723 results on '"Ronald S. Go"'
Search Results
2. Clinical features and outcomes in primary nervous system histiocytic neoplasms
- Author
-
Nabeela Nathoo, Joon H. Uhm, Alyx B. Porter, Julie Hammack, Kurt A. Jaeckle, Maciej M. Mrugala, Brian A. Crum, Eoin P. Flanagan, Sean J. Pittock, Gaurav Goyal, Jason R. Young, Matthew J. Koster, Robert Vassallo, Jay H. Ryu, Caroline J. Davidge-Pitts, Corrie Bach, Aishwarya Ravindran, Julio C. Sartori Valinotti, N. Nora Bennani, Jithma P. Abeykoon, Mithun V. Shah, C. Christopher Hook, Karen L. Rech, Ronald S. Go, W. Oliver Tobin, and Mayo Clinic-University of Alabama at Birmingham Histiocytosis Working Group
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2024
- Full Text
- View/download PDF
3. Clinical Utility and Potential Cost Savings of Pharmacologic Monitoring of Eculizumab for Complement-Mediated Thrombotic Microangiopathy
- Author
-
Meera Sridharan, MD, PhD, Ronald S. Go, MD, and Maria A.V. Willrich, PhD
- Subjects
Medicine (General) ,R5-920 - Abstract
One of the treatment options for complement-mediated thrombotic microangiopathy (CM-TMA), also known as atypical hemolytic uremic syndrome, is the administration of the C5 complement inhibitor eculizumab. In vivo studies have reported a complete complement blockade with eculizumab serum concentrations above 50 μg/mL in the case of atypical hemolytic uremic syndrome. The eculizumab trough levels and C5 functional activity were monitored in patients with CM-TMA being treated with eculizumab. For those with eculizumab trough concentrations of more than 100 μg/mL, the frequency of eculizumab 1200-mg doses was decreased. In this article, we describe the pharmacologic monitoring data with the use of C5 functional activity and mass spectrometric assessments of eculizumab to allow for a tailored eculizumab schedule for 10 patients with CM-TMA. In 9 out of 10 (90%) patients with a standard administration schedule, eculizumab trough concentrations were more than 100 μg/mL. At the time of the last eculizumab follow-up (median, 250 days; range, 85-898 days), the interval between eculizumab infusions was extended to every 3-6 weeks for 8 patients; no disease relapse was found with the modified dosing interval. Altering the administration of maintenance eculizumab from every 2-3 weeks to 3-6 weeks yields a savings of $78,185 per patient for a 6-month eculizumab treatment course. Although larger standardized cohorts are necessary to confirm these findings, our data suggest that monitoring eculizumab levels in conjunction with C5 assessment allows for safe modification of eculizumab dosing and results in considerable cost savings.
- Published
- 2022
- Full Text
- View/download PDF
4. Second symptomatic COVID-19 infections in patients with an underlying monoclonal gammopathy
- Author
-
Saurabh Zanwar, Matthew Ho, Francis K. Buadi, Sikander Ailawadhi, Jeremy Larsen, Leif Bergsagel, Moritz Binder, Asher Chanan-Khan, David Dingli, Angela Dispenzieri, Rafael Fonseca, Morie A. Gertz, Wilson Gonsalves, Ronald S. Go, Suzanne Hayman, Prashant Kapoor, Taxiarchis Kourelis, Martha Q. Lacy, Nelson Leung, Yi Lin, Eli Muchtar, Vivek Roy, Taimur Sher, Rahma Warsame, Amie Fonder, Miriam Hobbs, Yi L. Hwa, Robert A. Kyle, S. Vincent Rajkumar, and Shaji Kumar
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2022
- Full Text
- View/download PDF
5. Clinical and therapeutic implications of BRAF fusions in histiocytic disorders
- Author
-
Saurabh Zanwar, Jithma P. Abeykoon, Surendra Dasari, Aishwarya Ravindran, Jason R. Young, Aldo A. Acosta-Medina, Karen L. Rech, Jonathan Schwartz, Aaron Mangold, Allison Rosenthal, N. Nora Bennani, Mithun V. Shah, Diana Morlote, Gaurav Goyal, and Ronald S. Go
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2022
- Full Text
- View/download PDF
6. Clinical features and outcomes of non-pulmonary unifocal adult Langerhans cell histiocytosis
- Author
-
Marie Hu, Gaurav Goyal, Jithma P. Abeykoon, Aldo A. Acosta-Medina, Gordan J. Ruan, Jason R. Young, Aishwarya Ravindran, N. Nora Bennani, Mithun V. Shah, Robert Vassallo, Jay H. Ryu, Caroline J. Davidge-Pitts, Matthew J. Koster, W. Oliver Tobin, Julio C. Sartori-Valinotti, Karen L. Rech, and Ronald S. Go
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2022
- Full Text
- View/download PDF
7. Isolated anemia in patients with large granular lymphocytic leukemia (LGLL)
- Author
-
Youssef Salama, Fang Zhao, Jennifer L. Oliveira, Ji Yuan, Dragan Jevremovic, Ronald S. Go, Wei Ding, Sameer A. Parikh, Mithun V. Shah, Paul J. Hampel, Aref Al-Kali, William G. Morice, and Min Shi
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Patients with large granular lymphocytic leukemia (LGLL) frequently present with neutropenia. When present, anemia is usually accompanied by neutropenia and/or thrombocytopenia and isolated anemia is uncommon. We evaluated a cohort of 244 LGLL patients spanning 15 years and herein report the clinicopathologic features of 34 (14%) with isolated anemia. The patients with isolated anemia showed a significantly male predominance (p = 0.001), a lower level of hemoglobulin (p
- Published
- 2022
- Full Text
- View/download PDF
8. A simple additive staging system for newly diagnosed multiple myeloma
- Author
-
Nadine H. Abdallah, Moritz Binder, S. Vincent Rajkumar, Patricia T. Greipp, Prashant Kapoor, Angela Dispenzieri, Morie A. Gertz, Linda B. Baughn, Martha Q. Lacy, Suzanne R. Hayman, Francis K. Buadi, David Dingli, Ronald S. Go, Yi L. Hwa, Amie L. Fonder, Miriam A. Hobbs, Yi Lin, Nelson Leung, Taxiarchis Kourelis, Rahma Warsame, Mustaqeem A. Siddiqui, Robert A. Kyle, P. Leif Bergsagel, Rafael Fonseca, Rhett P. Ketterling, and Shaji K. Kumar
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Risk stratification in multiple myeloma is important for prognostication, patient selection for clinical trials, and comparison of treatment approaches. We developed and validated a staging system that incorporates additional FISH abnormalities not included in the R-ISS and reflects the additive effects of co-occurring high-risk disease features. We first evaluated the prognostic value of predefined cytogenetic and laboratory abnormalities in 2556 Mayo Clinic patients diagnosed between February 2004 and June 2019. We then used data from 1327 patients to develop a risk stratification model and validated this in 502 patients enrolled in the MMRF CoMMpass study. On multivariate analysis, high-risk IgH translocations [risk ratio (RR): 1.7], 1q gain/amplification (RR: 1.4), chromosome17 abnormalities (RR: 1.6), ISS III (RR: 1.7), and elevated LDH (RR: 1.3) were independently associated with decreased overall survival (OS). Among 1327 evaluable patients, OS was 11.0 (95% CI: 9.2–12.6), 7.0 (95% CI: 6.3–9.2), and 4.5 (95% CI: 3.7–5.2) years in patients with 0 (stage I), 1 (stage II), and ≥2 (stage III) high-risk factors, respectively. In the MMRF cohort, median OS was 7.8 (95% CI: NR-NR), 6.0 (95% CI: 5.7-NR), and 4.3 (95% CI: 2.7-NR) years in the 3 groups, respectively (P
- Published
- 2022
- Full Text
- View/download PDF
9. Sirolimus as frontline therapy for PTEN-mutated histiocytic sarcoma
- Author
-
Karan L. Chohan, Jithma P. Abeykoon, Jason R. Young, W. Oliver Tobin, Mathew J. Koster, Mithun V. Shah, Jay H. Ryu, Robert Vassallo, Karen L. Rech., Aishwarya Ravindran, Gaurav Goyal, Ronald S. Go, and N. Nora Bennani
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
- Full Text
- View/download PDF
10. Hypovitaminosis D Is Prevalent in Patients With Renal AL Amyloidosis and Associated With Renal Outcome
- Author
-
Eli Muchtar, Matthew T. Drake, Nelson Leung, Angela Dispenzieri, Martha Q. Lacy, Francis K. Buadi, David Dingli, Suzanne R. Hayman, Prashant Kapoor, Yi Lisa Hwa, Amie Fonder, Miriam Hobbs, Wilson Gonsalves, Taxiarchis V. Kourelis, Rahma Warsame, Stephen Russell, Ronald S. Go, Moritz Binder, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar, and Morie A. Gertz
- Subjects
nephrotic syndrome ,dialysis ,proteinuria ,kidney survival ,vitamin D ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
IntroductionVitamin D deficiency is common, but no data have been reported on vitamin D levels in light chain (AL) amyloidosis.Patients and MethodsIn this exploratory study, stored serum samples from 173 patients with newly diagnosed AL amyloidosis were analyzed for vitamin studies which included 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D] and vitamin D binding protein (DBP). Measurements were made by liquid chromatography-tandem mass spectrometry. Kidney survival and overall survival (OS) were assessed in association to vitamin D status.ResultsCardiac and kidney involvement occurred in 69% and 63% of patients, respectively. 25(OH)D deficiency (5 gr/24-h) and vitamin D supplementation were independent predictors of 25(OH)D level on nominal multivariate regression analysis. 1,25(0H)2D deficiency was noted in 37.6% of patients and was independently associated with low eGFR and hypoalbuminemia. Progression to ESRD occurred in 23.7% of evaluable patients. Patients who progressed to ESRD had lower serum 25(OH)D and 1,25(OH)2D levels compared to those who did not progress to ESRD. On a multivariate analysis, severe 25(OH)D deficiency was an independent predictor of progression to ESRD as was renal stage, while 1,25(OH)2D deficiency was not.ConclusionsHypovitaminosis D is common in AL amyloidosis, particularly among patients with heavy proteinuria. Severe 25(OH)D deficiency at time of diagnosis predicts progression to ESRD.
