How to estimate stone volume and its use in stone surgery: a comprehensive review.

OBJECTIVE: Current interventional guidelines refer to the cumulative stone diameter to choose the appropriate surgical modality (ureteroscopy [URS], extracorporeal shockwave lithotripsy [ESWL] and percutaneous nephrolithotomy [PCNL]). The stone volume (SV) has been introduced recently, to better estimate the stone burden. This review aimed to summarize the available methods to evaluate the SV and its use in urolithiasis treatment. MATERIAL AND METHODS: A comprehensive review of the literature was performed in December 2022 by searching Embase, Cochrane and Pubmed databases. Articles were considered eligible if they described SV measurement or the stone free rate after different treatment modalities (SWL, URS, PCNL) or spontaneous passage, based on SV measurement. Two reviewers independently assessed the eligibility and the quality of the articles and performed the data extraction. RESULTS: In total, 28 studies were included. All studies used different measurement techniques for stone volume. The automated volume measurement appeared to be more precise than the calculated volume. In vitro studies showed that the automated volume measurement was closer to actual stone volume, with a lower inter-observer variability. Regarding URS, stone volume was found to be more predictive of stone free rates as compared to maximum stone diameter or cumulative diameter for stones >20 mm. This was not the case for PCNL and SWL. CONCLUSIONS: Stone volume estimation is feasible, manually or automatically and is likely a better representation of the actual stone burden. While for larger stones treated by retrograde intrarenal surgery, stone volume appears to be a better predictor of SFR, the superiority of stone volume throughout all stone burdens and for all stone treatments, remains to be proven. Automated volume acquisition is more precise and reproducible than calculated volume.

Laser safety, warnings, and limits in retrograde intrarenal surgery.

OBJECTIVE: To analyze the current information about laser safety in retrograde intrarenal surgery (RIRS), focusing on the two main laser technologies that we use in urology, the holmium:yttrium-aluminum-garnet (Ho:YAG) laser, and the thulium fiber laser (TFL). METHODS: Narrative overview of the most relevant articles published in MEDLINE and Scopus databases about this subject. RESULTS: TFL and Ho:YAG laser at similar settings (0.2 J/40 Hz) have similar volume-averaged temperature increase and the average heating rate increase proportionally to laser power, especially when high frequencies are used. Recent preclinical data, comparing both laser technologies at different laser settings, agreed that when the delivered energy increases in expenses of higher frequencies, the thermal damage increases too. Higher frequencies, despite of the rise of temperature in the irrigation medium, can cause accidental thermal lasering lesions. CONCLUSION: The use of low frequency settings and a proper irrigation is critical to avoid thermal injury in endoscopic laser lithotripsy. In addition, the use of laser safety eyeglasses is recommended in Ho:YAG and TFL ELL.

Ablation rates with Holmium:YAG and Thulium Fiber Laser: Influence of the stone phantom homogeneity. An in vitro study.

OBJECTIVES: The lithotripsy efficiency (LE) in vitro study requires artificial or human stone samples (AS, HS). With the development of dusting lithotripsy, less ex vivo HS are available. We aimed to compare Thulium Fiber Laser (TFL) and Holmium:YAG (Ho:YAG)'s LE and define the most accurate LE parameter. METHODS: Hard and soft homogenous- and heterogenous-AS (Ho-AS, He-AS) were made to reproduce calcium-oxalate monohydrate and uric acid stones, respectively by a rapid or slow brewing of BegostonePlus (Bego) and distilled water. One hundred and fifty and 272µm-laser fibers, connected to 50W-TFL and 30W-HoYAG generators, compared three settings for TFL (FD: 0.15J/100Hz; D: 0.5J/30Hz; Fr: 1J/15Hz) and two for Ho:YAG (D-Fr). An experimental setup consisted in immerged 10mm cubic stone phantoms with a 20 seconds' lasing spiral, in contact mode, repeated four times. Stones were dried, weighted and µ-scanned (ablation weight and volume [AW and AV]). RESULTS: With He-AS, dusting AV were four- and three-fold higher with TFL compared to Ho:YAG against hard and soft (P<0.05). In fragmentation, AV were two-fold higher with TFL compared to Ho:YAG against hard (P<0.05) and soft (P<0.05). Experiments with Ho-AS were associated with non-significant differences when comparing TFL-150µm and TFL-272µm. The ablation weight-volume correlation coefficients was higher with Ho-AS than with He-AS (P<0.0001), and with hard than soft AS. If the LE can be estimated by the AW with hard AS, this approximation is not consistent for soft AS. CONCLUSION: TFL presented higher ablation rates than Ho:YAG, significant with He-AS. If the AW is acceptable and less expensive for hard Ho-AS, AV are more accurate for He-AS, which are suggested to imitate closely HS.

