Feasibility and Outcome of Haploidentical Hematopoietic Stem Cell Transplant with Post-Transplantation Cyclophosphamide in High-Risk Malignancies in Children

The use of haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide (Haplo-PTCy) is increasing in adults, but also in children; this procedure is a good alternative for transplanting pediatric patients lacking a matched family donor; indeed, this is very relevant in regions with economic constraints or with a population which is not well represented in the international donor registries which make access to unrelated cord blood units or bone marrow donors difficult.

Prognostic impact of Epstein-Barr virus serostatus in patients with nonmalignant hematological disorders undergoing allogeneic hematopoietic cell transplantation: the study of Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation

BackgroundIn patients with acute leukemia, lymphoma and chronic malignancies, donor and/or recipient Epstein-Barr virus (EBV) seropositive status increases the risk of development of chronic graft-versus-host disease (cGVHD) after allo-hematopoietic cell transplantation (allo-HCT), while it has no influence on other transplant outcomes. No data are available on the impact of EBV serostatus on transplant outcomes in patients with nonmalignant hematological disorders.ObjectiveWe analyzed the influence of the recipient's (R) and donor's (D) EBV serostatus on transplant outcomes (overall survival (OS); relapse-free survival (RFS); relapse incidence (RI); nonrelapse mortality (NRM); acute graft-versus-host disease (aGVHD); cGVHD) in patients with nonmalignant hematological disorders undergoing allo-HCT.Patients and MethodsA total of 2,355 allo-HCTs performed between 1997 and 2016 for acquired bone marrow failure or hemoglobinopathies were included in this retrospective Registry megafile Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation (IDWP-EBMT) study.ResultsDemographics: The median age of recipient was 17.7 years (range: 0–77), and 50.8% were children. 79.0% of recipients and 75.4% of donors were EBV-seropositive. 67.8% had HCT from a matched family donor, 4.6% from a mismatched family donor, and 27.6% from an unrelated donor (UD). T-cell depletion was performed in vivo and ex vivo in 82.2% and 6.6% of patients, respectively. Conditioning regimen was myeloablative in 63.7% and reduced intensity conditioning (RIC) in 36.3% of patients. The median follow-up was 4.7 years. Transplant outcomes: EBV-seropositive recipients in comparison with EBV-seronegative recipients had lower OS (85.4% vs. 88.4%, p = 0.035) and higher NRM (10.0% vs. 6.4%, p = 0.018). No other significant differences were found for: RI, RFS, and aGVHD or cGVHD with respect to EBV pretransplant serostatus donor and/or recipient. Multivariate analysis: A trend toward higher risk of development of cGVHD (HR = 1.31; p = 0.081) and better survival (HR = 0.78; p = 0.087) in allo-HCT from EBV-seropositive donors was found. Allo-HCT in EBV-seropositive recipients had a trend toward lower risk of development of cGVHD (HR = 0.75; p = 0.065). When four subgroups (R−/D−, R−/D+, R+/D−, R+/D+ EBV serology) were analyzed, the EBV serostatus had no significant impact on OS, RFS, RI, NRM and development of aGVHD or cGVHD.ConclusionsAllo-HCT from EBV-seropositive versus EBV-seronegative donors are at 31% higher risk of cGVHD in patients with nonmalignant hematological disorders undergoing allo-HCT; however this difference is nonsignificant in multivariate analysis.