- Published
- 2022
- Full Text
- View/download PDF
11. Prolonged remission with pembrolizumab and radiation therapy in a patient with multisystem Langerhans cell sarcoma
- Author
-
Saurabh Zanwar, Aishwarya Ravindran, Jithma P. Abeykoon, Jason R. Young, Timothy F. Kozelsky, Karen L. Rech, Gaurav Goyal, and Ronald S. Go
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2022
- Full Text
- View/download PDF
12. MASS-FIX for the detection of monoclonal proteins and light chain N-glycosylation in routine clinical practice: a cross-sectional study of 6315 patients
- Author
-
Patrick W. Mellors, Surendra Dasari, Mindy C. Kohlhagen, Taxiarchis Kourelis, Ronald S. Go, Eli Muchtar, Morie A. Gertz, Shaji K. Kumar, Francis. K. Buadi, Maria A. V. Willrich, John A. Lust, Prashant Kapoor, Martha Q. Lacy, David Dingli, Yi Hwa, Amie Fonder, Miriam Hobbs, Susan Hayman, Rahma Warsame, Nelson R. Leung, Yi Lin, Wilson Gonsalves, Mustaqeem Siddiqui, Robert A. Kyle, S. Vincent Rajkumar, David L. Murray, and Angela Dispenzieri
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Immunoenrichment-based matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), termed MASS-FIX, offers several advantages over immunofixation for the detection and isotyping of serum monoclonal protein, including superior sensitivity and specificity, the ability to differentiate therapeutic monoclonal antibodies, and the rapid identification of light chain (LC) N-glycosylation. We identified 6315 patients with MASS-FIX performed at our institution since 2018. Of these, 4118 patients (65%) with a wide array of plasma cell disorders (PCD), including rare monoclonal gammopathies of clinical significance, had a positive MASS-FIX. Two-hundred twenty-one (5%) of the MASS-FIX positive patients had evidence of LC N-glycosylation, which was more commonly identified in IgM heavy chain isotype, kappa LC isotype, and in diagnoses of immunoglobulin light chain (AL) amyloidosis and cold agglutinin disease (CAD) compared to other PCD. This cross-sectional study describes the largest cohort of patients to undergo MASS-FIX in routine clinical practice. Our findings demonstrate the widespread utility of this assay, and confirm that LC N-glycosylation should prompt suspicion for AL amyloidosis and CAD in the appropriate clinical context.
- Published
- 2021
- Full Text
- View/download PDF
13. Impact of acquired del(17p) in multiple myeloma
- Author
-
Arjun Lakshman, Utkarsh Painuly, S. Vincent Rajkumar, Rhett P. Ketterling, Prashant Kapoor, Patricia T. Greipp, Angela Dispenzieri, Morie A. Gertz, Francis K. Buadi, Martha Q. Lacy, David Dingli, Amie L. Fonder, Suzanne R. Hayman, Miriam A. Hobbs, Wilson I. Gonsalves, Yi Lisa Hwa, Nelson Leung, Ronald S. Go, Yi Lin, Taxiarchis V. Kourelis, Rahma Warsame, John A. Lust, Stephen J. Russell, Steven R. Zeldenrust, Robert A. Kyle, and Shaji K. Kumar
- Subjects
Specialties of internal medicine ,RC581-951 - Abstract
Abstract: The high-risk abnormality del(17p) can be detected by fluorescence in situ hybridization on malignant plasma cells (PCs) and has an adverse prognostic impact in patients with multiple myeloma (MM). Patients with del(17p) have reduced overall survival (OS). Patients who acquire del(17p) later during the disease course are not well described. The disease characteristics at diagnosis predicting for acquired del(17p) and its overall impact on patient survival is not known. We compared 76 patients with MM who were negative for del(17p) at diagnosis and acquired it later with 152 control MM patients who did not acquire del(17p) at a comparable time point. Patients acquired del(17p) at a median of 35.6 months (range, 4.6-116.1 months) from diagnosis of MM after a median of 2 lines of therapy (range, 1-10 lines of therapy). When compared with controls, patients with acquired del(17p) had shorter median progression-free survival (PFS) (30.1 vs 23.0 months; P = .032) and OS (106.1 vs 68.2 months; P < .001) from diagnosis. After the detection of del(17p), the median PFS was 5.4 months and the median OS was 18.1 months. High lactate dehydrogenase level (odds ratio [OR], 3.69; 95% confidence interval [CI], 1.11-12.24) and presence of t(4;14) (OR, 2.66; 95% CI, 1.09-6.48) or any high-risk translocation (OR, 2.23; 95% CI, 1.00-4.95) at diagnosis predicted acquisition of del(17p). High PC proliferative rate predicted shorter OS from detection of del(17p) (hazard ratio, 2.28; 95% CI, 1.31-3.96; P = .004). Our study shows that acquisition of del(17p) is an important molecular event associated with reduction in OS in MM. Certain baseline factors may predict acquisition of del(17p). This needs validation in prospective data sets.
- Published
- 2019
- Full Text
- View/download PDF
14. Challenges in classification of novel CFH variants in patients with atypical hemolytic uremic syndrome
- Author
-
Meera Sridharan, Michelle L. Kluge, Ronald S. Go, Roshini S. Abraham, and Ann M. Moyer
- Subjects
Alternative pathway ,Thrombotic microangiopathy ,Complement factor H ,Genetic variant classification ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) characterized by dysregulation of the alternative pathway of complement. Heterozygous variants in complement and complement regulatory proteins may increase risk for aHUS and, to date, the highest frequency of disease-causing variants in aHUS has been identified in the CFH gene encoding complement factor H. Clinical laboratory classification of variants identified in CFH can be challenging, particularly in the case of novel variants. In this report, we describe 6 patients with aHUS found to have rare variants in CFH and highlight challenges faced with variant classification in rare disorders such as aHUS.
