Východiská: Alogénna transplantácia krvotvorných buniek (allogeneic hematopoietic stem cell transplantation – alloHSCT) predstavuje významný terapeutický výkon pre liečbu celého spektra závažných chorôb. Pokroky v liečbe a podpornej starostlivosti zlepšili celkové prežívanie, avšak napriek tomu sa alloHSCT naďalej vyznačuje značnou úmrtnosťou, najčastejšie zapríčinenou chorobou z reakcie štepu proti hostiteľovi (graft-versus-host disease – GvHD). Cieľom našej retrospektívnej analýzy bolo zistiť, ktoré z vybraných faktorov mali vplyv na celkové prežívanie a vývoj GvHD po alloHSCT od HLA-identických súrodencov. Analyzovali sme vek pacienta a darcu, kompatibilitu v AB0 systéme, zhodu pohlavia príjemcu a darcu, zdroj krvotvorných buniek, čas od diagnózy po alloHSCT, typ prípravného režimu, typ profylaxie GvHD a relaps. Pacienti a metódy: Sledovali sme 96 pacientov (54 mužov, 42 žien), ktorí podstúpili alloHSCT od HLA-identického súrodenca. Medián sledovania bol 64,5 mesiaca (rozsah 1–218 mesiacov), medián veku príjemcov aj darcov bol 34 rokov. Najčastejšou indikáciou alloHSCT bolo malígne hematologické ochorenie. Výsledky: Najvyšší počet úmrtí zapríčinila GvHD a jej komplikácie (n = 24; 46,2 %) a na druhom mieste bol relaps (n = 18; 34,6 %). Akútnu GvHD vyvinulo 30 (31,3%) a chronickú GvHD 25 (26,0%) z celkového počtu 96 pacientov. Celkovo GvHD vyvinulo 45 pacientov (46,9%). Pozorovali sme horšie celkové prežívanie pacientov mužského pohlavia, ktorí mali darkyne ženy v porovnaní s ostatnými pacientami (p = 0,01; HR = 2,33). Celkové prežívanie bolo lepšie u pacientov transplantovaných do 1 roka od stanovenia diagnózy, v porovnaní s pacientami transplantovanými po 1 roku (p = 0,03; HR = 1,93). Žiadny z faktorov nemal štatisticky významný vplyv na akutnú GvHD, chronickú GvHD a celkovo na GvHD. Záver: Potvrdili sme, že nezhoda pohlaví, ak darcom je žena a príjemcom muž, signifikantne negatívne ovplyvňuje celkové prežívanie po alloHSCT. Rovnako, celkové prežívanie mali signifikantne kratšie pacienti, ktorí podstúpili alloHSCT neskôr ako 1 rok od potvrdenia diagnózy.
Backgrounds: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a substantial therapeutic procedure for the treatment of a wide spectrum of severe diseases. Despite advancements in treatment and supportive care, alloHSCT still carries a considerable mortality risk, primarily caused by graft-versus-host disease (GvHD). Our retrospective analysis aimed to identify the factors influencing overall survival and GvHD development in HLA-identical sibling alloHSCT. We have analyzed patients’ and donors’ age, AB0 compatibility, recipient-donor gender match, stem cell source, time from the diagnosis to alloHSCT, conditioning regimen type, GvHD prophylaxis, and relapse. Patients and methods: Our study included 96 patients (54 male, 42 female) who underwent HLA-identical sibling alloHSCT. The median follow-up was 64.5 months (range 1–218 months), and the median age of both recipients and donors was 34 years. Malignant hematological diseases were the most common indications for alloHSCT. Results: GvHD and its complications accounted for the highest number of deaths (N = 24; 46.2%), followed by relapse (N = 18; 34.6%). Acute GvHD developed in 30 patients (31.3%), while chronic GvHD occurred in 25 patients (26.0%), resulting in a total of 45 patients (46.9%) experiencing GvHD. Male recipients with female donors had significantly worse overall survival compared to other patients (P = 0.01; HR = 2.33). Overall survival was better in patients transplanted within 1 year from the diagnosis compared to those transplanted after 1 year (P = 0.03; HR = 1.93). No factor reached statistical significance regarding the impact on acute GvHD, chronic GvHD, or overall GvHD. Conclusion: We confirmed that sex mismatch, specifically in the case of a female donor and a male recipient, significantly negatively affects overall survival after alloHSCT. Additionally, overall survival is significantly shorter when the interval between the diagnosis and alloHSCT exceeds one year.
