Laparoscopic and Robot-assisted Laparoscopic Reimplantation for Lower Ureter Pathology. A Multi-institutional Comparative Study in 1343 Patients.

OBJECTIVE: To evaluate the outcomes of children with vesicoureteral reflux (VUR) and obstructive megaureter (OM) utilizing various laparoscopic and robot-assisted approaches. MATERIALS AND METHODS: Retrospective review of all pediatric laparoscopic and robot-assisted cases for lower ureter pathology was performed between 2016-2022 in 13 academic centers worldwide. Five surgical approaches were assessed: LEUR, LVCUR, LDECUR, RALUR, and RADECUR. RESULTS: One thousand three hundred forty-three patients (490 boys and 853 girls) with a median age of 30 months (IQR 12-63) were treated at 13 centers. Nine hundred and eight patients (68%) underwent reimplantation due to VUR (unilateral in 818 and bilateral in 90 patients). Four hundred thirty-five (32%) had a surgery due to ureterovesical junction (UVJ) obstruction. Mean length of follow-up was 14 months (IQR 8-33). Median operative time was 202 minutes (IQR 142-220) in the robotic arm compared to 240 minutes (IQR 160-267) in the laparoscopic (P = .45). Intracorporeal excisional tapering was performed in 118 (8%) of the patients. Six patients in the OM group required additional surgery due to progressive obstruction. In the VUR group, 84% underwent voiding cystourethrography postoperatively. 5.6% showed residual reflux. Grade 1-2 Clavien-Dindo complications occurred in 10 patients (0.7%) and 6 (0.4%) in the laparoscopic and robotic arm, respectively. Grade 3 complications occurred in 17 (1.2%) and 8 (0.5%) in both arms, respectively. Surgical success was achieved in 96% of patients. CONCLUSION: Laparoscopic and robot-assisted laparoscopic approaches are simple, safe, and effective for treating all grades of VUR and OM. Robot-assisted approach is beneficial in terms of operative time, intracorporeal suturing, and lower complications rate.

Low-symmetry A3 B-type 6H-1,4-diazepinoporphyrazines with anti-Kasha effect as promising photosensitizers.

A series of tribenzo[g,l,q]-6H-1,4-diazepino[2,3-b]porphyrazines has been synthesized. A temperature-dependent steric effect was applied in the mixed Linstead macrocyclization of phthalonitrile and 5,7-bis(2'-arylethenyl)-6-propyl-6H-1,4-diazepine-2,3-dicarbonitrile to achieve high yield of low-symmetry A3 B-type Mg(II) tribenzo[g,l,q]-6H-1,4-diazepino[2,3-b]porphyrazinate. The analysis of photophysical and photochemical properties of the obtained complexes showed the anti-Kasha effect: the ultrafast spin changes successfully compete with the IC. TD-DFT calculations showed that the presence of 1,4-diazepine heterocycle in the porphyrazine structure leads to the formation of additional charge-transfer triplet state T2 . We propose, it could participate in the pumping of T1x state alongside with T1y state (these states are degenerate in D4h symmetry) and, therefore, increase singlet oxygen (1 Δg ) generation. Stable micellar nanoparticles have been obtained based on the tribenzo[g,l,q]-6H-1,4-diazepino[2,3-b]porphyrazine Mg(II) and Zn(II) complexes using polyvinylpyrrolidone. The nanoparticles effectively interact with model biological structures (FBS and brain homogenate), leading to disaggregation of the macrocycles. They also exhibit pronounced phototoxic effects in MCF-7 cells upon red light irradiation. We propose that enhancement in PDT activity could be explained by their increased resistance to aggregation due to the presence of n-propyl substituent directly attached to the C6 position of the 1,4-diazepine moiety. The demonstrated results show the promising potential of tribenzo-6H-1,4-diazepinoporphyrazines as heavy atom-free photosensitizers.

A pilot study of implication of machine learning for relapse prediction after allogeneic stem cell transplantation in adults with Ph-positive acute lymphoblastic leukemia.

