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This retrospective study evaluated 35 children (median age 5.2 years; range 0.4-18) with myelofibrosis (MF), including 33 with primary myelofibrosis and 2 with secondary myelofibrosis transplanted from matched sibling donor (MSD) (n = 17) or non-MSD (n = 18) between 2000 and 2022. Conditioning was usually chemotherapy-based (n = 33) and myeloablative (n = 32). Fifteen patients received bone marrow (BM), 14 haematopoietic cells (HC) from peripheral blood (PB), and 6 from cord blood (CB). Day +100 acute GvHD II-IV incidence was significantly lower after MSD-haematopoietic cell transplantation (MSD-HCT) than after non-MSD-HCT [18.8% (4.3-41.1) vs 58.8% (31-78.6); p = 0.01]. Six-year non-relapse mortality (NRM) was 18% (7.1-32.8), relapse incidence was 15.9% (5.6-30.9), progression-free survival (PFS) was 66.1% (47-79.7), GvHD-free relapse-free survival was 50% (30.6-66.7), and overall survival (OS) was 71.1% (51.4-84). Six-year PFS and OS were significantly higher after BM transplantation compared to HCT from other sources [85.1% (52.3-96.1) vs 50.8% (26.3-71), p = 0.03, and 90.9% (50.8-98.7) vs 54% (28.1-74.2), p = 0.01, respectively], whereas NRM was significantly lower [0% vs 32% (12.3-53.9); p = 0.02]. This first multicentre study on outcomes of allogeneic HCT in children with myelofibrosis proves feasibility and curative effect of transplantation in these children, suggests that bone marrow transplantation is associated with better outcomes, and indicates the need for further studies., (© 2024. The Author(s).)

In children with acute myeloid leukemia (AML) who lack a human leukocyte antigen (HLA) identical sibling, the donor can be replaced with an HLA-matched unrelated donor (MUD) or a haploidentical donor (haplo). We compared outcomes of patients <18 years with AML in first and second complete remission (CR1 and CR2) undergoing a hematopoietic stem cell transplantation (HCT) either with a MUD with anti-thymocyte globulin (ATG) (N=420) or a haplo HCT with post-transplant cyclophosphamide (PT-CY) (N=96) after a myeloablative conditioning regimen (MAC) between 2011 and 2021, reported to the European Society for Blood and Marrow Transplantation. A matched pair analysis was performed to adjust for differences among groups. The final analysis was performed on 253 MUD and 95 haplo-HCT. In the matched cohort, median age at HCT was 11.2 and 10 years and median year of HCT was 2017 and 2018, in MUD and haplo-HCT recipients, respectively. The risk of grade III-IV acute graft-versus-host disease (aGVHD) was significantly higher in the haplo group (hazard ratio [HR]=2.33, 95% confidence interval [CI]: 1.18-4.58; P=0.01). No significant differences were found in 2 years overall survival (OS; 78.4% vs. 71.5%; HR=1.39, 95% CI: 0.84-2.31; P=0.19), leukemia-free survival (LFS; 72.7% vs. 69.5%; HR=1.22, 95% CI: 0.76-1.95; P=0.41), CI of relapse (RI; 19.3% vs. 19.5%; HR=1.14, 95% CI: 0.62-2.08; P=0.68) non-relapse-mortality (NRM; 8% vs. 11%; HR=1.39, 95% CI: 0.66-2.93; P=0.39) and graft-versus-host free relapse-free survival (GRFS; 60.7% vs. 54.5%, HR=1.38, 95% CI: 0.95-2.02; P=0.09) after MUD and haplo-HCT respectively. Our study suggests that haplo-HCT with PT-CY is a suitable option to transplant children with AML lacking a matched related donor.

