Busulfan-fludarabine versus busulfan-cyclophosphamide for allogeneic transplant in acute myeloid leukemia: long term analysis of GITMO AML-R2 trial.

We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40-65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches.

Predictability of expansion movements performed by clear aligners in mixed dentition in both arches: a retrospective study on digital casts.

BACKGROUND: to evaluate the predictability of expansion achieved in patients in early mixed dentition treated with Clear Aligners (CA), analyzing the efficiency of the expansion at the end of the first set of aligners and at the end of the therapy in the upper and lower arch. METHODS: 36 patients (20 F, 16 M; mean age 8.3 ± 1.5 years) were selected retrospectively from the Department of Orthodontics of the Hospital of Rome "Tor Vergata". All subjects were treated with CA with no other auxiliaries than attachments. For each patient a standardized sequential expansion protocol was planned for both arches. Digital dental casts were created at three observation periods from an intraoral scanner: prior to treatment (T0), at the end of the first set of aligners (T1), at the end of treatment (T2). The 3D models in planned position determined by the first Clincheck (CC) were obtained for comparison with T1 and T2. Six linear transversal measurements were used to evaluate the dimensional changes and the predictability of expansion movements, comparing T1-CC and T2-CC. RESULTS: a statistically significant increase within the pre-treatment and the final outcomes for all the variables examined was found. In the upper arch, the greatest level of predictability was detected at the level of the first (46.44%) and second deciduous molar width (44.95%) at T1. The analysis of T2-CC changes showed a significant increase in the percentage of predictability of expansion at the level of the first permanent molars, at mesial (54.86%) and distal (58.92%) width. In the lower arch, a higher percentage of predictability than the upper arch was reported at T1-CC and T2-CC, with the greatest values at the level of second (T1-CC: 48.70%; T2-CC: 75.32%) and first deciduous molar width (T1-CC: 45.71%; T2-CC: 72.75%). CONCLUSIONS: CA can induce significant transversal increments. The predictability of expansion is variable, but it did not exceed the 50% during the first set of aligners. It was necessary to apply refinement set to achieve a good predictability for expansion of about 70%. The expansion in the lower arch was observed to be more predictable than in the upper arch.

Molecular prognostication for transplant decision making of patients with myelodysplastic syndromes: A retrospective single-center study.

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option for patients with Myelodysplastic syndromes (MDS). For many years, the selection of patients to allogeneic HSCT has been largely based on use of the International Prognostic Scoring System-Revised (IPSS-R). However, the recent broader application of next generation sequencing in clinical practice provided an abundance of molecular data and led to the introduction of molecular prognostic scores as IPSS-Molecular (IPSS-M). In this paper, we retrospectively analyzed the outcomes of 57 consecutive MDS patients treated with allogeneic HSCT in our center. Re-stratification from IPSS-R to IPSS-M occurred in almost half of patients. The application of IPSS-M to our cohort demonstrated a stronger prognostic separation compared to IPSS-R and improved the C-index. Very high-risk IPSS-M patients showed worse outcomes following HSCT compared to high-risk patients. This study provides data supporting the need of integrating molecular information in the transplant decision making of patients with MDS. This allows an earlier and better identification of patients to whom the transplant should be advised.

Safety and efficacy of narsoplimab in pediatric and adult patients with transplant-associated thrombotic microangiopathy: a real-world experience.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication following hematopoietic stem cell transplantation (HSCT). No approved treatments are currently available. This study presents real-world data obtained with narsoplimab, a human immunoglobulin G4 monoclonal antibody that inhibits MASP-2, the effector enzyme of the lectin pathway of the complement system. Between January 2018 and August 2023, 20 (13 adult and 7 pediatric) patients diagnosed with TA-TMA received narsoplimab under an ongoing compassionate use program. The diagnosis was based on internationally defined criteria for pediatric and adult patients. Fifteen patients fulfilled the criteria recently established by an international consensus on TA-TMA. Nineteen patients exhibited high-risk characteristics. Thirteen patients (65%) responded to narsoplimab, achieving transfusion independence and significant clinical improvement. The one-hundred-day Overall Survival (OS) post-TA-TMA diagnosis was 70%, and 100% for responders. Narsoplimab proved to be effective and safe in the treatment of high-risk TA-TMA, with no increased infectious complications or other safety signals of concern across all age groups. The high response rates and the encouraging survival outcomes underscore the potential of narsoplimab as a valuable therapeutic option, particularly for high-risk cases.