Incidence and prognostic impact of U2AF1 mutations and other gene alterations in myelodysplastic neoplasms with isolated 20q deletion.

BACKGROUND: In myelodysplastic neoplasms (MDS), the 20q deletion [del(20q)] is a recurrent chromosomal abnormality that it has a high co-occurrence with U2AF1 mutations. Nevertheless, the prognostic impact of U2AF1 in these MDS patients is uncertain and the possible clinical and/or prognostic differences between the mutation type and the mutational burden are also unknown. METHODS: Our study analyzes different molecular variables in 100 MDS patients with isolated del(20q). RESULTS & CONCLUSIONS: We describe the high incidence and negative prognostic impact of U2AF1 mutations and other alterations such as in ASXL1 gene to identify prognostic markers that would benefit patients to receive earlier treatment.

In vitro assessment of the combined effect of letermovir and sirolimus on cytomegalovirus replication.

OBJECTIVE: Letermovir (LMV) is used for prophylaxis of cytomegalovirus (CMV) reactivation and end-organ disease in adult CMV-seropositive allogeneic hematopoietic stem cell transplant recipients (allo-HSCT). In turn, sirolimus (SLM) which displays in vitro anti-CMV activity, is frequently employed for prophylaxis of Graft vs. Host disease in allo-HSCT. Here, we aimed at assessing whether LMV and SLM used in combination may act synergistically in vitro on inhibiting CMV replication. METHODS: The antiviral activity of LMV and SLM alone or in combination was evaluated by a checkerboard assay, using ARPE-19 cells infected with CMV strain BADrUL131-Y. LMV and SLM were used at concentrations ranging from 24 nM to 0.38 nM and 16 nM to 0.06 nM, respectively. RESULTS: The mean EC50 for LMV and SLM was 2.44 nM (95% CI, 1.66-3.60) and 1.40 nM (95% CI, 0.41-4.74), respective. LMV and SLM interaction yielded mainly additive effects over the range of concentrations tested. CONCLUSIONS: The additive nature of the combination of LMV and SLM against CMV may have relevant clinical implications in management of CMV infection in allo-HSCT recipients undergoing prophylaxis with LMV.

Recommendations on the use of azole antifungals in hematology-oncology patients.

The administration of antifungals for therapeutic and, especially, prophylactic purposes is virtually a constant in patients requiring hematology-oncology treatment. Any attempt to prevent or treat Aspergillus or Mucor infections requires the administration of some drugs in the azole group, which include voriconazole, posaconazole and isavuconazole, noted for their activity against these pathogens. One very relevant aspect is the potential risk of interaction when associated with one of the antineoplastic drugs used to treat hematologic tumors, with serious complications. In this regard, acalabrutinib, bortezomib, bosutinib, carfilzomib, cyclophosphamide, cyclosporine A, dasatinib, duvelisib, gilteritinib, glasdegib, ibrutinib, imatinib, nilotinib, ponatinib, prednisone, ruxolitinib, tacrolimus, all-transretinoic acid, arsenic trioxide, venetoclax, or any of the vinca alkaloids, are very clear examples of risk, in some cases because their clearance is reduced and in others because of increased risk of QTc prolongation, which is particularly evident when the drug of choice is voriconazole or posaconazole.

To evaluate whether there is a relationship between occlusion and body posture as delineated by a stabilometric platform: A systematic review.

OBJECTIVE: To evaluate whether there is a relationship between occlusion and body posture evaluated using a stabilometric platform. METHODS: Observational studies that analyzed the relationship between dental occlusion (changes in mandibular position and/or dental malocclusion) and body posture evaluated with a stabilometric platform in patients older than 13 years without orthodontic or orthopedic intervention and systemically healthy were considered eligible for inclusion. PubMed, EMBASE, Science Direct, LILACS, and Google Scholar databases were searched to obtain articles published from September 2019 up to March 2020. RESULTS: Twelve articles met the inclusion criteria, of which 66.7% showed a relationship between dental occlusion and body posture, and 33.3% found no relationship. The marked heterogeneity between studies did not allow data to be combined for meta-analyses. CONCLUSION: For the mandibular positions, the postural changes were mainly in the mediolateral direction, while in the malocclusions, they were in the anteroposterior direction.