- Published
- 2020
- Full Text
- View/download PDF
15. Correction: MASS-FIX for the detection of monoclonal proteins and light chain N-glycosylation in routine clinical practice: a cross-sectional study of 6315 patients
- Author
-
Patrick W. Mellors, Surendra Dasari, Mindy C. Kohlhagen, Taxiarchis Kourelis, Ronald S. Go, Eli Muchtar, Morie A. Gertz, Shaji K. Kumar, Francis. K. Buadi, Maria A. V. Willrich, John A. Lust, Prashant Kapoor, Martha Q. Lacy, David Dingli, Yi Hwa, Amie Fonder, Miriam Hobbs, Susan Hayman, Rahma Warsame, Nelson R. Leung, Yi Lin, Wilson Gonsalves, Mustaqeem Siddiqui, Robert A. Kyle, S. Vincent Rajkumar, David L. Murray, and Angela Dispenzieri
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2021
- Full Text
- View/download PDF
16. Bone marrow findings in Erdheim-Chester disease: increased prevalence of chronic myeloid neoplasms
- Author
-
Gaurav Goyal, Aishwarya Ravindran, Yuanhang Liu, Rong He, Mithun V. Shah, N. Nora Bennani, Mrinal M. Patnaik, Karen L. Rech, and Ronald S. Go
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2020
- Full Text
- View/download PDF
17. Clinicopathological features, treatment approaches, and outcomes in Rosai-Dorfman disease
- Author
-
Gaurav Goyal, Aishwarya Ravindran, Jason R. Young, Mithun V. Shah, N. Nora Bennani, Mrinal M. Patnaik, Grzegorz S. Nowakowski, Gita Thanarajasingam, Thomas M. Habermann, Robert Vassallo, Taimur Sher, Sameer A. Parikh, Karen L. Rech, and Ronald S. Go
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Rosai-Dorfman disease is a rare subtype of non-Langerhans cell histiocytosis. With the last major report published in 1990, there is a paucity of contemporary data on this disease. Our objective was to report the clinicopathological features, treatments and outcomes of patients seen at a tertiary referral center. Sixty-four patients with histopathological diagnosis of Rosai-Dorfman disease were identified from 1994 to 2017 (median age 50 years; range, 2-79). The median duration from symptom onset to diagnosis was seven months (range, 0-128), which was also reflected in the number of biopsies required to establish the diagnosis (median 2; range, 1-6). The most common presentation was subcutaneous masses (40%). Of the 64 patients, 8% had classical (nodal only) and 92% had extra-nodal disease (67% extra-nodal only). The most common organs involved were skin and subcutaneous tissue (52%), followed by lymph nodes (33%). Three patients had an overlap with Erdheim-Chester disease, which had not been described before. Two of these were found to have MAP2K1 mutations. Commonly utilized first line treatments were surgical excision (38%) and systemic corticosteroids (27%). Corticosteroids led to a response in 56% of the cases. Of those treated initially, 15 (30%) patients developed recurrent disease. The most commonly used systemic agent was cladribine (n=6), with 67% overall response rate. Our study demonstrates that Rosai-Dorfman disease has diverse clinical manifestations and outcomes. While this disease has been historically considered a benign entity, a subset of patients endures an aggressive course necessitating the use of systemic therapies.
- Published
- 2020
- Full Text
- View/download PDF
18. Erdheim-Chester disease with concomitant Rosai-Dorfman like lesions: a distinct entity mainly driven by MAP2K1
- Author
-
Jérôme Razanamahery, Eli L. Diamond, Fleur Cohen-Aubart, Karl-Heinz Plate, Giota Lourida, Frederic Charlotte, Zofia Hélias-Rodzewicz, Gaurav Goyal, Ronald S. Go, Ahmet Dogan, Omar Abdel-Wahab, Benjamin Durham, Neval Ozkaya, Zahir Amoura, Jean-Francois Emile, and Julien Haroche
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2020
- Full Text
- View/download PDF
19. Monoclonal Gammopathy of Undetermined Significance
- Author
-
Ronald S. Go, MD, Herbert C. Heien, MS, Lindsey R. Sangaralingham, MPH, Elizabeth B. Habermann, PhD, and Nilay D. Shah, PhD
- Subjects
Medicine (General) ,R5-920 - Abstract
Objective: To determine follow-up practice patterns of US patients with monoclonal gammopathy of undetermined significance (MGUS) and their concordance with 4 clinical practice guidelines. Patients and Methods: In a retrospective analysis of adult patients using the OptumLabs Data Warehouse database, we identified those who had an incident diagnosis of MGUS from January 1, 2006, through December 31, 2013, no history or subsequent diagnosis of lymphoplasmacytic malignancy, and at least 2 years of follow-up. Results: A total of 11,676 patients with MGUS were included in the study. During the first 2 years after MGUS diagnosis, the distribution of patients by mean interval between visits was as follows: less than 6 months, 12.7%; every 6 to 12 months, 25.2%; every 13 to 24 months, 17.7%; and longer than 24 months, 44.4%. A higher proportion of patients were followed up at intervals of less than 13 months over time, from 32.7% to 41.1% (P
- Published
- 2017
- Full Text
- View/download PDF
20. Risk of progression of monoclonal gammopathy of undetermined significance into lymphoplasmacytic malignancies: determining demographic differences in the USA
- Author
-
Ronald S. Go, Herbert C. Heien, Lindsey R. Sangaralingham, Elizabeth B. Habermann, and Nilay D. Shah
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2018
- Full Text
- View/download PDF
21. Pseudo-monoclonal gammopathy: a report of four cases
- Author
-
Majd D. Jawad, Ronald S. Go, Thomas E. Witzig, Joseph R. Mikhael, Aishwarya Ravindran, and David L. Murrray
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2017
- Full Text
- View/download PDF
22. Immunoparesis status in immunoglobulin light chain amyloidosis at diagnosis affects response and survival by regimen type
- Author
-
Eli Muchtar, Angela Dispenzieri, Shaji K. Kumar, David Dingli, Martha Q. Lacy, Francis K. Buadi, Suzanne R. Hayman, Prashant Kapoor, Nelson Leung, Rajshekhar Chakraborty, Stephen Russell, John A. Lust, Yi Lin, Ronald S. Go, Steven Zeldenrust, Robert A. Kyle, S. Vincent Rajkumar, and Morie A. Gertz
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Clinical tools to guide in the appropriate treatment selection in immunoglobulin light chain (AL) amyloidosis are not well developed. We evaluated the response and outcome for various regimens at first-line treatment (n=681) and first progression (n=240) stratified by the immunoparesis status at diagnosis. Immunoparesis was assessed by the average relative difference of the uninvolved immunoglobulins, classifying patients into a negative average relative difference (i.e. significant immunoparesis) or a positive average relative difference (no/modest immunoparesis). Treatment was categorized as autologous stem cell transplant and four non-transplant regimens (melphalan-based; bortezomib-based, immunomodulatory drug-based and dexamethasone alone). Patients with significant immunoparesis who underwent stem cell transplant had a significantly lower rate of very good partial response or better response (58%), progression-free survival (median 30 months) and overall survival (108 months), compared to those without significant immunoparesis (80%, 127 months, median not reached, respectively; P
- Published
- 2016
- Full Text
- View/download PDF
23. Patients with diffuse large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome, irrespective of MYC status: a report from an International DLBCL rituximab-CHOP Consortium Program Study
- Author
-
Carlo Visco, Alexander Tzankov, Zijun Y. Xu-Monette, Roberto N. Miranda, Yu Chuan Tai, Yan Li, Wei-min Liu, Emanuele S. G. d'Amore, Yong Li, Santiago Montes-Moreno, Karen Dybkær, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Huan-You Wang, Cherie H. Dunphy, Eric D. His, X. Frank Zhao, William WL. Choi, Xiaoying Zhao, J. Han van Krieken, Qin Huang, Weiyun Ai, Stacey O'Neill, Maurilio Ponzoni, Andres JM. Ferreri, Brad S. Kahl, Jane N. Winter, Ronald S. Go, Stephan Dirnhofer, Miguel A. Piris, Michael B. Møller, Lin Wu, L. Jeffrey Medeiros, and Ken H. Young
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Diffuse large B-cell lymphoma can be classified by gene expression profiling into germinal center and activated B-cell subtypes with different prognoses after rituximab-CHOP. The importance of previously recognized prognostic markers, such as Bcl-2 protein expression and BCL2 gene abnormalities, has been questioned in the new therapeutic era. We analyzed Bcl-2 protein expression, and BCL2 and MYC gene abnormalities by interphase fluorescence in situ hybridization in 327 patients with de novo disease treated with rituximab-CHOP. Isolated BCL2 and MYC rearrangements were not predictive of outcome in our patients as a whole, but only in those with the germinal center subtype of lymphoma. The prognostic relevance of isolated MYC rearrangements was weaker than that of BCL2 isolated translocations, but was probably limited by the rarity of the rearrangements. Seven of eight patients with double hit lymphoma had the germinal center subtype with poor outcome. The germinal center subtype patients with isolated BCL2 translocations had significantly worse outcome than the patients without BCL2 rearrangements (P=0.0002), and their outcome was similar to that of patients with the activated B-cell subtype (P=0.30), but not as bad as the outcome of patients with double hit lymphoma (P
- Published
- 2013
- Full Text
- View/download PDF
24. The association between platelet autoantibody specificity and response to intravenous immunoglobulin G in the treatment of patients with immune thrombocytopenia
- Author
-
Ronald S. Go, Kaye L. Johnston, and Kent C. Bruden
- Subjects
Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
We retrospectively investigated the association between platelet autoantibody specificity and response to intravenous immunoglobulin G (IVIG) in 17 patients with immune thrombocytopenia (ITP). Platelet-associated antibodies against glycoprotein (GP) IIb/IIIa, GPIb/IX, and GPIa/IIa were detected in 13, 10, and 8 patients, respectively. A response occurred in 7 of 7 patients without anti-GPIb/IX, but in only 3 of 10 patients with anti-GPIb/IX (p
- Published
- 2007
- Full Text
- View/download PDF
25. Complement gene variant effect on relapse of complement-mediated thrombotic microangiopathy after eculizumab cessation
- Author
-
Aldo A. Acosta-Medina, Ann M. Moyer, Ronald S. Go, Maria Alice V. Willrich, Fernando C. Fervenza, Nelson Leung, Christianne Bourlon, Jeffrey L. Winters, Grant M. Spears, Sandra C. Bryant, and Meera Sridharan
- Subjects
Hematology - Abstract
Eculizumab is effective for complement-mediated thrombotic microangiopathy (CM-TMA), also known as atypical hemolytic uremic syndrome. Although lifelong therapy had been suggested, discontinuation does not universally lead to relapse. Comprehensive data evaluating risk factors for recurrence following discontinuation are limited. Our aim was to systematically review available literature assessing the role of complement genetic variants in this setting. Reports on CM-TMA and eculizumab withdrawal published before 1 January 2021, were included. Key reasons for patient exclusion were no follow-up after drug withdrawal and patients lacking complement genetic testing. Two-hundred eighty patients from 40 publications were included. Median age was 28 years, and 25 patients had a known history of renal transplant. Complement genetic variants were identified in 60%, most commonly in CFH (n = 59) and MCP/CD46 (n = 38). Of patients with a complement gene variant, 51.3% had ≥1 likely pathogenic/pathogenic variant whereas the remaining had variants of uncertain significance (VUS). Overall relapse rate after therapy discontinuation was 29.6%. Relapse rate was highest among patients with CFH variants and MCP/CD46 variants in canonical splice regions. VUS (P < .001) and likely pathogenic/pathogenic variants (P < .001) were associated with increased relapse. Presence of a renal allograft (P = .009); decreasing age (P = .029); and detection of variants in CFH (P < .001), MCP/CD46 (P < .001), or C3 (P < .001) were all independently associated with relapse after eculizumab discontinuation. Eculizumab discontinuation is appropriate in specific patients with CM-TMA. Caution should be exerted when attempting such a strategy in patients with high risk of recurrence, including a subgroup of patients with MCP/CD46 variants.