- MeSH
- Survival Analysis * MeSH
- Adult MeSH
- Hematologic Neoplasms mortality therapy MeSH
- Histocompatibility MeSH
- Transplantation, Homologous mortality statistics & numerical data MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Graft vs Host Disease epidemiology mortality MeSH
- Siblings MeSH
- Statistics as Topic MeSH
- Bone Marrow Transplantation * mortality statistics & numerical data MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Clinical Study MeSH
Optimizing natural killer (NK) cell alloreactivity could further improve outcome after allogeneic hematopoietic cell transplantation (alloHCT). The donor's Killer-cell Immunoglobulin-like Receptor (KIR) genotype may provide important information in this regard. In the past decade, different models have been proposed aiming at maximizing NK cell activation by activating KIR-ligand interactions or minimizing inhibitory KIR-ligand interactions. Alternative classifications intended predicting outcome after alloHCT by donor KIR-haplotypes. In the present study, we aimed at validating proposed models and exploring more classification approaches. To this end, we analyzed samples stored at the Collaborative Biobank from HLA-compatible unrelated stem cell donors who had donated for patients with acute myeloid leukemia (AML) or myelodysplastic neoplasm (MDS) and whose outcome data had been reported to EBMT or CIBMTR. The donor KIR genotype was determined by high resolution amplicon-based next generation sequencing. We analyzed data from 5,017 transplants. The median patient age at alloHCT was 56 years. Patients were transplanted for AML between 2013 and 2018. Donor-recipient pairs were matched for HLA-A, -B, -C, -DRB1, and -DQB1 (79%) or had single HLA mismatches. Myeloablative conditioning was given to 56% of patients. Fifty-two percent of patients received anti-thymocyte-globulin-based graft-versus-host disease prophylaxis, 32% calcineurin-inhibitor-based prophylaxis, and 7% post-transplant cyclophosphamide-based prophylaxis. We tested several previously reported classifications in multivariable regression analyses but could not confirm outcome associations. Exploratory analyses in 1,939 patients (39%) who were transplanted from donors with homozygous centromeric (cen) or telomeric (tel) A or B motifs, showed that the donor cen B/B-tel A/A diplotype was associated with a trend to better event-free survival (HR 0.84, p=.08) and reduced risk of non-relapse mortality (NRM) (HR 0.65, p=.01). When we further dissected the contribution of B subtypes, we found that only the cen B01/B01-telA/A diplotype was associated with a reduced risk of relapse (HR 0.40, p=.04) while all subtype combinations contributed to a reduced risk of NRM. This exploratory finding has to be validated in an independent data set. In summary, the existing body of evidence is not (yet) consistent enough to recommend use of donor KIR genotype information for donor selection in routine clinical practice.
- MeSH
- Leukemia, Myeloid, Acute * therapy MeSH
- Genotype MeSH
- Histocompatibility * MeSH
- Middle Aged MeSH
- Humans MeSH
- Ligands MeSH
- Myelodysplastic Syndromes * therapy MeSH
- Prognosis MeSH
- Receptors, KIR * genetics MeSH
- Hematopoietic Stem Cell Transplantation * standards MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
Immunisation against Human Leucocyte Antigens (HLA) can be caused by pregnancy, blood transfusion, or organ transplants. The HLA antibody status of a given patient significantly influences their access and waiting time to transplant. For some highly sensitised patients (HSP) there is hardly any suitable donor available in the deceased donor pool of their allocation organisation and therefore they wait a very long time before being offered a kidney for transplant. Especially patients with rare HLA phenotypes in relation to the actual donor pool are waiting extremely long. As HLA phenotypes are different in the various European populations, we hypothesized that extension of the donor pool outside the respective allocation system will increase the chance of receiving a compatible transplant for this subgroup of highly sensitised patients. One of the objectives of the EUROSTAM project, (a Europe-wide Strategy to enhance Transplantation of highly sensitised patients on the basis of Acceptable HLA Mismatches) was to develop a tool to compare the chance of transplanting HSP in different European populations with donor organs from within and outside their own donor pool. Information on the HLA type and ABO blood group of the actual donor population, as well as the acceptable mismatches of long waiting HSP were obtained from the EUROSTAM partner organizations i.e. Eurotransplant (ET), UK National Health Service Blood and Transplant (NHSBT), Barcelona, Prague and Athens. Results from simulations using the newly developed tool shows that 195 (27%) of the 724 long waiting highly sensitised patients registered at each partner organisation have increased chances of transplant in a different European donor pool. This makes a strong case for sharing kidneys between European countries for selected difficult to transplant patients.