The posttransplant relapse in Ph-positive ALL increases the risk of death. There is an unmet need for instruments to predict the risk of relapse and plan prophylaxis. In this study, we analyzed posttransplant data by machine learning algorithms. Seventy-four Ph-positive ALL patients with a median age of 30 (range 18-55) years who previously underwent allo-HSCT, were retrospectively enrolled. Ninety-three percent of patients received prophylactic/preemptive TKIs after allo-HSCT. The values of the BCR::ABL1 level at serial assessments and over variables were collected in specified intervals after allo-HSCT. They were used to model relapse risk with several machine-learning approaches. GBM proved superior to the other algorithms and provided a maximal AUC score of 0.91. BCR::ABL1 level before and after allo-HSCT, prediction moment, and chronic GvHD had the highest value in the model. It was shown that after Day + 100, both error rates do not exceed 22%, while before D + 100, the model fails to make accurate predictions. As a result, we determined BCR::ABL1 levels at which the relapse risk remains low. Thus, the current BCR::ABL1 level less than 0.06% in patients with chronic GvHD predicts low risk of relapse. At the same time, patients without chronic GVHD after allo-HSCT should be classified as high risk with any level of BCR::ABL1. GBM model with posttransplant laboratory values of BCR::ABL1 provides a high prediction of relapse after allo-HSCT in the era of TKIs prophylaxis. Validation of this approach is warranted.

Posttransplant cyclophosphamide versus antithymocyte globulin in patients with acute lymphoblastic leukemia treated with allogeneic hematopoietic cell transplantation from matched unrelated donors: A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

BACKGROUND: The aim of this study was to compare two immunosuppressive strategies, based on the use of either rabbit antithymocyte globulin (ATG) or posttransplant cyclophosphamide (PTCY), as a prophylaxis of graft-versus-host disease (GVHD) for patients with acute lymphoblastic leukemia (ALL) in first complete remission who underwent hematopoietic cells transplantation from matched unrelated donors. METHODS: Overall, 117 and 779 adult patients who received PTCY and ATG, respectively, between the years 2015 and 2020 were included in this retrospective study. The median patient age was 40 and 43 years in the PTCY and ATG groups, respectively, and 37% and 35% of patients, respectively, had Philadelphia chromosome-positive ALL. RESULTS: In univariate analysis, the cumulative incidence of acute and chronic GVHD did not differ significantly between the study groups. The cumulative incidence of relapse at 2 years was reduced in the PTCY group (18% vs. 25%; p = .046) without a significant impact on nonrelapse mortality (11% vs. 16% in the ATG group; p = .29). The rates of leukemia-free survival (LFS) and overall survival were 71% versus 59%, respectively (p = .01), and 82% versus 74%, respectively (p = .08). In multivariate analysis, the receipt of ATG compared with PTCY was associated with a reduced risk of extensive chronic GVHD (hazard ratio, 0.54; 95% confidence interval, 0.3-0.98; p = .04) and an increased risk of low LFS (hazard ratio, 1.57; 95% confidence interval, 1.01-2.45; p = .045). CONCLUSIONS: The receipt of ATG compared with PTCY, despite the reduced risk of extensive chronic GVHD, is associated with inferior LFS in adults with ALL who undergo hematopoietic cell transplantation from 10/10 human leukocyte antigen-matched unrelated donors. These findings warrant verification in prospective trials.

Comparative analysis of epigenetic variability in two pine species exposed to chronic radiation in the Chernobyl and Fukushima affected zones.

Comparative analysis of epigenetic variability in two pine species affected as a result of the Chernobyl and Fukushima accidents is presented. The absorbed dose rate within the affected Chernobyl sites varies over a wider range (1.5-24.6 µGy/h) than within the Fukushima sites (3.5-6.5 µGy/h). It was shown that chronic irradiation can change the level of whole genome methylation in pine populations, but in different ways. The genomes of Japanese red pines are hypomethylated, and the degree of methylation and hydroxymethylation decreases with an increase in the level of radiation exposure. In contrast, the percentages of genome methylation and hydroxymethylation in Scots pine populations exceed the reference levels. The observed discrepancy in the patterns of genome-wide DNA methylation can be attributed partly to the design of the study (differences in the climate, radiation dose, age and species of the pines) which could affect the results. In the frame of IRAP analysis, a larger number of different bands was observed in the Chernobyl populations compared to the Japanese populations. Both the Japanese and Chernobyl populations are characterized by significant genetic variability. However, the main part of this variability is observed within populations. The dendrograms, based on presence/absence of IRAP fragments and Nei's genetic distances, revealed subdivisions of the Chernobyl and Japanese populations according to the level of radioactive contamination. Analysis of the results presented will improve our understanding of the mechanisms underlying the responses of pine trees to chronic radiation exposure.

Long term results of non-refluxing ureteral reimplantation in the pediatric population.

