A retrospective study of treosulfan versus busulfan-based conditioning in pediatric patients.

OBJECTIVES: To compare the outcomes of treosulfan-based vs busulfan-based conditioning regimens in allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients. METHODS: Retrospective study of all consecutive patients (2012-2019) treated with allogenic HSCT and treosulfan- or busulfan-based conditioning regimens at a single center. RESULTS: A total of 101 HSCT were included: 66 HSCT with busulfan and 35 with treosulfan. In malignant diseases (n = 62), busulfan-based conditioning was more commonly employed than treosulfan: 82.3% vs 17.7%. However, the use of treosulfan for malignant diseases increased over time: 6.5% of HSCT in 2012-2015 vs 29% of HSCT in 2015-2019 (p = .02). The cohort of treosulfan had more children under 1-year of age than the busulfan cohort (31 vs 13%; p = .033). The percentage of patients who received serotherapy was 73 and 89% in the nonmalignant and malignant groups, respectively. The engraftment, time to neutrophil, and platelet engraftment were not significantly different between the busulfan and the treosulfan cohorts. Rate of grade II-IV acute GvHD was significantly higher in the busulfan cohort than the treosulfan cohort (39% vs 15%; p = .016). No differences were observed in endothelial damage complications, chronic GvHD, relapse, overall survival, and transplant-related mortality. CONCLUSIONS: Busulfan-based conditioning regimens are used more frequently for children undergoing allogenic HSCT, but treosulfan-based conditioning is gaining acceptance. Treosulfan-based conditioning is associated with lower rates of acute GvHD, and no significant differences on overall survival were observed compared with busulfan.

The role of early natural killer cell adoptive infusion before engraftment in protecting against human herpesvirus-6B encephalitis after naïve T-cell-depleted allogeneic stem cell transplantation.

BACKGROUND: Naïve T-cell-depleted grafts have been employed as an ex vivo T-cell depletion (TCD) platform to prevent graft-versus-host disease (GvHD) and improve immune reconstitution by providing rapid donor memory T-cell reconstitution after allogenic hematopoietic stem cell transplantation (allo-HSCT). CD45RA- memory T cells confer protection against viruses such as cytomegalovirus, Epstein-Barr virus, and adenovirus; however, reports have shown an unexpectedly high incidence of human herpesvirus (HHV)-6B encephalitis among pediatric allo-HSCT patients. METHODS: We report the first 18 consecutive allo-HSCT, 16 haplo-HSCT, and two human leukocyte antigen-matched related donors implanted with naïve TCD grafts. All donors were administered three cell products: first, a CD34+ stem cell product; second, a CD45RA+ TCD graft, followed by an adoptive natural killer (NK) cell infusion within 10 days after HSCT. The study's primary endpoint was the incidence of HHV-6B encephalitis. RESULTS: Engraftment was achieved in 94.5% of cases; 2-year overall survival, event-free survival, and GvHD/relapse-free survival were 87.2% (95% CI 78.6-95.8), 67.3% (95% CI 53.1-81.5), and 64% (95% CI 50.5-78.1), respectively. HHV-6B reactivation occurred in 7 of the haplo-HSCT patients, six of who received a cell infusion with an NK/CD4 ratio <2. None of the patients developed encephalitis. CONCLUSIONS: In this clinical study, we show that early adoptive NK cell infusion after a 45RA+ TCD allo-HSCT graft is safe and can prevent HHV-6B encephalitis. We recommend infusing adoptive NK cells after allo-HSCT using CD45RA+ TCD grafts.

Diagnosis of nontuberculous mycobacterial lymphadenitis: the role of fine-needle aspiration.

Nontuberculous mycobacterial lymphadenitis often presents a diagnostic challenge. This study aimed to evaluate the role of fine-needle aspiration cytology in the diagnosis of nontuberculous mycobacterial lymphadenitis in children. We conducted a retrospective review of fine-needle aspiration cytology performed in patients < 17 year-old with subacute lymphadenitis from 2003 to 2016 in a tertiary hospital in Spain. Confirmed nontuberculous mycobacterial lymphadenitis (isolation of nontuberculous mycobacterial in culture from fine-needle aspiration cytology or biopsy samples) and probable nontuberculous mycobacterial lymphadenitis ("granulomatous inflammation" in cytopathologic examinations from fine-needle aspiration cytology or biopsy and clinical-epidemiological history compatible with nontuberculous mycobacterial) were selected. Forty-one patients with nontuberculous mycobacterial lymphadenitis were included: 14 confirmed and 27 probable. Fine-needle aspiration cytology was done in all of them. For 34 patients with excised lymphadenopathy, cytopathology from fine-needle aspiration cytology was concordant with biopsy in 100% cases. Culture results were available from 78.0% (32/41) of patients with fine-needle aspiration cytology and from 85.3% (29/34) with excisional biopsy. Among 22 patients with microbiological results from fine-needle aspiration cytology and biopsy, fine-needle aspiration cytology allowed advanced results in concordance with biopsy or with positive isolation not found in biopsy in 90.1% (20/22) of patients. Sensitivity of nontuberculous mycobacterial cultures obtained by fine-needle aspiration cytology compared to biopsy was 45.5% vs. 36.4% (p = 0.07). Two patients with previous skin alterations presented fistulas after fine-needle aspiration cytology (4.9%); no other complications were described.Conclusion: Fine-needle aspiration cytology provides quick cytopathologic information and is an accurate and safe technique for the diagnosis of nontuberculous mycobacterial lymphadenitis, especially in cases with challenging work-up. What is Known: • Nontuberculous mycobacterial (NTM) infection is an important cause of subacute lymphadenitis in children. • Fine-needle aspiration cytology (FNAC) is an available technique for the diagnosis of lymphadenitis of unknown etiology. What is New: • FNAC is an accurate and safe technique for the diagnosis of NTM lymphadenitis in children. • FNAC can provide reliable samples for cytopathological studies and even a better sensitivity for microbiological culture than excisional biopsy in the study of suspected NTM lymphadenitis.