Vishesh Khanna

All Publications

• Outcomes with molecularly targeted agents as salvage therapy following frontline venetoclax + hypomethylating agent in adults with acute myeloid leukemia: A multicenter retrospective analysis. Leukemia research Khanna, V., Azenkot, T., Liu, S. Q., Gilbert, J., Cheung, E., Lau, K., Pollyea, D. A., Traer, E., Jonas, B. A., Zhang, T. Y., Mannis, G. N. 2023; 131: 107331

  View details for DOI 10.1016/j.leukres.2023.107331

  View details for PubMedID 37263072

• Outcomes of allogeneic hematopoietic stem cell transplantation in secondary central nervous system lymphoma: a case series LEUKEMIA & LYMPHOMA Gaut, D., Oliai, C., Mead, M. 2023; 64 (2): 507-510

  Abstract

  The rate of MRD clearance in AML with standard consolidation chemotherapy is not well defined. A multi-institution retrospective analysis was performed on 107 consecutively treated AML patients in morphologic complete remission with detectable MRD post-induction therapy who received standard chemotherapy consolidation. In response to standard intermediate/high-dose cytarabine consolidation therapy, 26 of 60 patients (43.3%) with MRD threshold of detection of at least 0.1% converted to MRD-negative status (undetectable with assay used), and 6 of 47 patients (12.8%) with MRD threshold of detection > 0.1% converted to MRD-negative status. Multivariable logistic regression for patients with MRD threshold of detection of at least 0.1% showed that, when controlling for age, ELN risk category, dose of cytarabine, and use of a combination agent, treatment with 1 cycle of consolidation cytarabine versus ≥2 cycles decreased the odds of conversion of AML to MRD-negative (OR = 0.24, 95% CI 0.07-0.85, p = 0.03).

  View details for DOI 10.1080/10428194.2022.2151839

  View details for Web of Science ID 000917955500001

  View details for PubMedID 37801340

• Measurable Residual Disease Conversion Rate with Consolidation Chemotherapy in Acute Myeloid Leukemia Gaut, D., Oliai, C., Boiarsky, J., Zhang, S., Azenkot, T., Kennedy, V. E., Khanna, V., Gutierrez, K., Shukla, N. D., Moskoff, B., Patel, A., Jeyakumar, D., Mannis, G. N., Logan, A. C., Jonas, B. A., Schiller, G. J. AMER SOC HEMATOLOGY. 2022: 3374-3376

  View details for DOI 10.1182/blood-2022-156842

  View details for Web of Science ID 000893223203180

• Characterization of Clinical, Molecular, and Prognostic Features of the WHO 2022 Classification System for Myelodysplastic Neoplasms (MDS) Khanna, V., Lu, R., Kumar, J., Stehr, H., Spinner, M. A., Silva, O., Fernandez-Pol, S., Oak, J. S., Tan, B., Greenberg, P. L. AMER SOC HEMATOLOGY. 2022: 6955-6957

  View details for DOI 10.1182/blood-2022-165841

  View details for Web of Science ID 000893223206427

• Correlation of Mutational Profiles and Cytogenetics with Morphologic Dysplasia in Myelodysplastic Syndromes Kumar, J., Khanna, V., Lu, R., Stehr, H., Spinner, M. A., Silva, O., Fernandez-Pol, S., Oak, J. S., Greenberg, P. L., Tan, B. AMER SOC HEMATOLOGY. 2022: 4053-4055

  View details for DOI 10.1182/blood-2022-160237

  View details for Web of Science ID 000893223204027

• Abemaciclib in metastatic or locally advanced anaplastic thyroid cancer. Khanna, V., Miles, C., Sundaram, V., Sheth, S., Steffen, M., Biedermann, S., Jun, D., Winters, E., Khan, S. A. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680305043

• Ependymoma, NOS and anaplastic ependymoma incidence and survival in the United States varies widely by patient and clinical characteristics, 2000-2016. Neuro-oncology practice Achey, R. L., Vo, S. n., Cioffi, G. n., Gittleman, H. n., Schroer, J. n., Khanna, V. n., Buerki, R. n., Kruchko, C. n., Barnholtz-Sloan, J. S. 2020; 7 (5): 549–58