Poor-risk (PR) cytogenetic/molecular abnormalities generally direct pediatric patients with acute myeloid leukemia (AML) to allogeneic hematopoietic stem cell transplant (HSCT). We assessed the predictive value of cytogenetic risk classification at diagnosis with respect to post-HSCT outcomes in pediatric patients. Patients younger than 18 years at the time of their first allogeneic HSCT for AML in CR1 between 2005 and 2022 who were reported to the European Society for Blood and Marrow Transplantation registry were subgrouped into four categories. Of the 845 pediatric patients included in this study, 36% had an 11q23 abnormality, 24% had monosomy 7/del7q or monosomy 5/del5q, 24% had a complex or monosomal karyotype, and 16% had other PR cytogenetic abnormalities. In a multivariable model, 11q23 (hazard ratio [HR] = 0.66, P = 0.03) and other PR cytogenetic abnormalities (HR = 0.55, P = 0.02) were associated with significantly better overall survival when compared with monosomy 7/del7q or monosomy 5/del5q. Patients with other PR cytogenetic abnormalities had a lower risk of disease relapse after HSCT (HR = 0.49, P = 0.01) and, hence, better leukemia-free survival (HR = 0.55, P = 0.01). Therefore, we conclude that PR cytogenetic abnormalities at diagnosis predict overall survival after HSCT for AML in pediatric patients., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Allogeneic hematopoietic stem cell transplantation (HSCT) is the gold standard curative therapy for infants and children with many inborn errors of immunity (IEI), but adolescents and adults with IEI are rarely referred for transplant. Lack of published HSCT outcome data outside small, single-center studies and perceived high risk of transplant-related mortality have delayed the adoption of HSCT for IEI patients presenting or developing significant organ damage later in life. This large retrospective, multicenter HSCT outcome study reports on 329 IEI patients (age range, 15-62.5 years at HSCT). Patients underwent first HSCT between 2000 and 2019. Primary endpoints were overall survival (OS) and event-free survival (EFS). We also evaluated the influence of IEI-subgroup and IEI-specific risk factors at HSCT, including infections, bronchiectasis, colitis, malignancy, inflammatory lung disease, splenectomy, hepatic dysfunction, and systemic immunosuppression. At a median follow-up of 44.3 months, the estimated OS at 1 and 5 years post-HSCT for all patients was 78% and 71%, and EFS was 65% and 62%, respectively, with low rates of severe acute (8%) or extensive chronic (7%) graft-versus-host disease. On univariate analysis, OS and EFS were inferior in patients with primary antibody deficiency, bronchiectasis, prior splenectomy, hepatic comorbidity, and higher hematopoietic cell transplant comorbidity index scores. On multivariable analysis, EFS was inferior in those with a higher number of IEI-associated complications. Neither age nor donor had a significant effect on OS or EFS. We have identified age-independent risk factors for adverse outcome, providing much needed evidence to identify which patients are most likely to benefit from HSCT., (© 2022 by The American Society of Hematology.)

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for patients affected by Wiskott-Aldrich syndrome (WAS). Reported HSCT outcomes have improved over time with respect to overall survival, but some studies have identified older age and HSCT from alternative donors as risk factors predicting poorer outcome. We analyzed 197 patients undergoing transplant at European Society for Blood and Marrow Transplantation centers between 2006 and 2017 who received conditioning as recommended by the Inborn Errors Working Party (IEWP): either busulfan (n = 103) or treosulfan (n = 94) combined with fludarabine ± thiotepa. After a median follow-up post-HSCT of 44.9 months, 176 patients were alive, resulting in a 3-year overall survival of 88.7% and chronic graft-versus-host disease (GVHD)-free survival (events include death, graft failure, and severe chronic GVHD) of 81.7%. Overall survival and chronic GVHD-free survival were not significantly affected by conditioning regimen (busulfan- vs treosulfan-based), donor type (matched sibling donor/matched family donor vs matched unrelated donor/mismatched unrelated donor vs mismatched family donor), or period of HSCT (2006-2013 vs 2014-2017). Patients aged <5 years at HSCT had a significantly better overall survival. The overall cumulative incidences of grade III to IV acute GVHD and extensive/moderate/severe chronic GVHD were 6.6% and 2.1%, respectively. Patients receiving treosulfan-based conditioning had a higher incidence of graft failure and mixed donor chimerism and more frequently underwent secondary procedures (second HSCT, unconditioned stem cell boost, donor lymphocyte infusion, or splenectomy). In summary, HSCT for WAS with conditioning regimens currently recommended by IEWP results in excellent survival and low rates of GVHD, regardless of donor or stem cell source, but age ≥5 years remains a risk factor for overall survival., (© 2022 by The American Society of Hematology.)

Data on stem cell transplantation (SCT) for Diamond-Blackfan Anemia (DBA) is limited. We studied patients transplanted for DBA and registered in the EBMT database. Between 1985 and 2016, 106 DBA patients (median age, 6.8 years) underwent hematopoietic stem cell transplantation from matched-sibling donors (57%), unrelated donors (36%), or other related donors (7%), using marrow (68%), peripheral blood stem cells (20%), both marrow and peripheral blood stem cells (1%), or cord blood (11%). The cumulative incidence of engraftment was 86% (80% to 93%), and neutrophil recovery and platelet recovery were achieved on day +18 (range, 16 to 20) and +36 (range, 32 to 43), respectively. Three-year overall survival and event-free survival were 84% (77% to 91%) and 81% (74% to 89%), respectively. Older patients were significantly more likely to die (hazard ratio, 1.4; 95% confidence interval, 1.06 to 1.23; P < .001). Outcomes were similar between sibling compared to unrelated-donor transplants. The incidence of acute grades II to IV of graft-versus-host disease (GVHD) was 30% (21% to 39%), and the incidence of extensive chronic GVHD was 15% (7% to 22%). This study shows that SCT may represent an alternative therapeutic option for transfusion-dependent younger patients., (Copyright © 2021. Published by Elsevier Inc.)

