Identification of Acute Lymphocytic Leukemia Extramedullary Relapse and PTLD after Allo-HSCT by FISH Monitoring Sex Chromosome Chimeric Status

Objectives: To explore the role of fluorescence in situ hybridization (FISH) monitoring sex chromosome chimeric status in the identification of leukemic extramedullary relapse and post-transplant lymphoproliferative disease (PTLD) in acute lymphocytic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods: Six ALL patients who received sex-mismatched allo-HSCT manifested extravisceral lymphadenectasis or local lump were investigated. The sex chromosome chimeric status in tumor tissues and bone marrow (BM) were monitored by FISH, and EBV-RNA in the tumor tissues were detected by in situ hybridization (ISH).

Results: The sex chromosomes in BM of all 6 patients were 100% donor-derived. Among the sex chromosome chimeric status of tumor tissues, those of three patients were mainly recipient-derived, and the percentage of sex chromosomes derived from recipients were 100%, 100% and 98.0%, respectively, and then they were diagnosed leukemic extramedullary relapse. And those of the other 3 patients were donor-derived, the percentage was 98.5%, 96.0% and 91.5%, respectively, and diagnosed PTLD. EBV-RNA and latent membrane protein (LMP-1) were positive in 2 patients with PTLD and negative in the other 4 patients. One patient with extramedullary relapse obtained partial remission, one with PTLD gained complete remission, and the others died eventually after therapy.

Conclusion: Monitoring the sex chromosome chimeric status by FISH is an effective method to distinguish leukemic extramedullary relapse from PTLD in ALL received sex-mismatched donor HSCT.