A phase I/II dose-escalation multi-center study to evaluate the safety of infusion of natural killer cells or memory T cells as adoptive therapy in coronavirus pneumonia and/or lymphopenia: RELEASE study protocol.

BACKGROUND: Moderate/severe cases of COVID-19 present a dysregulated immune system with T cell lymphopenia and a hyper-inflammatory state. This is a study protocol of an open-label, multi-center, double-arm, randomized, dose-finding phase I/II clinical trial to evaluate the safety, tolerability, alloreactivity, and efficacy of the administration of allogeneic memory T cells and natural killer (NK) cells in COVID-19 patients with lymphopenia and/or pneumonia. The aim of the study is to determine the safety and the efficacy of the recommended phase 2 dose (RP2D) of this treatment for patients with moderate/severe COVID-19. METHODS: In the phase I trial, 18 patients with COVID-19-related pneumonia and/or lymphopenia with no oxygen requirement or with an oxygen need of ≤ 2.5 liters per minute (lpm) in nasal cannula will be assigned to two arms, based on the biology of the donor and the patient. Treatment of arm A consists of the administration of escalating doses of memory T cells, plus standard of care (SoC). Treatment of arm B consists of the administration of escalating doses of NK cells, plus SoC. In the phase II trial, a total of 182 patients with COVID-19-related pneumonia and/or lymphopenia requiring or not oxygen supplementation but without mechanical ventilation will be allocated to arm A or B, considering HLA typing. Within each arm, they will be randomized in a 1:1 ratio. In arm A, patients will receive SoC or RP2D for memory T cells plus the SoC. In arm B, patients will receive SoC or RP2D for NK cells plus the SoC. DISCUSSION: We hypothesized that SARS-CoV-2-specific memory T-lymphocytes obtained from convalescent donors recovered from COVID-19 can be used as a passive cell immunotherapy to treat pneumonia and lymphopenia in moderate/severe patients. The lymphopenia induced by COVID-19 constitutes a therapeutic window that may facilitate donor engraftment and viral protection until recovery. TRIAL REGISTRATION: ClinicalTrials.gov NCT04578210 . First Posted : October 8, 2020.

Phase I dose-escalation single centre clinical trial to evaluate the safety of infusion of memory T cells as adoptive therapy in COVID-19 (RELEASE).

BACKGROUND: Effective treatments are still needed to reduce the severity of symptoms, time of hospitalization, and mortality of COVID-19. SARS-CoV-2 specific memory T-lymphocytes obtained from convalescent donors recovered can be used as passive cell immunotherapy. METHODS: Between September and November 2020 a phase 1, dose-escalation, single centre clinical trial was conducted to evaluate the safety and feasibility of the infusion of CD45RA- memory T cells containing SARS-CoV-2 specific T cells as adoptive cell therapy against moderate/severe cases of COVID-19. Nine participants with pneumonia and/or lymphopenia and with at least one human leukocyte antigen (HLA) match with the donor were infused. The first three subjects received the lowest dose (1 × 105 cells/kg), the next three received the intermediate dose (5 × 105 cells/kg) and the last three received the highest dose (1 × 106 cells/kg) of CD45RA- memory T cells. Clinicaltrials.gov registration: NCT04578210. FINDINGS: All participants' clinical status measured by National Early Warning Score (NEWS) and 7-category point ordinal scales showed improvement six days after infusion. No serious adverse events were reported. Inflammatory parameters were stabilised post-infusion and the participants showed lymphocyte recovery two weeks after the procedure. Donor microchimerism was observed at least for three weeks after infusion in all patients. INTERPRETATION: This study provides preliminary evidence supporting the idea that treatment of COVID-19 patients with moderate/severe symptoms using convalescent CD45RA- memory T cells is feasible and safe. FUNDING: Clinical Trial supported by Spanish Clinical Research Network PT17/0017/0013. Co-funded by European Regional Development Fund/European Social Fund. CRIS CANCER Foundation Grant to AP-M and Agencia Valenciana de Innovación Grant AVI-GVA COVID-19-68 to BS.

