Giovanna Giorgiani

Despite the substantial transfusion requirements, there are few studies on the optimal transfusion strategy in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Our study aimed to retrospectively analyze red blood cell (RBC) and platelet (PLT) transfusion practices during the first 100 days after HSCT at the pediatric hematology/oncology unit of our hospital between 2016 and 2019, due to a more restrictive approach adopted after 2016. We also evaluated the impact on patient outcomes. A total of 146 consecutive HSCT patients were analyzed. In patients without hemorrhagic complications, the Hb threshold for RBC transfusions decreased significantly from 2016 to 2017 (from 7.8 g/dL to 7.3 g/dL; p = 0.010), whereas it remained the same in 2017, 2018, and 2019 (7.3, 7.2, and 7.2 g/dL, respectively). Similarly, the PLT threshold decreased significantly from 2016 to 2017 (from 18,000 to 16,000/μL; p = 0.026) and further decreased in 2019 (15,000/μL). In patients without severe hemorrhagic complications, the number of RBC and PLT transfusions remained very low over time. No increase in 100-day and 180-day non-relapse mortality or adverse events was observed during the study period. No patient died due to hemorrhagic complications. Our preliminary observations support robust studies enrolling HSCT patients in patient blood management programs.

To study vaginal development and sexual functioning in young women after childhood hemopoietic stem cell transplantation (HSCT) and radio/chemotherapy. Observational case–control study on 30 young sexually active women survived after HSCT and/or radio/chemotherapy for childhood malignancies or hematologic diseases and 48 controls matched for age. Female Sexual Function Index was lower (median 24.05, IQR = 17.30–28.30 vs. 29.00, IQR = 25.30–31.40, p = 0.001), Female Sexual Distress Scale higher (median 16.00, IQR = 8.00–23.00 vs. 2.00, IQR = 0.00–4.00, p < 0.001), vaginal length shorter (mean difference = 21.1 mm; 95% CI = 19.3–23, p < .001) and vaginal maturation index worst in cases than in controls. Subjects treated by irradiation before HSCT had lower FSFI (median 21.85, IQR = 9.60–31.10 vs. 24.90, IQR = 17.30–28.30) and shorter vaginal length (median 45.55, IQR = 42.60–45.80 vs. 50.10, IQR = 45.30–52.90) compared to those who had not received conditioning treatment (p-values = 0.004 and p = 0.05, respectively). Compared to untreated subjects, women receiving hormonal replacement therapy had higher overall FSFI (p = 0.02), lower FSDS (0.04), and better VMI. Gonadotoxic therapies have adverse effects on vaginal development, sexual functioning, and distress in young females. Hormonal replacement therapy should be shortly considered after main gonodatoxic treatments to improve vaginal and sex health.

