Food is Medicine for HIV: Improved health and hospitalizations in the Changing Health through Food Support (CHEFS-HIV) pragmatic randomized trial.

BACKGROUND: Policy support for "Food is Medicine"-medically tailored meals or groceries to improve health-is rapidly growing. No randomized trials have heretofore investigated the benefits of medically tailored food programs for people living with HIV (PLHIV). METHODS: The CHEFS-HIV pragmatic randomized trial included PLHIV who were clients of Project Open Hand (POH), a San Francisco-based nonprofit food organization. The intervention arm (n = 93) received comprehensive medically tailored meals, groceries, and nutritional education. Control participants (n = 98) received less intensive (POH "standard of care") food services. Health, nutrition, and behavioral outcomes were assessed at baseline and 6 months later. Primary outcomes measured were viral non-suppression and health related quality of life. Mixed models estimated treatment effects as differences-in-differences between arms. RESULTS: The intervention arm had lower odds of hospitalization (odds ratio [OR] = 0.11), food insecurity (OR = 0.23), depressive symptoms (OR = 0.32), antiretroviral therapy adherence <90% (OR = 0.18), and unprotected sex (OR = 0.18), and less fatty food consumption (ß= -0.170 servings/day) over 6 months, compared to the control arm. There was no difference between study arms in viral non-suppression and health-related quality of life over 6 months. CONCLUSIONS: A "Food-is-Medicine" intervention reduced hospitalizations and improved mental and physical health among PLHIV, despite no impact on viral suppression. CLINICAL TRIALS REGISTRATION: NCT03191253.

A phase II study of ibrutinib in combination with ixazomib in patients with Waldenström macroglobulinaemia.

This phase II study evaluated time-limited (24 cycles) treatment with ibrutinib and ixazomib in newly diagnosed (NDWM; n = 9) and relapsed/refractory (RRWM; n = 12) Waldenström macroglobulinaemia (WM). The overall response rate (ORR) was 76.2% (n = 16) in 21 evaluable patients with no patient achieving a complete response (CR). The median duration of treatment was 15.6 months, and after a median follow-up time of 25.7 months, the median progression-free survival (PFS) was 22.9 months. While the primary end-point was not met (CR rate at any time) and 28.5% discontinued treatment due to toxicity, ibrutinib plus ixazomib led to a clinically meaningful ORR and PFS. Combined Bruton's tyrosine kinase (BTK) and proteasome inhibition merits further evaluation in WM.

Daratumumab-lenalidomide and daratumumab-pomalidomide in relapsed lenalidomide-exposed or refractory multiple myeloma.

Daratumumab is an anti-CD38 mAb, used frequently in combination with lenalidomide and pomalidomide. No studies compared daratumumab plus lenalidomide and dexamethasone (DRd) to daratumumab plus pomalidomide and dexamethasone (DPd) in lenalidomide-exposed multiple myeloma. We identified 504 consecutive multiple myeloma patients who received daratumumab at Mayo Clinic between January 2015 and April 2019. We excluded patients who received daratumumab in the first line, received more than four lines of therapy prior to daratumumab use, did not receive lenalidomide prior to daratumumab, or had an unknown status of lenalidomide exposure, and patients who received daratumumab combinations other than DRd or DPd. We examined the impact of using DRd compared to DPd on progression-free survival (PFS) and overall survival (OS) in patients with relapsed/refractory multiple myeloma. Out of 504 patients, 162 received DRd or DPd and were included; 67 were lenalidomide-exposed and 95 were lenalidomide-refractory. DRd was used in 76 (47%) and DPd in 86 (53%) patients. In lenalidomide-exposed multiple myeloma, there was no difference in median PFS; 34.2 months [95% confidence interval (CI), 22.8-44.6] for DRd compared to 25.2 months (95% CI, 4.9-35.3) for DPd, P  = 0.2. In lenalidomide-refractory multiple myeloma, there was no difference in median PFS; 18.6 months (95% CI, 13-32) for DRd compared to 9 months (95% CI, 5.2-14.6) for DPd, P  = 0.09. No difference in median OS was observed in DRd compared to DPd. Our study shows combining daratumumab with lenalidomide in patients with prior lenalidomide use is a viable and effective treatment option.

Sepsis: network pathophysiology and implications for early diagnosis.

