Variable number tandem repeat polymorphism as atool of chimerism detection in allogeneic stem cell transplantation

Abstract EN

Background : allogeneic haematopoeitic stem cell transplantation currently represents the only available therapeutic approach in several malignant and nonmalignant haematologic disorders.

Evaluation of post-transplantation chimerism by PCR has become a routine approach to monitor its clinical outcome.

Variable number tandem repeat (VNTR) loci are a group of DNA sequences that represents a source of highly polymorphic markers and that have been employed for the evaluation of the state of chimerism.

Material and Methods : in this work, seven VNTR loci (Apo-B, 33.1, 33.4, 33.6, YNZ-22, D1S80 and H-Ras) were studied in 158 donors for the relative distribution of their various alleles and the discriminative power of the different loci was studied in 105 patient / donor pairs.

PCR was used to amplify different loci and an informative locus was selected for post-transplantation chimerism detection in each patient.

In our series 84 transplanted patients (34 post myeloablative and 50 post nonmyeloablative conditioning regimens) were followed up for the state of chimer-ism.

Results : Apo-B was the most polymorphic VNTR locus with 12 detected alleles.

The discriminative power of different loci ; excluding H-Ras, ranged from 46 % to 58 %.

The 6 studied loci were informative in 95% of patient/donor pairs.

The incidence of complete chimerism (CC) was 91 % post myeloablative and 63% post nonmy-eloablative.

The incidence of mixed chimerism (MC) was 6 % post myeloablative and 20 % post nonnmyeloablative transplant.

Autologous recovery (AR) occurred in 3 % postmyeloablative and 17 % post nonmyeloablative transplant.

Conclusion : Assessment of chimerism is an indispensable tool to manipulate patients after nonmyeloablative conditioning.

It permits the evaluation of engraftment, differential diagnosis of pancytopenia and early detection of impending relapse or rejection after both myeloablative and nonmyeloablative transplantation.