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GRAFT-Versus-Host Disease Clinical Profile and Duration of Immunosuppression Among Patients WHO Received Cord Blood STEM CELL Transplant: A Single Center Experience
Objectives: Determine clinical features of GVHD and duration of therapy in patients who received CBT.
Patients and Methods: From 1993 to 2013, 196 patients received CBT were retrospectively analised and divided into two categories. Group 1: 64 patients who developed GVHD. Group 2: 132 patients without this complication. Acute GVHD was graded according to Glucksberg criteria and Chronic Graft versus Host Disease was graded by NIH consensus criteria. Statistical analysis: Kaplan Meier (survival) and Fisher test (comparison of categorical variables). P level of significance was <0.05.
Results: Thirty three percent of patients developed GVHD (40 males and 24 females). Median age was 6 years old (1-31). 61 patients received CBT from a mismatched donor. Thirty (48%) were transplanted for malignancies. Five transplants were from a related and 59 from an unrelated donor. Conditioning: Reduced intensity (RIC) in 6 cases and myeloablative in 58. Engraftment was complete in 48 cases (75%). Median survival in group 1 was 1832d (27-7283) versus 201d in group 2 (1-6242). Twenty nine patients have died. Forty one patients developed acute GVHD (aGVHD), 6 patients classic chronic GVHD (cGVHD) and 17 had an overlap syndrome. Grade II-IV aGVHD was seen in 49 cases (84.4%). Among cGVHD patients 9 (39.2%) were mild, 6 (26%) moderate and 8 (34.8%) severe. Median time for the onset of aGVHD was 23d (7-227) and cGVHD was 176d (64-659). The main sites of aGVHD were skin: 55(86%), gut: 22 (34%) and liver:14 (21%). Among cGVHD patients, 14 had skin (21%), liver:12 (18%), mouth:9 (14%), gut and lung (BO): 6(9%) each. Median time of cyclosporine therapy was 923d (7-3365). Steroids were used for a median time of 290d (8-4303). GVHD was less common in patients with a full match donor (p=0,001), those who used thymoglobuline (p<0,0001) and methotrexate (MTX) (p=0,0133). In contrast, GVHD rates were higher in patients who had an early (p=0,0111) and complete (p<0,0001) engraftment and had bacterial (p=0,0133) or viral (p=0,0086) infections during the pre-engraftment time. Survival rates were higher in patients who developed GVHD (p=0,0256), had a myeloablative conditioning regimen (p=0,048), children <14 yo (p=0,0002), patients who used cyclosporine for at least one year (p<0,0001) and full chimerism (p<0,0001).
Conclusions: We conclude GVHD can be frequent and even serious in CBT recipients. Risk factors included early and complete engraftment, mismatched donor, viral or bacterial infection during the pre-engraftment period, use of RIC and lack of MTX. Risk factors for survival were absence of GVHD, RIC, older age, and lack of full engraftment.