XX/XY in Opposite Sex Bone Marrow Transplantation, FISH
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Bone marrow transplantation (BMT) is an important treatment for patients with certain malignant hematologic disorders and hereditary conditions.
Conventional cytogenetic studies can identify chromosome abnormalities, establish the proportion of donor and recipient metaphase cells to monitor the success of BMT engraftment, and detect residual disease after treatment. However, conventional chromosome studies are usually done on only 20 to 30 metaphase cells and may be less sensitive than other methods.
When the donor and recipient are of opposite sex, the donor and recipient cells can be readily identified by their sex chromosome complement. FISH using probes for the X and Y chromosomes can be used to estimate the proportion of donor and recipient interphase cells in bone marrow or peripheral blood. Monitoring the proportion of host and recipient cells over time also may be useful to identify significant clinical changes.
This method is easy, objective, and permits analysis of large numbers of cells. Our experience also suggests that FISH is economical, rapid, and accurate.(1) FISH specimens are preprocessed in the same manner as chromosome analysis specimens. If FISH results or clinical circumstances suggest the possibility of disease relapse, chromosome studies can be performed on the same specimen to determine if an abnormal clone is present.
To maximize the cost-effectiveness of FISH and chromosome analysis, we recommend conventional chromosome analysis prior to BMT to establish the karyotype of the malignant cell line. After BMT, the use of FISH alone on either bone marrow or peripheral blood may be sufficient to monitor the success of the engraftment.
Evaluating engraftment success by determining the proportion of donor and recipient interphase cells present in opposite sex bone marrow transplant recipients
Monitoring the proportion of host and recipient cells over time may be useful to identify significant clinical changes
Specimens from females that have >0.6% XX interphase cells have residual XX host cells.
Specimens from males that have >0.3% XY interphase cells have residual XY host cells.
The results of both conventional chromosome studies and FISH are best interpreted when findings before and after bone marrow transplantation are compared. Our reports include a summary of the percentage of host and donor cells present in prior studies from the same patient.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is designed for opposite sex bone marrow transplants (BMTs) only; results are not useful for same sex bone marrow transplants.
Examination of the sex chromosome complement of interphase cells using FISH does not distinguish between malignant and normal cells. We strongly recommend using both FISH and cytogenetic studies to monitor patients.
A single X chromosome is sometimes lost in bone marrow cells of females, and the Y chromosome is sometimes lost in bone marrow cells of males, regardless of whether the specimen is from the donor, recipient, or a post-BMT patient.
Rare males may have an unusual Y chromosome that cannot be identified with these probes, but this finding should be readily apparent by analysis of metaphase cells using FISH.
Occasional patients may have chromosome polymorphisms that may hybridize with the Y probe, but this should be readily apparent by analysis of metaphase cells using FISH.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
< or =0.3% cells with XY signals for pretransplant females
< or =0.6% cells with XX signals for pretransplant males
Clinical References Provides recommendations for further in-depth reading of a clinical nature
Dewald GW, Schad CR, Christensen ER, et al: Fluorescence in situ hybridization with X and Y chromosome probes for cytogenetic studies on bone marrow cells after opposite sex transplantation. Bone Marrow Transplant 1993;12:149-154