- Published
- 2023
26. Ophthalmologic Involvement in Adults with Histiocytic Disorders
- Author
-
Samantha A. Banks, M. Tariq Bhatti, Ronald S. Go, Jithma P. Abeykoon, Aldo A. Acosta-Medina, Antonious Z. Hazim, Gaurav Goyal, Jason R. Young, Matthew J. Koster, Robert Vassallo, Jay H. Ryu, Caroline J. Davidge-Pitts, Aishwarya Ravindran, Julio C. Sartori Valinotti, N. Nora Bennani, Mithun V. Shah, Karen L. Rech, James A. Garrity, and W. Oliver Tobin
- Subjects
Ophthalmology - Published
- 2023
27. Sarcopenia identified by computed tomography imaging using a deep learning–based segmentation approach impacts survival in patients with newly diagnosed multiple myeloma
- Author
-
Bharat Nandakumar, Francis Baffour, Nadine H. Abdallah, Shaji K. Kumar, Angela Dispenzieri, Francis K. Buadi, David Dingli, Martha Q. Lacy, Suzanne R. Hayman, Prashant Kapoor, Nelson Leung, Amie Fonder, Miriam Hobbs, Yi Lisa Hwa, Eli Muchtar, Rahma Warsame, Taxiarchis V. Kourelis, Ronald S. Go, Robert A. Kyle, Morie A. Gertz, S. Vincent Rajkumar, Jason Klug, Panagiotis Korfiatis, and Wilson I. Gonsalves
- Subjects
Cancer Research ,Oncology - Abstract
Sarcopenia increases with age and is associated with poor survival outcomes in patients with cancer. By using a deep learning-based segmentation approach, clinical computed tomography (CT) images of the abdomen of patients with newly diagnosed multiple myeloma (NDMM) were reviewed to determine whether the presence of sarcopenia had any prognostic value.Sarcopenia was detected by accurate segmentation and measurement of the skeletal muscle components present at the level of the L3 vertebrae. These skeletal muscle measurements were further normalized by the height of the patient to obtain the skeletal muscle index for each patient to classify them as sarcopenic or not.The study cohort consisted of 322 patients of which 67 (28%) were categorized as having high risk (HR) fluorescence in situ hybridization (FISH) cytogenetics. A total of 171 (53%) patients were sarcopenic based on their peri-diagnosis standard-dose CT scan. The median overall survival (OS) and 2-year mortality rate for sarcopenic patients was 44 months and 40% compared to 90 months and 18% for those not sarcopenic, respectively (p .0001 for both comparisons). In a multivariable model, the adverse prognostic impact of sarcopenia was independent of International Staging System stage, age, and HR FISH cytogenetics.Sarcopenia identified by a machine learning-based convolutional neural network algorithm significantly affects OS in patients with NDMM. Future studies using this machine learning-based methodology of assessing sarcopenia in larger prospective clinical trials are required to validate these findings.
- Published
- 2022
28. Risk factors for severe infection and mortality in COVID-19 and monoclonal gammopathy of undetermined significance
- Author
-
Matthew Ho, Saurabh Zanwar, Francis K. Buadi, Sikander Ailawadhi, Jeremy Larsen, Leif Bergsagel, Moritz Binder, Asher Chanan-Khan, David Dingli, Angela Dispenzieri, Rafael Fonseca, Morie A. Gertz, Wilson Gonsalves, Ronald S. Go, Suzanne Hayman, Prashant Kapoor, Taxiarchis Kourelis, Martha Q. Lacy, Nelson Leung, Yi Lin, Eli Muchtar, Vivek Roy, Taimur Sher, Rahma Warsame, Amie Fonder, Miriam Hobbs, Yi L. Hwa, Robert A. Kyle, S. Vincent Rajkumar, and Shaji Kumar
- Subjects
Risk Factors ,Immunology ,Paraproteinemias ,Humans ,COVID-19 ,Cell Biology ,Hematology ,Multiple Myeloma ,Monoclonal Gammopathy of Undetermined Significance ,Biochemistry - Abstract
Two Letters to Blood address the risks of COVID-19 in populations with precursors of hematological disease. In the first article, Miller and colleagues report on whether clonal hematopoiesis of intermediate potential (CHIP) is associated with adverse outcomes with COVID-19, finding no association between CHIP and 28-day mortality while providing data indirectly linking IL-6 signaling and patient outcomes. In the second article, Ho and colleagues investigate the outcomes of patients with monoclonal gammopathy of undetermined significance (MGUS) with COVID-19, reporting that one-fourth had a severe infection and that on multivariable analysis, adverse outcomes are more likely if immunoparesis is present.
- Published
- 2022
29. Risk factors for severe infection and mortality In patients with <scp>COVID</scp> ‐19 in patients with multiple myeloma and <scp>AL</scp> amyloidosis
- Author
-
Matthew Ho, Saurabh Zanwar, Francis K. Buadi, Sikander Ailawadhi, Jeremy Larsen, Leif Bergsagel, Moritz Binder, Asher Chanan‐Khan, David Dingli, Angela Dispenzieri, Rafael Fonseca, Morie A. Gertz, Wilson Gonsalves, Ronald S. Go, Suzanne Hayman, Prashant Kapoor, Taxiarchis Kourelis, Martha Q. Lacy, Nelson Leung, Yi Lin, Eli Muchtar, Vivek Roy, Taimur Sher, Rahma Warsame, Amie Fonder, Miriam Hobbs, Yi L. Hwa, Robert A. Kyle, S. Vincent Rajkumar, and Shaji Kumar
- Subjects
Hematology - Abstract
Patients with multiple myeloma (MM) have a lower efficacy from COVID-19 vaccination and a high rate of mortality from COVID-19 in hospitalized patients. However, the overall rate and severity of COVID-19 infection in all settings (including non-hospitalized patients) and the independent impact of plasma cell-directed therapies on outcomes needs further study. We reviewed the medical records of 9225 patients with MM or AL amyloidosis (AL) seen at Mayo Clinic Rochester, Arizona, and Florida between 12/01/2019 and 8/31/2021 and identified 187 patients with a COVID-19 infection (n = 174 MM, n = 13 AL). The infection rate in our cohort was relatively low at 2% but one-fourth of the COVID-19 infections were severe. Nineteen (10%) patients required intensive care unit (ICU) admission and 5 (3%) patients required mechanical ventilation. The mortality rate among hospitalized patients with COVID-19 was 22% (16/72 patients). Among patients that were fully vaccinated at the time of infection (n = 12), two (17%) developed severe COVID-19 infection, without any COVID-related death. On multivariable analysis, treatment with CD38 antibody within 6 months of COVID-19 infection [Risk ratio (RR) 3.6 (95% CI: 1.2, 10.5), p = .02], cardiac [RR 4.1 (95% CI: 1.3, 12.4), p = .014] or pulmonary comorbidities [RR 3.6 (95% CI 1.1, 11.6); p = .029] were independent predictors for ICU admission. Cardiac comorbidity [RR 2.6 (95% CI: 1.1, 6.5), p = .038] was an independent predictor of mortality whereas MM/AL in remission was associated with lower mortality [RR 0.4 (95% CI: 0.2-0.8); p = .008].
