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Page 37
allied
academies
August 23-24, 2018 | London, UK
Hematology and Oncology
2
nd
International Conference on
Journal of Hematology and Blood Disorder | Volume 2
In vitro culture of BM cells and CytB polymorphisms can predict the
In-vivo
Hematological response
induced by deferasirox
Muhammad Shahzad Ali
University of Turin, Italy
Background:
Many studies showed that iron chelation therapy
(ICT) can induce hematological improvement and transfusion
independence in a significant percentage of MDS patients. At
nowwe do not have clinical or biological parameters to identify
the patients with high probablility of hematological response.
The aim of the study was to set up an in vitro assay able to
predict in vivo hematological improvement to deferasirox
treatment and to identify additional markers of response.
Methods:
22 MDS patients from 9 Italian centres were enrolled
in the study. Five were RA, 4 RARS, 8 RCMD, 4 RAEB I , 1 CMML.
In 6 of them ICT induced RBC transfusion independence during
the first 6 months of therapy, one experienced hematological
improvement but he stopped therapy after few months for
progression. BM samples were collected from 22 patients
before deferasirox treatment and during follow up. BM cells
were incubated with deferasirox 50 micromolar for 12 hrs and
tested for colony formation in semisolid culture. In addition,
different mitochondrial genes were sequenced, including COX1,
COX2 and CytB in all the patients enrolled.
Results:
In 8 out of 22 patients (3 RA, 2 RARS, 2 RCMD, 1 CMML)
the in
vitro
incubation with deferasirox resulted in a significant
increase of colonies (BFU-E, CFU-GM and CFUGEMM). (mean
value of BFU-E: 9±4 before incubation and 19±11 after
incubation). Interestingly, 6 of these 8 patients who showed an
“
In vitro
” response experienced transfusion independence after
In vivo
treatment with deferasirox, one showed hematological
improvement according to Cheeson’s criteria but he died for
progression few months after starting therapy and one could
not be evaluated because of intolerance to treatment. By
contrast patients who did not respond in vitro to deferasirox did
not significantly reduce the transfusion requirement. In parallel
we analysed mtDNA in BM MNC cells and we found a strict
association between two polymorphisms of CytB (14766 and
15326) and the hematological response to deferasirox therapy.
Conclusion:
The hematological improvement during deferasirox
therapy in MDS patients can be predicted by colony assay after
in vitro incubation with deferasirox. In addition, mitochondrial
gene polymorphisms can be associated with hematological
response. Finally, although not conclusive, the fact that 12
hours of deferasirox incubation can increase the number of
BFU-E suggests that deferasirox is probably able to overcome
the defect of erytroid progenitors thus pushing the MDS
clone towards terminal differentiation rather than to reduce
the number of MDS cells thus favoring the normal cells.
e:
muhammad.ali79@edu.unito.it