Neoplasms Research Articles

Linfoma ocular unilateral em um felino

The aim of this report is to describe the occurrence of unilateral intraocular lymphoma in a feline infected with Feline Immunodeficiency Virus – FIV and Feline leukemia virus – FELV. Lymphoma is a neoplasm of higher prevalence in cats as well as secondary intraocular neoplasms. The uvea is the most common site for the occurrence of lymphoma due to its wide vascularity, but there are reports in several sites of the ocular bulb. Felines with FIV and FELV infections are predisposed to the presentation of lymphoma. In the present case, a feline who tested positive for FIV and FELV was observed, presenting ophthalmologic alterations in the right eye characteristic to uveitis, such as mild corneal opacity, iris bombe, blackened pigmentation points in the iris, irregularity in pupillary cleft and irresponsive pupillary reflex to direct light stimulus. After death, a necropsy was performed, and the presence of neoformation in the iris was noted, as well as signs of metastasis in the kidneys, compatible with lymphoma.

Secondary neoplasms in survivors of pediatric acute lymphoblastic leukemia and lymphoblastic lymphoma: a single-center, retrospective study

BackgroundAcute lymphoblastic leukemia (ALL)-based therapeutic regimens have markedly improved the survival of children with ALL and lymphoblastic lymphoma (LBL). However, survivors are at risk of secondary neoplasms. Few studies on such secondary neoplasms have been conducted outside of Europe and the United States. The aim of this study was to evaluate the incidence of, risk factors for, and outcomes of secondary neoplasms in long-term survivors of ALL and LBL at a tertiary pediatric oncology center in Mie prefecture, Japan.ProcedureWe retrospectively reviewed 188 patients with ALL and LBL who were treated with an ALL-based therapeutic regimen at Mie University Hospital from January 1, 1977 to December 31, 2022 and followed up.ResultsTen patients developed secondary neoplasms, with 10-year and 20-year cumulative incidences of 2.9% [standard error (SE) = 1.5%] and 5.5% (SE = 2.3%), respectively. The median interval between the primary-cancer diagnosis and secondary-neoplasm diagnosis was 18.5 years (range: 7.8–41.7 years). All 10 secondary neoplasms were central nervous system (CNS) tumors (6 meningiomas and 4 high-grade gliomas). Radiotherapy (p = 0.007) and CNS involvement in the primary cancer (p < 0.001) increased the risk of secondary neoplasms among long-term survivors. Gliomas occurred significantly earlier than meningiomas (p = 0.047), and three patients died of secondary neoplasms (all gliomas).ConclusionsAs secondary gliomas occurred earlier than meningiomas and are associated with poor outcomes, physicians should take great pains to minimize their risk to improve long-term survival and quality of life.

Pediatric Transplant and Cellular Therapy Consortium RESILIENT Conference on Pediatric Chronic Graft-versus-Host Disease Survivorship after Hematopoietic Cell Transplantation: Part II. Organ Dysfunction and Immune Reconstitution Considerations for children with chronic GVHD after Hematopoietic Cell Transplantation.

While highly morbid forms of chronic graft versus host disease (cGVHD) and severe late effects of allogeneic hematopoietic cell transplant (HCT) can impact children and adults alike, unique considerations arise in pediatric cases regarding diagnosis, monitoring, treatment, and likelihood of resolution. As children can present with atypical features of cGVHD, and with more significant disease due to inability to communicate symptoms, they may be at increased risk for highly morbid forms of cGVHD and incur greater subsequent late effects, which may be more pronounced in those with underlying chromosomal breakage syndromes, with higher prevalence in pediatric HCT recipients. The long-term effects of cGVHD and its therapies include impaired immune reconstitution, leading to increased risks of infection and secondary malignant neoplasms. However, children also have the greatest potential for full immune reconstitution, due to thymus recovery that could impact the timing of vaccination with respect to tolerance and restoration of optimal immunity. Developing strategies to mitigate the late effects incurred with, and as a result of cGVHD, is of critical importance. The working group recommends surveillance strategies for late effects in patients with cGVHD, increased utilization of emerging diagnostic tools, integration of monitoring for cGVHD treatment response, development of new treatments, and provides aims for future research endeavors.

Second Primary Neoplasms in Pediatric Cancer Survivors With Single Institution Experience From Turkey.