Severe Crowding Associated with Lower Canine Premature Resorption: Interceptive Treatment with Clear Aligners-A Pilot Study.

BACKGROUND: Early mixed dentition represents a critical phase since crowding conditions can occur. The interceptive resolution of dental crowding allows favorable arch and occlusal development. The aim of the present investigation was to evaluate dentoalveolar changes of clear aligner treatment planned to manage lower incisor crowding, loss of arch length, and midline deviation in early mixed dentition. METHODS: A total of 13 patients (7 females, 6 males, 9.4 ± 1.2 age) treated with clear aligners were selected. Arch dimensions and incisor inclinations were evaluated before (T0) and at the end of interceptive treatment (T1). A paired t-test was chosen to compare T1-T0 changes. The level of significance was set at 5%. RESULTS: The greatest significant increase in mandibular width was observed at the level of the first deciduous molars (+2.44 ± 1.4 mm), followed by the second permanent molars (+2.16 ± 1.4 mm). Lower arch length and arch depth showed a statistically relevant increase (2 ± 0.6 mm and 4.5 ± 1.6 mm, respectively). The mean lower dental midline changes were statistically significant (1.42 ± 0.73 mm). CONCLUSIONS: Early treatment with clear aligners, including the combination of transversal arch development, maintenance of leeway space, and guidance of eruption, represents a valid treatment strategy in early mixed dentition to manage arch crowding and occlusion development.

Rituximab added to conditioning regimen significantly improves erythroid engraftment in major incompatible ABO-group hematopoietic stem cell transplantation.

ABO-group major incompatibility hematopoietic stem cell transplantation (HSCT) increases the risk of delayed red cell engraftment and other immunological complications. In this study, we evaluated the efficacy of pre-transplant infusion of rituximab in patients with ABO-incompatibility in improving red blood cell engraftment after HSCT, measured by time to reach transfusion independence. We performed a retrospective, single-center study including 131 consecutive patients transplanted with major or bidirectional ABO-incompatible grafts between 1st January 2013 and 31st December 2019. Fifty-one patients received an infusion of rituximab during the conditioning regimen, while 80 patients did not receive any additional preventive treatment. Time to transfusion independence was significantly reduced for patients treated with rituximab (1 month, 95% CI, 0.5-2) compared with the control group (3.2 months, 95% CI 1.5-3.2, p = 0.02). By multivariable analysis, rituximab use was associated with a faster red blood cell (RBC) engraftment (RR 1.88, 95% CI 1.17-3.03, p = 0.009), while a pre-transplant anti-donor isohemagglutinins titer >1:128 was associated with delayed transfusion independence (RR 0.61, 95% CI 0.37-0.99, p = 0.05). Although limited by the retrospective nature of the study, the results of this analysis suggest that rituximab added to conditioning regimens is feasible, safe, and able to improve post-transplant red blood cell engraftment.

Friction and wear behavior of a mechanical oscillating strip system used for interproximal enamel reduction: a quantitative and qualitative scanning electronic microscope evaluation.

OBJECTIVES: To evaluate wear and friction properties of oscillating strips in order to validate the importance of a standardized interproximal enamel reduction (IPR) sequence to preserve their efficiency and lifetime. MATERIALS AND METHODS: Fifteen complete oscillating IPR sequences were tested by means of tribological tests (Linear Reciprocating Tribometer, C.S.M. Instruments, Peseaux, Switzerland). Fifteen single 0.2-mm metallic strips underwent a long continuous cycle of 240 minutes. Strip surface roughness and waviness measurements were assessed by means of a contact probe surface profiler (TalySurf CLI 2000; Taylor Hobson, Leicester, UK) and TayMap software. Statistical analysis was performed with independent-samples t-test. Significance was at the P < .05 level. Scanning electronic microscopy analysis of strip surfaces was conducted with an FEI Quanta 200 (Hillsboro, Ore) in high vacuum at 30.00 kV. RESULTS: Resin strips revealed a significant reduction in surface roughness (Ra, Rt, RDq) and a significant increase in waviness parameters (Wa, Wt). Rt and RDq values significantly decreased upon use of the metallic strips. Significantly higher values of Wa (+ 2.84 µm) and Wt (+0.1 µm) were observed only for the 0.2-mm metallic strips. Higher friction values were observed when the metallic strips were tested singularly rather than within the entire sequence. Lower Ra and Rt values were revealed when 0.2-mm metallic strips were tested up to 240 minutes. CONCLUSIONS: The application of a standardized oscillating sequence allows for more efficient wear performance of the strips with a significant impact on their abrasive power and lifetime.