Sepsis, a medical emergency, is the overwhelming host response to infection leading to organ failure. The pathophysiology of this heterogeneous disease includes an inflammatory response that stimulates a complex interaction between endothelial and complements with associated coagulation abnormalities. Despite a more comprehensive understanding of sepsis pathophysiology, there exists a translational gap to improve sepsis diagnosis clinically. Many of the proposed biomarkers to diagnose sepsis lack sufficient specificity and sensitivity to be used in routine clinical practice. There has also been a lack of progress in diagnostic tools due to the focus on the inflammatory pathway. Inflammation and coagulation are known to be linked to the innate immune response. Early immunothrombotic changes could result in the early switch from infection to sepsis and aid in sepsis diagnosis. This review integrates both preclinical and clinical studies that highlight sepsis pathophysiology providing a framework for how the development of immunothrombosis could be used as a starting point to investigate biomarkers for early sepsis diagnosis.

Capillary module haemodynamics and mechanisms of blood flow regulation in skeletal muscle capillary networks: Experimental and computational analysis.

The capillary module (CM), consisting of parallel capillaries from terminal arteriole to post-capillary venule, is classically considered to be the building block of complex capillary networks. In skeletal muscle, CMs form interconnected columns spanning thousands of microns, which we recently described as the capillary fascicle. However, detailed evaluation of CM haemodynamics has not been described, and may provide insight into mechanisms of blood flow regulation in the microcirculation. We used intravital videomicroscopy from resting extensor digitorum longus muscle in rats (n = 9 networks, 112 capillary modules), as well as dual-phase computational modelling of blood flow in simulated CM geometries. We found that the mean driving pressure across CMs was 3.236 ± 1.833 mmHg. Red blood cell (RBC) flow was independent of CM resistance, and the ratio of blood flow in adjacent modules was not correlated with their ratio of resistances. In simulated CM geometries, increases to driving pressure produced a direct linear increase to RBC and plasma flow, with no changes to RBC distribution; increases to arteriolar inflow haematocrit resulted in increased RBC flow, but with viscosity-dependent increases to CM resistance. CM RBC flow heterogeneity was higher than plasma flow heterogeneity in experimental data, in contrast to simulated geometries, suggesting that time-dependent flow variability may have important consequences for RBC distribution. In summary, these findings suggest that CMs are active participants in microvascular flow regulation, likely achieved through adjustments to CM driving pressure using pre- and post-capillary loci of flow control. Increases to CM viscosity may be important during the regulation of functional hyperaemia. KEY POINTS: The capillary module (CM), consisting of parallel capillaries from the arteriole to venule, is classically considered to be the building block of capillary networks in skeletal muscle. A detailed evaluation of module haemodynamics may provide insight into mechanisms of blood flow regulation in the microcirculation. Using experimental data from resting skeletal muscle in rats, as well as dual-phase computational models of blood flow, we analysed haemodynamic relationships and the impact of variations to boundary conditions on red blood cell and plasma distribution. We showed that driving pressure across CMs is low, and that simulated increases to inflow haematocrit have important viscosity-dependent effects on module resistance. We found that red blood cell flow was independent from module resistance, which strongly suggests the regulation of driving pressure at the level of the capillary module using pre- and post-capillary loci of flow control. These findings place CMs as central participants in microvascular flow regulation, with important consequences for disease and functional hyperaemia.

Phase locking of lasers with Gaussian coupling.

A unique approach for steady in-phase locking of lasers in an array, regardless of the array geometry, position, orientation, period or size, is presented. The approach relies on the insertion of an intra-cavity Gaussian aperture in the far-field plane of the laser array. Steady in-phase locking of 90 lasers, whose far-field patterns are comprised of sharp spots with extremely high power density, was obtained for various array geometries, even in the presence of near-degenerate solutions, geometric frustration or superimposed independent longitudinal modes. The internal phase structures of the lasers can also be suppressed so as to obtain pure Gaussian mode laser outputs with uniform phase and overall high beam quality. With such phase locking, the laser array can be focused to a sharp spot of high power density, useful for many applications and the research field.

Controlling Nonlinear Interaction in a Many-Mode Laser by Tuning Disorder.

A many-mode laser with nonlinear modal interaction could serve as a model system to study many-body physics. However, precise and continuous tuning of the interaction strength over a wide range is challenging. Here, we present a unique method for controlling lasing mode structures by introducing random phase fluctuation to a nearly degenerate cavity. We show numerically and experimentally that as the characteristic scale of phase fluctuation decreases by two orders of magnitude, the transverse modes become fragmented and the reduction of their spatial overlap suppresses modal competition for gain, allowing more modes to lase. The tunability, flexibility, and robustness of our system provides a powerful platform for investigating many-body phenomena.