This study aims to establish the characteristics of second primary neoplasms (SPNs) and the long-term follow-up status of a tertiary pediatric oncology center. Records of 1799 patients followed up in the pediatric oncology division between January 1981 and December 2022 were evaluated retrospectively. Thirty-four (1.9%) cases of secondary neoplasms were identified throughout 42 years. The 5-year and 10-year cumulative incidence was 1% and 4%, respectively. The 3 most common SPNs were thyroid carcinomas (TC), central nervous system (CNS) tumors, and leukemias. The shortest median latent period of SPN detection was 15.5 (2 to 35) months in secondary leukemias, whereas 8 (0 to 17) years in all SPNs. Secondary solid tumors that occurred within the radiation field were TC and meningiomas with a 5.5 (3 to 12) and 16 (6 to 22) years latency period, respectively. Ten patients died; the median death time from the diagnosis of SPN was 10 months in all secondary leukemias and 3.5 months in CNS tumors. The 5-year overall survival was 91%, with a median follow-up time of 13.1 years in all patients with SPN. Considering the SPN-inducing effects of radiotherapy and chemotherapy, patient-protective improvements in treatment protocols are required. Multidisciplinary and long-term follow-up is essential even in adulthood because of the long latency period of some SPN occurring in pediatric cancer survivors.

Exploring the influence of age on the causes of death in advanced nasopharyngeal carcinoma patients undergoing chemoradiotherapy using machine learning methods

The present study analyzed the impact of age on the causes of death (CODs) in patients with nasopharyngeal carcinoma (NPC) undergoing chemoradiotherapy (CRT) using machine learning approaches. A total of 2841 patients (1037 classified as older, ≥ 60 years and 1804 as younger, < 60 years) were enrolled. Variations in the CODs between the two age groups were analyzed before and after applying inverse probability of treatment weighting (IPTW). Additionally, seven different machine learning models were employed as predictive tools to identify key variables and assess the therapeutic outcomes in NPC patients receiving CRT. The younger group exhibited a significantly longer overall survival (OS) than the older group, both before the IPTW adjustment (140 vs. 50 months, P < 0.001) and after the adjustment (137 vs. 53 months, P < 0.001). After IPTW, the older group was associated with worse 5-, 10-, and 15-year cumulative incidences in terms of NPC-related deaths (30, 34, and 38% vs. 21, 27, and 30%; P < 0.001), cardiovascular disease (CVD; 4.1, 7.2, and 8.8% vs. 0.5, 1.8, and 3.0%; P < 0.001), and other causes (8.3, 17, and 24% vs. 4.1, 8.7, and 12%; P < 0.001). However, cumulative incidences of secondary malignant neoplasms were comparable between the two groups (P = 0.100). The random forest (RF) model demonstrated the highest concordance index of 0.701 among all models. Time-dependent variable importance plots indicated that age was the most influential factor affecting 3-, 5-, and 10-year survival, followed by metastasis and tumor stage. Younger patients had significantly longer OS than their older counterparts. Older patients had a higher likelihood of dying from non-NPC-related causes, particularly CVDs. The RF model showed the best predictive accuracy, identifying age as the most critical factor influencing OS in NPC patients undergoing CRT.

Long-Term Outcomes and Quality of Life of High-Risk Neuroblastoma Patients Treated with a Multimodal Treatment Including Anti-GD2 Immunotherapy: A Retrospective Cohort Study.

The incorporation of anti-GD2 antibodies such as ch14.18/SP2/0 into the multimodal treatment of high-risk neuroblastoma (HR-NB) patients has improved their outcomes. As studies assessing the long-term outcomes, long-term sequelae, and health-related quality of life (HRQoL) of this treatment are limited, this retrospective analysis aimed to explore these. Between 1991 and 2002, 65 children received a multimodal treatment, including ch14.18/SP2/0, for primary HR-NB. All received chemotherapy according to the NB90/NB97 trial, 51 received high-dose chemotherapy, and all received ch14.18/SP2/0 treatment. We analyzed the long-term sequelae and HRQoL (EORTC QLQ-C30), and evaluated overall and event-free survival (OS/EFS). Twenty-five survivors were evaluated for HRQoL and long-term effects. All reported long-term sequelae, including ototoxicity in 16/25 (64%), cardiac toxicity in 6/25 (24%), and endocrine toxicity in 19/25 (76%) patients. Chronic diarrhea was reported in 20% of female patients. Seven patients developed autoimmune diseases. HRQoL scores were better across multiple scales than those of the matched German general population. Twenty-five-year OS and EFS were 50.8% (95% confidence interval: 31-55) and 43% (30.1-55.3), with 33 (50.8%) long-term survivors. Thirty-two patients died: 28 (43.1%) because of progression/relapse and 4 (6.2%) because of secondary neoplasms. Multimodal treatment, including ch14.18/SP2/0, can achieve long-term survival in HR-NB patients, with a substantial proportion of survivors reporting better HRQoL compared to the general population. All patients reported long-term side effects mostly attributable to chemotherapy and radiotherapy. The relatively high prevalence of autoimmune diseases and persistent diarrhea warrants additional longitudinal research on individuals treated with anti-GD2 antibodies.