SARS-CoV-2-Specific Memory T Lymphocytes From COVID-19 Convalescent Donors: Identification, Biobanking, and Large-Scale Production for Adoptive Cell Therapy.

Syndrome coronavirus 2 (SARS-CoV-2) pandemic is causing a second outbreak significantly delaying the hope for the virus' complete eradication. In the absence of effective vaccines, we need effective treatments with low adverse effects that can treat hospitalized patients with COVID-19 disease. In this study, we determined the existence of SARS-CoV-2-specific T cells within CD45RA- memory T cells in the blood of convalescent donors. Memory T cells can respond quickly to infection and provide long-term immune protection to reduce the severity of COVID-19 symptoms. Also, CD45RA- memory T cells confer protection from other pathogens encountered by the donors throughout their life. It is of vital importance to resolve other secondary infections that usually develop in patients hospitalized with COVID-19. We found SARS-CoV-2-specific memory T cells in all of the CD45RA- subsets (CD3+, CD4+, and CD8+) and in the central memory and effector memory subpopulations. The procedure for obtaining these cells is feasible, easy to implement for small-scale manufacture, quick and cost-effective, involves minimal manipulation, and has no GMP requirements. This biobank of specific SARS-CoV-2 memory T cells would be immediately available "off-the-shelf" to treat moderate/severe cases of COVID-19, thereby increasing the therapeutic options available for these patients.

Host immune genetic variations influence the risk of developing acute myeloid leukaemia: results from the NuCLEAR consortium.

The purpose of this study was to conduct a two-stage case control association study including 654 acute myeloid leukaemia (AML) patients and 3477 controls ascertained through the NuCLEAR consortium to evaluate the effect of 27 immune-related single nucleotide polymorphisms (SNPs) on AML risk. In a pooled analysis of cohort studies, we found that carriers of the IL13rs1295686A/A genotype had an increased risk of AML (PCorr = 0.0144) whereas carriers of the VEGFArs25648T allele had a decreased risk of developing the disease (PCorr = 0.00086). In addition, we found an association of the IL8rs2227307 SNP with a decreased risk of developing AML that remained marginally significant after multiple testing (PCorr = 0.072). Functional experiments suggested that the effect of the IL13rs1295686 SNP on AML risk might be explained by its role in regulating IL1Ra secretion that modulates AML blast proliferation. Likewise, the protective effect of the IL8rs2227307 SNP might be mediated by TLR2-mediated immune responses that affect AML blast viability, proliferation and chemorresistance. Despite the potential interest of these results, additional functional studies are still warranted to unravel the mechanisms by which these variants modulate the risk of AML. These findings suggested that IL13, VEGFA and IL8 SNPs play a role in modulating AML risk.

Use of micafungin as antifungal prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Spain (GETH-MIC).

OBJECTIVE: The fungal infections remain an important problem in the allogeneic stem cell trasnsplantation (allo-SCT) setting and thus, anti-fungal prophylaxis is commonly used. The antifungal drug should offer activity, at least against Candida and Aspergillus spp., a good safety profile and low probability interactions. Micafungin could theoretically fulfill these requisites. The aim of the study was to describe the experience with micafungin as primary prophylaxis in patients undergoing allo-SCT in a cohort of Spanish centres, and to evaluate its efficacy and tolerability in this population. METHODS: Retrospective multicentre observational study including all consecutive adult patients admitted for allo-SCT in participating centres of the Grupo Español de Trasplante Hematopoyético (GETH), from January 2010 to December 2013, who received micafungin as primary prophylaxis during the neutropenic period. RESULTS: A total of 240 patients from 13 centres were identified and 159 patients were included for the analysis. Most patients (95.6%) received 50 mg/day of micafungin. During the follow-up, 7 (4.4%) patients developed breakthrough invasive fungal disease, 1 proven and 6 probable; one patient discontinued the drug because of serious drug interactions. Prophylaxis with micafungin was considered effective in 151 (94.9%) patients. CONCLUSIONS: According to our experience, micafungin is an appropriate alternative for antifungal prophylaxis in patients undergoing an allo-HSCT, because its efficacy, its low profile of drug interactions and side-effects.

Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis.

Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the ARNT2 and CX3CR1 genes influence the risk of IA in high-risk hematological patients. We genotyped selected SNPs in a cohort of 500 hematological patients (103 of those had been diagnosed with proven or probable IA), and we evaluated their association with the risk of developing IA. The association of the most interesting markers of IA risk was then validated in a replication population, including 474 subjects (94 IA and 380 non-IA patients). Functional experiments were also performed to confirm the biological relevance of the most interesting markers. The meta-analysis of both populations showed that carriers of the ARNT2rs1374213G, CX3CR1rs7631529A, and CX3CR1rs9823718G alleles (where the RefSeq identifier appears as a subscript) had a significantly increased risk of developing IA according to a log-additive model (P value from the meta-analysis [PMeta] = 9.8 · 10-5, PMeta = 1.5 · 10-4, and PMeta =7.9 · 10-5, respectively). Haplotype analysis also confirmed the association of the CX3CR1 haplotype with AG CGG with an increased risk of IA (P = 4.0 · 10-4). Mechanistically, we observed that monocyte-derived macrophages (MDM) from subjects carrying the ARNTR2rs1374213G allele or the GG genotype showed a significantly impaired fungicidal activity but that MDM from carriers of the ARNT2rs1374213G and CX3CR1rs9823718G or CX3CR1rs7631529A alleles had deregulated immune responses to Aspergillus conidia. These results, together with those from expression quantitative trait locus (eQTL) data browsers showing a strong correlation of the CX3CR1rs9823718G allele with lower levels of CX3CR1 mRNA in whole peripheral blood (P = 2.46 · 10-7) and primary monocytes (P = 4.31 · 10-7), highlight the role of the ARNT2 and CX3CR1 loci in modulating and predicting IA risk and provide new insights into the host immune mechanisms involved in IA development.

[Concordance between the equations "Chronic Kidney Disease Epidemiological Collaboration" and "Modification of Diet in Renal Disease" with the "Berlin Initiative Study" to estimate renal function in the elderly]. / Concordancia entre las ecuaciones «Chronic Kidney Disease Epidemiological Collaboration¼ y «Modification of Diet in Renal Disease¼ con la «Berlin Initiative Study¼ para estimar la función renal en las personas mayores.

OBJECTIVE: Estimated glomerular filtration rate (eGFR) is calculated routinely using creatinine-based formulas, but their reliability in the elderly is limited. The aim of this study was to analyse the concordance between the BIS1 equation which is specific for the elderly, and the usual CKD-EPI and MDRD-IDMS in a large population over 70 years of age. MATERIAL AND METHODS: Retrospective cross-sectional study in which the eGFR was calculated using BIS1, CKD-EPI and MDRD-IDMS equations based on gender, age, and creatinine data of 85,089 subjects (58.5% women, mean age 78 years [IQR 73-83]).The following statistics were carried out: Wilcoxon test, Bland-Altman graphic analysis, study of the concordance using the intraclass correlation coefficient (ICC), and comparison tables for the classification of CKD. RESULTS: The median of the eGFRs using BIS1 was 58mL/min/1.73m2 (IQR 48-70), using CKD-EPI was 68mL/min/1.73m2 (IQR 53-84), and using MDRD it was 68mL/min/1.73m2 (IQR 53-82). The concordance between BIS1 and CKD-EPI (intraclass correlation coefficient =0.87) was found to be acceptable. It was lower with MDRD (intraclass correlation coefficient =0.81). A mean difference of 8mL/min/1.73m2 (SD 2.6-18) was found BIS1 vs. CKD-EPI, and 10mL/min/1.73m2 (SD 6-27) with BIS1 vs. MDRD, which was maintained when stratifying by gender and age groups. CONCLUSIONS: Despite the acceptable statistical agreement, the eGFR obtained with the BIS1 equation is not interchangeable with CKD-EPI or with MDRD-IDMS. The BIS1 equation gives lower values than CKD-EPI, and classifies patients into a higher level of CKD, mainly when the eGFR is above 30mL/min/1.73 m2.

Noncontiguous operon is a genetic organization for coordinating bacterial gene expression.

