Gaurav Goyal

• MD
• Professor (Assistant) at University of Alabama at Birmingham

Among 64 patients with Erdheim-Chester disease treated with a BRAF-inhibitor (median follow up 4 years), we found high response rates (85%) but frequent discontinuations (61%), primarily due to adverse events. Additionally, patients experienced persistently poor health-related quality of life.

Introduction Little is known about long‐term outcomes and causes of death for individuals with cutaneous T‐cell lymphoma. Methods We used SEER‐18 registry data to examine outcomes among 9886 adults with mycosis fungoides (MF), Sézary syndrome (SS), primary cutaneous anaplastic large cell lymphoma (pcALCL), and subcutaneous panniculitis‐like T‐cell...

Endocrinopathies are frequently the initial presentation of histiocytic neoplasms, which are rare hematologic disorders affecting multiple organ systems. Langerhans cell histiocytosis and Erdheim–Chester disease are 2 such disorders known to infiltrate the hypothalamus and/or pituitary gland, leading to arginine vasopressin deficiency (AVP-D) and a...

Anxiety and depression are common in many cancers but have not been systematically studied in patients with histiocytic neoplasms (HN). We sought to estimate rates of anxiety and depression and identify clinical features and patient-reported outcomes (PROs) associated with anxiety and depression in patients with HN. A registry-based cohort of patie...

PURPOSE BRAF and MEK inhibitors are standard treatments in histiocytic disorders, such as Erdheim-Chester disease (ECD). Some patients lack MAPK-pathway alterations, making these treatments less effective. METHODS We describe three patients with histiocytic disorders who have novel non-MAPK pathway alterations. These alterations were studied throu...

Background: CAR T-cell therapy is a promising treatment option for hematological malignancies. However, toxicities such as cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) associated with CAR T-cell therapies are challenging to manage. Tocilizumab, an anti-interleukin - 6 receptor (IL-6R) monoclonal...

Background: Erdheim-Chester disease (ECD) manifests as multi-organ infiltration of clonal histiocytes with mutations primarily in the mitogen-activated protein kinase (MAPK) pathway. The revised classification of histiocytosis (2016) categorizes ECD with typical bilateral, symmetric osteosclerosis of the lower extremity long bones as classical (C)...

Introduction. Erdheim-Chester disease (ECD), Langerhans cell histiocytosis (LCH) and Rosai-Dorfman disease (RDD) belong to a group of histiocytic neoplasms often driven by mutations in the mitogen activated protein kinase (MAPK) pathway, most commonly in BRAF, MAP2K1 and K/NRAS. Currently, there are 2 drugs approved by the US Food and Drug Administ...

Background: The Optimized Hemophagocytic Lymphohistiocytosis (HLH) Inflammatory (OHI, Zoref-Lorenz et al, Blood, 2022) index, defined by the combined elevation in serum soluble CD25 (sCD25) and ferritin, has emerged as a promising prognostic tool for patients with newly diagnosed hematologic malignancies, demonstrating superior performance in predi...

Introduction Malignant histiocytoses (MH), encompassing histiocytic sarcoma (HS), interdigitating dendritic cell sarcoma (IDCS), and Langerhans cell sarcoma (LCS), are a group of rare, hematologic neoplasms with diverse clinical presentations and poor outcomes. There are no established or effective treatments for patients with MH. The discovery of...

A.S.L, D.J., and H.J.L. contributed equally I.W.F., J.S.A., and A.F.H. contributed equally Introduction: Maximizing treatment efficacy while minimizing late effects is critical in patients with early stage classic Hodgkin lymphoma (cHL). We hypothesized that the incorporation of brentuximab vedotin (BV) and nivolumab (nivo) in early stage cHL would...

Introduction: Autoimmunity in Rosai-Dorfman disease (RDD) has been reported in several case reports and small case series. The recent consensus RDD guidelines even classify “immune-related RDD” as a distinct entity, but little is known about the prevalence and patterns of autoimmune conditions in this rare disease. We conducted this study to evalua...