Surgical Site Infection after Craniotomy in Neuro-Oncology (SINO): A protocol for an international prospective multicentre service evaluation across the United Kingdom and Ireland.

Given its proximity to the central nervous system, surgical site infections (SSIs) after craniotomy (SSI-CRAN) represent a serious adverse event. SSI-CRAN are associated with substantial patient morbidity and mortality. Despite the recognition of SSI in other surgical fields, there is a paucity of evidence in the neurosurgical literature devoted to skin closure, specifically in patients with brain tumors. The primary objective of this service evaluation is to ascertain the incidence and the risk factors associated with SSI-CRAN. The secondary objectives would be a) to ascertain the incidence of SSI-CRAN in sutured versus stapled wounds, after accounting for patient, surgical and hospital confounders of SSI-CRAN and b) to determine the percentage of patients with gliomas that begin adjuvant oncological treatment in patients with infection versus those without infection. Surgical Site Infection after Craniotomy in Neuro-Oncology (SINO) is a international prospective multicentre service evaluation that will include patients with an intracranial neoplasm, both primary and secondary neoplasms, treated with cranial surgery (including biopsy). Consecutive paediatric (<18 years) and adult (≥18 years) patients diagnosed with a brain tumour, undergoing cranial surgery between 1st October 2024 and 1st December 2024 will be included. Prospective data will be collected with a follow-up of 90 days.

Nevus Sebaceous of Jadassohn Mimicking a Pilonidal Sinus of Forehead: A Rare Case Presentation

Nevus Sebaceous of Jadassohan (NSJ) is a hamartoma that presents as a cutaneous lesion, which can be considered an overgrowth of sebaceous glands, hair follicles, and other epidermal structures. Although it is usually a benign condition, the lesion is capable of producing secondary neoplasms, both benign and infrequently, malignant. This case report discusses a 21-year-old male patient who presented with a lesion on the forehead, manifesting as a pilonidal sinus due to the presence of a tuft of hair at the end of the sinus tract following childhood trauma. The presence of a sinus tract with hair growth in the glabellar region is a rare and diagnostically challenging presentation of NSJ. This case highlights the complexities of managing such chronic wounds and the potential complications arising from trauma.

Synthetic MRI derived relaxometry parameters: a new insight into characterization of ring enhancing lesions of brain.

Synthetic MRI utilizes the quantitative relaxometry parameters to generate multiple contrast images through a single acquisition. We tried to explore the utility of synthetic MRI derived relaxometry parameters in evaluation of ring enhancing lesions of brain. This was a prospective study. 40 subjects with ring enhancing lesions in brain underwent pre and post contrast synthetic MRI using MDME sequence. Pre and post contrast R1, R2 and PD values were recorded from the core, wall and perilesional edema of lesions and sub group analysis was done among infective, primary neoplastic and secondary neoplastic (metastatic) lesion groups. Pre and post contrast R1, R2 values from core were higher in the infective group compared to the others. Pre and post contrast R1, R2 values were lower in the wall where as it was significantly higher in the perilesional edema of primary neoplastic group. Post-pre the values increased significantly in the perilesional edema of primary neoplasms. R1 value of ≥ 0.689 and R2 value of ≥ 7.481 in the perilesional edema predicts a primary neoplasm over infection with 70.6% sensitivity and 85.7% specificity and over secondary neoplasm with 64.7% sensitivity and 100% specificity. Synthetic MRI derived relaxometry parameters in ring enhancing lesions were found to be significantly different across sub groups and can be used to differentiate between primary neoplastic, secondary neoplastic and infective group with parameters from perilesional edema being the most useful.

Global disparities in drug-related adverse events of patients with multiple myeloma: a pharmacovigilance study

Multiple myeloma (MM) is a complex hematological malignancy of clonal plasma cells driven by alterations to the chromosomal material leading to uncontrolled proliferation in the bone marrow. Ethnic and racial disparities persist in the prevalence, diagnosis, management, and outcomes of MM. These disparities are multifaceted and intersect with various factors, including demographics, geography, socioeconomic status, genetics, and access to healthcare. This study utilized the openFDA human drug adverse events (AEs) to analyze global data pertaining to MM patients and patterns of treatment-related AEs. We identified ten most frequently used drugs and drug regimens in six distinct regions, including North America (NA), Europe (EU), Asia (AS), Africa (AF), Oceania (OC), and Latin America & the Caribbean (LA). AE patterns were evaluated using the reporting odds ratio combined with a 95% confidence interval. AE reports were more prevalent in men than in women across all regions. Cardiotoxicities were more likely observed in AS and EU, while secondary neoplasms were more frequently reported in the EU. Nephropathies were prominent in OC, AF (in males), and AS (in females), while vascular toxicity, including embolism and thrombosis, was more common in NA (in males). A notable improvement in survival, particularly in AS, EU, and NA, with a significant decline in death rates was observed. Hospitalization rates displayed less variation in AS and EU but exhibited more pronounced fluctuations in AF, LA, and OC. In conclusion, this comprehensive analysis offers valuable insights into the demographic, geographic, and AE patterns of MM patients across the globe.

