The impact of NKG2A and NKG2D receptors and HLA-E and MICA ligands polymorphisms on post-transplant complications after paediatric allogeneic HSCT: a single-centre experience

Introduction: Natural Killer cells are the first subpopulation of lymphocytes that reconstitute after allogeneic haematopoietic stem cell transplantation (HSCT). Their activity is regulated by various receptor-ligand interactions, including stimulation of the activating NKG2D receptor by the MICA molecule, and inhibitory NKG2A receptor interacting with the HLA-E. In this study the research effort focused on the effect of selected NKG2A and NKG2D receptors and their ligands (HLA-E and MICA molecules) polymorphisms that may affect the pathomechanisms of post-transplant complications after HSCT in children.Methods: One hundred donor-recipient pairs from a single paediatric transplantation centre were investigated. Altogether six single nucleotide substitutions (NKG2A rs7301582; NKG2D rs1049174, rs1154831; HLA-E rs1264457; MICA rs1051792, rs1063635) were genotyped, and the influence of polymorphisms was analysed on acute and chronic graft-versus-host disease (GvHD), cytomegalovirus (CMV) infection incidence, disease relapse and survival.Results: The distribution of the evaluated polymorphisms did not differ between patients and their donors. The results showed a significant influence of HLA-E rs1264457 polymorphism in patients’ HLA-E*01:01 allele, which was associated with increased risk of CMV infection (p = 0.050), especially in children positive for CMV IgG before transplantation (p = 0.001). Furthermore, the effect of HLA-E*01:01 allele on CMV infections was more evident in children above the age of 7 years (p = 0.031). Strong tendencies (0.05 < p < 0.10) towards association with the risk of acute GvHD were also observed for the NKG2A or MICA polymorphisms of the recipients. In addition, NKG2D rs1154831 AA and MICA rs1063635 GG might play a protective role as they were not present in any recipient who died after transplantation.Conclusion: In summary, there is emerging evidence that genotyping results of NKG2 receptors and their ligands, may have prognostic value for the outcome of paediatric allogeneic HSCT, but more extensive studies performed on larger groups of donors and transplant recipients are required to confirm these observations

Cord blood transplantations in Polish pediatric centers: report of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation

WstępPrzeszczepianie komórek krwiotwórczych krwi pępowinowej (CBT) jest uznaną metodą terapeutyczną, wykonywaną od roku 1988. Pierwsze przeszczepienie w Polsce wyłącznie z krwi pępowinowej wykonano 12 października 2000 r. w Poznaniu.Cel pracyAnaliza wyników przeszczepiania komórek krwiotwórczych w polskich ośrodkach pediatrycznych.Pacjenci i metodykaDo badań włączono 19 pacjentów (5 dziewcząt, 14 chłopców), w wieku 0,1–10 lat (mediana 4,3 roku), u których w latach 2000–2011 w polskich ośrodkach pediatrycznych wykonano przeszczepienie krwi pępowinowej. Pacjentów kierowano do CBT z powodu następujących rozpoznań: ostra białaczka limfoblastyczna (n=6), ostra białaczka mieloblastyczna (n=1), zespół mielodysplastyczny (n=2), zespół Wiskotta i Aldricha (n=3), niedokrwistość Fanconiego (n=2), adrenoleukodystrofia (n=1), histiocytoza Langerhansa (n=1), przewlekła choroba ziarniniakowa (n=1), zespół Kostmanna (n=1), zespół Sandhoffa (n=1). Zastosowano kondycjonowanie mieloablacyjne u 9 pacjentów oraz o zredukowanej toksyczności u 10 pacjentów. Krew pępowinowa pochodziła od dawcy rodzinnego w 8 przypadkach lub od dawcy niespokrewnionego w 11 przypadkach. Zgodność 6/6 HLA wystąpiła w 10 przypadkach.Wyniki10/19 (52,6%) dzieci żyje, mediana przeżycia 3,1 roku (95%CI=1,4–4,7), prawdopodobieństwo przeżycia 2-letniego wynosi 0,409±0,133. Przyczyny zgonów obejmowały brak przyjęcia przeszczepu (n=2), powikłania infekcyjne (n=3) lub wznowę (n=4). Dwoje dzieci z powodu nieprzyjęcia przeszczepu miało wykonane przeszczepienie haploidentyczne. W analizie wielowariantowej, jedynym czynnikiem prognostycznym mającym wpływ na całkowite przeżycie było wystąpienie udokumentowanego uogólnionego zakażenia do dnia +180.WnioskiU pacjentów niemających zgodnego dawcy CBT jest ważną opcją terapeutyczną, dającą szanse wyleczenia dla około połowy pacjentów.BackgroundCord blood transplantation (CBT) is accepted therapeutic method in transplantology since 1988. The first isolated CBT was performed on 12 October 2000 in Poznań.ObjectiveAnalysis of results of CBT in Polish pediatric centers.Patients and methodsA total numer of 19 patients (5 female, 14 male), aged 0.1–10 years (median 4.3yrs) transplanted with cord blood between 2000–2011 in Polish pediatric centers. The initial diagnosis was: acute lymphoblastic leukemia (n=6), acute myeloid leukemia (n=1), myelodysplstic syndrome (n=2), Wiskott-Aldrich syndrome (n=3), Fanconi anemia (n=2), adrenoleukodystrophy (n=1), Langerhans cell histiocytosis (n=1), chronic granulomatous disease (n=1), Kostmann syndrome (n=1), Sandhoff syndrome (n=1). Pre-transplant conditioning was myeloablative in 9 patients and reduced-intensity in 10 patients. The source of cord blood was family donor in 8 cases or unrelated donor in 11 cases. Histocompatibility 6/6 HLA between donor-recipient was present in 10 cases.Results10/19 (52.6%) children stay alive, median survival 3.1 years (95%CI=1.4–4.7), probability of 2-year survival was 0.409±0.133. The cause of death was primary graft failure (n=2), infectious complications (n=3) or relapse (n=4). Two children with primary graft failure had subsequent haploidentical transplantation. In multivariate analysis, generalized documented infection was the only predictive adverse factor of overall survival.ConclusionCBT is an important therapeutic option for patients lacking matched donor, offering positive outcome for a half of patients