Introduction: Adults older than 60 years constitute 20-25% of newly diagnosed classic Hodgkin lymphoma (cHL) and have inferior outcomes compared to younger patients (pts). Salvage therapy followed by an autologous stem cell transplant (ASCT) is a potentially curative option for pts with relapsed/refractory (R/R cHL). There is limited data regarding...

Introduction: ELA026 is a first-in-class human monoclonal antibody directed against signal regulatory protein (SIRP)α/β1/γ and is under clinical investigation in secondary hemophagocytic lymphohistiocytosis (sHLH). sHLH is a life-threatening hyperinflammatory condition caused by failure to terminate the activation and proliferation of natural kille...

Background: Incorporating brentuximab vedotin into the treatment of advanced-stage classic Hodgkin's lymphoma improves outcomes in adult and pediatric patients. However, brentuximab vedotin increases the toxic effects of treatment in adults, more than half of pediatric patients who receive the drug undergo consolidative radiation, and relapse rema...

PURPOSE Cancer Immunotherapy Trials Network 12 demonstrated safety of pembrolizumab in treating advanced cancer in people with HIV. Here, we report results of the Kaposi sarcoma (KS) cohort. METHODS In this multicenter phase I trial, we enrolled participants with HIV-associated KS on antiretroviral therapy with CD4 ⁺ ≥50 cells/μL and HIV plasma RN...

Background and Aims Liver involvement portends poor prognosis in adults. We aimed to characterize the clinical features, liver function tests, radiologic findings, molecular profiles, therapeutic approaches and outcomes of adults patients with Langerhans cell histiocytosis (LCH) with liver involvement. Methods We conducted a retrospective analysis...

Background Tyrosine kinase inhibitors (TKIs) have become the preferred drugs for the treatment of chronic phase (CP) chronic myeloid leukemia (CML). This study aims to compare the safety and efficacy of different TKIs as first-line treatments for CML using network meta-analysis (NMA), providing a basis for the precise clinical use of TKIs. Methods...

e23554 Background: Follicular dendritic cell sarcoma (FDCS) is a low-grade neoplasm arising from follicular dendritic cells. Its diagnosis is challenging due to its extreme rarity, and the optimal management remains unknown. Methods: We conducted a retrospective study of FDCS patients (pts) seen at Mayo Clinic, MN since 2018. Time to event analyses...

Langerhans cell histiocytosis (LCH) is a myeloid neoplastic disorder characterized by lesions with CD1a‐positive/Langerin (CD207)‐positive histiocytes and inflammatory infiltrate that can cause local tissue damage and systemic inflammation. Clinical presentations range from single lesions with minimal impact to life‐threatening disseminated disease...

Histiocytic neoplasms are diverse clonal haematopoietic disorders, and clinical disease is mediated by tumorous infiltration as well as uncontrolled systemic inflammation. Individual subtypes include Langerhans cell histiocytosis (LCH), Rosai–Dorfman–Destombes disease (RDD) and Erdheim–Chester disease (ECD), and these have been characterized with r...

Background: The COVID-19 pandemic impacted healthcare visit trends, transitioning care to utilize telemedicine. We aimed to investigate if the uptake in telemedicine during pandemic was equitable across racial groups for patients with hematologic malignancies. Methods: Using the nationwide Flatiron Health electronic health record (EHR)-derived de-i...

Malignant histiocytosis (MH) is an extremely rare neoplasm of the macrophage–dendritic cell lineage. We report the clinical characteristics, molecular aberrations, treatments, and outcomes of patients with MH seen at two referral centers from January 2000 to May 2023. We identified 43 patients with MH, of which 26 had histiocytic sarcoma (MH‐H), 9...