- Published
- 2022
30. Phase 2 trial of ixazomib, cyclophosphamide, and dexamethasone for previously untreated light chain amyloidosis
- Author
-
Eli Muchtar, Morie A. Gertz, Betsy R. LaPlant, Francis K. Buadi, Nelson Leung, Patrick O’Brien, P. Leif Bergsagel, Amie Fonder, Yi Lisa Hwa, Miriam Hobbs, Dania K. Helgeson, Erin E. Bradt, Wilson Gonsalves, Martha Q. Lacy, Prashant Kapoor, Mustaqueem Siddiqui, Jeremy T. Larsen, Rahma Warsame, Suzanne R. Hayman, Ronald S. Go, David Dingli, Taxiarchis V. Kourelis, Angela Dispenzieri, S. Vincent Rajkumar, and Shaji K. Kumar
- Subjects
Boron Compounds ,Male ,Glycine ,Amyloidosis ,Hematology ,Dexamethasone ,Bortezomib ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Female ,Multiple Myeloma ,Cyclophosphamide ,Proteasome Inhibitors ,Aged - Abstract
Bortezomib, a proteasome inhibitor (PI), has shown efficacy in the treatment of newly diagnosed and relapsed light chain (AL) amyloidosis, and is often used in combination with cyclophosphamide and dexamethasone. Ixazomib is the first oral PI to be approved in routine practice but has not yet been evaluated in the upfront treatment setting. Newly diagnosed AL amyloidosis patients with measurable disease and adequate organ function were enrolled. The primary objective was to determine the hematologic response rate of ixazomib in combination with cyclophosphamide and dexamethasone. Treatment was given for 12 cycles, followed by ixazomib maintenance until progression. Thirty-five patients were included; their median age was 67 years, and 69% were male. Major organ involvement included heart (66%) and kidneys (54%). A median of 4 induction cycles (range, 1-12) were administered. The overall hematologic response to induction was 63% and included complete response in 11.4% and very good partial response in 37.1% of patients. One patient was upstaged to complete response during maintenance. The most common reason for going off study was the institution of alternate therapy (61%). With a median follow-up of 29.7 months for the living patients, the 2-year progression-free survival and overall survival were 74% and 78%, respectively. The median time to alternate therapy was 7.5 months. Grade ≥3 hematologic and nonhematologic adverse events occurred in 23% and 49% of patients. Given ixazomib’s favorable toxicity profile, which is an important advantage for the typically frail AL population, further evaluation of ixazomib in other combinations in the upfront setting is warranted. This trial was registered at www.clinicaltrials.gov as #NCT01864018.
- Published
- 2022
31. Race, rituximab, and relapse in TTP
- Author
-
Shruti, Chaturvedi, Ana G, Antun, Andrew M, Farland, Ryan, Woods, Ara, Metjian, Yara A, Park, Gustaaf, de Ridder, Briana, Gibson, Raj S, Kasthuri, Darla K, Liles, Frank, Akwaa, Todd, Clover, Lisa, Baumann Kreuziger, J Evan, Sadler, Meera, Sridharan, Ronald S, Go, Keith R, McCrae, Harsh Vardhan, Upreti, Angela, Liu, Ming Y, Lim, Radhika, Gangaraju, X Long, Zheng, Jay S, Raval, Camila, Masias, Spero R, Cataland, Andrew, Johnson, Elizabeth, Davis, Michael D, Evans, and Marshall A, Mazepa
- Subjects
Purpura, Thrombotic Thrombocytopenic ,Adrenal Cortex Hormones ,Recurrence ,Immunology ,ADAMTS13 Protein ,Humans ,Thiamine ,Cell Biology ,Hematology ,Rituximab ,Biochemistry - Abstract
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by recurring episodes of thrombotic microangiopathy, causing ischemic organ impairment. Black patients are overrepresented in iTTP cohorts in the United States, but racial disparities in iTTP outcome and response to therapy have not been studied. Using the United States Thrombotic Microangiopathies Consortium iTTP Registry, we evaluated the impact of race on mortality and relapse-free survival (RFS) in confirmed iTTP in the United States from 1995 to 2020. We separately examined the impact of rituximab therapy and presentation with newly diagnosed (de novo) or relapsed iTTP on RFS by race. A total of 645 participants with 1308 iTTP episodes were available for analysis. Acute iTTP mortality did not differ by race. When all episodes of iTTP were included, Black race was associated with shorter RFS (hazard ratio [HR], 1.60; 95% CI, 1.16-2.21); the addition of rituximab to corticosteroids improved RFS in White (HR, 0.37; 95% CI, 0.18-0.73) but not Black patients (HR, 0.96; 95% CI, 0.71-1.31). In de novo iTTP, rituximab delayed relapse, but Black patients had shorter RFS than White patients, regardless of treatment. In relapsed iTTP, rituximab significantly improved RFS in White but not Black patients. Race affects overall relapse risk and response to rituximab in iTTP. Black patients may require closer monitoring, earlier retreatment, and alternative immunosuppression after rituximab treatment. How race, racism, and social determinants of health contribute to the disparity in relapse risk in iTTP deserves further study.
- Published
- 2022
32. Classical and <scp>non‐classical</scp> phenotypes of <scp>Erdheim–Chester</scp> disease: Correlating clinical, radiographic and genotypic findings
- Author
-
Antonious Z, Hazim, Aldo A, Acosta-Medina, Jason R, Young, Gordon J, Ruan, Jithma P, Abeykoon, Aishwarya, Ravindran, Robert, Vassallo, Jay H, Ryu, W Oliver, Tobin, Matthew J, Koster, N Nora, Bennani, Karen L, Rech, Mithun V, Shah, Thomas E, Witzig, Gaurav, Goyal, and Ronald S, Go
- Subjects
Diagnosis, Differential ,Erdheim-Chester Disease ,Phenotype ,Genotype ,Humans ,Hematology - Published
- 2022
33. Economic Cost and Sustainability of Oral Therapies in Precision Oncology
- Author
-
Aakash P, Desai, Caleb J, Scheckel, Leah C, Soderberg, Chelsee J, Jensen, Jacob J, Orme, Sri H, Tella, Anuhya, Kommalapati, Joshua C, Pritchett, Nandita, Khera, Amit, Mahipal, and Ronald S, Go
- Subjects
Male ,Oncology ,Oncology (nursing) ,Neoplasms ,Health Policy ,Humans ,Androgen Antagonists ,Antineoplastic Agents ,Precision Medicine ,Medicare ,United States ,Aged - Abstract
PURPOSE: Precision oncology promises improved outcomes but the cost-effectiveness and accessibility of targeted therapies is debatable. We report price change patterns from 2015 to 2019 for several oral anticancer medications for common solid tumor malignancies. METHODS: We collected provider utilization and payment data from the public Medicare Part D database and extracted drug price information for commonly prescribed targeted oral anticancer agents for lung, breast, and prostate cancer. We then calculated median Pearson correlation coefficient values for various drugs (containing more than two data points) within each therapeutic class. We also calculated compound annual growth rates (CAGRs) for medication costs within each class and compared them with the consumer price index (CPI). RESULTS: Our study included six epidermal growth factor receptor inhibitors (EGFRi; one generic), five anaplastic lymphoma kinase inhibitors (ALKi), two B-Raf inhibitors (BRAFi), three hormonal agents (one generic), three cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i), two poly-ADP-ribose inhibitors (PARPi), and seven antiandrogen agents (two generic). The median (range) Pearson correlation coefficient values for cost of drugs within each therapeutic class were 0.967 (0.915-0.978) for EGFRi, 0.981 (0.966-0.989) for ALKi, 0.996 for BRAFi, 0.994 (0.992-0.999) for CDK4/6i, 0.855 for PARPi, and 0.442 (–0.522 to 0.962) for antiandrogens. Therapies with two or fewer data points (generic erlotinib, dacomitinib, abiraterone, apalutamide, and darolutamide) were excluded. The median CAGRs in costs over the 5-year period were 4.56% (EGFRi), 6.40% (ALKi), 2.58% (BRAFi), 5.48% (hormonal agents), 5.21% (CDK4/6i), 27.29% (PARPi), and 34.8% (antiandrogens). The CPI over 5 years was 2.26%/year, and the average inflation rate was 1.90%/year. CONCLUSION: The median CAGR in costs for modern oral precision-driven cancer therapeutic classes mostly outpaced CPI and the average inflation. Increase in cost within the same class should be weighed against incremental clinical benefit for the patients to ensure that rising costs do not limit access to targeted therapies.
