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العنوان
Post allogenic stem cell transplant cyclophosphamide as graft versus host disease prophylaxis in acute leukemia /
المؤلف
El-Shamy, Alaa Nabil.
هيئة الاعداد
باحث / الاء نبيل احمد الشامى
مشرف / محمد نصر محمد معبد
مشرف / عصام علي عبدالمحسن
مناقش / عمادالدين عزمي حسن
مناقش / محمد عبدالمعطي سمره
الموضوع
Acute leukemia - Diagnosis. Leukemia. Stem cell. Acute leukemia - Cytodiagnosis. Acute leukemia - Cytodiagnosis.
تاريخ النشر
2020.
عدد الصفحات
online resource (115 pages) :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الطب الباطني
تاريخ الإجازة
1/1/2020
مكان الإجازة
جامعة المنصورة - كلية الطب - قسم الباطنة العامة
الفهرس
Only 14 pages are availabe for public view

from 139

from 139

Abstract

Allo-HSCT is a potent curative treatment for Hematological Malignancies. Its curative potential is mainly based on immune-mediated graft-versus-leukemia effects caused by donor T cells. However, donor T cells are also the cause of GvHD which is one of the most recognized and life-threatening complications of HSCT. Calcineurin inhibitor (CNI) and methotrexate (MTX) have been used as the standard GvHD prophylaxis in HLA-matched HSCT. Although Haplo SCT was originally associated with high incidences of GvHD and graft rejection, it‟s now considered a promising alternative source and it is readily available for almost all patients. Promising clinical trial data using High dose Post-transplant Cyclophosphamide (PT-Cy) with or without additional immunosuppressive agents (IS) have shown that it‟s an effective, well tolerated alternative and has crossed the HLA barriers of Haplo SCT. To compare clinical outcomes of allogeneic HSCT after post- transplant cyclophosphamide versus methotrexate based regimens, we analyzed 80 patients (Pts) with Acute Leukaemia (53 males, 27 females) with age ranges from 18 to 60 years underwent fully matched allogenic HSCT and haploidentical HSCT using reduced intensity chemotherapy at Maadi Armed Forces Medical Hospital. The Pts were randomized into 2 groups according to GvHD prophylaxis regimen. The 1st group (40 patients) received MTX in the following doses; day+2 (15mg), day +4 (10 mg), day +6 (10 mg) with Cyclosporine (5mg/kg) from day -3 till day +90 and Mycophenolate (MMF) (2 -3gm/day) from day +1 till day +30. The 2nd group received PT-Cy (45 mg/kg/day) on days +3 and +4 with Cyclosporine (5mg/kg) from day +5 till day +30 & MMF:(2-3gm /day) from day +5 till +30. 87.5% of Pts in group 1 and 90 % of Pts in group 2 were engrafted with full donor chimerism on day +30 (P=0.72). The risk of graft failure has no statistically significant difference between the MTX group (12.5%) and the PT-Cy group (10%). Incidence of acute GvHD (aGvHD) was (47%, 37.5%) in group 1, 2 respectively (P=0.48). Thirty percent of Pts in group 1 suffered severe aGvHD while only 12.5% of group 2 experienced it (P=0.056). PT-Cy was associated with statistically significant lowering of chronic GVHD (cGvHD) incidence compared to MTX group (20%, 77%) respectively (P=0.002). PT-Cy was associated with reduced risk of extensive cGvHD to 5% compared to 30% in MTX group (P =0.003). Pts received MTX had higher incidence of renal & liver toxicity when compared to PT-Cy group (P=0.018, P 0.013) respectively. PT-Cy group was associated with higher incidence of Hemorrhagic Cystitis (HC) when compared to MTX (P=0.006). Haplo HSCT was associated with higher incidence of HC when compared to fully matched (P=0.006). The cumulative incidence of relapse at 2 years after transplantation was 17.5 % (7 patients) for group 1 and 30 % (12 patients) for group 2 (P > 0.05). The cumulative 4 years Disease Free Survival (DFS) & Overall survival (OS) in PT-Cy group were (45, 7%, 46.9%) respectively while (43.4%, 43.7%) in MTX group which is statistically non-significant (P>0.05). Conclusion. PT-Cy with addition of IS drugs has statistically significant difference in reducing the incidence of cGvHD in both fully matched & Haplo SCT with less hepatic & renal toxicity. No effect on engraftment, relapse, DFS and OS when compared with methotrexate based regimen.