PURPOSE: To evaluate the long-term results of UR and to determine the difference between patients with VUR and OMU in terms of re-obstruction rate, complications associated with pregnancy, and de novo reflux. METHODS: Two-site retrospective study with 69 patients (36 females and 33 males) with a mean age of 5 ± 3.4 years. Fifty-nine (85.5%) underwent UR due to VUR and 10 (14.5%) due to OMU. Mean length of surgery and hospitalization was 90 ± 29.2 min and 9 ± 2.4 days, respectively. RESULTS: Eight (13.5%) patients with VUR suffered from febrile UTI with a mean of 2.1 ± 1.3 events. In the OMU group, 1 (10%) patient suffered from febrile UTI. None of the patients showed recurrence, obstruction or de novo VUR. Two patients (20%) with OMU suffered from CKD. In the VUR group, 3 (5.1%) patients suffered from CKD. Three women suffered from UTIs during pregnancy. Mean follow-up was 17.5 ± 4.6 years. CONCLUSIONS: Successful UR is associated with a decreased rate of febrile UTI in patients with VUR. Patients with OMU maintained and improved renal function in the long term. None demonstrated technical failures in the long term. Patients who presented with bilateral VUR are more prone to developing major complications.

Impact of measurable residual disease on outcomes of unrelated donor haematopoietic cell transplantation with post-transplant cyclophosphamide in AML in first complete remission.

Pre-transplant measurable residual disease (MRD) predicts relapse and outcome of allogeneic haematopoietic cell transplantation (allo-HCT). The impact of MRD on the outcomes of post-transplant cyclophosphamide (PTCy)-based allo-HCT from a matched unrelated donor (UD) is unknown. This study assessed the impact of MRD in acute myeloid leukaemia (AML) in the first complete remission (CR1). A total of 272 patients (MRD negative [MRD-], n = 165; MRD positive [MRD+], n = 107) with a median follow-up of 19 (range: 16-24) months were studied. The incidence of grades II-IV and grades III-IV acute GVHD at day 180 was 25.2% and 25% (p = 0.99), and 10.6% and 6.8% (p = 0.29), respectively, and 2-year chronic GVHD was 35% and 30.4% (p = 0.96) in MRD+ and MRD- cohorts, respectively. In multivariate analysis, MRD+ status was associated with a higher incidence of relapse (RI) (hazard ratio [HR] = 2.56, 95% CI: 1.39-4.72), lower leukaemia-free survival (LFS) (HR = 2.04, 95% CI: 1.23-3.39), overall survival (OS) (HR = 1.83, 95% CI: 1.04-3.25) and GVHD-free, relapse-free survival (GRFS) (HR = 1.69, 95% CI: 1.10-2.58). MRD status did not have a significant impact on non-relapse mortality (NRM), or acute or chronic GVHD risk. Among patients with AML undergoing UD allo-HCT with PTCy, pre-transplant MRD+ status predicted a higher relapse rate, lower LFS, OS and GRFS.

First-line steroid-free systemic treatment of acute and chronic graft-versus-host disease after novel prophylaxis regimens.

In the early randomized trials the efficacy of calcineurin inhibitors (CNI) in the treatment of graft-versus-host disease (GVHD) was comparable to corticosteroids (CS), but these results became obsolete with the introduction of CNIs in prophylaxis. Recently several effective CNI-free GVHD prophylaxis regimens were introduced based on posttransplantation cyclophosphamide (PTCY) and αß ex vivo T-cell depletion (αß-TCD). Among patients treated under these protocols 34 patients with grade II-IV acute (aGVHD) and 40 with moderate and severe chronic (cGVHD) disease were treated with CNIs or other CS-free regimens as the first line. Overall response rate (ORR) was significantly higher in cGVHD than in aGVHD: 80% (95% CI 68-92) vs 47% (95% CI 30-64%), p = 0.0031. In aGVHD it was almost completely restricted to isolated stage III skin GVHD. In cGVHD patients with moderate disease ORR was higher than in severe: 96% (95% CI 88-100%) vs 56% (95%CI 32-81%), p = 0.0022. Two-year overall survival was 76% (95% CI 58-87%) in aGVHD and 95% (95% CI 81-99%) in cGVHD. Failure-free survival was 21% (95% CI 9-37%) in aGVHD and 81% (95% CI 64-91%) in cGVHD. Patients responding to steroid-free regimens had lower use of systemic antibiotics (p = 0.0095), antifungals (p = 0.0319) and antivirals (p < 0.0001).

Laparoscopic Ureteral Reimplantation after Failed Open Surgery: Incorporating the Psoas Hitch Maneuver for Sufficient Tunnel Length.