- Published
- 2022
34. Insurance-based disparities impact survival outcomes in Waldenström macroglobulinemia within the United States
- Author
-
Karan L. Chohan, Jithma P. Abeykoon, Stephen M. Ansell, Morie A. Gertz, Prashant Kapoor, Aneel Paulus, Sikander Ailawadhi, Craig B. Reeder, Thomas E. Witzig, Thomas M. Habermann, Martha Q. Lacy, Robert A. Kyle, Ronald S. Go, and Jonas Paludo
- Subjects
Male ,Medically Uninsured ,Cancer Research ,Insurance, Health ,Medicaid ,Hematology ,Middle Aged ,Medicare ,United States ,Insurance Coverage ,Oncology ,Humans ,Waldenstrom Macroglobulinemia ,Healthcare Disparities ,Aged - Abstract
Considerable healthcare resource utilization and financial burden have been associated with the treatment of WM; however, the impact of health insurance status on outcomes has not been previously reported. We conducted a National Cancer Database analysis of newly diagnosed cases of active WM between 2004 and 2017 to evaluate the impact of insurance status on outcomes. For patients65 years old (
- Published
- 2022
35. Targeted testing of bone marrow specimens with cytoplasmic vacuolization to identify previously undiagnosed cases of VEXAS syndrome
- Author
-
Alexander S Hines, Matthew J Koster, Allison R Bock, Ronald S Go, Kenneth J Warrington, Horatiu Olteanu, Terra L Lasho, Mrinal M Patnaik, and Kaaren K Reichard
- Subjects
Rheumatology ,Pharmacology (medical) - Abstract
Objective To retrospectively identify patients with VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome) among male patients with bone marrow vacuolization using a clinically applicable, targeted-screening approach. Methods Bone marrow reports from 1 May 2014 through 18 Feb 2022 were reviewed for documentation of cytoplasmic vacuolization. Patients with acute leukaemia, lymphoma, metastatic solid tumor, amyloidosis, or POEMS were excluded as were those without clinical records available for direct chart review. Cases were rated for suspicion of VEXAS syndrome using a 5-point scale based on the presence of laboratory findings, clinical features, and treatment response. Patients with available DNA material and moderate (3 pts) or high (4–5 pts) suspicion were tested for somatic UBA1 variants associated with VEXAS syndrome. Results 315 reports from 292 unique patients included documentation of vacuolization. Following exclusion criteria, 64 patients underwent direct medical chart review to assess likelihood of VEXAS syndrome for which 21 patients met moderate to high suspicion. Available DNA was present in 8 patients of which 7 (87.5%) had a pathogenic somatic UBA1 variant consistent with VEXAS syndrome. The distribution of cytoplasmic vacuolization in the bone marrow biopsy reports among patients with VEXAS syndrome were erythroid and myeloid precursors (6/7), erythroid precursors only (1/7), and myeloid precursors only (0/7). Conclusion In this study, the utilization of a clinically applicable targeted-screening approach to test bone marrow specimens (with vacuolization) for the presence of previously undiagnosed VEXAS syndrome resulted in a positive detection rate of 87.5%.
- Published
- 2023
36. Relationship of paroxysmal nocturnal hemoglobinuria (PNH) granulocyte clone size to disease burden and risk of major vascular events in untreated patients: results from the International PNH Registry
- Author
-
David Dingli, Jaroslaw P. Maciejewski, Loree Larratt, Ronald S. Go, Britta Höchsmann, Ke Zu, Philippe Gustovic, and Alexander D. Kulagin
- Subjects
Hematology ,General Medicine - Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is caused by acquired gene mutations resulting in deficiency of glycosylphosphatidylinositol (GPI)–anchored complement regulatory proteins on the surface of blood cells, leading to terminal complement–mediated intravascular hemolysis and increased risk of major adverse vascular events (MAVEs). Using data from the International PNH Registry, this study investigated the relationship between the proportion of GPI-deficient granulocytes at PNH onset and (1) the risk for MAVEs (including thrombotic events [TEs]) and (2) the following parameters at last follow-up: high disease activity (HDA); lactate dehydrogenase (LDH) ratio; fatigue; abdominal pain; and rates of overall MAVEs and TEs. A total of 2813 patients untreated at enrollment were included and stratified by clone size at PNH disease onset (baseline). At last follow-up, higher proportion of GPI-deficient granulocytes (≤ 5% vs. > 30% clone size) at baseline was associated with significantly increased HDA incidence (14% vs. 77%), mean LDH ratio (1.3 vs. 4.7 × upper limit of normal), and rates of MAVEs 1.5 vs. 2.9 per 100 person-years) and TEs (0.9 vs. 2.0 per 100 person-years). Fatigue was evident in 71 to 76% of patients regardless of clone size. Abdominal pain was more frequently reported with clone size > 30%. A larger clone size at baseline appears to indicate a greater disease burden and risk of TEs and MAVEs and may inform decision making among physicians managing PNH patients at risk of experiencing TEs or other MAVEs. ClinicalTrials.gov ID: NCT01374360.
- Published
- 2023
37. Antineutrophil cytoplasmic antibody–associated vasculitis and <scp>VEXAS</scp> syndrome: comment on the article by Muratore et al
- Author
-
Matthew J. Koster, Umar Ghaffar, Tanaz A. Kermani, Mrinal M. Patnaik, Ronald S. Go, Abhishek A. Mangaonkar, Kaaren K. Reichard, Horatiu Olteanu, and Kenneth J. Warrington
- Subjects
Rheumatology ,Immunology ,Immunology and Allergy - Published
- 2023
38. Spectrum of clonal hematopoiesis in VEXAS syndrome
- Author
-
Fernanda Gutierrez-Rodrigues, Yael Kusne, Jenna Fernandez, Terra L Lasho, Ruba N Shalhoub, Xiaoyang Ma, Hugh Alessi, Christy M. Finke, Matthew J. Koster, Abhishek A. Mangaonkar, Kenneth J Warrington, Kebede Begna, Zhuoer Xie, Amanda K Ombrello, David S Viswanatha, Marcela A. Ferrada, Lorena Wilson, Ronald S. Go, Taxiarchis V. Kourelis, Kaaren K Reichard, Horatiu Olteanu, Ivana Darden, Dalton Hironaka, Lemlem Alemu, Sachiko Kajigaya, Rodrigo T. Calado, Emma M. Groarke, Sofia Rosenzweig, Daniel L Kastner, Katherine R Calvo, Colin O. Wu, Peter C. Grayson, Neal S Young, David B. Beck, Bhavisha A. Patel, and Mrinal M. Patnaik
- Subjects
Immunology ,Cell Biology ,Hematology ,Biochemistry - Abstract
VEXAS is caused by somatic mutations in UBA1 (UBA1mut) and characterized by heterogenous systemic auto-inflammation and progressive hematologic manifestations, meeting criteria for myelodysplastic syndrome (MDS) and plasma cell dyscrasias. The landscape of myeloid-related gene mutations leading to typical clonal hematopoiesis (CH) in these patients is unknown. Retrospectively, we screened 80 VEXAS patients for CH in their peripheral blood (PB) and correlated findings with clinical outcomes in 77. UBA1mutwere most common at hotspot p.M41 (median variant allele frequency/VAF = 75%). Typical CH mutations co-occurred with UBA1mut in 60% of patients, mostly in DNMT3A and TET2, and were not associated with inflammatory or hematologic manifestations. In prospective single-cell proteogenomic sequencing (scDNA), UBA1mutwas the dominant clone, present mostly in branched clonal trajectories. Based on integrated bulk and scDNA analyses, clonality in VEXAS followed two major patterns: with either typical CH preceding UBA1mutselection in a clone (Pattern 1), or occurring as an UBA1mutsubclone or in independent clones (Pattern 2). VAF in PB differed markedly between DNMT3A and TET2 clones (median VAF of 25% vs 1%). DNMT3A and TET2 clones associated with hierarchies representing patterns 1 and 2, respectively. Overall survival for all patients was 60% at 10 years. Transfusion-dependent anemia, moderate thrombocytopenia, and typical CH mutations, each correlated with poor outcome. In VEXAS, UBA1mut cells are the primary cause of systemic inflammation and marrow failure, being a new molecularly defined somatic entity associated with MDS. VEXAS-associated MDS is distinct from classical MDS in its presentation and clinical course.
