N.N. Mamaev1, A.V. Gorbunova1, T.L. Gindina1, E.V. Morozova1, Ya.V. Gudozhnikova1, O.A. Slesarchuk1, V.N. Ovechkina1, A.A. Rats1, E.G. Boichenko2, E.A. Ukrainchenko3, V.M. Kravtsova1, A.V. Evdokimov1, I.M. Barkhatov1, S.N. Bondarenko1, B.V. Afanas’ev1
1 R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 12 Rentgena str., Saint Petersburg, Russian Federation, 197022
2 Municipal Children’s Hospital No. 1, 14 Avangardnaya str., Saint Petersburg, Russian Federation, 198205
3 Alexandrovskaya Municipal Hospital No. 17, 4 pr-t Solidarnosti, Saint Petersburg, Russian Federation, 193312
For correspondence: N.N. Mamaev, DSci, Professor, 12 Rentgena str., Saint Petersburg, Russian Federation, 197022; Tel: +7(812)233-12-43; e-mail: firstname.lastname@example.org
For citation: Mamaev N.N., Gorbunova A.V., Gindina T.L., Morozova E.V., Gudozhnikova Ya.V., Slesarchuk O.A., Ovechkina V.N., Rats A.A., Boichenko E.G., Ukrainchenko E.A., Kravtsova V.M., Evdokimov A.V., Barkhatov I.M., Bondarenko S.N., Afanas’ev B.V. Allogeneic Hematopoietic Stem Cell Transplantation in Myelodysplastic Syndromes and Clinical Significance of WT1 Gene Overexpression. Klin. Onkogematol. 2014; 7(4): 551–563 (In Russ.).
The results of allogeneic hematopoietic stem cell transplantation (HSCT) in 17 patients (pts, 11 male, 6 female) with myelodysplastic syndromes (3 RA/RARS/RCMD, 5 RAEB-1, 7 RAEB-2, 2 JMML) are presented. The median age was 26 years with a range between 1 and 55 years. Serial cytogenetic investigations were carried out in all of them. Seven pts demonstrated monosomy 7, which was associated with other chromosome abnormalities in 4 cases. In addition, deletion at 11q23 (n = 3), trisomy 8 (n = 2) and 21 (n = 2), involvement into rearrangement at 3q (n = 2), t(6;9) translocation, and others more rare abnormalities were found. Prior to aHSCT, 11 of 7 received hypomethylating agents (HA) which proved to be effective in a half of them. In order to prepare for aHSCT, ablative (busulfan, cyclophosphamide) or non-ablative (fludarabine, cyclophosphamide) conditioning regimes were applied (4 and 13 respectively). Repeated aHSCT was carried out in 6 pts because of transplant rejection or post-transplant relapses. Molecular monitoring of minimal residual disease as well as early diagnosis of these relapses was performed by means of serial tests of the WT1 gene level expression and donor chimerism. Maximum WT1 values varied between 15 and 43133 copies/104 copies of ABL gene; and molecular relapses were registered in a half of them, including 5 patients with transformation into acute leukemia (AL). HA were used for prevention and treatment of relapses in 4 (24 %) patients; and HA were combined with donor lymphocyte infusions. Standard chemotherapy was applied for these purposes relatively rarely. This study demonstrated WT1 gene overexpression to be not only an important marker for diagnosis of post-transplant MDS/AL relapses, but it also can be used for evaluation of the treatment efficacy.
Keywords: myelodysplastic syndromes, allogeneic HSCT, post-transplant relapses, minimal residual disease, molecular monitoring, serial WT1 gene expression.
Accepted: September 30, 2014
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