1. at First Pavlov State Medical University of Saint-Petersburg, Russia
PROGNOSTIC SIGNIFICANCE OF THE CYTOGENETIC EVOLUTION AFTER THE ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN PEDIATRIC ACUTE LEUKEMIA
Tatiana Gindina, Nikolay Mamaev, Natalia Stancheva, Olga Slesarchuk, Elena Nikolaeva,
Irina Petrova, Alexander Alyanskiy, Lyudmila Zubarovskaya and Boris Afanasyev
R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation
at First Pavlov State Medical University of Saint-Petersburg, Russia
Results
Background and Aims
Thirty children and fifteen adolescents with post-transplant relapse were included in this study. The bone marrow karyotypic changes were analyzed before and after allo-HSCT of 45 patients (pts). Twenty-six (58 %) pts were male, and median age at alloHSCT was 10 years (range, 1,2-21). Seventeen (38 %) pts are still alive. Thirteen (29 %) pts received related transplantation, fifteen (33 %) did unrelated HSCT, and seventeen (38 %) did haploidentical HSCT. Four (9 %) pts had normal karyotype, twenty-two (49 %) had one chromosomal abnormality, four (9 %) had two abnormalities, and fifteen (33 %) had more than three abnormalities before HSCT. Median follow-up after HSCT was 500 days (40-861). Twenty-eight (62 %) pts showed gain or loss of chromosomal abnormalities from original one (group 1), sixteen (36 %) showed no karyotypic change between HSCT, and one (2 %) showed totally different karyotype. We defined the cytogenetic evolution group as group 1, and others as group 2. Median time from transplantation to relapse was not different between group 1 and 2. Shorter survival after relapse was observed for group 1 (8,9 % vs 51,5 % at 2-year post-relapse survival, P=0,041). Moreover, survival after relapse was inferior for pts with two or three abnormal cytogenetic clones (n = 10) compared to pts with one abnormal cytogenetic clone (n=35) (0% vs 32,5 % at 2 year post-relapse survival, P=0,016) (Fig.1).
Cytogenetic abnormalities at diagnosis having significant impact on disease outcome and clonal evolution at cytogenetic level is considered to be associated with relapse and refractoriness to chemotherapy. Relapse of acute leukemia was reported to be associated with cytogenetic clonal evolution in 40% of patients who have received chemotherapy. The cytogenetic clonal evolution in post-transplant relapse has been recently studied in adult acute myeloid leukemia (AML) by Yuasa et al. They showed the cytogenetic clonal evolution is an important predictor of resistance to therapy after allogeneic hematopoietic stem cell transplantation (alloHSCT). The aim of our work to study whether karyotypic changes in the pediatric acute leukemia relapsed after allo-HSCT and the cytogenetic evolution have a prognostic impact.
Patients and Methods
Children and adolescents diagnosed as AML or ALL who underwent allo-HSCT at our Institute from 2009 to 2014 were retrospectively reviewed to analyze the cytogenetic evolution patterns at relapse of acute leukemia after HSCT.
Conclusion
Survival time of pediatric acute leukemia pts was similar with those of the above-mentioned adult AML being significantly shorter for group 1 than group 2. It supports that cytogenetic clonal evolution may be an important predictor of resistance to therapy after allo-HSCT, and needs novel therapeutic approaches.
References
Figure 1 (A,B)
Yausa M, et al. Prognostic significance of the cytogenetic evolution after the hematopoietic stem cell transplantation in adult acute leukemia. Blood 2013, 122(21): 1391 (abstract).
Impact of karyotype change (A) and a number of abnormal cytogenetic clones (B) on survival time after relapse.