  Abstract

  Ependymoma is a rare CNS tumor arising from the ependymal lining of the ventricular system. General differences in incidence and survival have been noted but not examined on a comprehensive scale for all ages and by histology. Despite the rarity of ependymomas, morbidity/mortality associated with an ependymoma diagnosis justifies closer examination.Incidence data were obtained from the Central Brain Tumor Registry of the United States in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, and survival data from Surveillance Epidemiology and End Results, from 2000 to 2016 for anaplastic ependymoma and ependymoma, not otherwise specified (NOS). Age-adjusted incidence rates (IRs) per 100 000 person-years were analyzed by age, sex, race, and location. Survival analysis was performed with Kaplan-Meier curves and multivariable Cox proportional hazards models.Incidence of anaplastic ependymoma was highest in ages 0 to 4 years. African American populations had lower incidence but had a 78% increased risk of death compared to white populations (hazard ratio [HR]: 1.78 [95% CI, 1.30-2.44]). Incidence was highest for anaplastic ependymoma in the supratentorial region. Adults (age 40+ years) had almost twice the risk of death compared to children (ages 0-14 years) (HR: 1.97 [95% CI, 1.45-2.66]). For ependymoma, NOS, subtotal resection had a risk of mortality 1.86 times greater than gross total resection ([HR: 1.86 [95% CI, 1.32-2.63]).African American populations experienced higher mortality rates despite lower incidence compared to white populations. Extent of resection is an important prognostic factor for survival. This highlights need for further evaluation of treatment patterns and racial disparities in the care of patients with ependymoma subtypes.

  View details for DOI 10.1093/nop/npaa023

  View details for PubMedID 33014396

  View details for PubMedCentralID PMC7516115

• Genomic landscape of Neutrophilic Leukemias of Ambiguous Diagnosis. Blood Zhang, H., Wilmot, B., Bottomly, D., Dao, K. T., Stevens, E., Eide, C. A., Khanna, V., Rofelty, A., Savage, S., Reister-Schultz, A., Long, N., White, L., Carlos, A., Henson, R. A., Lin, C., Searles, R., Collins, R. H., DeAngelo, D. J., Deininger, M. W., Dunn, T., Than, H., Luskin, M. R., Medeiros, B. C., Oh, S. T., Pollyea, D. A., Steensma, D. P., Stone, R. M., Druker, B. J., McWeeney, S. K., Maxson, J. E., Gotlib, J. R., Tyner, J. W. 2019

  Abstract

  Chronic neutrophilic leukemia (CNL), atypical chronic myeloid leukemia (aCML), and myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U) are a group of rare, heterogeneous myeloid disorders. There is strong morphologic resemblance amongst these distinct diagnostic entities as well as lack of specific molecular markers and limited understanding of disease pathogenesis, which has made diagnosis challenging in certain cases. The treatment has remained empirical, resulting in dismal outcomes. We, therefore, performed whole exome and RNA-sequencing of these rare hematologic malignancies and present the most complete survey of the genomic landscape of these diseases to date. We observed a diversity of combinatorial mutational patterns that generally do not cluster within any one diagnosis. Gene expression analysis reveals enrichment, but not co-segregation of clinical and genetic disease features with transcriptional clusters. In conclusion, these group of diseases represent a continuum of related diseases rather than discrete diagnostic entities.

  View details for DOI 10.1182/blood.2019000611

  View details for PubMedID 31366621

• Nonmalignant and malignant meningioma incidence and survival in the elderly, 20052015, using the Central Brain Tumor Registry of the United States NEURO-ONCOLOGY Achey, R. L., Gittleman, H., Schroer, J., Khanna, V., Kruchko, C., Barnholtz-Sloan, J. S. 2019; 21 (3): 380–91

  View details for DOI 10.1093/neuonc/noy162

  View details for Web of Science ID 000462164400011

• Non-malignant and malignant meningioma incidence and survival in the elderly from 2005-2015 using the Central Brain Tumor Registry of the United States. Neuro-oncology Achey, R. L., Gittleman, H., Schroer, J., Khanna, V., Kruchko, C., Barnholtz-Sloan, J. S. 2018

