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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.

This prospective multicentre trial evaluated the safety and the efficacy of a thiotepa/melphalan-based reduced intensity conditioning (RIC) haematopoietic stem cell transplantation (HSCT) in children and adolescents with chronic myeloid leukaemia (CML) in chronic phase (CP). Thirty-two patients were transplanted from matched siblings or matched unrelated donors. In 22 patients, HSCT was performed due to insufficient molecular response or loss of response to first- or second-generation tyrosine kinase inhibitor (TKI), with pretransplant BCR::ABL1 transcripts ranging between 0.001% and 33%. The protocol included a BCR::ABL1-guided intervention with TKI retreatment in the first year and donor lymphocyte infusions (DLI) in the second-year post-transplant. All patients engrafted. The 1-year transplant-related mortality was 3% (confidence interval [CI]: 0%-6%). After a median follow-up of 6.3 years, 5-year overall survival and event-free survival are 97% (CI: 93%-100%) and 91% (CI: 79%-100%) respectively. The current 5-year leukaemia-free survival with BCR::ABL1 <0.01% is 97% (CI: 88%-100%) and the current TKI- and DLI-free survival is 95% (CI: 85%-100%). The incidence of chronic graft-versus-host disease (GvHD) was 32%, being severe in four patients (13%). At last follow-up, 31 patients are GvHD-free and have stopped immunosuppression. RIC HSCT following pretreatment with TKI is feasible and effective in children and adolescents with CP-CML with an excellent disease-free and TKI-free survival., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Despite aggressive multimodal treatment, the outcomes of pediatric patients with high-risk (HR) neuroblastoma (NB) remain poor. The rationale for allogeneic hematopoietic stem cell transplantation (allo-HCT) to treat NB was based on the possible graft-versus-tumor effect; however, toxicity limits its efficacy. We sought to prospectively assess the feasibility and efficacy of allo-HCT using a reduced-intensity conditioning regimen in pediatric patients with HR NB in a multicenter phase II trial. Primary endpoints were the rate of neutrophil and platelet engraftment, 5-year transplantation-related mortality (TRM), and disease-free survival (DFS). Secondary endpoint measures included the incidence of acute graft-versus-host disease (aGVHD) and chronic GVHD. Fifty-one patients were enrolled in the study. The 5-year cumulative incidence (CuI) of TRM was 29.4 ± 6.4%, and that of DFS was 11.8 ± 4.5%. Patients undergoing allo-HCT within 1 year of diagnosis or with bone marrow as their stem cell source had a higher DFS probability. The CuI of neutrophil engraftment, platelet engraftment, and grade II-IV aGVHD was 97.9 ± 2.1%, 93.8 ± 3.5%, and 47.1 ± 7.0%, respectively. The development of new therapeutic strategies could further improve disease control., (Copyright © 2024. Published by Elsevier Inc.)

