Korean J Pediatr Hematol Oncol.  2005 Apr;12(1):70-88.

Chimerism Analysis after Allogeneic Stem Cell Transplantation in Children by Genetic Polymorphism of Hypervariable Regions and Fluorescent in situ Hybridization for X-Chromosome

Affiliations
  • 1Blood and Marrow Transplantation Center, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju, Korea. hoonkook@chonnam.ac.kr
  • 2Department of Pediatrics, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju, Korea.
  • 3Department of Forensic Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju, Korea.
  • 4Department of Laboratory Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju, Korea.
  • 5Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju, Korea.

Abstract

PURPOSE
In order to monitor the clinical outcome of pediatric allogeneic stem cell transplantation (SCT), serial evaluations of chimerism were performed to compare the risk of relapse or graft rejection between patients with complete chimerism (CC) and mixed chimerism (MC). METHODS: Between January, 1996 and April, 2004, 64 cases who underwent SCTs were prospectively enrolled. Serial genotyping of VNTR (variable number of tandem repeats) /STR (short tandem repeats) loci and/or X-chromosome-specific FISH (fluorescent in situ hybridization) were performed at regular intervals. RESULTS: The "informative loci" were found in all 64 patient/donor pairs. CC was persistently detected in 44 cases (68.7%), while MC was detected at least once in 20 (31.3%). In cases with malignancy (n=40), relapse was more frequently encountered in MC group (7/8) than in CC group (7/32) (P < .001), as was death (75% vs. 28%, P < .05). The Kaplan-Meier 5-year overall survival was higher in CC than in MC (69.1% vs. 16.6%; P < .05). In cases with non-malignancy, MC group showed higher rate of graft rejection than CC group (7/12 vs. 1/12, P < .01). Survival was not different between the two groups. The chimerism status was not influenced by sex, donor type, source of stem cells, and inclusion of radiation in conditioning. CONCLUSION: Detection and sequential assessment of MC might be an important tool to predict relapse of disease in malignant diseases as well as to portend graft rejection in non-malignant illnesses. Earlier intervention to circumvent those life-threatening complications should be pursued based on the chimerism analyses.

Keyword

Mixed chimerism (MC) VNTR; STR; FISH

MeSH Terms

Child*
Chimerism*
Graft Rejection
Humans
In Situ Hybridization, Fluorescence*
Polymorphism, Genetic*
Prospective Studies
Recurrence
Stem Cell Transplantation*
Stem Cells*
Tissue Donors
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