- MeSH
- Tissue Donors MeSH
- Histocompatibility MeSH
- HLA Antigens genetics immunology MeSH
- Immunization MeSH
- Humans MeSH
- Transplant Recipients MeSH
- Waiting Lists MeSH
- Histocompatibility Testing methods MeSH
- Kidney Transplantation * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Editorial MeSH
- Geographicals
- Europe MeSH
This analysis included 56 myelofibrosis (MF) patients transplanted from family mismatched donor between 2009 and 2015 enrolled in the European Society for Blood and Marrow Transplantation database. The median age was 57years (range, 38 to 72); 75% had primary MF and 25% had secondary MF. JAK2 V617F was mutated in 61%. Donors were HLA mismatched at 2 or more loci. Stem cells were sourced from bone marrow in 66% and peripheral blood in 34%. The median CD34+ cell dose was 4.8 × 106/kg (range, 1.7 to 22.9; n = 43). Conditioning was predominantly myeloablative in 70% and reduced intensity in the remainder. Regimens were heterogeneous with thiotepa, busulfan, fludarabine, and post-transplant cyclophosphamide used in 59%. The incidence of neutrophil engraftment by 28days was 82% (range, 70% to 93%), at a median of 21days (range, 19 to 23). At 2years the cumulative incidence of primary graft failure was 9% (95% CI 1% to 16%) and secondary graft failure was 13% (95% CI 4% to 22%). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II to IV and III to IV was 28% (95% CI 16% to 40%) and 9% (95% CI 2% to 17%) at 100days. The cumulative incidence of chronic GVHD at 1 year was 45% (95% CI 32% to 58%), but the cumulative incidence of death without chronic GVHD by 1 year was 20% (95% CI 10% to 31%). With a median follow-up of 32 months, the 1- and 2-year overall survival was 61% (95% CI 48% to 74%) and 56% (95% CI 41% to 70%), respectively. The 1- and 2- year progression-free survival was 58% (95% CI 45% to 71%) and 43% (95% CI 28% to 58%), respectively, with a 2-year cumulative incidence of relapse of 19% (95% CI 7% to 31%). The 2-year nonrelapse mortality was 38% (95% CI 24% to 51%). This retrospective study of MF allo-SCT using family mismatched donors demonstrated feasibility of the approach, timely neutrophil engraftment in over 80% of cases, and acceptable overall and progression-free survival rates with relapse rates not dissimilar to the unrelated donor setting. However, strategies to minimize the risk of graft failure and the relatively high nonrelapse mortality need to be used, ideally in a multicenter prospective fashion.
- MeSH
- Survival Analysis MeSH
- Databases, Factual MeSH
- Adult MeSH
- Histocompatibility * MeSH
- Transplantation, Homologous MeSH
- Middle Aged MeSH
- Humans MeSH
- Graft vs Host Disease MeSH
- Graft Survival MeSH
- Primary Myelofibrosis mortality therapy MeSH
- Transplantation Conditioning MeSH
- Recurrence MeSH
- Retrospective Studies MeSH
- Family * MeSH
- Aged MeSH
- Societies, Medical MeSH
- Hematopoietic Stem Cell Transplantation methods MeSH
- Bone Marrow Transplantation statistics & numerical data MeSH
- Peripheral Blood Stem Cell Transplantation statistics & numerical data MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
Extended molecular characterization of HLA genes in the IHWG reference B-lymphoblastoid cell lines (B-LCLs) was one of the major goals for the 17th International HLA and Immunogenetics Workshop (IHIW). Although reference B-LCLs have been examined extensively in previous workshops complete high-resolution typing was not completed for all the classical class I and class II HLA genes. To address this, we conducted a single-blind study where select panels of B-LCL genomic DNA samples were distributed to multiple laboratories for HLA genotyping by next-generation sequencing methods. Identical cell panels comprised of 24 and 346 samples were distributed and typed by at least four laboratories in order to derive accurate consensus HLA genotypes. Overall concordance rates calculated at both 2- and 4-field allele-level resolutions ranged from 90.4% to 100%. Concordance for the class I genes ranged from 91.7 to 100%, whereas concordance for class II genes was variable; the lowest observed at HLA-DRB3 (84.2%). At the maximum allele-resolution 78 B-LCLs were defined as homozygous for all 11 loci. We identified 11 novel exon polymorphisms in the entire cell panel. A comparison of the B-LCLs NGS HLA genotypes with the HLA genotypes catalogued in the IPD-IMGT/HLA Database Cell Repository, revealed an overall allele match at 68.4%. Typing discrepancies between the two datasets were mostly due to the lower-resolution historical typing methods resulting in incomplete HLA genotypes for some samples listed in the IPD-IMGT/HLA Database Cell Repository. Our approach of multiple-laboratory NGS HLA typing of the B-LCLs has provided accurate genotyping data. The data generated by the tremendous collaborative efforts of the 17th IHIW participants is useful for updating the current cell and sequence databases and will be a valuable resource for future studies.