Background Langerhans cell histiocytosis (LCH) is a rare highly heterogeneous histiocytosis, which can be divided into single system and multiple system disease according to site of involvement. There is a paucity of studies examining unifocal LCH in adults in the molecular era. Results We retrospectively analysed records from 70 patients with uni...

Introduction The discovery of MAPK/ERK pathway mutations has revolutionized the care for patients with histiocytic neoplasms. However, mutational analysis on biopsy specimens is often limited by low tumor cellularity leading to testing failure or disease involvement of difficult-to-reach sites (e.g., central nervous system). Recently, molecular ana...

Introduction The treatment of Erdheim-Chester disease (ECD) has been revolutionized by the discovery of MAPK/ERK pathway mutations, most common being BRAF-V600E (50%). The US-FDA approved single-agent vemurafenib for BRAF-V600-mutated ECD in 2017 based on a phase II trial that included 22 patients with ECD and 4 with Langerhans cell histiocytosis (...

Introduction: DH/THL also classified as high-grade B cell lymphomas (HGBCL) with MYC and BCL2 and/or BCL6 rearrangements have higher risk of progression after initial treatment and poor response to salvage therapies compared to diffuse large B cell lymphoma (DLBCL), NOS. Recently, CART cell therapy has shown encouraging responses in treatment of re...

Purpose: Advances in targeted therapeutics for histiocytic neoplasms have led to a growing survivor population, especially for Erdheim-Chester disease (ECD), Langerhans cell histiocytosis (LCH), and Rosai-Dorfman disease (RDD). This growing population is at risk of adverse health-related quality of life (HRQoL) as a result of the disease or treatme...

Purpose: The understanding of cardiac-involved ECD (ECD-CV) and how this affects outcomes and pre-existing diseases remains limited. We aimed to determine the association, burden, and severity of pre-existing and de novo cardiovascular (CV) comorbidities with ECD-CV compared to patients (pts) without cardiac-involved ECD (ECD-noCV). Methods: Record...

Purpose: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening inflammatory syndrome. Lymphoma is the most common cause of HLH in adults. Previous studies have indicated poor patient outcomes in lymphoma-associated HLH. The recently introduced optimized HLH inflammatory (OHI) index has improved prognostication and identification of the hyp...

Purpose: The discovery of MAPK/ERK pathway mutations has led to the approval of MEK-inhibitor (MEKi) cobimetinib in histiocytic neoplasms. However, the pivotal clinical trial that led to the approval of cobimetinib included only 4 patients with Langerhans cell histiocytosis (LCH). Therefore, there is a need to define outcomes with MEKi therapy in p...

Background Langerhans cell histiocytosis (LCH) is a rare, heterogeneous histiocytic disorder. We demonstrated liver involvement at baseline indicated poor survival in adult LCH in our previous study. Aims The aim of this study was to describe clinical features, liver biochemistry, radiology findings, genomic analyses, treatment approaches, and outc...

Primary bone diffuse large B cell lymphoma (DLBCL) is a rare variant of extranodal non-Hodgkin lymphoma (NHL) historically treated with induction chemotherapy followed by consolidative radiation therapy (RT). It remains unknown whether RT confers additional benefit following rituximab-based chemoimmunotherapy (CIT) induction in patients with limite...

In pre-novel agent era, median post progression overall survival (PPS) of classic Hodgkin lymphoma (cHL) patients (pts) who progress after ASCT have been 2-3 years. Recently, Checkpoint inhibitors (CPI) and brentuximab vedotin (BV) have improved depth and durability of response in this population. Here we report estimate of PPS in pts with relapsed...

Advances in the treatment of Langerhans cell histiocytosis (LCH) have resulted in a growing survivor population. There is a lack of data on long-term outcomes among adults with LCH. We conducted a retrospective review of 219 adults (age ≥ 18y) with LCH. Most common presentation was multisystem (34.2%), followed by single system pulmonary (32%), uni...

