Abstract

Aim The goal of the study was to evaluate a correlation of an HLA restricted minor histocompatibility antigen (mHAg) with the development of graft versus host disease (GVHD). The objective was to assess whether testing for mHAgs should be done on a prospective basis, to guide donor selection and reduce the high incidence of GVHD in post-transplant allografts when treating hematologic malignancies. Methods A cohort of 45 patient/unrelated donor pairs, 10/10 HLA match, in the NCI protocol 07-C-0195 were typed for 18 mHAgs using an SSP-PCR typing kit (Minor Histocompatibility Antigen Typing Kit; Life Technologies, Carlsbad, CA). GVHD data was obtained from the clinical protocol database. Patients were determined not evaluable if they relapsed or had residual disease requiring a donor lymphocyte infusion or additional chemotherapy. Due to clinical status, one patient could not be evaluated for acute or chronic GVHD. In addition, 4 patients could not be evaluated for chronic GVHD. Therefore, 44 out of 45 patients were evaluated for acute GVHD and 40 out of 45 patients for chronic GVHD. Statistical analysis was performed using the Fisher exact test. Results Patients with mHAg mismatches were analyzed for both acute and chronic GVHD. Preliminary analysis demonstrates that out of the 45 patient/donor pairs, 30 pairs had mHAgs mismatched in the GVHD direction. 19 of the 30 patients (63%) with mismatches developed acute GVHD (P = 0.062) and 15 of the 30 patients (50%) with mismatches developed chronic GVHD (P = 0.061). Nine of these patients developed both acute and chronic GVHD. Conclusions Data suggests some correlation regarding mHAg mismatches and the development of GVHD. Further study and a larger cohort may allow a gauge for the efficacy of testing for the mHAgs on a prospective basis. Testing on a prospective basis could give clinicians more knowledge to select donors with a favorable mHAg constellation to reduce the risk of their transplant patients developing GVHD.

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