Ibrutinib, lenalidomide and dexamethasone in patients with relapsed and/or refractory multiple myeloma: Phase I trial results.

Therapeutic strategies that target novel pathways are urgently needed for patients with relapsed/refractory multiple myeloma (RRMM). Ibrutinib is an oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in MM cells. This phase 1 dose-escalation study examined various doses of ibrutinib in combination with standard doses of lenalidomide (25 mg) and dexamethasone (40 mg) using a standard 3 + 3 design in RRMM patients. The primary objective was to determine the maximum tolerated dose (MTD) of ibrutinib in combination with lenalidomide and dexamethasone. Patients (n = 15) had received a median of 4 prior regimens, 53% were triple-class exposed, 33% were penta-exposed, and 54% were lenalidomide-refractory. The MTD of ibrutinib was 840 mg (n = 6) and only 1 dose-limiting toxicity; a grade 3 rash possibly related to ibrutinib was noted. The most common ≥ grade 3 adverse events were rash in 2 (13%), lymphopenia in 2 (13%), leukopenia, neutropenia, thrombocytopenia, and anemia all occurring in 3 (20%) patients each. One patient achieved a partial response for an overall response rate of 7%. The clinical benefit rate was 80%. The median time to progression was 3.8 months. Ibrutinib, lenalidomide and dexamethasone appears to be a safe and well-tolerated regimen with reasonable efficacy in heavily pretreated RRMM patients.

NCCN Guidelines® Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 3.2022.

The treatment landscape of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has significantly evolved in recent years. Targeted therapy with Bruton's tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors has emerged as an effective chemotherapy-free option for patients with previously untreated or relapsed/refractory CLL/SLL. Undetectable minimal residual disease after the end of treatment is emerging as an important predictor of progression-free and overall survival for patients treated with fixed-duration BCL-2 inhibitor-based treatment. These NCCN Guidelines Insights discuss the updates to the NCCN Guidelines for CLL/SLL specific to the use of chemotherapy-free treatment options for patients with treatment-naïve and relapsed/refractory disease.

The capillary fascicle in skeletal muscle: Structural and functional physiology of RBC distribution in capillary networks.

KEY POINTS: The capillary module, consisting of parallel capillaries from arteriole to venule, is classically considered as the building block of complex capillary networks. In skeletal muscle, this structure fails to address how blood flow is regulated along the entire length of the synchronously contracting muscle fibres. Using intravital video microscopy of resting extensor digitorum longus muscle in rats, we demonstrated the capillary fascicle as a series of interconnected modules forming continuous columns that align naturally with the dimensions of the muscle fascicle. We observed structural heterogeneity for module topology, and functional heterogeneity in space and time for capillary-red blood cell (RBC) haemodynamics within a module and between modules. We found that module RBC haemodynamics were independent of module resistance, providing direct evidence for microvascular flow regulation at the level of the capillary module. The capillary fascicle is an updated paradigm for characterizing blood flow and RBC distribution in skeletal muscle capillary networks. ABSTRACT: Capillary networks are the fundamental site of oxygen exchange in the microcirculation. The capillary module (CM), consisting of parallel capillaries from terminal arteriole (TA) to post-capillary venule (PCV), is classically considered as the building block of complex capillary networks. In skeletal muscle, this structure fails to address how blood flow is regulated along the entire length of the synchronously contracting muscle fibres, requiring co-ordination from numerous modules. It has previously been recognized that TAs and PCVs interact with multiple CMs, creating interconnected networks. Using label-free intravital video microscopy of resting extensor digitorum longus muscle in rats, we found that these networks form continuous columns of linked CMs spanning thousands of microns, herein denoted as the capillary fascicle (CF); this structure aligns naturally with the dimensions of the muscle fascicle. We measured capillary-red blood cell (RBC) haemodynamics and module topology (n = 9 networks, 327 modules, 1491 capillary segments). The average module had length 481 µm, width 157 µm and 9.51 parallel capillaries. We observed structural heterogeneity for CM topology, and functional heterogeneity in space and time for capillary-RBC haemodynamics within a module and between modules. There was no correlation between capillary RBC velocity and lineal density. A passive inverse relationship between module length and haemodynamics was remarkably absent, providing direct evidence for microvascular flow regulation at the level of the CM. In summary, the CF is an updated paradigm for characterizing RBC distribution in skeletal muscle, and strengthens the theory of capillary networks as major contributors to the signal that regulates capillary perfusion.