In this retrospective study, BRAFmutation status did not correlate with disease extent or (event-free) survival in 156 adults with LCH. BRAFV600E was associated with an increased incidence of second malignancies, often comprising hematological cancers - which may be clonally related.

Significant variations exist related to the end of induction practices in the management of Acute Promyelocytic Leukemia (APL). These variations include all-trans retinoic acid (ATRA)-arsenic trioxide (ATO) in fixed doses versus continuation until hematologic complete remission (CR) and performance versus omission of post-induction bone marrow biop...

Objectives Understanding of histiocytic disorders has been revolutionized by demonstration of mitogen-activated protein kinase (MAPK) pathway mutations, most commonly BRAFV600E. The optimal testing strategy to assess BRAFV600E is unknown. We aimed to compare performance of testing modalities, to propose a framework for evaluation of BRAFV600E mutat...

The malignant histiocytoses (MH), or 'M group' of the Histiocyte Society classification, are characterized by neoplastic histiocytes with large pleomorphic nuclei. MH encompasses the diagnoses of histiocytic sarcoma, interdigitating dendritic cell sarcoma and Langerhans cell sarcoma. We aimed to define the phenotypic spectrum of MH and examine the...

Background: B-cell prolymphocytic leukemia (B-PLL) is a rare mature B-cell tumor with an aggressive clinical course and poor prognosis. It is characterized by prominent splenomegaly and prolymphocytes exceeding 55% of the lymphoid cells in the blood. Purine analog-based chemo-immunotherapy is the first-line therapy for B-PLL. Owing to its rarity,...

12089 Background: Advances in anti-retroviral therapy (ART) have led to improved life expectancy of PWH and a growing population of PWH who are at an increased risk of NADC. While the risk of CHCs in HIV uninfected cancer survivors is well known, the burden of morbidity (CHCs) borne by PWH-NADC remains unstudied and can adversely influence long-ter...

Importance: The COVID-19 pandemic has led to a reduction in routine in-person medical care; however, it is unknown whether there have been any changes in visit rates among patients with hematologic neoplasms. Objective: To examine associations between the COVID-19 pandemic and in-person visits and telemedicine use among patients undergoing activ...

Purpose of Review Histiocytic disorders, including Erdheim-Chester disease (ECD), Langerhans cell histiocytosis (LCH), and Rosai-Dorfman disease (RDD), are rare neoplasms that may present with a spectrum of neurologic involvement. Diagnostic delay is common due to heterogeneity in presentation and challenging pathology. Recent Findings Recent adva...

Sixteen cycles of Brentuximab vedotin (BV) after autologous stem cell transplant (ASCT) in high-risk relapsed/refractory classical Hodgkin lymphoma (r/r cHL) demonstrated an improved 2-year progression free survival (PFS) over placebo. However, most patients are unable to complete all 16 cycles at full dose due to toxicity. This retrospective, mult...

Histiocytosis Cavernous sinus Magnetic resonance imaging Meningioma a b s t r a c t Anaplastic lymphoma kinase (ALK)-positive histiocytosis is an uncommon condition, recently considered a separate condition from other histiocytosis by WHO 5th edition. It can involve intracranial structures. This manuscript describes a case of ALK-positive histiocy-...

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 cob...

With the advent of targeted therapeutics in Langerhans cell histiocytosis (LCH), there is a growing survivor population that might be at risk for late mortality from non-LCH causes, including second primary malignancies (SPMs). We undertook a large study using the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the patterns...

Clinical trials of novel salvage therapies have encouraging outcomes for relapsed/refractory transplant‐eligible classic Hodgkin lymphoma (R/R cHL) but comparison with conventional chemotherapy is lacking. Herein, we report the final analysis of a multicenter retrospective cohort of R/R cHL assessing outcomes by type of salvage therapy before autol...

