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Abstract Over the past 40 years, bone marrow and hematopoietic stem cell transplantation have been used with increasing frequency to treat numerous malignant and nonmalignant diseases. Although; marked improvements in survival rate following allogeneic HSCT was achieved, graft versus host disease (GVHD) remains the major cause of morbidity and mortality associated with allogeneic transplantation and stands as a significant barrier to this therapy. Graft versus host disease (GVHD) is an immune driven disorder where donor T cells react and proliferate in response to host antigens leading to an immune reaction that can affect several target organs including liver, skin, and the gastrointestinal tract. Rates of GVHD vary from (30-40%) in transplant from related donors to (60-80%) in transplant from unrelated donors. Some reports have been done discussing the role of adenosine-tri phosphate (ATP) as an endogenous dangerous signal evoking systemic inflammatory response enhancing GVHD and affecting tumor growth and spread.Recent murine studies using CD73-deficient mice have shown that CD73-generated adenosine can be manipulated to influence both the severity of GVHD and the strength of the GVL effect. A prospective study was held at Ain Shams University BMT unit with recruitment of 30 donors as control and30 patients who were eligible for allo-HSCT for diverse benign and malignant hematological disorders. All of these patients had fully matched donors except for one patient who received haplotype transplants from her mother. Of these patients, 19 were males (63.3%) and 11 were females (36.7%). Their age ranged from 16-55 years old, whereas 22 donors (73.3%) were males and 8 were females (26.7%) and their age ranged from 16-65 years old. Enrolled cases have different diagnosis including: 13 cases with AML, six cases with ALL, six patients had aplastic anemia, two patients had MDS, another two patients diagnosed with NHL, and finally the last case had CML. All of the cases were subjected to routine pre-transplant history taking, thorough clinical examination and different investigations as complete blood picture, liver profile, kidney function test, bone marrow aspiration, trephine, flowcytometry, cytogenetic study, and viral markers. Assessment of CD73 positive cells via flowcytometry on peripheral blood samples in donors and in recipients were done before conditioning and once GVHD occurs (within 6 months) with assessment of severity of GVHD via clinical examination, and other investigations as needed. Patients were subjected to variable conditioning protocols according to diagnoses. Candidates were followed up for 6 months post-transplant for disease recurrence, complications with different investigations ordered on demand. Acute GVHD, affected six patients (20%) with two of them (33.3%) with grade III and another two (33.3%) with severe grade IV aGVHD. On the other hand, cGVHD affected 10 patients (33.3%). six patients (20%) had chronic hepatic GVHD. Four patients (13.3%) had chronic cutaneous GVHD, 3 patients (10%) had pulmonary cGVHD, while chronic gut GVHD had occurred in 2cases (6.7%).Secondary graft failure affected only two patients (7.4%), whereas no cases of primary graft failure were reported in our study. Bacterial infections nearly affected the majority of studied population (25 patients= 83.3%), 20 patients (66.7%) had viral infection mostly CMV, and 17 ceases (56.7%) had fungal infections with only two of them (6.7%) had severe mucormycosis. Assessment of plasma level of CD73 in both recipients and donors were done and showed higher levels in recipients either pre-transplant (m=58.24 ±19.68) or at time of GVHD (m=65.78 ±19.03) compared to donors (m=29.08 ±14.14). Correlation of plasma level of CD73 in recipients with incidence of post-transplant complications showed that its pre-transplant levels in recipients was correlated with chronic GVHD and mortality rate with statistical significance (pvalue 0.004, 0.013 respectively), while it didn’t show any correlation with either aGVHD or relapse (p-value 0.270, 0.988 respectively). Pre-transplant CD73 level in recipients showed a negative correlation of significance with aGVHD grading (P –value 0.0499) while it was statistically insignificant with severity of cGVHD (p-value 0.658). As regard role of CD73 in prediction of post-transplant complications, recipients’ CD73 levels were a good predictor of cGVHD with sensitivity of 100% and specificity of 65% at levels ≤61.07%, also it could predict mortality with a sensitivity of 92.9% and specificity of 75% at levels >57.67%. While in donors, CD73 had a good predictive value with sensitivity of 100% and specificity of 78.6% at levels ≤26.86%, as well CD73 at level >27.14% could predict mortality with a sensitivity of 85.7% and specificity of 62.5%. So, finally we conclude that CD73 expression in recipients was an independent predictor of cGVHD, while it’s expression in both recipients and donors were an independent predictor of mortality. |