BACKGROUND: Failure after open ureteral reimplantation has been reported to occur in 2 to 7% of cases. While a second open reconstructive surgery is appropriate in most cases, there are data suggesting similar outcomes utilizing the laparoscopic approach. The objective of this study is to describe a modification and report our experience with laparoscopic ureteral reimplantation after failed open reimplantation reinforced with a psoas hitch. MATERIALS AND METHODS: A retrospective review of pediatric patients who underwent laparoscopic ureteral reimplantation after failed open surgery between September 2012 and April 2018 at three different academic centers was performed. Patient demographics, surgical indications, complications, and outcomes were reviewed. Either ipsilateral ureteral reimplantation with a combined intravesical and extravesical approaches or a cross-trigonal extravesical approach was utilized, depending on the length of the ureter. In all cases, a psoas hitch was performed to gain a longer submucosal tunnel and relieve tension, thus facilitating an efficient antireflux mechanism. RESULTS: Seventeen patients underwent a laparoscopic ureteral reimplantation after failed open surgery. Median age at second surgery was 106 months (interquartile range [IQR]: 53-122.5). Ipsilateral ureteral reimplantation with a combined intravesical and extravesical approaches was performed in 11 cases and cross-trigonal extravesical approach in 6 cases. Median ureteral diameter before the redo surgery was 16 mm (IQR: 14.5-18.5) and after surgery was 6 mm (IQR: 3.5-8.5) (p < 0.001). Postoperative mercaptoacetyltriglycine renal scan showed a nonobstructive pattern and stable renal function in all cases. CONCLUSION: Laparoscopic ureteral reimplantation with incorporation of a psoas hitch after failed open reimplantation is safe and effective.

Standardized single-stage laparoscopic Fowler-Stephens orchiopexy regardless of testis position: Modification of technique eliminates the need for intra-operative decision-making.

Background / Purpose: It is generally perceived that a primary laparoscopic orchiopexy has superior outcomes due to preservation of the testicular artery, and thus should be the choice when achievable. The two-stage laparoscopic Fowler-Stephens orchiopexy (LFSO) is considered superior regarding success rate compared to the one-stage procedure when the artery must be transected. Outcomes can be jeopardized when a primary orchiopexy is ultimately realized to be the incorrect procedure due to insufficient testicular artery length. It is preferable to decide the approach before initiating dissection, however, in reality, this does not always occur. A single uniform approach to all intraabdominal testes (IAT) that takes into consideration the main challenges encountered when performing laparoscopic orchiopexy can simplify the approach and potentially achieve good outcomes. We present our experience with a standardized approach for IAT regardless of testicular position and describe the surgical modification needed to achieve good results with the one-stage LFSO. Materials and Methods: Key surgical maneuvers implicated in the modified one-stage LFSO (M-LFSO) include preservation of a wide peritoneal flap between the vessels and the vas deferens, dissecting the vessels as proximal as possible and avoiding manipulation of the epididymis and vessels between the vas and epididymis when transferring the testis to the scrotum. Results: Our cohort included 55 boys (59 testes). Median age and weight at surgery were 13.3 months (interquartile range [IQR] 9.2-32.4) and 10.4 kg (IQR 9.2-12.6). The mean operative time was 70 min (IQR 60-85). The median follow-up was 11 months (IQR 7-12). There was one case of testicular atrophy (2%) and two cases of suboptimal testicular position in the scrotum at 6 months. Conclusions: M-LFSO is a standardized approach for all cases of IAT regardless of testicular position. Preservation of a wide peritoneal flap and proximal dissection of the vessels may contribute to the adequate testicular blood supply. The proposed approach eliminates the need for intra-operative decision-making and for ancillary procedures.

Augmented FLAMSA-Bu versus FluBu2 reduced-intensity conditioning in patients with active relapsed/refractory acute myeloid leukemia: an EBMT analysis.

Comparative data of fludarabine, cytarabine and amsacrine (FLAMSA) chemotherapy followed by busulfan (Bu)-based reduced-intensity conditioning (RIC) (FLAMSA-Bu) versus RIC regimens are lacking in patients with active relapsed/refractory (R/R) acute myeloid leukemia (AML) at the time of allogeneic hematopoietic stem cell transplantation (alloSCT). Here, we retrospectively analyzed outcomes after FLAMSA-Bu versus fludarabine/busulfan (FluBu2) conditioning in this patient population. A total of 476 patients fulfilled the inclusion criteria, of whom 257 received FluBu2 and 219 FLAMSA-Bu. Median follow-up was 41 months. Two-year non-relapse mortality (21%), graft-versus-host disease-free, relapse-free survival (24%) and chronic graft-versus-host disease (GVHD) (29%) were not statistically different between cohorts. FLAMSA-Bu was associated with lower 2-year relapse incidence (RI) (38 vs 49% after FluBu2, p = 0.004), and increased leukemia-free survival (LFS) (42 vs 29%, p = 0.001), overall survival (47 vs 39%, p = 0.008) and grades II-IV acute GVHD (36 vs 20%, p = 0.001). In the multivariate analysis, FLAMSA-Bu remained associated with lower RI (HR 0.69, p = 0.042), increased LFS (HR 0.74, p = 0.048) and a higher risk of acute GVHD (HR 2.06, p = 0.005). Notwithstanding the limitations inherent in this analysis, our data indicate that FLAMSA-Bu constitutes a tolerable conditioning strategy, resulting in a long-term benefit in a subset of patients reaching alloSCT with active disease.

Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide versus Cyclosporine A and Methotrexate in Matched Sibling Donor Transplantation.

Cyclosporine A (CSA) and methotrexate (MTX) is the standard graft-versus-host disease (GVHD) prophylaxis regimen for matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT). Recently, post-transplantation cyclophosphamide (PTCy) has been shown to be effective in GVHD prevention. In this registry-based study, we compared outcomes of 118 patients treated with PTCy and 1202 patients with CSA/MTX who underwent MSD allo-HCT for acute myelogenous leukemia. In a matched-pair analysis, PTCy was associated with a higher incidence of relapse at 2 years compared with CSA/MTX (41.1% versus 21.3%; P = .039). The incidences of day +180 grade II-IV acute GVHD and 2-year chronic GVHD were comparable in the PTCy and CSA/MTX arms (25.2% versus 25.4% [P = .90] and 42.6% versus 42.6% [P = .84], respectively). Similarly, 2-year leukemia-free survival (LFS; 54.4% versus 74.32%; P = .052), overall survival (OS; 70.6% versus 79.7%; P = .15), and GVHD-free relapse-free survival (GRFS; 38.1% versus 52.5%; P = .49) were not statistically different in the 2 arms. Our data show that GVHD prophylaxis with PTCy is feasible, resulting in similar incidences of GVHD, GRFS, LFS, and OS as seen with conventional CSA/MTX in patients undergoing allo-HCT from an MSD. The higher rate of relapse observed with PTCy needs further evaluation in a prospective study. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Extracorporeal Photopheresis in Children with Chronic Graft-Versus-Host Disease.

Chronic graft versus host disease (cGVHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). It significantly decreases survival and quality of life. The present study demonstrates retrospective data on extracorporeal photopheresis (ECP) in children with cGVHD. A total of 42 children with steroid-refractory cGVHD were enrolled in the study. The majority of patients had acute leukemia (n = 32, 76%). All patients received ECP as second (n = 18, 43%) or third (n = 24, 57%) line of therapy. Initial ECP schedule consisted of bimonthly regimen for two consecutive days with possibility of further tapering according to response. Any concurrent treatment administered before ECP could be continued if considered necessary. Complete response to ECP was registered in seven (17%) patients and partial response in 24 (57%). Overall response according to organ involvement was as follows: skin (n = 24, 75%), mucous membranes (n = 16, 73%), liver (n = 8, 80%), gut (n = 4, 80%), lungs (n = 2, 22%) and joints (n = 2, 67%). Five-year overall, progression-free and failure-free survival was 57%, 56% and 30%, respectively. Non-relapse mortality at 5 years was 14%. We didn't observe any clinically significant complications in children that could be attributed to the procedure. ECP remains important and safe treatment option in children with cGVHD.

Graft-versus-Host Disease Prophylaxis with Post-Transplantation Bendamustine in Patients with Refractory Acute Leukemia: A Dose-Ranging Study.