  Abstract

  Background: Meningioma incidence increases significantly with age. In the expanding elderly population, we lack complete understanding of population-based trends in meningioma incidence/survival. We provide an updated, comprehensive analysis of meningioma incidence and survival for individuals aged over 65.Methods: Data were obtained from the Central Brain Tumor Registry of the United States (CBTRUS) from 2005-2015 for non-malignant and malignant meningioma. Age-adjusted incidence rates per 100,000 person-years were analyzed by age, sex, race, ethnicity, location, and treatment modalities. Survival was analyzed using Kaplan-Meier and multivariable Cox proportional hazards models for a subset of CBTRUS data.Results: Non-malignant meningioma incidence doubled from adults age 65-69 years to adults over age 85 years and was significantly greater in females than males for all ages. Malignant meningioma incidence did not differ by sex for any age grouping. Non-malignant and malignant meningioma incidence was significantly greater in Black populations versus others. Non-malignant meningioma survival was worse with age, in Black populations, and in males, including when analyzed by five-year age groups. Surgical resection and radiation did not improve survival compared to resection alone in non-malignant meningioma.Conclusions: This study reports increasing non-malignant meningioma incidence in the elderly, increased incidence in Black populations, and in females. In contrast, malignant meningioma incidence did not differ between sexes. Risk of death was higher for Black individuals and males. Additionally, radiation did not confer a survival advantage when combined with resection for non-malignant meningioma. Thus, we identify clinically relevant discrepancies in meningioma incidence/survival that require further study.

  View details for PubMedID 30295804

• Incidence and survival trends for medulloblastomas in the United States from 2001 to 2013. Journal of neuro-oncology Khanna, V., Achey, R. L., Ostrom, Q. T., Block-Beach, H., Kruchko, C., Barnholtz-Sloan, J. S., de Blank, P. M. 2017; 135 (3): 433-441

  Abstract

  Population-based data examining recent epidemiological trends in medulloblastoma, the most common pediatric brain malignancy, are limited. Therefore, we sought to examine recent population-level trends in medulloblastoma incidence and survival. Central Brain Tumor Registry of the United States (CBTRUS) data were analyzed from 2001 to 2013. Age-adjusted incidence rates (IR) and annual percent changes (APCs) with 95% confidence intervals (CI) were calculated by age, sex, and race. Relative survival rates were calculated by age, sex, and race using Surveillance, Epidemiology and End-Results (SEER) registries; subsets of CBTRUS data. Kaplan-Meier and Cox proportional hazards models were used to examine survival differences. Medulloblastoma incidence remained relatively stable from 2001 to 2013, with minor fluctuations from 2001 to 2009 (APC = 2.2, 95% CI 0.8, 3.5) and 2009-2013 (APC = -4.1, 95% CI -7.5, -0.6). Incidence was highest in patients aged 1-4 years at diagnosis, but patients aged 10-14 years showed increased incidence from 2000 to 2013 (APC = 3.2, 95% CI 0.6, 5.8). Males displayed higher IR relative to females (males: 0.16 vs. females: 0.12), except in patients <1 year-old. Compared to Whites, Blacks displayed a non-significant increase in incidence (APC = 1.7, 95% CI -0.4, 4.0) and in mortality risk (hazard ratio for survival = 0.74; p = 0.09). The current study reports no overall change in medulloblastoma incidence from 2001 to 2013. Male and female patients <1 year-old had equal medulloblastoma incidence rates and poor 5-year relative survival compared to other ages. Non-significant trends in the data suggest disparities in medulloblastoma incidence and survival by race. Thus, analysis of tumor-specific trends by demographic variables can uncover clinically informative trends in cancer burden.

  View details for DOI 10.1007/s11060-017-2594-6

  View details for PubMedID 28828582

• Recurrent cyclin D2 mutations in myeloid neoplasms LEUKEMIA Khanna, V., Eide, C. A., Tognon, C. E., Maxson, J. E., Wilmot, B., Bottomly, D., McWeeney, S., Edwards, D. K., Druker, B. J., Tyner, J. W. 2017; 31 (9): 2005–8

  View details for PubMedID 28630439

• Incidence and survival trends in oligodendrogliomas and anaplastic oligodendrogliomas in the United States from 2000 to 2013: a CBTRUS Report. Journal of neuro-oncology Achey, R. L., Khanna, V., Ostrom, Q. T., Kruchko, C., Barnholtz-Sloan, J. S. 2017; 133 (1): 17-25