- Published
- 2023
39. Autoimmune Hemolytic Anemia: Diagnosis and Differential Diagnosis
- Author
-
Caleb J, Scheckel and Ronald S, Go
- Subjects
Diagnosis, Differential ,Anemia, Hemolytic ,Coombs Test ,Oncology ,Humans ,Anemia, Hemolytic, Autoimmune ,Hematology ,Autoantibodies - Abstract
The causes of hemolytic anemia are numerous and a systematic approach is critical for proper identification and classification. The direct antiglobulin test can establish the diagnosis and subclassify the majority of autoimmune hemolytic anemias. Further testing to identify the driver of AIHA can have significant implications in overall management. Advanced testing for rare nonimmune acquired hemolytic anemias or hereditary hemolytic anemias may be necessary if DAT testing is negative.
- Published
- 2022
40. Supplementary Table S1 from ECOG Phase II Trial of Graded-Dose Peginterferon α-2b in Patients with Metastatic Melanoma Overexpressing Basic Fibroblast Growth Factor (E2602)
- Author
-
John M. Kirkwood, Ahmad A. Tarhini, Robert M. Conry, Dean A. Jobe, Steven M. Callister, Donghoon Shin, Sandra J. Lee, and Ronald S. Go
- Abstract
PDF file 80K, Angiogenic factor concentrations in the plasma and urine before and after Peg-IFN treatment
- Published
- 2023
41. Data from ECOG Phase II Trial of Graded-Dose Peginterferon α-2b in Patients with Metastatic Melanoma Overexpressing Basic Fibroblast Growth Factor (E2602)
- Author
-
John M. Kirkwood, Ahmad A. Tarhini, Robert M. Conry, Dean A. Jobe, Steven M. Callister, Donghoon Shin, Sandra J. Lee, and Ronald S. Go
- Abstract
Purpose: We investigated the use of graded-dose peginterferon α-2b (Peg-IFN) in patients with stage IV melanoma overexpressing basic fibroblast growth factor (FGF-2). The primary objective was suppression of plasma FGF-2 to within reference range (≤7.5 pg/mL).Experimental Design: Plasma FGF-2 was measured at baseline (step 1), and patients with concentrations of 15 pg/mL or more were eligible for study treatment (step 2). Peg-IFN was given weekly at a starting dose of 0.5 μg/kg/wk with increment every 3 weeks based on serial FGF-2 concentrations.Results: Two hundred seven patients entered step 1; 45 (22%) overexpressed FGF-2 (median = 22 pg/dL). Twenty-nine eligible patients entered step 2 and received treatment. Patients' median age was 64 years (range, 29–84 years). Most had more than two prior therapies. FGF-2 decreased in 28 (97%) patients, with suppression to reference range in 10 (35%). Median time to FGF-2 suppression was 30 days. The best clinical responses were partial response (7%) and stable disease (17%). Median progression-free survival (PFS) and overall survival (OS) were 2.0 and 9.7 months, respectively. Patients who achieved FGF-2 suppression were more likely than those who did not to have a response or stable disease (P = 0.03). VEGF concentrations decreased in 27 patients (93%) during treatment and paralleled those of FGF-2 over time. We found no compensatory increase in VEGF among those with FGF-2 suppression.Conclusions: Graded-dose Peg-IFN suppresses FGF-2 in patients with metastatic melanoma who overexpress FGF-2. Over one third of patients had complete suppression of plasma FGF-2, which correlated with clinical response to this therapy. Clin Cancer Res; 19(23); 6597–604. ©2013 AACR.
- Published
- 2023
42. Cutaneous involvement in VEXAS syndrome: clinical and histopathologic findings
- Author
-
Alexander S. Hines, Nessa A. Mohandesi, Julia S. Lehman, Matthew J. Koster, Hafsa M. Cantwell, Afsaneh Alavi, Kenneth J. Warrington, Abhishek A. Mangaonkar, Ronald S. Go, Mrinal M. Patnaik, and Julio C. Sartori‐Valinotti
- Subjects
Dermatology - Published
- 2023
43. Successful Treatment of Non-Langerhans Cell Histiocytosis with the MEK Inhibitor Trametinib: A Multicenter Analysis
- Author
-
Ashley Aaroe, Razelle Kurzrock, Gaurav Goyal, Aaron Michael Goodman, Harsh Patel, Gordon J Ruan, Gary Ulaner, Jason R. Young, Ziyi Li, Derek Dustin, Ronald S. Go, Eli L Diamond, and Filip Janku
- Subjects
Hematology - Abstract
Erdheim-Chester disease (ECD) and Rosai-Dorfman disease (RDD) are rare non-Langerhans cell histiocytoses (non-LCHs) for which therapeutic options are limited. MAPK pathway activation through BRAFV600E mutation or other genomic alterations is a histiocytosis hallmark and correlates with favorable response to BRAF inhibitors and the MEK inhibitor cobimetinib. However, there has been no systematic evaluation of alternative MEK inhibitors. To assess the efficacy and safety of the MEK inhibitor trametinib, we retrospectively analyzed outcomes of 26 adult patients (17 with ECD, 5 with ECD/RDD, 3 with RDD, and 1 with ECD/LCH) treated with orally administered trametinib at four major US care centers. The most common treatment-related toxicity was rash (27% of patients). For most patients, disease was effectively managed at lower doses (0.5-1.0 mg trametinib daily). The response rate in the 17 evaluable patients was 71% (with 73% (8/11) without a detectable BRAF V600E achieving response). At a median follow-up of 23 months, treatment effects were durable, with a median time-to-treatment failure of 37 months, while median progression-free and overall survival had not been reached (at 3 years, 90.1% of patients were alive). Most patients harbored mutations in BRAF (either classic BRAFV600E or other BRAF alterations); or alterations in other genes involved in the MAPK pathway, e.g., MAP2K1, NF1, GNAS or RAS. Most patients required lower than standard doses of trametinib but were responsive to the lower doses. Our data suggest that the MEK inhibitor trametinib is an effective treatment for ECD and RDD, including those without the BRAFV600E mutation.
- Published
- 2023
44. Analysis of Female Participant Representation in Registered Oncology Clinical Trials in the United States from 2008 to 2020
- Author
-
Nirosha D Perera, Tiffany R Bellomo, Walker M Schmidt, Henry K Litt, Margaret Shyu, MaKenna A Stavins, Max M Wang, Alexander Bell, Massoud Saleki, Katherine I Wolf, Ruxandra Ionescu, Jacqueline J Tao, Sunjong Ji, Ryan M O’Keefe, Matthew Pun, Jordan M Takasugi, Jecca R Steinberg, Ronald S Go, Brandon E Turner, and Amit Mahipal
- Subjects
Cancer Research ,Oncology - Abstract
BackgroundFemale underrepresentation in oncology clinical trials can result in outcome disparities. We evaluated female participant representation in US oncology trials by intervention type, cancer site, and funding.Materials and MethodsData were extracted from the publicly available Aggregate Analysis of ClinicalTrials.gov database. Initially, 270 172 studies were identified. Following the exclusion of trials using Medical Subject Heading terms, manual review, those with incomplete status, non-US location, sex-specific organ cancers, or lacking participant sex data, 1650 trials consisting of 240 776 participants remained. The primary outcome was participation to prevalence ratio (PPR): percent females among trial participants divided by percent females in the disease population per US Surveillance, Epidemiology, and End Results Program data. PPRs of 0.8-1.2 reflect proportional female representation.ResultsFemales represented 46.9% of participants (95% CI, 45.4-48.4); mean PPR for all trials was 0.912. Females were underrepresented in surgical (PPR 0.74) and other invasive (PPR 0.69) oncology trials. Among cancer sites, females were underrepresented in bladder (odds ratio [OR] 0.48, 95% CI 0.26-0.91, P = .02), head/neck (OR 0.44, 95% CI 0.29-0.68, P < .01), stomach (OR 0.40, 95% CI 0.23-0.70, P < .01), and esophageal (OR 0.40 95% CI 0.22-0.74, P < .01) trials. Hematologic (OR 1.78, 95% CI 1.09-1.82, P < .01) and pancreatic (OR 2.18, 95% CI 1.46-3.26, P < .01) trials had higher odds of proportional female representation. Industry-funded trials had greater odds of proportional female representation (OR 1.41, 95% CI 1.09-1.82, P = .01) than US government and academic-funded trials.ConclusionsStakeholders should look to hematologic, pancreatic, and industry-funded cancer trials as exemplars of female participant representation and consider female representation when interpreting trial results.