Cytokine storm syndrome (CSS), which is frequently fatal, has garnered increased attention with the ongoing coronavirus pandemic. A variety of hyperinflammatory conditions associated with multiorgan system failure can be lumped under the CSS umbrella, including familial hemophagocytic lymphohistiocytosis (HLH) and secondary HLH associated with infe...

Introduction: Multiple myeloma (MM) is an incurable plasma cell neoplasm. In this study, we aimed to analyze the impact of time to initiation of systemic therapy for MM on overall survival (OS). Methods: We identified cases diagnosed with MM from the National Cancer Database from 2004 to 2013. Results: A total of 38,178 MM patients were includ...

Importance Rosai-Dorfman disease (RDD) is a rare histiocytic neoplasm with recent studies showing alterations in the MAPK pathway, most commonly in the KRAS and MEK genes in about 40% of patients. Reports on the use of MEK-inhibitor therapy in RDD have been limited to small case studies. There are no approved treatments for this neoplasm, and there...

Purpose To evaluate the clinical presentation, treatment, and outcomes in adult patients with histiocytic disorders with ocular, orbital, optic nerve, or cavernous sinus involvement. Design Observational retrospective chart review. Participants Adult patients (age ≥18 years) at Mayo Clinic from January 1, 1996, to July 1, 2021, with histiocytic d...

7514 Background: The AETHERA trial demonstrated improvement in PFS with 16 cycles of brentuximab vedotin (BV) after autologous stem cell transplant (ASCT) in BV-naive patients with high-risk relapsed/refractory classical Hodgkin lymphoma (r/r cHL). However, in real world, patients are rarely able to complete all 16 cycles of BV at full dose. We per...

Background Patients with Diffuse Large Bcell Lymphoma (DLBCL) with MYC and BCL2 and/or BCL6 gene rearrangements [double-hit lymphoma/triple-hit lymphoma (DHL/THL)] have poor prognosis in the relapsed/refractory setting. Methods We utilized a real-world deidentified database of DLBCL patients and report patterns of therapy utilization in relapsed/r...

Background: Central nervous system (CNS) mucormycosis is insidious and difficult to diagnose. It progresses rapidly and causes high mortality. Rare cases have been reported during ibrutinib use, which have poor prognosis. Through this case, we share the experience of successful diagnosis and treatment. We also emphasize the importance of focusing...

7515 Background: Primary refractory disease (PRD) and early relapse (ER) are predictors of poor prognosis in classic Hodgkin lymphoma (cHL). In this multicenter retrospective study, we describe outcomes of PRD and ER in pts with relapsed/refractory (R/R) cHL treated with salvage therapy (ST) and autologous stem cell transplant (ASCT). Methods: Of 1...

Mantle cell lymphoma (MCL) is considered incurable with the available chemoimmunotherapy approaches, and therefore newer, effective targeted therapies such as Bruton Tyrosine Kinase (BTK) inhibitors are increasingly used in MCL as chronic suppressive therapy, especially in the elderly. We aimed to describe the treatment patterns in MCL at different...

Erdheim–Chester disease (ECD) is a rare, multisystem non-Langerhans cell histiocytosis that typically presents in middle age and frequently has cardiovascular manifestations. Of 103 consecutive biopsy-proven ECD patients at a single center who underwent cardiac imaging, 33 had cardiac involvement. The most commonly affected location was the right a...

Survival outcomes of patients with histiocytic neoplasms are poor, with no standard-of-care treatments available for these malignancies. Recent characterization of the genomic landscape of various histiocytic neoplasms have shown a predominance of activating driver mutations within the MAPK/ERK pathway (ie, BRAF, MEK, KRAS, MAPK, and NRAS). Subsequ...

Langerhans cell histiocytosis (LCH) can affect children and adults with wide variety of clinical manifestations, including unifocal, single-system multifocal, single-system pulmonary (smoking-associated), or multisystem disease. The existing paradigms in the management of LCH in adults are mostly derived from the pediatric literature. Over the last...