  Abstract

  Measuring tumor-specific trends in incidence is necessary to elucidate tumor-type contribution to overall cancer burden in the US population. Recently, there have been conflicting reports concerning the incidence of oligodendrogliomas (OD) and anaplastic oligodendrogliomas (AOD). Therefore, our goal was to examine trends in OD and AOD incidence and survival by age, gender and race. Data was analyzed from the Central Brain Tumor Registry of the United States (CBTRUS) from 2000 to 2013. Age-adjusted incidence rates per 100,000 person-years with 95% confidence intervals (CI) and annual percent changes (APCs) with 95% CI were calculated for OD and AOD by age, sex and race. Survival rates were calculated for age, sex and race using a subset of the CBTRUS data. OD and AOD incidence peaked at 36-40 and 56-60 years, respectively. AOD:OD ratio increased up to age 75. Overall, OD and AOD incidence decreased [OD: APC -3.2 (2000-2013), AOD: -6.5 (2000-2007)]. OD incidence was highest in Whites but decreased significantly (2000-2013: APC -3.1) while incidence in Black populations did not significantly decrease (2000-2013: APC -1.6). Survival rates decreased with advancing age for OD, while persons aged 0-24 had the lowest survival for AOD. The current study reports a decrease in overall OD and AOD incidence from 2000 to 2013. Furthermore, AOD makes up an increasing proportion of oligodendroglial tumors up to age 75. Lower AOD survival in 0-24 years old may indicate molecular differences in pediatric cases. Thus, surveillance of tumor-specific trends by age, race and sex can reveal clinically relevant variations.

  View details for DOI 10.1007/s11060-017-2414-z

  View details for PubMedID 28397028

• Molecularly targeted drug combinations demonstrate selective effectiveness for myeloid- and lymphoid-derived hematologic malignancies. Proceedings of the National Academy of Sciences of the United States of America Kurtz, S. E., Eide, C. A., Kaempf, A. n., Khanna, V. n., Savage, S. L., Rofelty, A. n., English, I. n., Ho, H. n., Pandya, R. n., Bolosky, W. J., Poon, H. n., Deininger, M. W., Collins, R. n., Swords, R. T., Watts, J. n., Pollyea, D. A., Medeiros, B. C., Traer, E. n., Tognon, C. E., Mori, M. n., Druker, B. J., Tyner, J. W. 2017

  Abstract

  Translating the genetic and epigenetic heterogeneity underlying human cancers into therapeutic strategies is an ongoing challenge. Large-scale sequencing efforts have uncovered a spectrum of mutations in many hematologic malignancies, including acute myeloid leukemia (AML), suggesting that combinations of agents will be required to treat these diseases effectively. Combinatorial approaches will also be critical for combating the emergence of genetically heterogeneous subclones, rescue signals in the microenvironment, and tumor-intrinsic feedback pathways that all contribute to disease relapse. To identify novel and effective drug combinations, we performed ex vivo sensitivity profiling of 122 primary patient samples from a variety of hematologic malignancies against a panel of 48 drug combinations. The combinations were designed as drug pairs that target nonoverlapping biological pathways and comprise drugs from different classes, preferably with Food and Drug Administration approval. A combination ratio (CR) was derived for each drug pair, and CRs were evaluated with respect to diagnostic categories as well as against genetic, cytogenetic, and cellular phenotypes of specimens from the two largest disease categories: AML and chronic lymphocytic leukemia (CLL). Nearly all tested combinations involving a BCL2 inhibitor showed additional benefit in patients with myeloid malignancies, whereas select combinations involving PI3K, CSF1R, or bromodomain inhibitors showed preferential benefit in lymphoid malignancies. Expanded analyses of patients with AML and CLL revealed specific patterns of ex vivo drug combination efficacy that were associated with select genetic, cytogenetic, and phenotypic disease subsets, warranting further evaluation. These findings highlight the heuristic value of an integrated functional genomic approach to the identification of novel treatment strategies for hematologic malignancies.

  View details for PubMedID 28784769

• Durable Disease Control with MEK Inhibition in a Patient with NRAS-mutated Atypical Chronic Myeloid Leukemia. Cureus Khanna, V., Pierce, S. T., Dao, K. T., Tognon, C. E., Hunt, D. E., Junio, B., Tyner, J. W., Druker, B. J. 2015; 7 (12): e414

  Abstract

  Atypical chronic myeloid leukemia (aCML) and chronic neutrophilic leukemia (CNL) are rare hematologic neoplasms characterized by leukocytosis and a hypercellular bone marrow. Although recurrent mutations in the colony-stimulating factor 3 receptor (CSF3R) are frequently observed in patients with (CNL), the mutational landscape in (aCML) is less well-defined. In this report, we describe an 81-year-old male who was diagnosed with aCML. He presented with leukocytosis and anemia but no significant clinical symptoms. Standard laboratory studies revealed the absence of the Philadelphia chromosome. Massively parallel sequencing demonstrated no mutations in CSF3R, but the presence of a heterozygous NRAS-G12D variant (47% allele frequency). The patient was started on treatment with trametinib, an MEK1/2 inhibitor with Food and Drug Administration approval for malignant melanoma. Therapy with trametinib resulted in exceptional improvements in his blood counts and continued disease control with 14 months of follow-up. This case highlights the need for clinical trials evaluating the safety and efficacy of MEK1/2 as a therapeutic target for the treatment of patients with NRAS-mutated aCML/CNL.