- Published
- 2023
45. Cold Agglutinin Disease: New Direction for an Old Disease
- Author
-
Surbhi Shah and Ronald S. Go
- Subjects
General Medicine - Published
- 2023
46. Pulmonary manifestations in VEXAS syndrome
- Author
-
Marta Casal Moura, Misbah Baqir, Yasmeen K. Tandon, Matthew J. Samec, Alexander S. Hines, Kaaren K. Reichard, Abhishek A. Mangaonkar, Ronald S. Go, Kenneth J. Warrington, Mrinal M. Patnaik, Mathew J. Koster, and Jay H. Ryu
- Subjects
Pulmonary and Respiratory Medicine - Published
- 2023
47. Langerhans cell histiocytosis with lung involvement in isolation and multisystem disease: Staging, natural history, and comparative survival
- Author
-
Karen L. Rech, Matthew J. Koster, Antonious Z. Hazim, Aishwarya Ravindran, Jay H. Ryu, Jithma P. Abeykoon, Marie Hu, Christian W. Cox, Gaurav Goyal, Robert Vassallo, W. Oliver Tobin, Ronald S. Go, N. Nora Bennani, Mithun Vinod Shah, Jason R. Young, Gordon Ruan, and Caleb Scheckel
- Subjects
Adult ,Male ,medicine.medical_specialty ,Radiography ,Disease ,Gastroenterology ,Young Adult ,Langerhans cell histiocytosis ,Internal medicine ,Humans ,Medicine ,Lung ,Aged ,Retrospective Studies ,Fluorodeoxyglucose ,business.industry ,Retrospective cohort study ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,Confidence interval ,Multisystem disease ,Natural history ,Histiocytosis, Langerhans-Cell ,Female ,business ,medicine.drug - Abstract
Langerhans cell histiocytosis (LCH) is a histiocytic neoplasm that can involve the lungs as single system (LCH-SSL) or multisystem disease (LCH-MSL). The role of full-body radiographic staging to determine whether patients have LCH-SSL or LCH-MSL is unclear. Long-term outcomes of LCH-SSL versus LCH-MSL and multisystem without lung involvement (LCH-MSNL) are unknown. A retrospective study of adult LCH patients seen at our center from January 2000 to 2020 was performed. In Part 1, we addressed utility of whole-body staging imaging among those presenting with isolated pulmonary signs or symptoms. Staging was defined as fluorodeoxyglucose positron emission tomography-computed tomography (CT) or whole-body CT obtained within 3 months of diagnosis. In Part 2, we examined the frequency of developing extra-pulmonary disease over time and mortality in patients with LCH-SSL. In Part 3, we compared the overall survival of LCH-SSL, LCH-MSL, and LCH-MSNL. Part 1: 240 patients with LCH were identified. A total of 112 (47%) had pulmonary signs or symptoms at presentation. Thirty-four (30%) underwent radiographic staging and only one showed evidence of extra-pulmonary disease. Part 2: 108 (45%) were LCH-SSL. Median follow-up duration of 4.5 years (95% confidence interval [CI]: 2.9-6.0). None developed extra-pulmonary disease. Part 3: 5-year survival: 94% (95% CI: 84%-98%) for LCH-SSL, 78% (95% CI: 59%-90%) for LCH-MSL, and 75% (95% CI: 53%-89%) for LCH-MSNL. LCH patients presenting with isolated pulmonary signs or symptoms rarely have extra-pulmonary involvement at the time of diagnosis and generally do not develop extra-pulmonary progression. LCH-SSL has the best overall survival, while LCH-MSL and LCH-MSNL have similar clinical outcomes.
- Published
- 2021
48. Practical Anemia Bundle for Sustained Blood Recovery (PABST-BR) in critical illness: a protocol for a randomised controlled trial
- Author
-
Matthew A Warner, Ronald S Go, Phillip J Schulte, William B Beam, Jonathan E Charnin, Laurie Meade, Kim A Droege, Brenda K Anderson, Matthew L Johnson, Brad Karon, Andrea Cheville, Ognjen Gajic, and Daryl J Kor
- Subjects
Phlebotomy ,Critical Illness ,Quality of Life ,Humans ,Anemia ,Heart ,General Medicine ,United States ,Randomized Controlled Trials as Topic - Abstract
IntroductionAnaemia is highly prevalent in critical illness and is associated with impaired outcomes during and after hospitalisation. However, the impact of interventions designed to attenuate or treat anaemia during critical illness on post-hospitalisation haemoglobin recovery and functional outcomes is unclear.Methods and analysisThe Practical Anemia Bundle for Sustained Blood Recovery (PABST-BR) clinical trial is a pragmatic, open-label, parallel group, single-centre, randomised clinical trial assessing the impact of a multifaceted anaemia prevention and treatment strategy versus standard care for improvement of haemoglobin concentrations and functional outcomes after critical illness. The intervention, which will be delivered early in critical illness for those with moderate-to-severe anaemia (ie, haemoglobin Ethics and disseminationThe study has been approved by the Institutional Review Board of the Mayo Clinic in Minnesota, USA. A Data Safety Monitoring Plan has been created in accordance with the policies of the Institutional Review Board and the study funder, the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH). The study will comply with NIH data sharing and dissemination policies. Results will be presented at national and international meetings and published in peer-reviewed journals. Designing and testing strategies to optimise haemoglobin recovery and improve functional outcomes after critical illness remain important research gaps. The PABST-BR trial will inform the development of a larger multicentre clinical trial.Trial registration numberNCT05167734.
- Published
- 2022
49. Reduced intensity conditioning allogeneic hematopoietic stem cell transplantation in <scp>VEXAS</scp> syndrome: Data from a prospective series of patients
- Author
-
Abhishek A. Mangaonkar, Kimberly J. Langer, Terra L. Lasho, Christy Finke, Mark R. Litzow, William J. Hogan, Mithun V. Shah, Ronald S. Go, Gabriel Bartoo, Jade Kutzke, Kristen B. McCullough, Matthew Koster, Matthew Samec, Kenneth J. Warrington, Kaaren K. Reichard, Horatiu Olteanu, Mary Riwes, Mrinal M. Patnaik, and Hassan B. Alkhateeb
- Subjects
Hematology - Published
- 2022
50. Disease outcomes and biomarkers of progression in smouldering Waldenström macroglobulinaemia
- Author
-
Rahma Warsame, Ronald S. Go, Morie A. Gertz, Stephen M. Ansell, David Dingli, Wilson I. Gonsalves, Thomas M. Habermann, Prashant Kapoor, Dirk R. Larson, Colin L. Colby, Rong He, Robert A. Kyle, Grzegorz S. Nowakowski, Jonas Paludo, Jithma P. Abeykoon, Saurabh Zanwar, Rebecca L. King, Martha Q. Lacy, Shaji Kumar, Carrie A. Thompson, Thomas E. Witzig, Patricia T. Greipp, and S. Vincent Rajkumar
- Subjects
Male ,Receptors, CXCR4 ,medicine.medical_specialty ,Multivariate analysis ,Genotype ,Survival ,Population ,CXCR4 ,Asymptomatic ,Gastroenterology ,Hemoglobins ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,medicine ,Humans ,education ,Aged ,Retrospective Studies ,education.field_of_study ,business.industry ,Beta-2 microglobulin ,Hematology ,Middle Aged ,Confidence interval ,Relative risk ,Multivariate Analysis ,Mutation ,Myeloid Differentiation Factor 88 ,Cohort ,Disease Progression ,Female ,Waldenstrom Macroglobulinemia ,medicine.symptom ,beta 2-Microglobulin ,business ,Biomarkers ,Follow-Up Studies - Abstract
Patients with asymptomatic/smouldering Waldenstrom macroglobulinaemia (SWM) have a variable risk of progression to active WM. Our study evaluated 143 patients with SWM consecutively seen between January 1996 and December 2013. With a median [95% confidence interval (CI)] follow-up of 9·5 [8·1-11·5] years, the cumulative rate of progression was 11% at 1 year, 38% at 3 years and 55% at 5 years. On multivariate analysis, haemoglobin (Hb) ≤123 g/l [risk ratio (RR) 2·08; P = 0·009] and β2 -microglobulin (β2 M) ≥2·7 µg/ml (RR 2·0; P = 0·01) were independent predictors of a shorter time-to-progression (TTP) to active WM. Patients with myeloid differentiation factor 88 wild type (MYD88WT ) genotype (n = 11) demonstrated a trend toward shorter TTP [median (95% CI) 1·7 (0·7-8·7) vs. 4·7 (2·4-7·7) years for the MYD88L265P cohort, n = 42; P = 0·11]. The presence of C-X-C chemokine receptor type 4 (CXCR4) mutation (n = 29) did not impact the TTP (median: 3 years for CXCR4WT vs. 5·6 years for CXCR4MUT , P = 0·34). The overall survival (OS) for patients with SWM (median: 18·1 years) was comparable to an age-, sex- and calendar year-matched USA population (median: 20·3 years, P = 0·502). In conclusion, Hb and β2 M at diagnosis represent independent predictors of progression to active WM. Comparable survival of SWM and a matched USA population argues against pre-emptive intervention in this patient population.
- Published
- 2021
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.