A robust and validated integrated prognostic index for defining risk groups in adult acute lymphoblastic leukemia: an EWALL collaborative study.

ABSTRACT: Risk stratification is crucial to the successful treatment of acute lymphoblastic leukemia (ALL). Although numerous risk factors have been identified, an optimal prognostic model for integrating variables has not been developed. We used individual patient data from 4 contemporary academic national clinical trials, UKALL14, NILG-ALL10/07, GIMEMA-LAL1913, and PETHEMA-ALL-HR2011, to generate and validate the European Working Group for Adult ALL prognostic index (EWALL-PI), which is based on white blood cell count, genetics, and end of induction minimal residual disease (MRD). Individual patient risk scores were calculated for 778 patients aged 15 to 67 years in complete remission using the validated UKALL-PI formula, applying minor modifications to reflect differences between pediatric and adult ALL. Per-trial analysis revealed that EWALL-PI correlated with relapse and death. Regression analysis revealed that each unit increase in EWALL-PI increased the risk of relapse or death by ∼30% with no evidence of heterogeneity across trials or patient subgroups. EWALL-PI-defined risk models outperformed the stratification algorithms used by each trial. Threshold analysis revealed an EWALL-PI threshold that divided patients with B cell and T cell into standard (EWALL-PI <2.50) and high (EWALL-PI ≥2.50) risk groups, respectively. Per-trial analysis showed that patients at high risk had a significantly increased relapse rate and inferior survival compared with patients with standard risk (subdistribution hazard ratio for relapse, ranged from 1.85 to 3.28; hazard ratio for death, 1.73 to 3.03). Subgroup analysis confirmed the robustness of these risk groups by sex, age, white blood cell count, and lineage. In conclusion, we validated an integrated risk model across 4 independent adult ALL clinical trials, demonstrating its utility defining clinically relevant risk groups.

Long-term effects produced by early treatment of Class III malocclusion with rapid maxillary expansion and facemask followed by fixed appliances: A multicentre retro-prospective controlled study.

OBJECTIVE: To assess the short- and long-term dentoskeletal effects of early Class III treatment with rapid maxillary expansion and facemask (RME/FM) followed by fixed appliances. MATERIALS AND METHODS: A total of 44 patients (27 females, 17 males) treated consecutively with RME/FM were included from the archives of 3 centres. Three lateral cephalograms were available: T0 (before the start of RME/FM therapy, mean age 8.1 ± 1.8 years), T1 (immediately after RME/FM, mean age 9.8 ± 1.6 years), and T2 (long-term observation, mean age 19.5 ± 1.6 years). A control group of 17 untreated Class III subjects (12 females and 5 males) also was selected. Between-group statistical comparisons were performed with ANCOVA. RESULTS: No statistically significant differences for any of the cephalometric variables were found at T0. In the short term, the treated group showed significant improvements in ANB (+2.9°), Wits appraisal (+2.7 mm), SNA (+1.8°) and SNB (-1.1°). A significant closure of CoGoMe angle (-1.3°) associated with smaller increments along Co-Gn (-2.4 mm) also was found together with a significant increase in intermaxillary divergence (+1.3°). In the long-term, significant improvements in ANB (+2.6°), Wits appraisal (+2.7 mm) and SNB (-1.7°) were recorded together with a significant closure of the CoGoMe angle (-2.9°). No significant long-term changes in vertical skeletal relationships were found. CONCLUSIONS: RME/FM therapy was effective in improving Class III dentoskeletal relationships in the short term. These changes remained stable in the long-term due mainly to favourable mandibular changes.