The prognosis of acute leukemia refractory to induction chemotherapy or immunotherapy is dismal. Salvage allogeneic hematopoietic stem cell transplantation (HSCT) is widely used option for these patients, but only 10% to 15% of patients are cured by the procedure. Preclinical studies indicate that substitution of post-transplantation cyclophosphamide with bendamustine (PTB) in a prophylaxis regimen may be associated with an augmented graft-versus-leukemia (GVL) reaction. The aim of this study was to establish the optimal dose of PTB and evaluate the antileukemic effect of HSCT with this type of graft-versus-host disease (GVHD) prophylaxis. In the prospective trial (NCT02799147), PTB was administered in doses of 140, 100, and 70 mg/m2 on days +3 and +4. Myeloablative conditioning with fludarabine and oral busulfan was provided to all patients. The first 12 patients received single-agent PTB, and subsequent patients received combination therapy with tacrolimus and mycophenolate mofetil (MMF). Inclusion criteria were acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) refractory to at least one induction course of chemotherapy or target therapy and ≥5% clonal blasts in the bone marrow. The study cohort comprised 22 patients with AML and 5 with ALL. Seven patients were enrolled in the 140 mg/m2 group (due to a stopping rule), and 10 each were enrolled in the 100 mg/m2 and 70 mg/m2 groups. Primary refractory disease was documented in 41% of the patients, and secondary refractory was documented in 59%. The median blast count in the bone marrow at the start of the conditioning was 18% (range, 6% to 97%). Transplantation was performed with a matched sibling donor in 5 patients, a matched or mismatched unrelated donor in 15, and a haploidentical donor in 7. Engraftment was documented in 93% of the patients, including 89% with complete remission and 63% without measurable residual disease. After PTB prophylaxis, we observed an unusual complication, a cytokine release syndrome (CRS), in 70% of the patients, including grade 3 to 5 CRS in 44%. The most frequent clinical symptoms included high fever in 67% of patients, abnormal liver function tests in 67%, pancreatitis in 63%, skin vasculitis in 56%, enterocolitis in 48%, inflammation of oral mucosa in 37%, disseminated intravascular coagulation in 37%, and central nervous system toxicity in 26%. The development of CRS was associated with use of an HLA-mismatched donor (75% versus 20%; P = .0043). Classic acute GVHD was documented in 44% of the patients. Grade II-IV acute GVHD was associated with grade 3 to 5 CRS (67% versus 25%; P = .031). Moderate and severe chronic GVHD in the 100-day survivors were more often observed after single-agent PTB than after the combination immunosuppression (100% versus 18%; P = .002). A relatively low relapse rate was observed for this patient population. Three-year overall survival was 28% (95% confidence interval [CI], 13% to 46%), and event-free survival was 29% (95% CI, 13% to 46%). Nonrelapse mortality was 46% (95% CI, 25% to 64%), and the cumulative incidence of relapse was 26% (95% CI, 11% to 44%). No relapses were documented after day +100. There were no statistically significant differences among the dose groups (P = .3481); however, survival was higher in the 100 mg/kg group. Survival was higher in patients with AML compared with those with ALL (35% versus 0%; P = .0157). PTB represents a promising option to augment the GVL effect in refractory AML; however, the high CRS-associated mortality necessitates additional studies to reduce the risk of this complication. Thus, routine clinical application of PTB cannot be currently recommended. Combination immunosuppression with tacrolimus and MMF partially ameliorates these complications, at least in the setting of HLA-matched allografts. Biological mechanisms of CRS and GVL after PTB require further elucidation.

Outcome of haploidentical versus matched sibling donors in hematopoietic stem cell transplantation for adult patients with acute lymphoblastic leukemia: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

BACKGROUND: Non-T-cell depleted haploidentical hematopoietic stem cell transplantation (HaploSCT) is being increasingly used in acute lymphoblastic leukemia (ALL) with improving patient outcomes. We have recently reported that outcomes of adult patients (pts) with ALL in complete remission (CR) receiving HaploSCT are comparable to unrelated donor transplants. We now compared HaploSCT and matched sibling donor (MSD) transplants in pts with ALL. AIM: To assess transplantation outcomes of HaploSCT and MSD transplants in pts with ALL in CR. METHODS: We retrospectively analyzed adult patients (≥ 18 years) with ALL who underwent their first allogeneic stem cell transplantation (alloSCT) in first or second CR between 2012 and 2018, either from a T cell replete Haplo or MSD donor, and whose data were reported to the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT). Multivariate analysis (MVA) adjusting for differences between the groups was performed using the Cox proportional hazards regression model. Propensity score matching was also performed to reduce confounding effects. RESULTS: The analysis comprised 2304 patients: HaploSCT-413; MSD-1891. Median follow-up was 25 months. Median age was 37 (range 18-75) and 38 (18-76) years in HaploSCT and MSD, respectively. HaploSCT patients were transplanted more recently than those transplanted from MSD (2016 vs 2015, p < 0.0001). A higher rate of HaploSCT was in CR2 (33.4% vs 16.7%, p < 0.0001), respectively, and fewer received myeloablative conditioning (68% vs 83.2%, p < 0.0001). Cytomegalovirus (CMV) seropositivity was lower in HaploSCT patients (22% vs 28%, p = 0.01) and donors (27.1% vs 33%, p < 0.02), and a higher proportion of the HaploSCTs were performed using a bone marrow (BM) graft (46.2% vs 18.6%, p < 0.0001). The 2 groups did not differ with regard to gender, Karnofsky performance status score, ALL phenotype, Philadelphia chromosome (Ph) positivity and pre-alloSCT measurable residual disease (MRD). Graft versus host disease (GVHD) prophylaxis was mainly post-transplant cyclophosphamide (PTCy) based (92.7%) in the HaploSCT setting, while it was mostly pharmacologic in the setting of MSD (18.7% received ATG). Cumulative incidence of engraftment at day 60 was higher in MSD transplants compared to HaploSCT (98.7% vs 96.3%, p = 0.001), respectively. Day 180 incidence of acute (a) GVHD II-IV and III-IV was higher in HaploSCT vs. MSD: 36.3% vs 28.9% (p = 0.002 and 15.2% vs 10.5% (p = 0.005), respectively. Conversely, the 2-year chronic (c) GVHD and extensive cGVHD were 32% vs 38.8% (p = 0.009) and 11.9% vs 19.5% (p = 0.001) in HaploSCT vs MSD, respectively. Main causes of death were leukemia (31.8% vs 45%), infection (33.1% vs 19.7%) and GVHD (16.6% vs 19.7%) for HaploSCT and MSD, respectively. Two-year relapse incidence (RI), non-relapse mortality (NRM), leukemia-free survival (LFS), overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were 26% vs 31.6%, 22.9% vs 13%, 51% vs 55.4%, 58.8% vs 67.4% and 40.6% vs 39% for HaploSCT and MSD, respectively. In the MVA, RI was significantly lower in HaploSCT in comparison with MSD, hazard ratio (HR) = 0.66 (95% CI 0.52-0.83, p = 0.004), while NRM was significantly higher, HR = 1.9 (95% CI 1.43-2.53, p < 0.0001). aGVHD grade II-IV and grade III-IV were higher in HaploSCT than in MSD HR = 1.53 (95% CI 1.23-1.9, p = 0.0002) and HR = 1.54 (95% CI 1.1-2.15, p = 0.011), respectively. Extensive cGVHD was lower in HaploSCT compared with MSD, HR = 0.61 (95% CI 0.43-0.88, p = 0.007), while total cGVHD did not differ significantly, HR = 0.94 (95% CI 0.74-1.18, p = 0.58). LFS, OS and GRFS did not differ significantly between the 2 transplant groups, HR = 0.96 (95% CI 0.81-1.14, p = 0.66); HR = 1.18 (95% CI 0.96-1.43, p = 0.11) and HR = 0.93 (95% CI 0.79-1.09, p = 0.37), respectively. These results were confirmed in a matched-pair analysis. CONCLUSIONS: Outcomes of adult patients with ALL in CR receiving alloSCT from haploidentical donors are not significantly different from those receiving transplants from MSD in terms of LFS, OS and GRFS.