Advances in translational imaging of the microcirculation.

The past few decades have seen an explosion in the development and use of methods for imaging the human microcirculation during health and disease. The confluence of innovative imaging technologies, affordable computing power, and economies of scale have ushered in a new era of "translational" imaging that permit us to peer into blood vessels of various organs in the human body. These imaging techniques include near-infrared spectroscopy (NIRS), positron emission tomography (PET), and magnetic resonance imaging (MRI) that are sensitive to microvascular-derived signals, as well as computed tomography (CT), optical imaging, and ultrasound (US) imaging that are capable of directly acquiring images at, or close to microvascular spatial resolution. Collectively, these imaging modalities enable us to characterize the morphological and functional changes in a tissue's microcirculation that are known to accompany the initiation and progression of numerous pathologies. Although there have been significant advances for imaging the microcirculation in preclinical models, this review focuses on developments in the assessment of the microcirculation in patients with optical imaging, NIRS, PET, US, MRI, and CT, to name a few. The goal of this review is to serve as a springboard for exploring the burgeoning role of translational imaging technologies for interrogating the structural and functional status of the microcirculation in humans, and highlight the breadth of current clinical applications. Making the human microcirculation "visible" in vivo to clinicians and researchers alike will facilitate bench-to-bedside discoveries and enhance the diagnosis and management of disease.

Atrial fibrillation in patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib: risk prediction, management, and clinical outcomes.

BACKGROUND: Ibrutinib therapy is associated with an increased risk of atrial fibrillation (AF) in chronic lymphocytic leukemia (CLL). Risk assessment tools and outcomes of AF in these patients are not well described. METHODS: We performed a retrospective review of patients with CLL treated with ibrutinib at Mayo Clinic between October 2012 and November 2018. RESULTS: Two hundred ninety-eight patients were identified with a median time on ibrutinib of 19 months (range 0.23-69.7 months). Fifty-one patients developed treatment-emergent AF; the risk of treatment-emergent AF at 6 months, 1 year, and 2 years was 9%, 12%, and 16%, respectively. The following were associated with an increased risk of treatment-emergent AF on multivariable analyses: past history of AF (hazard ratio [HR] 3.5, p = 0.0072) and heart failure (HR 3.4, p = 0.0028). Most patients are able to continue ibrutinib therapy (dose reduced in 43%). Development of treatment-emergent AF was associated with shorter event-free survival (EFS; HR 2.0, p = 0.02) and shorter overall survival (OS; HR 3.2, p = 0.001), after adjusting for age, prior treatment status, TP53 disruption, heart failure, valvular disease, and past history of AF. CONCLUSIONS: Patient comorbidities, rather than CLL-related factors, predict risk of treatment-emergent AF in patients treated with ibrutinib. Although the vast majority of patients with treatment-emergent AF are able to continue ibrutinib (with dose reduction in 43%), treatment-emergent AF appears to be associated with worse outcomes, independent of other adverse prognostic factors.

Assessment of fixed-duration therapies for treatment-naïve Waldenström macroglobulinemia.

Comparative data guiding initial therapy for Waldenström macroglobulinemia (WM), an infrequently encountered non-Hodgkin lymphoma, are sparse. We evaluated three commonly used rituximab-based frontline regimens: rituximab-bendamustine (R-Benda); dexamethasone, rituximab, cyclophosphamide (DRC); and bortezomib, dexamethasone, rituximab (BDR) in 220 treatment-naïve patients with WM, seen at Mayo Clinic between November 1, 2000 and October 31, 2019. The median follow-up was 4.5 (95%CI: 4-5) years. The R-Benda cohort (n = 83) demonstrated superior overall response rate (ORR: 98%), in comparison to DRC (n = 92, ORR: 78%) or BDR (n = 45, ORR: 84%) cohorts, p = 0.003. Similarly, longer progression-free survival (PFS) was evident with R-Benda use [median 5.2 vs. 4.3 (DRC) and 1.8 years (BDR), p < 0.001]. The time-to-next therapy (TTNT) favored R-Benda [median, not-reached, 4.4 (DRC) and 2.6 years (BDR), p < 0.001). These endpoints were comparable between the DRC and BDR cohorts. Overall survival (OS) was similar across the three cohorts, p = 0.77. In a subset analysis of 142 patients genotyped for MYD88L265P mutation, the ORR, PFS and TTNT were unaffected by the patients' MYD88 signature within each cohort. In conclusion, ORR, PFS and TTNT with R-Benda are superior compared to DRC or BDR in treatment-naïve patients with active WM. The patient outcomes with any one of these three regimens are unaffected by the MYD88L265P mutation status.