New insights into risk factors for transplant-associated thrombotic microangiopathy in pediatric HSCT

This study aimed to identify a risk profile for development of transplant-associated thrombotic microangiopathy (TA-TMA) in children undergoing hematopoietic stem cell transplantation (HSCT). Between 2013 and 2016, 439 children underwent 474 HSCTs at 2 supraregional United Kingdom centers. At a median of 153 days post-HSCT, TA-TMA occurred among 25 of 441 evaluable cases (5.6%) with no evidence of center variation. Sex, underlying disease, intensity of the conditioning, total body irradiation–based conditioning, the use of calcineurin inhibitors, venoocclusive disease, and viral reactivation did not influence the development of TA-TMA. Donor type: matched sibling donor/matched family donor vs matched unrelated donor vs mismatched unrelated donor/haplo-HSCT, showed a trend toward the development of TA-TMA in 1.8% vs 6.1% vs 8.3%, respectively. Presence of active comorbidity was associated with an increased risk for TA-TMA; 13% vs 3.7% in the absence of comorbidity. The risk of TA-TMA was threefold higher among patients who received >1 transplant. TA-TMA rates were significantly higher among patients with acute graft-versus-host disease (aGVHD) grades III to IV vs aGVHD grade 0 to II. On multivariate analysis, the presence of active comorbidity, >1 transplant, aGVHD grade III to IV were risk factors for TA-TMA (odds ratio [OR]: 5.1, 5.2, and 26.9; respectively), whereas the use of cyclosporine A/tacrolimus-based GVHD prophylaxis was not a risk factor for TA-TMA (OR: 0.3). Active comorbidity, subsequent transplant, and aGVHD grades III to IV were significant risk factors for TA-TMA. TA-TMA might represent a form of a vascular GVHD, and therefore, continuing control of aGVHD is important to prevent worsening of TA-TMA associated with GVHD.

Kiedy pacjent jest oporny na leczenie – historia dziewczynki z aplazją szpiku

Acquired aplastic anemia (AAA) is a rare disease of the haematopoietic system in children. In the absence of a compatible family donor of bone marrow, immunosuppressive therapy is used in combination with anti-thymocytic globulin and cyclosporine. We present a 6-year-old girl diagnosed with severe aplastic anemia (SAA), initially treated only with cyclosporine (CSA) due to lack of a drug in Ukraine. In 2 months of therapy, the child was admitted to a Polish clinic. Due to the persistence of aplasia, she received standard treatment with CSA and anti-lymphocyte globulin, to which she did not respond. In view of disease progression and the lack of a completely compatible unrelated donor. It was decided to transplant from a 9/10 compatible donor, which was successful. Now the child is in remission of the disease and has 100% donor chimerism. Despite the difficulties in therapy, the girl has been healthy for over 2 years.

Feasibility of Peripheral Blood Stem Cell Collection from Heterozygoussickle Cell Trait Donors

Introduction Allogeneic haematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for sickle cell disease (SCD) offered to patients with a fully matched sibling (MSD) or matched unrelated donor (MUD). With a MSD/MUD donor availability of below 20% a haploidentical HSCT from a family donor either with post-transplant cyclophosphamide (post-cy) or with a TCRαß/CD19 depleted graft (T-haplo) is an increasingly successful alternative for the majority of patients. In contrast to post-cy where mostly bone marrow is used, T-haploHSCT requires the generation of a G-CSF stimulated peripheral stem cell grafts. Almost uniformly haploidentical relatives of SCD patients are heterozygous carriers of SC trait. For these donors with a genetically heterozygous sickle trait, G-SCF represents a major safety concern with regard to triggering a sickle cell crisis. Therefore, the use of sickle trait donors is prohibited or not recommended in several countries, and guidelines are currently not available due to lack of evidence. Methods Haploidentical related donors with heterozygousSCD (group S, n=13) as well as healthy donors (group O, n=9) were stimulated with G-CSF. In all donors a similar mobilizations schedule using G-CSF was applied. All donors were applied 10µg/kg body weight (Neupogen®or Granocyte®) sub cutaneous daily with first apheresis on day 5 and day 6 when necessary. The amount of mobilized CD34+ cells were assessed after mobilization. In addition, the harvested stem cell preparations were analysed for CD34 content after apheresis and patients monitored for potential serious adverse effects (AE) during and after the apheresis. Results Mobilization was tolerated well with only mild and typical AE related to apheresis procedure such as citrate reactions, joint pain, ostealgia and headache, observed equally in both groups. In most of the donors (n=13/13 and 8/9), we were able to collect a sufficient amount of CD34+peripheral stem cells (mean of 16.3 and 8.2 x 10^6/kg in group S and O, respectively). We observed slight increases in LDH and reticulocyte counts in few donors also without significant differences between both groups. In particular, there were no severe neurologic side effects and no problems like sickle cell crisis despite mean pre-apheresis hemoglobin concentrations of 14.1 (range 11.9-17.5) g/dL in group S. Conclusions Collectively, these data indicate that in the absence of a MSD or MUD donor, haploidentical family donors with heterozygoussickle cell trait provide a safe and effective alternative for collection of peripheral CD34+stem cells for a T-haplo HSCT. Disclosures No relevant conflicts of interest to declare.