Minimal invasive approach for lower pole uretero-pelvic junction obstruction (UPJO) in duplication anomaly: A multi-institutional study.

PURPOSE: We present a multi-institution experience of laparoscopic and robotic-assisted reconstruction approach of lower-pole UPJO (ureteropelvic junction obstruction) in duplicated collecting systems. METHODS: Retrospective review of patients who underwent laparoscopic or robotic pyeloplasty for lower pole UPJO between 2011 and 2020. Patient demographics, perioperative surgical data, complications and outcomes are described. Surgical approach was adjusted to the anatomic variant. Success was defined as improved hydronephrosis, indicated by improved Society of Fetal Urology classification at 9 months follow up. RESULTS: Forty-one patients underwent MIS reconstruction surgery of lower pole UPJO (38- laparoscopy, 3- robot assisted). Median age at surgery was 13 months (IQR, 5-32). Mean operative time was 80 min (IQR, 70-110). There were no intraoperative complications, no conversions and estimated blood loss was negligible. Lower pole dismembered pyeloplasty was performed in 19 (46%) patients, uretero-pyelostomy (lower pole pelvis to upper pole ureter) in 15 (36.5%), concomitant obstruction of the upper pole moiety was encountered in 4 (10%) patients; lower pole dismembered pyeloplasty and upper pole ureter to lower pole pelvis (end-to-side uretero-pyelostomy) was performed and concomitant ipsilateral upper pole partial nephrectomy was carried out in 3 (7%) patients. Overall, 3 patients had grade 1 or 2 Clavien-Dindo postoperative complications and one patient developed a grade 3 complication. Surgical success was achieved in 38/41 (93%), 3 patients required an additional procedure. CONCLUSIONS: UPJO of lower pole of duplication anomaly is highly variable anatomically; therefore, an individualized surgical approach is mandatory. The minimal invasive approach is feasible and safe with good outcomes.

Robotic versus laparoscopic ipsilateral uretero-ureterostomy for upper urinary tract duplications in the pediatric population: A multi-institutional review of outcomes and complications.