  View details for DOI 10.7759/cureus.414

  View details for PubMedID 26870618

  View details for PubMedCentralID PMC4725740

• Clinical Management of Type 2 Diabetes Mellitus after Bariatric Surgery. Current atherosclerosis reports Khanna, V., Kashyap, S. R. 2015; 17 (10): 59

  Abstract

  Bariatric surgery has emerged as an effective treatment for type 2 diabetes in the setting of obesity, with recent clinical trials demonstrating biochemical remission (i.e., euglycemia) in up to 40 % of subjects at 3 years post-surgery. Conversely, these trials also highlight that a significant proportion of individuals undergoing bariatric surgery experience residual diabetes (i.e., they do not achieve remission or experience diabetes recurrence). The management of residual diabetes following surgery requires personalized attention, yet limited evidence exists on which to base clinical decisions. Hence, we aim to review the evidence that does exist and propose clinical management strategies in patients with persistent hyperglycemia following bariatric surgery.

  View details for DOI 10.1007/s11883-015-0537-2

  View details for PubMedID 26303454

• Adults with long-duration type 2 diabetes have blunted glycemic and β-cell function improvements after bariatric surgery. Obesity (Silver Spring, Md.) Khanna, V., Malin, S. K., Bena, J., Abood, B., Pothier, C. E., Bhatt, D. L., Nissen, S., Watanabe, R., Brethauer, S. A., Schauer, P. R., Kirwan, J. P., Kashyap, S. R. 2015; 23 (3): 523-6

  Abstract

  This study investigated the effect of type 2 diabetes duration on glucose regulation 24 months post-bariatric surgery.Twenty-seven adults with short- (<5 years) and long-duration (≥10 years) type 2 diabetes received a mixed-meal tolerance test at baseline and 24 months postsurgery. Body weight, insulin sensitivity, first- and second-phase meal-stimulated insulin secretion, disposition index (i.e., DI or pancreatic β-cell function), and incretin responses were examined.Adults with short-duration type 2 diabetes had better HbA(1c), greater insulin secretory capacity, and greater DI compared with adults with long-duration type 2 diabetes, despite similar weight loss and incretin responses. Diabetes duration correlated with smaller improvements in HbA(1c) and DI but not weight loss.Enhanced β-cell function characterizes the effect of bariatric surgery in adults with diabetes for <5 years, independent of weight loss or incretins. Additional therapy postsurgery may be required to improve glycemia for people with long-standing type 2 diabetes.

  View details for DOI 10.1002/oby.21021

  View details for PubMedID 25651277

  View details for PubMedCentralID PMC4340772

• Histone deacetylase-4 is required during early cranial neural crest development for generation of the zebrafish palatal skeleton. BMC developmental biology DeLaurier, A., Nakamura, Y., Braasch, I., Khanna, V., Kato, H., Wakitani, S., Postlethwait, J. H., Kimmel, C. B. 2012; 12: 16

  Abstract

  Histone deacetylase-4 (Hdac4) is a class II histone deacetylase that inhibits the activity of transcription factors. In humans, HDAC4 deficiency is associated with non-syndromic oral clefts and brachydactyly mental retardation syndrome (BDMR) with craniofacial abnormalities.We identify hdac4 in zebrafish and characterize its function in craniofacial morphogenesis. The gene is present as a single copy, and the deduced Hdac4 protein sequence shares all known functional domains with human HDAC4. The zebrafish hdac4 transcript is widely present in migratory cranial neural crest (CNC) cells of the embryo, including populations migrating around the eye, which previously have been shown to contribute to the formation of the palatal skeleton of the early larva. Embryos injected with hdac4 morpholinos (MO) have reduced or absent CNC populations that normally migrate medial to the eye. CNC-derived palatal precursor cells do not recover at the post-migratory stage, and subsequently we found that defects in the developing cartilaginous palatal skeleton correlate with reduction or absence of early CNC cells. Palatal skeletal defects prominently include a shortened, clefted, or missing ethmoid plate, and are associated with a shortening of the face of young larvae.Our results demonstrate that Hdac4 is a regulator of CNC-derived palatal skeletal precursors during early embryogenesis. Cleft palate resulting from HDAC4 mutations in human patients may result from defects in a homologous CNC progenitor cell population.

  View details for DOI 10.1186/1471-213X-12-16

  View details for PubMedID 22676467

  View details for PubMedCentralID PMC3426487