The allogeneic hematopoietic stem cell transplantation (alloHSCT) constitutes a recommended therapy of many proliferative, especially hemato-oncologic diseases. Despite the fact, that hematopoietic stem cell transplantology develops very dynamically, and almost 40 years have passed since the first alloHSCT, early and late complications of post-transplant care remain unresolved. Early complications include conditioning toxicity (nausea, vomitus, alopecia, hemorrhagic cystitis, sinusoidal obstruction syndrome, interstitial pneumonia, thrombotic microangiopathy), pancytopenia with related infections and acute graft-versus-host disease (a-GVHD). Late complications include those related to conditioning toxicity (infertility, cataract, hypothyreosis, secondary malignancies) and chronic graft-versus-host disease (cGVHD).

Although the prognosis after alloHSCT depends mainly of the disease, long survival is being estimated in the range of 40-70%. Infectious complications and GVHD (30-40%), organ toxicity of chemotherapy (20%) and relapse (20-30%) are the most frequent causes of failures.

The possession of a HLA-matched donor is a key requirement for alloHSCT therapy. Tissue histocompatibility is determined by genes of major histocompatibility complex (MHC), which in man is known as a HLA (human leukocyte antigens). The genes encoding HLA antigens system are located in the short arm of chromosome 6. The products of the HLA genes can be divided into class I (HLA-A,-B,-C) and class II (HLA-DP,-DQ,-DR) molecules. Class I HLA antigens are expressed on most of nucleated cells, excluding red blood cells and cells of the nervous system, while class II HLA molecules occur mainly on B cells, macrophages, dendritic cells and thymic epithelial cells. Molecules of both classes differ in structure, tissue distribution and characteristics of peptide presentation to T-lymphocytes which plays a major role in creating immunity. HLA typing- key element of donor-recipient pair matching- is managed with use of serological and more accurate bio-molecular methods based on identification of HLA-antigens encoding DNA.

The DNA typing methods include:

a) specific sequences of DNA nucleotides (SSOP – sequence-specific oligonucleotide probe),

b) DNA sequence-specific primers (SSP – sequence specific primers),

c) direct nucleotide sequencing (SBT – sequence based typing),

d) other methods such as using a hetero-duplex analysis.

Matching of HLA compatible donor is the most important single factor determining the outcome of allogeneic transplantation, affecting the possible loss of graft, the incidence and severity of GVHD and survival.

Siblings are the first to be tested in order to find an optimal donor of hematopoietic cells. The odds ratio for HLA compatibility in siblings is 1:4. The probability of having a compatible donor among siblings by a particular patient is determined by the formula 1- (0.75)n, where n is the number of possessed siblings. In case of the absence of siblings or lack of compliance, search of an unrelated donor is performed. When not successful, it is followed by an alternative donor search, i.e. an unrelated HLA mismatched, or donor from extended family.

The probability of finding an unrelated donor is dependent upon the prevalence of certain haplotypes in the general population. Odds ratio of finding an unrelated donor is about 1:10 000, but in case of a search of world registers which contain search determinants currently of more than 15 million donors, it is possible to find one for the majority of patients in need.

Unfortunately, failure of treatment is observed in some patients despite full HLA-match of donor-recipient pair, a state of disease remission before transplantation and the best course of transplant procedure. Excluding the possibility of incorrect HLA typing it can be suspected, that mismatched minor histocompatibility antigens (mHAgs) may be responsible. These antigens belong to a very heterogeneous group of peptides, usually composed of 9-12 amino-acids. Disparities in the mHAgs result from polymorphism of amino-acids which they are composed of, as a consequence of polymorphisms of genes encoding them. The product of each polymorphic gene in combination with molecules of the major histocompatibility complex MHC may induce a response and act as a transplant mHAg. mHAg are encoded by autosomal genes or gender genes located on the Y chromosome, which thus do not occur in women. Most of mHAgs are encoded by one immunogenic and one non-immunogenic allele, and in fact one allele determines the potential strength of their immunogenicity. mHAgs are being presented after binding to the appropriate binding site of the HLA class I or class II molecule. The dependence of mHAgs immunogenicity from the presence of specific HLA molecule possessing an adequate peptide binding site specific for each particular mHAg is called MHC restriction. Autosomal and Y-chromosome encoded mHAgs are presented in Tables 1 and 2, respectively.