Hematopoietic cell transplantation (HCT) remains the sole available curative treatment for Fanconi anemia (FA), with particularly favorable outcomes reported after matched sibling donor (MSD) HCT. This study aimed to describe outcomes, with a special focus on late complications, of FA patients who underwent umbilical cord blood transplantation (UCBT). In this retrospective analysis of allogeneic UCBT for FA performed between 1988 and 2021 in European Society for Blood and Marrow Transplantation (EBMT)-affiliated centers, a total of 205 FA patients underwent UCBT (55 related and 150 unrelated) across 77 transplant centers. Indications for UCBT were bone marrow failure in 190 patients and acute leukemia/myelodysplasia in 15 patients. The median age at transplantation was 9 years (range, 1.2 to 43 years), with only 20 patients aged >18 years. Among the donor-recipient pairs, 56% (n = 116) had a 0 to 1/6 HLA mismatch. Limited-field radiotherapy was administered to 28% (n = 58) and 78% (n = 160) received a fludarabine (Flu)-based conditioning regimen. Serotherapy consisted of antithymocyte globulin (n = 159; 78%) or alemtuzumab (n = 12; 6%). The median follow-up was 10 years for related UCBT and 7 years for unrelated UCBT. Excellent outcomes were observed in the setting of related UCBT, including a 60-day cumulative incidence (CuI) of neutrophil recovery of 98.1% (95% confidence interval [CI], 93.9% to 100%), a 100-day CuI of grade II-IV acute graft-versus-host disease (GVHD) of 17.3% (95% CI, 9.5% to 31.6%), and a 5-year CuI of chronic GVHD (cGVHD) of 22.7% (95% CI, 13.3% to 38.7%; 13% extensive). Five-year overall survival (OS) was 88%. In multivariate analysis, none of the factors included in the model predicted a better OS. In unrelated UCBT, the 60-day CuI of neutrophil recovery was 78.7% (95% CI, 71.9% to 86.3%), the 100-day CuI of grade II-IV aGVHD was 31.4% (95% CI, 24.6% to 40.2%), and the 5-year CuI of cGVHD was 24.3% (95% CI, 17.8% to 32.2%; 12% extensive). Five-year OS was 44%. In multivariate analysis, negative recipient cytomegalovirus serology, Flu-based conditioning, age <9 years at UCBT, and 0 to 1/6 HLA mismatch were associated with improved OS. A total of 106 patients, including 5 with acute leukemia/myelodysplasia, survived for >2 years after UCBT. Nine of these patients developed subsequent neoplasms (SNs), including 1 donor-derived acute myelogenous leukemia and 8 solid tumors, at a median of 9.7 years (range, 2.3 to 21.8 years) post-UCBT (1 related and 8 unrelated UCBT). In a subset of 49 patients with available data, late nonmalignant complications affecting various organ systems were observed at a median of 8.7 years (range, 2.7 to 28.8 years) post-UCBT. UCB is a valid source of stem cells for transplantation in patients with FA, with the best results observed after related UCBT. After unrelated UCBT, improved survival was observed in patients who underwent transplantation at a younger age, with Flu-based conditioning, and with better HLA parity. The incidence of organ-specific complications and SNs was relatively low. The incidence of SNs, mostly squamous cell carcinoma, increases with time. Rigorous follow-up and lifelong screening are crucial in survivors of UCBT for FA., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

A survey within hematopoietic stem cell transplant (HSCT) centers of the Gruppo Italiano Trapianto Midollo Osseo (GITMO) was performed in order to describe current antiemetic prophylaxis in patients undergoing HSCT. The multicenter survey was performed by a questionnaire, covering the main areas on chemotherapy-induced nausea and vomiting (CINV): antiemetic prophylaxis guidelines used, antiemetic prophylaxis in different conditioning regimens, and methods of CINV evaluation. The survey was carried out in November 2016, and it was repeated 6 months after the publication of the Multinational Association of Supportive Care in Cancer (MASCC)/European Society for Medical Oncology (ESMO) specific guidelines on antiemetic prophylaxis in HSCT. The results show a remarkable heterogeneity of prophylaxis among the various centers and a significant difference between the guidelines and the clinical practice. In the main conditioning regimens, the combination of a serotonin 3 receptor antagonist (5-HT 3 -RA) with dexamethasone and neurokin 1 receptor antagonist (NK1-RA), as recommended by MASCC/ESMO guidelines, increased from 0 to 15% (before the publication of the guidelines) to 9-30% (after the publication of the guidelines). This study shows a lack of compliance with specific antiemetic guidelines, resulting mainly in under-prophylaxis. Concerted strategies are required to improve the current CINV prophylaxis, to draft shared common guidelines, and to increase the knowledge and the adherence to the current recommendations for CINV prophylaxis in the specific field of HSCT.

Post-transplant high-dose cyclophosphamide (PTCy) is a novel approach to prevent graft-versus-host disease (GVHD) and rejection in patients given haploidentical hematopoietic stem cell transplantation (HSCT). Thirty-three patients with high-risk hematologic malignancies and lacking a match-related or -unrelated donor were treated with PTCy haploidentical HSCT in 5 Italian AIEOP centers. Nineteen patients had a nonmyeloablative preparative regimen (57%), and 14 patients received a full myeloablative conditioning regimen (43%). No patients received serotherapy; GVHD prophylaxis was based on PTCy (50 mg/kg on days +3 and +4) combined with mycophenolate plus tacrolimus or cyclosporine A. Neutrophil and platelet engraftment was achieved on days +17 (range, 14 to 37) and +27 (range, 16 to 71). One patient had autologous reconstitution for anti-HLA antibodies. Acute GVHD grades II to IV and III to IV and chronic GVHD developed in 22% (95% CI, 11 to 42), 3% (95% CI, 0 to 21), and 4% (95% CI, 0 to 27) of cases, respectively. The 1-year overall survival rate was 72% (95% CI, 56 to 88), progression-free survival rate was 61% (95% CI, 43 to 80), cumulative incidence of relapse was 24% (95% CI, 13 to 44), and transplant-related mortality was 9% (95% CI, 3 to 26). The univariate analysis for risk of relapse incidence showed how 3 significant variables, mother as donor (P = .02), donor gender as female (P = .04), and patient gender as female (P = .02), were significantly associated with a lower risk of relapse. Disease progression was the main cause of death. PTCy is a safe procedure also for children and adolescents who have already received several lines of chemotherapy. Among the different diseases, a trend for better 1-year rates of overall survival was obtained for nonacute leukemia patients., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