OBJECTIVE: To review and compare robotic ipsilateral uretero-ureterostomy (RIUU) and laparoscopic ipsilateral uretero-ureterostomy (LIUU) in terms of safety, efficacy, and outcomes. MATERIALS AND METHODS: A retrospective chart review, including all pediatric patients who underwent RIUU and LIUU at 5 different medical centers, between 2015 and 2019, was performed. Patient's demographics, perioperative data, surgical techniques, complications, and results were compared. RESULTS: The study included 66 pediatric patients, 22 RIUU and 44 LIUU. Median age at surgery was 12 month (IQR 7-52) and median weight was 12 kg (IQR 9-16). Upper to lower IUU was performed in 55 cases and lower to upper IUU in 11 cases. Median operative times for RIUU and LIUU were 90 min (IQR 75-97.5) and 112.5 min (IQR 81.5-121.25), respectively (p = 0.034). Clavien-Dindo grade 3 postoperative complications occurred in two LIUU patients. One patient underwent an ancillary procedure with laparoscopic distal ureteral stump removal. All patients had resolution of symptoms and improvement in hydronephrosis or a non-obstructed curve on MAG3 diuretic renal scan. CONCLUSION: RIUU and LIUU are both safe and effective minimally invasive approaches for duplex upper urinary tract anomalies in the pediatric population. RIUU demonstrated shorter operating times .

Minimally Invasive Dismembered Extravesical Cross-Trigonal Ureteral Reimplantation for Obstructed Megaureter: A Multi-Institutional Study Comparing Robotic and Laparoscopic Approaches.

OBJECTIVE: To compare 2 minimally invasive surgical options for the treatment of obstructed megaureter: robot assisted dismembered extravesical cross-trigonal ureteral reimplantation (RADECUR) and laparoscopic dismembered extravesical cross-trigonal ureteral reimplantation (LDECUR). METHODS: A 2 arm retrospective comparative study, including all pediatric patients who underwent ureteral reimplantation of unilateral obstructed megaureter, either by RADECUR or LDECUR. Patient demographics, perioperative surgical data, complications, and results are described. The surgical technique in both arms was similar: dismembering of the ureter, performing an extravesical cross-trigonal detrusorotomy, and intracorporeal tailoring of the ureter when indicated, were the pivotal maneuvers utilized. RESULTS: The study included 95 patients (48 and 47 in the RADECUR and LDECUR arms, respectively) operated between the years 2016 and 2019. Overall, median age at surgery was 24 months (IQR 12-48) and median weight was 14 kg (IQR 11-21). Median operative time was 93 minutes (IQR 90-120) for RADECUR and 130 minutes (IQR 105-160) for LDECUR (P< 0.001). Intracorporeal excisional tapering was performed in 11 of the RADECUR patients and 19 LDECUR patients. Grade 1-2 Clavien-Dindo complications occurred in 7 patients, and grade 3 complication in 1 patient in the RADECUR arm. In the LDECUR arm, grade 1-2 complications occurred in 2 patients, and 2 had a grade 3 complications. Surgical success was achieved in 97% and 94% in the RADECUR and LDECUR groups, respectively. CONCLUSION: Unilateral robotic extravesical cross-trigonal ureteral re-implantation for treatment of obstructed megaureter in the pediatric population is safe and effective both for RADECUR and LDECUR. Operative time is significantly shorter for RADECUR.

A Prospective Pilot Study of Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide and Ruxolitinib in Patients with Myelofibrosis.

INTRODUCTION: This prospective study evaluated a calcineurin inhibitor-free graft-versus-host disease (GVHD) prophylaxis regimen of ruxolitinib in combination with post-transplant cyclophosphamide (PTCy). Patents and Methods: Twenty patients with primary or secondary myelofibrosis were prospectively enrolled. Reduced intensity conditioning was performed, followed by allogeneic stem cell transplantation from related (n = 7) or unrelated (n = 13) donors. GVHD prophylaxis included only PTCy and ruxolitinib (45 mg) from day-7 to day-2, and 15 mg from day+5 to day+100. This trial was registered at www.clinicaltrials.gov as #NCT02806375. RESULTS: Primary engraftment was documented in 17 patients. One patient experienced primary graft failure and 2 died before engraftment. Eleven patients demonstrated severe poor graft function (SPGF), which required ruxolitinib dose reduction. The regimen was well tolerated, with grade 3-4 non-haematological toxicity in 30%, viral reactivation in 45%, and severe sepsis in 15% of patients. The incidence of acute GVHD grade II-IV was 25%, grade III-IV GVHD was 15%, and moderate chronic GVHD was 20%, with no severe cases. Only 2 patients required systemic steroids. Haematological relapse was documented in 1 patient. Two-year non-relapse mortality was 15%, 2-year overall survival was 85%, and 2-year event-free survival was 72%. CONCLUSION: GVHD prophylaxis with PTCy and ruxolitinib is associated with low toxicity, good acute and chronic GVHD control, and low relapse incidence. However, the relatively high rate of SPGF should be taken into account. SPGF could possibly be mitigated by ruxolitinib dose reduction.