Introduction. Although rabbit anti-thymocyte globulin (ATG) is largely used for preventing immune-mediated complications in patients given allogeneic hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor (MUD), the optimal dosage of this drug in children is still undefined. We conducted an academic open-label, multicenter, randomized trial comparing two different dosages of rATG in children with hematological malignancies transplanted with either bone marrow (BM) or peripheral blood stem cell (PBSC) from a MUD selected using high-resolution typing for HLA class I/II (i.e. A, B, C, DRB1) loci. The study aimed at testing whether a higher dose of rATG (30 mg/Kg over 3 days, from day -4 to day -2) was superior to a lower dose (15 mg/Kg over 3 days, from day -4 to day -2) in terms of grade II-IV acute graft-versus-host disease (GvHD) prevention. Secondary end-points included cumulative incidence (CI) of chronic GvHD, non-relapse mortality (NRM), disease recurrence and event-free survival (EFS). The drug was kindly provided by Fresenius/Neovii. Patients and methods. Inclusion criteria were: diagnosis of acute or chronic leukemia in remission/chronic phase, non-Hodgkin lymphoma or myelodysplasia; age at HSCT 0-19 years; availability of an unrelated donor selected using high-resolution molecular typing of HLA-A, B, C and DRB1 loci, completely matched or with a single allelic disparity at one of the HLA loci or with 2 allelic disparities, or with one antigenic disparity; use of G-CSF-mobilized PBSC or BM-derived hematopoietic stem cells. From January 2008 to September 2012, 180 patients were enrolled in the study. Eight patients, 5 randomized to the rATG 30 mg/kg group and 3 to the 15 mg/kg group, did not proceed to transplant due to further relapse before HSCT. The remaining 172 patients, 84 belonging to the 30 mg/kg group and 88 belonging to the 15 mg/kg group, were transplanted and included in this analysis; 94 children had acute lymphoblastic and 42 acute myeloid leukemia. The 2 randomization groups were comparable for all demographic and transplant-related variables evaluated (see Table 1). Patients were stratified according to the stem cell source (BM vs. PBSC), degree of HLA compatibility with the donor (unrelated donor perfectly matched or with 1 allelic disparity vs. unrelated donor with 2 allelic disparities or with 1 antigenic disparity) and disease risk group (standard- vs. high-risk, SR and HR). All patients received a fully myeloablative preparative regimen. All patients received cyclosporine-A and short-term methotrexate as post-transplant GvHD prophylaxis. The trial was registered at ClinicalTrials.gov (NCT00934557). Data were analyzed as of January 31^st, 2016. Results. With a median follow-up of 4.5 years (range 3.3-7.6 years), the 100-day CI of grade II-IV acute GvHD in the high and low rATG group was 29% and 36%, respectively (P=NS, Figure 1A); the CI of extensive chronic GvHD in the two groups was 6% and 10%, respectively (P=NS, Figure 1B). The CI of NRM was 19% and 9% in the high and low rATG group, respectively (P=0.09). Children receiving the higher rATG dosage had a greater incidence of viral reactivations as compared to those who received the lower dosage. The difference was statistically significant for EBV reactivation (37% vs. 23%; P = 0.038) and for Adenovirus reactivation (12% vs. 1%; P = 0.004). The overall CI of disease recurrence was 17% and did not differ between high and low dose rATG. The 5-year EFS for the whole cohort of patients was 69%; it was 61% and 77% for children given high and low dose rATG, respectively (P=0.028, Figure 1C). EFS was 78% and 55% in the SR and HR groups, respectively (P=0.001, Figure 1D). EFS of the 136 children with acute leukemia given either high or low dose rATG was 60% and 77%, respectively (P=0.049). In multivariate analysis on EFS, the following variables were associated with an unfavorable outcome: rATG dose of 30 mg/kg (relative risk 1.90; P=0.026), HLA mismatch > 1 allele (relative risk 2.08; P=0.01) and HR disease (relative risk 2.46; P=0.0015). Conclusions. Our data indicate that, in children with hematological malignancies transplanted from a MUD selected through high-resolution HLA typing, the use of low dose rATG results into decreased incidence of NRM and better EFS. Low dose rATG is able to spare life-threatening viral infections, without significantly increasing the incidence of acute and chronic GvHD.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only cure for marrow failure associated with dyskeratosis congenita (DC). Data on transplants from alternative donors are limited. We describe a boy with DC and severe aplastic anemia who underwent haploidentical T-cell depleted HSCT using a reduced-intensity conditioning regimen. He underwent engraftment without toxicity or GVHD. His posttransplant course was complicated by EBV reactivation, treated with rituximab and EBV-specific T lymphocytes. After 26 months, he is in complete chimerism, with normal blood count and no sign of GVHD or pulmonary dysfunction. To the best of our knowledge, this is the first report of DC successfully treated with allogeneic HSCT from a haploidentical family donor.

Summary: Although allogeneic haematopoietic stem cell transplantation (HSCT) still represents the only consolidated possibility of cure for sickle cell disease (SCD) patients, its use has been limited by the risk of morbidity and mortality associated with conventional myeloablative therapy. The introduction of treosulfan to replace busulfan in conditioning regimens has recently been explored by virtue of its lower toxicity profile. We report our experience with a treosulfan/thiotepa/fludarabine conditioning for human leucocyte antigen (HLA)‐matched sibling or unrelated donor‐HSCT in 15 children with SCD, and compare patient outcomes with those of a historical cohort (15 patients) given a busulfan‐based regimen. Engraftment was achieved in 28 out of 30 patients (93%), with one case of graft failure in either group. The conditioning regimen was well tolerated in both groups, with no cases of grade III‐IV regimen‐related toxicity. The 7‐year overall survival (OS) and disease‐free survival (DFS) for the whole cohort were 100% and 93%, respectively, with a 93% DFS in both busulfan and treosulfan groups. No SCD‐related adverse events occurred after engraftment in patients with complete or mixed donor chimerism. This retrospective analysis suggests that a treosulfan‐based conditioning regimen is able to ensure engraftment with excellent OS/DFS and low regimen‐related toxicity in patients with SCD.

We analyzed the outcome of 243 children with high-risk (HR) AML in first CR1 enrolled in the AIEOP-2002/01 protocol, who were given either allogeneic (ALLO; n=141) or autologous (AUTO; n=102) hematopoietic SCT (HSCT), depending on the availability of a HLA-compatible sibling. Infants, patients with AML-M7, or complex karyotype or those with FLT3-ITD, were eligible to be transplanted also from alternative donors. All patients received a myeloablative regimen combining busulfan, cyclophosphamide and melphalan; [corrected] AUTO-HSCT patients received BM cells in most cases, while in children given ALLO-HSCT stem cell source was BM in 96, peripheral blood in 19 and cord blood in 26. With a median follow-up of 57 months (range 12-130), the probability of disease-free survival (DFS) was 73% and 63% in patients given either ALLO- or AUTO-HSCT, respectively (P=NS). Although the cumulative incidence (CI) of relapse was lower in ALLO- than in AUTO-HSCT recipients (17% vs 28%, respectively; P=0.043), the CI of TRM was 7% in both groups. Patients transplanted with unrelated donor cord blood had a remarkable 92.3% 8-year DFS probability. Altogether, these data confirm that HSCT is a suitable option for preventing leukemia recurrence in HR children with CR1 AML.