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العنوان
Outcome of Sex-mismatched Allogeneic Hemopoietic Stem Cell Transplantation from Human Leukocyte Antigen identical sibling donors in Patients with Hematological diseases /
المؤلف
Bokhary,Mahmoud Tarek Sayed Ahmed.
هيئة الاعداد
باحث / Mahmoud Tarek Sayed Ahmed Bokhary
مشرف / Mohamed Osman Azzazi Elmesery
مشرف / Mohamed Abdel-Mooti Mohamed Samra
مشرف / Rasha Kamel Fathy
تاريخ النشر
2018
عدد الصفحات
154p.;
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
أمراض الدم
تاريخ الإجازة
1/1/2018
مكان الإجازة
جامعة عين شمس - كلية الطب - امراض الدم
الفهرس
Only 14 pages are availabe for public view

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from 154

Abstract

The main goal of post-transplantation monitoring is to predict unwanted events such as disease relapse, graft rejection and GVHD, in order to initiate the relevant treatment. In this context, chimerism analysis is, beyond doubt, an important method in monitoring post HSCT outcome. In fact, several previous works suggest that an accurate quantitative analysis of chimerism kinetics would permit early differentiation between the absence of engraftment and a delay in engraftment, as well as early detection of patients with a high risk of GVHD or those
liable to relapse.
The presence of mixed chimerism is to a major extent considered as being a phenomenon parallel to disease evolution post HSCT. The occurrence of mixed chimerism is dependenton several factors such as the disease for which HSCT has been performed, the intensity of the conditioning regimen, the use of T-cell depletion, the number of stem cells infused, the sensitivity of the technique utilized and the timing at which the assay is performed. The chimerism detection technique, therefore, should be selected with extreme care, so that an accurate status can be detected and exact information obtained regarding relapse, GVHD or GVL effect. For all these clinical applications, the optimal methodological approach needs to be informative, sensitive and quantitatively accurate. Quantitative real-time PCR using biallelic markers seems to be the best method for detection of autologous hematopoiesis.
For female recipients of allograft, donor sex has no detectable effect on HSCT outcomes. In contrast, for male recipients, female donors are associated with a decreased incidence of relapse, an increased incidence of NRM and chronic GVHD, while male donors are associated with an increased incidence of relapse. As a result, both OS and PFS are might be worse for all male recipients, regardless of donor sex or with female donors. Furthermore, because OS and PFS are similar between F→M and M→M, one could argue that male recipients fare better with male donors considering the chronic GVHD related quality of life. However, it is not obvious whether quality of life would be more severely affected by GVHD or by management of relapse, so that it may be premature to make recommendations about the preferred donor sex for male recipients until additional studies that include quality of life are conducted. Finally, it is important to recognize that the absolute differences in clinical outcomes across recipient and donor sex combinations are small (within 5% across all sex combinations) and much smaller than those attributable to important prognostic factors such as disease risk index and donor-recipient HLA match.
There is a direct and important bearing on the choice of HSCT donors. The donor sex distribution seemed to be skewed toward male donors for male recipients (64% vs. 42% sex matched in female recipients), which may reflect the commonly held view that a male donor is preferable for a male recipient, which was perhaps derived from the clinical reports in previous years. However, recipient sex rather than donor sex appears to be the predominant prognostic driver. Consequently, donor sex should not be considered in the donor selection algorithm until a better insight into the biology of sex-based alloreactivity.
Overall survival is affected by the presence of an H–Y mismatch after BM (but not PB) transplantation. This observation is relevant because many studies take patients receiving BM and PB together when analysing risk factors for clinical outcome after allogeneic stem cell transplantation. The presence of an H–Y mismatch may influence the outcome after allogeneic transplantation for acute leukaemia, CML or MDS depending on the stem cell source. It may reflect the different allorecognition of mHags depending on the precedence of the infused cells. If this is true, it also becomes relevant that the analysis of genetic risk factors for acute GVHD or TRM (mHags or gene polymorphisms) should include two
different cohorts (BM and PB).