Bacterial genes are typically grouped into operons defined as clusters of adjacent genes encoding for proteins that fill related roles and are transcribed into a single polycistronic mRNA molecule. This simple organization provides an efficient mechanism to coordinate the expression of neighboring genes and is at the basis of gene regulation in bacteria. Here, we report the existence of a higher level of organization in operon structure that we named noncontiguous operon and consists in an operon containing a gene(s) that is transcribed in the opposite direction to the rest of the operon. This transcriptional architecture is exemplified by the genes menE-menC-MW1733-ytkD-MW1731 involved in menaquinone synthesis in the major human pathogen Staphylococcus aureus We show that menE-menC-ytkD-MW1731 genes are transcribed as a single transcription unit, whereas the MW1733 gene, located between menC and ytkD, is transcribed in the opposite direction. This genomic organization generates overlapping transcripts whose expression is mutually regulated by transcriptional interference and RNase III processing at the overlapping region. In light of our results, the canonical view of operon structure should be revisited by including this operon arrangement in which cotranscription and overlapping transcription are combined to coordinate functionally related gene expression.

The kinetics of torque teno virus plasma DNA load shortly after engraftment predicts the risk of high-level CMV DNAemia in allogeneic hematopoietic stem cell transplant recipients.

Monitoring Torque teno virus (TTV) DNA load helps to estimate the risk of opportunistic infections in solid organ transplant recipients. We investigated whether the early kinetic pattern of plasma TTV DNA load after allogeneic hematopoietic stem cell transplantation (allo-HSCT) associates with subsequent CMV and EBV DNAemia. This study included 71 allo-HSCT patients. We found that the area under the curve (AUC) for log10 TTV DNA loads quantified by days 20 and 30 after transplantation (TTV DNA load AUC20-30), was significantly lower (P=0.036) in patients who subsequently developed CMV DNAemia requiring preemptive antiviral therapy (n=17) than in those who did not (n=8) or had no CMV DNAemia (n=19). Patients displaying TTV DNA load AUC20-30⩽2.8 copies × days × mL-1 were more likely to have high-level CMV DNAemia. A trend towards a direct correlation between TTV DNA AUC20-30 and CMV-specific interferon-γ CD8+ T-cell counts by day +30 was noted (P=0.095). However, this dynamic parameter was not useful for anticipating the occurrence of either CMV recurrences (n=12) or EBV DNAemia (n=34). In summary, it may be possible to identify a subset of allo-HSCT patients at a high risk of developing high-level CMV DNAemia by analyzing the kinetics of plasma TTV DNA load early after engraftment.

Characterization of three new HLA Class I Alleles in Spanish Caucasians, HLA-A*02:620, HLA-B*27:150 and HLA-B*07:05:01:02.

Three new HLA class I alleles, HLA-A*02:620, HLA-B*27:150 and HLA-B*07:05:01:02, were described in the Spanish Caucasoid population.

Tacrolimus plus sirolimus with or without ATG as GVHD prophylaxis in HLA-mismatched unrelated donor allogeneic stem cell transplantation.

HLA-matched related or unrelated donors are not universally available. Consequently, patients can be offered hematopoietic stem cell transplantation (HSCT) from alternative donors, including mismatched unrelated donors (MMURD), known to cause a higher incidence of acute GVHD (aGVHD) and chronic GVHD. In vivo T-cell-depletion strategies, such as antithymocyte globulin (ATG) therapy, significantly decrease the risk of GVHD. We performed a multicenter, retrospective study comparing tacrolimus (TAC) and sirolimus (SIR) with or without ATG in 104 patients (TAC-SIR=45, TAC-SIR-ATG=59) who underwent MMURD HSCT. Use of ATG was associated with a lower incidence, albeit not statistically significant, of grades 2-4 aGVHD (46% vs 64%, P=0.09), no difference in grades 3-4 aGVHD (10% vs 15%, P=0.43), a trend for a lower incidence of moderate/severe chronic GVHD (16% vs 37%, P=0.09) and more frequent Epstein-Barr virus reactivation (54% vs 18%, P=0.0002). There were no statistically significant differences in 3-year overall survival (OS) (TAC-SIR-ATG=40% (95% confidence interval (CI)=24-56%) vs TAC-SIR=54% (95% CI=37-70%), P=0.43) or 3-year cumulative incidence of relapse/progression (TAC-SIR-ATG=40% (95% CI=28-58%) vs TAC-SIR=22% (95% CI=13-39%), P=0.92). An intermediate Center for International Blood & Marrow Transplant Research disease risk resulted in a significantly lower non-relapse mortality and better OS at 3 years. Our study suggests that addition of ATG to TAC-SIR in MMURD HSCT does not affect OS when compared with TAC-SIR alone.