Impact of HLA-C matching on acute graft-versus-host disease in allogenic hematopoietic stem cell transplantation

Outcome of unrelated donor marrow transplantation is influenced by donor/recipient matching for HLA. Prior studies assessing the effect of mismatch at specific HLA loci have yielded conflicting results. Disparity for HLA-A or HLA-B antigens increases the risk of poor marrow graft outcome, but little is known about the relevance of HLA-C matching. This work aimed to evaluate the effect of HLA-C matching on hematopoietic stem cell transplant, outcome specifically on the acute graft versus host disease [aGVHD]. Seventy patients given hematopoietic stem cell transplant [HSCT] in different transplant centers with their relevant donors were included in the study, HLA class I [HLA-A, -B] and class II [DRB1, DQR1, DPB1] typing was performed using polymerase chain reaction-sequence-specific oligonucleotide probe [PCR-SSOP] and HLA-C typed by PCR-sequence specific priming [PCR-SSP] technique. The risk of aGVHD during the first three months after HSCT was estimated. Fifty two [74.3%] donor/recipient pairs were mismatched for HLA class I alleles, eighteen [34.6%] of them experienced aGVHD. While no history ofaGVHD was reported in eighteen HLA class I full matched pairs [25.7%]. Higher incidence of aGVHD was observed with isolated HLA-A mismatch [28.6%], and for isolated HLA-B and HLA-C locus mismatch, the incidence were 25% and 16.7% respectively. The incidence of aGVHD was elevated if HLA-A or HLA-B mismatch is associated with HLA-C mismatch [40% and 37.5% respectively]. Much higher incidence of aGVHD was associated with combined HLA-A-B and-C mismatch [44.4%]. The estimated odds ratio [OR] of aGVHD for total HLA-C mismatch relative to matched pairs [univariable model] was 5.0 [95% CI 1.3-19.4; P= 0.01]. The degree of HLA-C allele mismatch [one or two alleys mismatch] were significantly related to aGVHD outcome [OR, 3.9, P= 0.03; OR, 10.8; P .009 respectively]. HLA-A or HLA-B allele disparity was also associated with aGVHD. As regard the analysis of total HLA-A and -B mismatched pairs with their corresponding matched locus, they demonstrated significant adverse effect on aGVHD [OR, 2.8; P=0.04; OR 3.0; P=0.03]. It was concluded that HLA-C may function as a powerful transplantation antigen. HLA-C compatibility should be incorporated into algorithms for donor selection to improve the outcome especially in patients who have an increased risk. The presence of HLA-C mismatch with either HLA-A or HIA-B mismatch leads to a synergistic increase in cytotoxic responses and poor graft outcomes [the development of aGVHD]; however, isolated HLA-C mismatch may be acceptable with respect to T-cell mediated alloreactivity

Evaluation of clinical significance of prostate specific antigen and other tumor markers in breast cancer

To evaluate the significance of prostate specific antigen [PSA], both total and free, carcinoembroynic antigen [CEA] and carbohydrate antigen 15 -3 [CA15- 3] in breast cancer serum levels of total and free PSA, CEA and CA15-3 were measured in 60 female patients with breast cancer at time of primary diagnosis. The patients were divided into 4 groups according to the stage of breast cancer and the results were compared with those of 25 apparently healthy females as controls. The study revealed that, total PSA was detected in serum of 4% [1/25] of healthy controls and 18% of breast cancer patients. Free PSA is the predominate molecular form of serological PSA in 54% of patients with increased total PSA levels. Free and total PSA, levels were highly significantly increased in advanced stages of breast cancer [III and IV] in comparison to control group, stage I and stage II [P < 0.001]. There was significant negative correlation between PSA [total and free] and age of breast cancer patients [r = 0.285,P< 0.05, r = -0.295, P<0.05 respectively]. There was significant positive correlation between PSA [total and free] and stage of breast cancer [r = + 0.470, P <0.001, r = +0.399, P <0.01 respectively] CEA levels were significantly increased in stage I [P< 0.05], stage II [P < 0.01] stage III and IV [P < 0.001] in comparison with control group. Levels of CEA and CA 15-3 were significantly high in stages III and IV compared with stages I and II [P < 0.001]. There was significant Positive correlation between [CEA, CA15-3] and stage of breast cancer [r = +0.314, P<0.05, r = + 0.547, P <0.01 respectively]. There is a positive correlation between [CEA and CA15-3 [r = +0.597, P<0.001]. In conclusion: Levels of serum PSA and CA 15-3 increased in late stages of breast cancer and so they cannot be used as a screening diagnostic tool for breast cancer. Although CEA increases early in breast cancer, it cannot be trusted as a diagnostic tool for breast cancer as its levels are elevated in a variety of cancers, so it may be used as a screening test. There is a positive correlation between CA 15-3 and CEA, which can be used together for follow up and prognosis of breast cancer