- MeSH
- Alleles MeSH
- B-Lymphocytes virology MeSH
- Exons genetics MeSH
- Genetic Variation MeSH
- Genetic Loci MeSH
- Genotype MeSH
- Haplotypes genetics MeSH
- Histocompatibility MeSH
- HLA Antigens genetics MeSH
- Homozygote MeSH
- Single-Blind Method MeSH
- Humans MeSH
- Histocompatibility Antigens Class I genetics MeSH
- Histocompatibility Antigens Class II genetics MeSH
- Sequence Analysis, DNA methods MeSH
- Data Accuracy MeSH
- Histocompatibility Testing methods MeSH
- Cell Line, Transformed MeSH
- Cell Transformation, Viral MeSH
- Herpesvirus 4, Human immunology MeSH
- High-Throughput Nucleotide Sequencing methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Tissue Donors supply & distribution MeSH
- History, 21st Century MeSH
- Histocompatibility genetics MeSH
- Immunogenetics history methods trends MeSH
- Immune Tolerance * MeSH
- Immunosuppressive Agents therapeutic use MeSH
- Humans MeSH
- Graft Survival physiology MeSH
- Graft Rejection diagnosis genetics immunology prevention & control MeSH
- Histocompatibility Testing MeSH
- Hematopoietic Stem Cell Transplantation methods MeSH
- Organ Transplantation methods MeSH
- Check Tag
- History, 21st Century MeSH
- Humans MeSH
- Publication type
- Historical Article MeSH
- Congress MeSH
- Geographicals
- Czech Republic MeSH
ABO-incompatible (ABOi) kidney transplantation represents a viable tool to increase the donor pool for kidney transplantation, however, increased alloimmune response has been debated. The early outcomes of 25 low-risk ABOi kidney transplant recipients were compared with thoroughly matched 50 ABO-compatible (ABOc) ones. The matching process was based on gender and age of recipients and immunologic parameters, such as panel reactive antibodies, number of human leukocyte antigen mismatches, and transplantation era. Three-month protocol kidney graft biopsy Banff scores and 1-year clinical outcomes were compared. Apart from C4d positivity, no statistically significant differences were found regarding the Banff scores between the two groups. Similarly, microvascular inflammation and tubulointerstitial injury revealed no differences either. The eGFR at 3 months and 1 year was similar in both groups. In conclusion, blood group incompatibility yields no additional microvascular and tubulointerstitial graft injury if desensitization protocol was applied to low-risk kidney transplant recipients.
- MeSH
- ABO Blood-Group System immunology MeSH
- Allografts immunology supply & distribution MeSH
- Biopsy MeSH
- Desensitization, Immunologic MeSH
- Adult MeSH
- Histocompatibility immunology MeSH
- Glomerular Filtration Rate MeSH
- Kidney blood supply immunology MeSH
- Middle Aged MeSH
- Humans MeSH
- Microvessels MeSH
- Blood Group Incompatibility complications immunology MeSH
- Graft Rejection immunology MeSH
- Kidney Transplantation methods MeSH
- Vasculitis immunology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
- MeSH
- Histocompatibility immunology MeSH
- Transplantation, Homologous MeSH
- Humans MeSH
- Graft Survival immunology drug effects MeSH
- Composite Tissue Allografts * immunology transplantation MeSH
- Transplantation Immunology immunology MeSH
- Transplantation Tolerance immunology drug effects MeSH
- Check Tag
- Humans MeSH
- MeSH
- Survival Analysis MeSH
- Histocompatibility MeSH
- HLA Antigens MeSH
- Humans MeSH
- Graft Survival MeSH
- Retrospective Studies MeSH
- Waiting Lists MeSH
- Kidney Transplantation mortality MeSH
- Check Tag
- Humans MeSH
- Publication type
- Multicenter Study MeSH
