MOLECULAR MONITORING OF CHIMERISM AFTER BONE MARROW TRANSPLANTATION IN BULGARIA
Velizarova M1, Zaharieva B2, Dimova I2, Nikolova D2, Atanasova S2, Avramova B3, Mihailov G3, Jordanova M3, Bobev D3, Toncheva D2,*
*Corresponding Author: Professor Draga Toncheva, Department of Medical Genetics, Medical Faculty of Sofia, 2 Zdrave str., 1431 Sofia, Bulgaria; Tel./Fax: +359-2-9520357; E-mail: dragatoncheva@yahoo.com
page: 37

RESULTS

In patient #1, NCC was detected 10 days after the transplantation (95%). It was evaluated once monthly for 6 months. Starting from the third month, the chimerism became MC (50%) with further temporary decreasing amounts of autologous DNA (Fig. 2a). The patient suffered hard graft versus host disease (GVHD), and after cytomegalovirus (CMV) infection, died. In patient #2, the donor cells increased from 6 to 70% over 3 months (Fig. 2b). He achieved full remission.
Patient #3 showed CC (100%) during most of the analyses with only a slight decrease in the percentage of donor cells (still more than 90%) in the ninth month (Fig. 2c). The clinico-hematological findings indicated remission. Patient #4 went from NCC to MC within 4 months, with clinico-hematological results that indicated an early relapse (Fig. 2d). In patient #5, only 22% MC was achieved. It decreased dramatically to 0% accompanied by graft failure within a month (Fig. 2e).
Patient #6 showed autologous recovery (98 to 0% chimerism) over 12 months. Unstable MC started in the fifth month. Decreasing levels of donor chimerism occurred prior to graft rejection. The patient is now in remission after a complete autologous recovery (Fig. 2f).
The three male-to-male donor-recipient pairs were studied for chimerism by genotyping of STR and VNTR markers. Patient #7, where the marker SERT was informative, showed chimerism after 3 months, followed by a recurrence of the illness. Patient #8 died before the first monitoring, and patient #9 was not studied because none of the molecular markers showed any informative results.

Table 1. Clinical data.

Patient code

Age

Sex

Diagnosis

Donor

1

8

M

ALL

Sister, full identical

2

13

M

MDS – RAEB

Sister, full identical

3

12

M

ALL

Sister, full identical

4

10

M

ANLL

Sister, full identical

5

M

Thalassemia major

Mother, full identical

6

37

F

Aplastic anaemia

Brother, full identical

7

10

M

ALL

Brother, haplo identical

8

10

M

ALL

Unrelated donor, full identical

9

15

M

AML

Father, full identical

Figure 1. Recipient (a) and donor (b) cells in recipient blood samples, evaluated by FISH.

Figure 2. Chimerism in patient 1.

Figure 3. Chimerism in patient 2.

Figure 4. Chimerism in patient 3.

Figure 5. Chimerism in patient 4.

Figure 6. Chimerism in patient 5.

Figure 7. Chimerism in patient 6.




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