Affect of Age on Survival and Complications after Hematopoietic Stem Cell Transplantation in Children with β-Thalassemia Major

Background/Objective:Adolescents are considered to be a high-risk group by pediatricians, and have long been regarded as high-risk patients by adult hematologists. Foreign related studies show that the degree of damage to the organ in older children after hematopoietic stem cell transplantation (HSCT) is more serious and late complications are more common in them. Considering this finding, we conducted an analysis on the age, the survival rate and complications among children who had had β-thalassemia major and received HSCT. Methods:Among the children who had β-thalassemia major and were treated with HSCT in the Pediatrics Department of the Nanfang Hospital of Southern Medical University, we collected the data of 332 valid β-thalassemia children patients from January 1st, 2012 to June 30th, 2018 and following up the cases until September 30th, 2018. 281 β-thalassemia patients received allo-HSCT from HLA-matched sibling or unrelated donor and 51 β-thalassemia children patients received haplo-identical family donor. Based on the age of the children patients, the case data was divided into three groups for discussion and comparison: group 1 for ≤4 years, group 2 for 5 to 8 years and group 3 for over 8 years. For the three age groups, the correlation between the age and the incidence of GVHD, grade I & II, III and IV aGVHD, cGVHD and some complications such as infection, septicemia, convulsion, EVB infection, etc, was analyzed. Furthermore, the survival curves of the OS and the ESF of all age groups were compared. Results:In 281 HLA-matched cases, OS and ESF after transplantation was 94.3% and 93.2% respectively and deaths in 16 cases(figure1). OS of group 1, 2 and 3 is 97.5%, 95% and 88.5%, respectively. OS of group 3 compared with group 1 is statistically significant with P-value =0.028 (P<0.05) and with group 2 is P=0.096(Kaplan-Meier estimator). EFS of group 1, 2 and 3 are 96.2%, 95% and 85.2%, respectively. EFS of group 3 compared with group 1 is P=0.020 (P<0.05) and with group 2 is P=0.018 (P<0.05)(Kaplan-Meier estimator). The age correlated with the incidence of GVHD, chronic GVHD, grade I & II acute graft-versus-host disease (Kaplan-Meier estimator), convulsion, oral infection and EVB infection (P < 0.05, χ2 test). In particular, the incidence was significantly higher in children above age 8 years as compared to the children under 8 years. In 51 haploidentical family donor cases, OS and ESF after transplantation were 94.1% and 90.2% respectively, the total deaths in 3 cases, the incidence of grade I & II acute GVHD and EVB infection correlated with the age(P<0.05, χ2 test). Conclusions:For HSCT of thalassemia, in HLA-matched cases, OS and ESF rates were lower in children above 8 years than the children below 8 years. In terms of GVHD, cGVHD, aGVHD grade I & II, seizure, oral infection, and EVB infection, the incidence was high in children aged above eight years as compared to below 8 years old, while the lowest incidence was observed in children aged below four years, which is statistically significant. In haplo-identical family donor cases, the incidence of aGVHD grade I and II was highest in children aged above eight years while lowest in children below four years old. Figure 1 Disclosures No relevant conflicts of interest to declare.