Final Diagnosis -- Myelodysplastic syndrome and bone marrow transplant engraftment failure


Recipients of bone marrow transplants from donors other than HLA-identical siblings have a higher risk for graft versus host disease. Therefore, it has been hypothesized that T-cell depletion methods may be of benefit to patients undergoing matched unrelated bone marrow transplants. One such method has been the use of Campath which has shown a reduction in GVHD in retrospective studies, but remain to be confirmed in prospective randomized trials (reviewed by Simpson, DR. Biodrugs 2003; 17(3):147-154).

The effect of Campath in generating a false-positive HLA antibody screen has been described previously in a case report of a patient receiving Campath as part of his treatment for chronic lymphocytic leukemia (CLL). In this report, they demonstrated that the T-cell reactivity detected by complement-mediated cell lysis was dependent on the presence of antihuman globulin (AHG) (Lyon, DC et al. Transfusion 2001; 41:1626-7). These findings are consistent with our findings that only the T-cell crossmatch, which was perfomed with AHG enhancement, was positive, while our B-cell crossmatch, which was performed without AHG enhancement, was negative.

In this particular case, several additional NMDP donors subsequently were evaluated for suitability as allograft donors, but the particular NMDP donor described above remained the most compatible based on HLA class I and II typing. The finding of a positive crossmatch with the NMDP donor had suggested an immune-mediated graft rejection, and was misleading to the clinical team until a thorough explanation was made regarding the reasons for the false positive result. Engraftment failure in this patient was most likely due to poor marrow stroma and not immune-mediated rejection of the donor cells. With these findings and after the Campath blood concentrations had declined sufficiently (half-life of Campath is 12 days; MicroMEDEX), a repeat crossmatch with the original NMDP donor was negative with both T- and B-cells.

Contributed by Mark K Fung, MD, PhD

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