Magnusiomyces capitatus (previously known as Geotrichum capitatum or Blastoschizomyces capitatus or Trichosporon capitatum ) is a rare cause of fungal infection in immunocompromised patients. Most of these cases (87%) have been reported from the Mediterranean region, as it is extremely rare to recognize it in other regions. Here we report a first case of disseminated M. capitatus infection in Slovakia. The patient - 19 year old woman with myelodysplastic syndrome was diagnosed with M. capitatus fungemia after allogeneic stem cell transplantation. The infection occurred despite antifungal prophylaxis with micafungin, which was in vitro sensitive to the yeast. The treatment according to minimal inhibitory concentrations (micafungin, voriconazol) and granulocyte transfusions were administered. M. capitatus was cleared out from the bloodstream. However, patient died of multiple organ failure. Autopsy showed multiple lesions in organs, but did not prove presence of yeast by histopathology. M. capitatus was confirmed by polymerase chain reaction from all tested organs: heart, brain, lungs, spleen, liver and kidneys. We present the post mortem pictures showing the yeast lesions in affected organs. 2012 Elsevier Ltd. All rights reserved.

We describe the implementation, optimization, sensitivity determination and first clinical results of polymerase chain reaction (PCR) amplification of polymorphic short tandem repeat (STR) markers and Amelogenin locus coupled with fluorescent detection and capillary electrophoresis in chimerism monitoring of patients transplanted at three different transplant centers using a commercially available multiplex microsatellite assay. The chimerism analysis was performed with genomic DNA extracted from unselected peripheral blood leukocytes of one hundred pediatric and adult patients, who underwent allogeneic stem cell transplantation (SCT) from human leukocyte antigen (HLA) matched or one antigen mismatched related or unrelated donors for malignant (70 patients) and non-malignant (30 patients) diseases. Tested were 79 donor recipient pairs for 15 STR systems and identified an informative marker in all but one of them (98,7%), using 6 selected systems out of these fifteen, that appeared highly informative in our patients population. In 21 sex-mismatched donor recipient pairs we used the Amelogenin locus to distinguish the X and Y chromosome. In sixty-three out of these 100 patients chimerism was regularly analyzed from blood samples taken at various time points after SCT with the median follow up of 17 months. Complete chimerism (CC), maintained over the whole follow-up period, was detected in 24 (38, 1%), stable and decreasing mixed chimerism (MC) in 28 (44, 4%) and increasing MC in 11 patients (17, 5%). Patients with CC, stable and decreasing MC showed a significantly better (p 0,005) overall survival rate (0, 81), compared to those with increasing MC (0, 24). These results demonstrate that STR-based chimerism monitoring with sensitivity above 1% and high informativity (98, 7% of donor recipient pairs) is necessary in establishing the origin of engrafted cells after an allogeneic SCT, in detecting graft rejection and that it may contribute in identifying patients with imminent leukemia relapse.

Immune thrombocytopenic purpura (ITP) is the most commonly acquired bleeding illness in children. 70-80% of children resolve from acute state within few weeks and months with a complete retrospective changes in recovery of reference values. The aim of this work was to evaluate a group of patients with diagnosis of ITP treated or followed from 1979 to 1999. There were found no differences in achieving the remission in the acute phase of ITP (this means till the 6th month from the first documented thrombocytopenia) according to retrospective analysis and comparison of three groups of children in whom the diagnosis of ITP was made from 1979 to 1991 (group A), from 1992 to 1994 (group B) and from 1995 to 1999 (group C). The groups differed in their therapeutic strategies in various time periods as to the time of the diagnosis. In group A, 75% of patients were treated with oral corticosteroids (prednisone). In group B, 10.8% of patients were treated with i.v. application of corticosteroids and 43.3% had no therapy in the acute phase. In group C, 28% of patients were treated with i.v. application of corticosteroids and 36.6% of patients had no therapy applied. A comparable degree of remission in the acute phase with 48%, 54%, or 50% of children with reference values of platelets at the time of six months from the beginning of the disease were achieved. In the group A, the remission was achieved in 85% of children at the end of the 5th year of the follow-up, in the group B in 75% of children to the latest control of platelets in our outcome clinic for children and follow up in the group C in 68% of children the remission was achieved after one year. (Tab. 4, Fig. 2, Ref. 10.)

The authors describe a case report of a six months old boy with autoimmune hemolytic anemia and giant cell hepatitis. This is a very rare syndrome in infancy. After eleven months of intensive immunosuppressive treatment (glucocorticoids, cyclosporin A, azathioprin, intravenous immunoglobulins, cyclophosphamid) no improvement of hemolysis was observed and therefore splenectomy was indicated. 1 year after the treatment was finished the patient is in good general condition and his hematologic and biochemical parameters are physiological.