from March 2003 to February 2011, were reviewed retrospectively. All the patients received tacrolimus since the day before transplantation at a dose of 0.03 mg/kg/day and MTX at a dose of 5 mg/m² on days 1, 3, 6, and 11.

Results

Of the 17 patients, 9 received human leukocyte antigen (HLA)-matched related donor transplants, and 8 received HLA-matched, or partially mismatched unrelated donor transplants. The median time for follow-up was 55 months. The incidence of aGVHD in the related and unrelated donor groups was 22.2% and 42.9%, respectively. cGVHD was not observed. To maintain therapeutic blood levels of tacrolimus, the younger group (<8 years of age) required an increased mean dose compared to the older group (≥8 years) (P=0.0075). The adverse events commonly associated with tacrolimus included hypomagnesemia (88%), nephrotoxicity (23%), and hyperglycemia (23%).

Conclusion

Tacrolimus and minidose MTX were well tolerated and effective in GVHD prophylaxis in pediatric patients undergoing allogeneic HSCT. Children <8 years of age undergoing HSCT required increased doses of tacrolimus to achieve therapeutic levels.

Keywords Tacrolimus, Methotrexate, Allogeneic hematopoietic stem cell transplantation, Acute graft-versus-host disease, Children

Article

Original Article

Korean J Hematol 2012; 47(2): 113-118

Published online June 26, 2012 https://doi.org/10.5045/kjh.2012.47.2.113

The effectiveness of tacrolimus and minidose methotrexate in the prevention of acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation in children: a single-center study in Korea

Seong Shik Park, So Eun Jun, and Young Tak Lim^*

Department of Pediatrics, Pusan National University College of Medicine, Busan, Korea.

Correspondence to: Correspondence to Young Tak Lim, M.D., Ph.D. Department of Pediatrics, Pusan National University College of Medicine, 1-10, Ami-dong, Seo-gu, Busan 602-739, Korea. Tel: +82-51-240-7298, Fax: +82-51-248-6205, limyt@pusan.ac.kr

Received: February 6, 2012; Revised: March 19, 2012; Accepted: May 16, 2012

Abstract

Background

Methods

Results

Conclusion

Keywords: Tacrolimus, Methotrexate, Allogeneic hematopoietic stem cell transplantation, Acute graft-versus-host disease, Children

Abstract

Table 1 . Patient demographics and characteristics..

Abbreviations: No., patient number; CR1, first complete remission; CR2, second complete remission; MLL, mixed-lineage leukemia..

Table 2 . Details of transplantation..

Abbreviations: Bu, busulfan; Flu, fludarabine; Mel, melphalan; ATG, rabbit anti-thymocyte globulin; Cy, cyclophosphamide; VP-16, etoposide; TBI, total body irradiation; HLA, human leukocyte antigen..

Table 3 . GVHD and clinical outcomes..

^a)CMV colitis, ^b)Bone marrow relapse at 40 months post-transplantation, ^c)Bone marrow relapse at 10 months post-transplantation, ^d)Granulocytic sarcoma at 7 months post-transplantation..

Abbreviations: No., patient number; aGVHD, acute graft-versus-host disease; cGVHD, chronic GVHD; CMV, cytomegalovirus; CR, complete remission; DOD, died of disease; TRD, transplantation-related death; PD, progression of disease after relapse; NA, not applicable; ARDS, acute respiratory distress syndrome; VOD, hepatic veno-occlusive disease; EF2, secondary engraftment failure..

Table 4 . Severity of GVHD based on donor states..

Abbreviations: aGVHD, acute graft-versus-host disease; cGVHD, chronic GVHD..

Table 5 . Mean doses of tacrolimus to maintain adequate blood levels based on age..

Table 6 . Toxicities of tacrolimus..