POI is a relevant late complication after HSCT and occurring more frequently after MAC than after RIC regimens. Reports on the frequency of POI after RIC in a large pediatric and adolescent population are lacking. In this study, we describe a girl affected by CML diagnosed at the age of 15 yr and treated with oncarbide and interferon followed by imatinib and dasatinib. She had two pregnancies shortly after RIC performed according to the CML-SCT I-BFM protocol including TT, FLU, and MEL. Hypergonadotropic hypogonadism occurred four months after HSCT; menstruations resumed regularly six months after HSCT. Eight and 20 months after HSCT, the patient became pregnant and then delivered, respectively, two babies at term by cesarean section. Both newborns had no neonatal complications. Donor chimerism at time of two pregnancies and five yr after transplantation demonstrated complete donor engraftment. These findings suggest that I-BFM CML-SCT protocol could be a promising treatment option for adolescents or young adults with CML eligible for HSCT., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Data on epidemiology of severe infectious complications, ie, bacteremia or invasive fungal disease (IFD), in children with acute graft-versus-host disease (aGVHD) after allogeneic hemopoietic stem cell transplantation (HSCT) are scarce. In a retrospective, single-center study, we analyzed the risk (hazard ratio [HR]) and the rate (episodes/1000 patients days at risk) of bacteremias and IFD in children receiving allogeneic HSCT, according to the type of donor (matched related [MRD] or alternative [AD]) and presence and grade of aGVHD. From 2000 to 2009, 198 children receiving 217 allogeneic HSCT developed 134 severe infectious episodes (103 bacteremias and 31 IFD). The type of donor (AD versus MRD) was the most important risk factor for the severe infections (P = .0052). In separate multivariable analysis for bacteremia and IFD, children receiving an AD HSCT had increased HR and rate of bacteremia compared with those receiving a MRD transplantation (P = .0171 and P = .0001, respectively), whereas the HR and the rate of IFD were significantly influenced by the grade of aGVHD (P = .0002 and P < .0001, respectively). Finally, infectious episodes occurred late after HSCT, especially in presence of severe aGVHD, and bacteremias were 3 to 6 times more frequent than IFD. These data may be important to design management strategies of infections in pediatric allogeneic HSCT., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Autoimmune hematological diseases (AHDs) may occur after allogeneic hematopoietic stem cell transplantation (HSCT), but reports on these complications in large cohorts of pediatric patients are lacking. Between 1998 and 2011, 1574 consecutive children underwent allogeneic HSCT in 9 Italian centers. Thirty-three children (2.1%) developed AHDs: 15 autoimmune hemolytic anemia (45%), 10 immune thrombocytopenia (30%), 5 Evans' syndrome (15%), 2 pure red cell aplasia (6%), and 1 immune neutropenia (3%). The 10-year cumulative incidence of AHDs was 2.5% (95% confidence interval, 1.7 to 3.6). In a multivariate analysis, the use of alternative donor and nonmalignant disease was statistically associated with AHDs. Most patients with AHDs (64%) did not respond to steroids. Sustained complete remission was achieved in 87% of cases with the anti-CD20 monoclonal antibody (rituximab). Four patients (9%) (1 autoimmune hemolytic anemia, 1 Evans' syndrome, 2 immune thrombocytopenia) died at a median of 87 days after AHD diagnosis as a direct or indirect consequence of their disorder. Our data suggest that AHDs are a relatively rare complication occurring after HSCT that usually respond to treatment with rituximab., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)