Dynamic tracking of microvascular hemoglobin content for continuous perfusion monitoring in the intensive care unit: pilot feasibility study.

PURPOSE: There is a need for bedside methods to monitor oxygen delivery in the microcirculation. Near-infrared spectroscopy commonly measures tissue oxygen saturation, but does not reflect the time-dependent variability of microvascular hemoglobin content (MHC) that attempts to match oxygen supply with demand. The objective of this study is to determine the feasibility of MHC monitoring in critically ill patients using high-resolution near-infrared spectroscopy to assess perfusion in the peripheral microcirculation. METHODS: Prospective observational cohort of 36 patients admitted within 48 h at a tertiary intensive care unit. Perfusion was measured on the quadriceps, biceps, and/or deltoid, using the temporal change in optical density at the isosbestic wavelength of hemoglobin (798 nm). Continuous wavelet transform was applied to the hemoglobin signal to delineate frequency ranges corresponding to physiological oscillations in the cardiovascular system. RESULTS: 31/36 patients had adequate signal quality for analysis, most commonly affected by motion artifacts. MHC signal demonstrates inter-subject heterogeneity in the cohort, indicated by different patterns of variability and frequency composition. Signal characteristics were concordant between muscle groups in the same patient, and correlated with systemic hemoglobin levels and oxygen saturation. Signal power was lower for patients receiving vasopressors, but not correlated with mean arterial pressure. Mechanical ventilation directly impacts MHC in peripheral tissue. CONCLUSION: MHC can be measured continuously in the ICU with high-resolution near-infrared spectroscopy, and reflects the dynamic variability of hemoglobin distribution in the microcirculation. Results suggest this novel hemodynamic metric should be further evaluated for diagnosing microvascular dysfunction and monitoring peripheral perfusion.

Improved Phase Locking of Laser Arrays with Nonlinear Coupling.

An arrangement based on a degenerate cavity laser for forming an array of nonlinearly coupled lasers with an intracavity saturable absorber is presented. More than 30 lasers were spatially phase locked and temporally Q switched. The arrangement with nonlinear coupling was found to be 25 times more sensitive to loss differences and converged five times faster to the lowest loss phase locked state than with linear coupling, thus providing a unique solution to problems that have several near-degenerate solutions.

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 4.2020, NCCN Clinical Practice Guidelines in Oncology.

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are characterized by a progressive accumulation of leukemic cells in the peripheral blood, bone marrow, and lymphoid tissues. Treatment of CLL/SLL has evolved significantly in recent years because of the improved understanding of the disease biology and the development of novel targeted therapies. In patients with indications for initiating treatment, the selection of treatment should be based on the disease stage, patient's age and overall fitness (performance status and comorbid conditions), and cytogenetic abnormalities. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with CLL/SLL.

Pomalidomide, bortezomib, and dexamethasone for patients with relapsed lenalidomide-refractory multiple myeloma.

This phase 1/2 trial evaluated the maximum tolerated doses, safety, and efficacy of pomalidomide, bortezomib, and dexamethasone (PVD) combination in patients with relapsed lenalidomide-refractory multiple myeloma (MM). In phase 1, dose level 1 consisted of pomalidomide (4 mg by mouth on days 1 to 21), IV or subcutaneous bortezomib (1.0 mg/m2 on days 1, 8, 15, and 22), and dexamethasone (40 mg by mouth on days 1, 8, 15, and 22) given every 28 days. Bortezomib was increased to 1.3 mg/m2 for dose level 2 and adopted in the phase 2 expansion cohort. We describe the results of 50 patients. Objective response rate was 86% (95% confidence interval [CI], 73-94) among all evaluable patients (stringent complete response, 12%; complete response, 10%; very good partial response, 28%; and partial response, 36%) and 100% among high-risk patients. Within a median follow-up of 42 months, 20% remain progression free, 66% are alive, and 4% remain on treatment. Median progression-free survival was 13.7 months (95% CI, 9.6-17.7). The most common toxicities were neutropenia (96%), leukopenia (84%), thrombocytopenia (82%), anemia (74%), and fatigue (72%); however, the majority of these were grade 1 or 2. The most common grade ≥3 toxicities included neutropenia (70%), leukopenia (36%), and lymphopenia (20%). Deep vein thrombosis occurred in 5 patients. In conclusion, PVD is a highly effective combination in lenalidomide-refractory MM patients. Weekly administration of bortezomib enhanced tolerability and convenience. Toxicities are manageable, mostly consisting of mild cytopenias with no significant neuropathy. This trial was registered at www.clinicaltrials.gov as #NCT01212952.

Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL.

Chronic lymphocytic leukemia (CLL) patients progressed early on ibrutinib often develop Richter transformation (RT) with a short survival of about 4 months. Preclinical studies suggest that programmed death 1 (PD-1) pathway is critical to inhibit immune surveillance in CLL. This phase 2 study was designed to test the efficacy and safety of pembrolizumab, a humanized PD-1-blocking antibody, at a dose of 200 mg every 3 weeks in relapsed and transformed CLL. Twenty-five patients including 16 relapsed CLL and 9 RT (all proven diffuse large cell lymphoma) patients were enrolled, and 60% received prior ibrutinib. Objective responses were observed in 4 out of 9 RT patients (44%) and in 0 out of 16 CLL patients (0%). All responses were observed in RT patients who had progression after prior therapy with ibrutinib. After a median follow-up time of 11 months, the median overall survival in the RT cohort was 10.7 months, but was not reached in RT patients who progressed after prior ibrutinib. Treatment-related grade 3 or above adverse events were reported in 15 (60%) patients and were manageable. Analyses of pretreatment tumor specimens from available patients revealed increased expression of PD-ligand 1 (PD-L1) and a trend of increased expression in PD-1 in the tumor microenvironment in patients who had confirmed responses. Overall, pembrolizumab exhibited selective efficacy in CLL patients with RT. The results of this study are the first to demonstrate the benefit of PD-1 blockade in CLL patients with RT, and could change the landscape of therapy for RT patients if further validated. This trial was registered at www.clinicaltrials.gov as #NCT02332980.

NCCN Guidelines Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 2.2019.

Chronic lymphocytic leukemia (CLL) is generally characterized by an indolent disease course. Histologic transformation (also known as Richter's transformation) to more aggressive lymphomas, such as diffuse large B-cell lymphoma or Hodgkin lymphoma, occurs in approximately 2% to 10% of patients and is associated with a poor prognosis. These NCCN Guidelines Insights discuss the recommendations for the diagnosis and management of patients with histologic transformation.

IGH translocations in chronic lymphocytic leukemia: Clinicopathologic features and clinical outcomes.

The prevalence, clinicopathologic correlates, and outcomes of previously untreated chronic lymphocytic leukemia (CLL) patients with IGH-BCL2 and IGH-BCL3 translocations are not well known. Using the Mayo Clinic CLL database, we identified patients seen between March 1, 2002 and September 30, 2016 who had FISH testing performed within 3 years of CLL diagnosis. The prognostic profile, time to first therapy (TTT), and overall survival (OS) of patients with IGH-BCL2 and IGH-BCL3 translocation were compared to patients without these abnormalities (non-IGH group). Of 1684 patients who met the inclusion criteria, 38 (2.2%) had IGH-BCL2, and 16 (0.9%) had IGH-BCL3 translocation at diagnosis. Patients with IGH-BCL3 translocation were more likely to have high and very-high CLL-International Prognostic Index, compared to patients with IGH-BCL2 translocation and the non-IGH group. The 5-year probability of requiring therapy was significantly higher for IGH-BCL3 compared to IGH-BCL2 and non-IGH groups (84% vs 33% vs 29%, respectively, P < 0.0001). The 5-year OS was significantly shorter for IGH-BCL3 compared to IGH-BCL2 and non-IGH groups (45% vs 89% vs 86%, respectively, P < 0.0001). On multivariable analyses, IGH-BCL3 translocation was associated with a shorter TTT (hazard ratio [HR] = 2.7; P = 0.005) and shorter OS (HR = 5.5; P < 0.0001); IGH-BCL2 translocation did not impact TTT and OS. In conclusion, approximately 3% of all newly diagnosed CLL patients have either an IGH-BCL2 or IGH-BCL3 translocation. Patients with IGH-BCL3 translocations have a distinct prognostic profile and outcome. These results support the inclusion of an IGH probe during the routine evaluation of FISH abnormalities in newly diagnosed CLL.