Wskazania do transplantacji komórek krwiotwórczych u dzieci i młodzieży – rekomendacje Polskiej Pediatrycznej Grupy ds. Transplantacji Komórek Krwiotwórczych – 2014

This article presents the current recommendations from the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation concerning the indications for hematopoietic stem cell transplantation (HSCT) in children and adolescents suffering from hematological malignancies, solid tumours, and congenital or acquired non-malignant disorders. Indications for HSCT are established in context of the recent results of conventional treatment, i.e. obtained with non-HSCT strategies; it means transplantation is justifiable exclusively, when it significantly increases individual patient's chances to be cured, despite of the risk of HSCT-related mortality. Hence, due to the advances of non-transplant treatment strategies as well as progress in the field of HSCT the indications for HSCT require to be regularly up-dated. The recommendations presented in this article are based on the current guidelines from the European Group for Blood and Bone Marrow Transplantation (EBMT), including those from the EBMT Pediatric Diseases Working Party and the EBMT Inborn Errors Working Party, and from the international treatment protocols currently applied in the centers of the Polish Pediatric Leukemia/Lymphoma Study Group and Polish Pediatric Solid Tumours Study Group. The recommendations are addressed not only to the Polish pediatric transplant centers, but first of all to the Polish pediatric centers involved in diagnostics and treatment of the malignancies and non-malignant disorders in children and adolescents with non-transplant strategies, because it is their responsibility to identify as soon as possible indications for HSCT and refer patient at the appropriate time to pediatric transplant center

National experience with adenosine deaminase deficiency related SCID in Polish children

IntroductionDeficiency of adenosine deaminase (ADA) manifests as severe combined immunodeficiency (SCID), caused by accumulation of toxic purine degradation by-products. Untreated patients develop immune and non-immune symptoms with fatal clinical course. According to ESID and EBMT recommendations enzyme replacement therapy (ERT) should be implemented as soon as possible to stabilize the patient’s general condition, normalize transaminases, treat pulmonary proteinosis, bone dysplasia, and protect from neurological damage. Hematopoietic stem cell transplantation (HSCT) from a matched related donor (MRD) is a treatment of choice. In absence of such donor, gene therapy (GT) should be considered. HSCT from a matched unrelated donor (MUD) and haploidentical hematopoietic stem cell transplantation (hHSCT) are associated with worse prognosis.Material and methodsWe retrospectively evaluated the clinical course and results of biochemical, immunological and genetic tests of 7 patients diagnosed in Poland with ADA deficiency since 2010 to 2022.ResultsAll patients demonstrated lymphopenia affecting of T, B and NK cells. Diagnosis was made on the basis of ADA activity in red blood cells and/or genetic testing. Patients manifested with various non-immunological symptoms including: lung proteinosis, skeletal dysplasia, liver dysfunction, atypical hemolytic-uremic syndrome, and psychomotor development disorders. Five patients underwent successful HSCT: 3 patients from matched unrelated donor, 2 from matched sibling donor, and 1 haploidentical from a parental donor. In 4 patients HSCT was preceded by enzyme therapy (lasting from 2 to 5 months). One patient with multiple organ failure died shortly after admission, before the diagnosis was confirmed. None of the patients had undergone gene therapy.ConclusionsIt is important to diagnose ADA SCID as early as possible, before irreversible multi-organ failure occurs. In Poland HSCT are performed according to international immunological societies recommendations, while ERT and GT are less accessible. Implementation of Newborn Screening (NBS) for SCID in Poland could enable recognition of SCID, including ADA-SCID

Viral infections after hematopoetic stem cell transplantation in children with acute lymphoblastic leukemia: the Polish experience

Introduction: Allogeneic hematopoetic stem cell transplantation (allo-HSCT) is one of the therapeutic options in pediatric acute lymphoblastic leukemia (ALL). Most previous analyses have concerned the reactivation of viruses in the entire population of children after allo-HSCT, regardless of the disease entity being an indication for transplantation. In our report, we aimed to evaluate the occurrence, etiology, risk factors and clinical outcome of viral infections in pediatric patients with ALL. Material and methods: 83 post-HSCT ALL patients from 2020 through 2021 were analyzed for infections with polioma BK virus (BKV), cytomegalovirus (CMV), Epstein-Bárr virus, severe acute respiratory syndrome coronavirus 2, adenovirus, respiratory syncytial virus, norovirus, rotavirus, influenza, human herpes virus-6, parainfluenza and rhinovirus. Results: Viral infections were detected after 41% of the transplantations. The viruses most commonly detected were BKV (26.2%) and CMV (23.8%). The analyzed potential risk factors for viral infections were total body irradiation (TBI), graft-versus-host disease, complete remission status, and donor type. Overall survival in the investigated group was 0.815. Conclusions: Complications occurred more frequently in patients without TBI and we did not confirm the impact of other factors. Viral infections in children with ALL after allo-HSCT remain a significant problem. Our results highlight the importance of frequent monitoring and anti-viral prophylaxis