Contemporary trends in utilization of metastasectomy in the era of targeted and immunotherapies.

Metastasectomy is a useful adjunct in the management of metastatic cancer. Widespread adoption of novel targeted and immunotherapies has improved the survival profiles of multiple malignancies, which has potentially altered the role of metastasectomy. This study aimed to characterize trends in metastasectomy across five primary cancers eligible for these therapies. The National Inpatient Sample was used to identify patients who underwent metastasectomy in the United States (2016-2021). Patients with procedure codes for resection of the lung, liver, adrenal gland, brain, or small bowel and concurrent diagnosis codes for secondary malignant neoplasm of that site were included. Subjects were subcategorized by primary malignancy: colorectal cancer, lung cancer, breast cancer, melanoma, or renal cancer. Sample weights were used to produce national estimates, which were incidence adjusted by primary malignancy. Trends in utilization were calculated with average annual percent change (AAPC) and linear regression coefficients. Colorectal cancer was the most frequent indication for metastasectomy (n=57,644 cases), followed by lung cancer (n=55,090 cases), breast cancer (n=12,616 cases), renal cancer (n=8427 cases), and melanoma (n=5658 cases). Utilization of metastasectomy increased over the study period for breast cancer (AAPC, +10.6%; p=.013) and melanoma (AAPC, +8.3%; p=.040) but did not change for lung cancer (AAPC, -1.6%; p=.26), colorectal cancer (AAPC, +0.3%; p=.83), or renal cancer (AAPC, +2.3%; p=.36). Between 2016 and 2021, utilization of metastasectomy increased significantly for melanoma and breast cancer. The role of metastasectomy will likely continue to develop as new treatment protocols improve survival profiles for patients with metastatic disease.

Optimal Time for Nevus Sebaceous Excision and Predictors of Surgical Outcomes and Secondary Intralesional Neoplasms: The Mayo Clinic Experience Over 37 Years.

Controversy exists around the optimal timing of resection of nevus sebaceous (NS). The authors aim to determine optimal timing of NS resection and identify predictors of surgical outcomes and secondary intralesional neoplasms. Retrospective chart review of all patients with biopsy-proven NS diagnosis treated at the authors' institution between 1987 and 2024. A total of 632 patients (317 females) underwent biopsy at a median age of 17 (interquartile range 11.7-36.9) years. Benign secondary intralesional neoplasms were found in 67 (10.6%) patients, with syringocystadenoma papilliferum being the most common. Malignant secondary intralesional neoplasms were diagnosed in 62 (9.8%) patients, with basal cell carcinoma being the most common. The incidence of secondary intralesional neoplasms was 3.9%, 24.4%, 36.05%, and 54%, in patients aged 0 to 20, 20 to 40, 40 to 60, and 60 to 80 years, respectively (P<0.001). Age and NS area were associated with an increased risk of developing benign and malignant intralesional neoplasms (P=0.01). Younger patients were more likely to need general anesthesia for excision (median age 10.42 versus 17 years, P<0.001). Surgical complications occurred in 10 cases, and 6 patients required unanticipated revision surgery. The risk of developing secondary intralesional neoplasms was similar across different NS anatomic regions (log-rank, P=0.09). Surgical excision of NS is safe and has an acceptable risk profile. The findings of this study support our historic practice of NS excision before puberty (before the accelerated growth phase) to reduce the risk of developing secondary intralesional neoplasms.

Nivolumab-containing therapy in patients with newly diagnosed classical Hodgkin lymphoma: own clinical observations and literature review

Classical Hodgkin’s lymphoma (cHL) is a lymphoproliferative disease characterized by the presence of Hodgkin anderezovsky–Reed–Sternberg cells and a tumor microenvironment. Currently, much attention is paid to the microenvironment in cLH. A detailed understanding of the interaction between the tumor and its microenvironment opens up prospects for the cHL diagnosis and treatment. Innovative immunotherapeutic agents such as nivolumab make it possible to control and activate the immune response. Despite the high efficiency of standard protocols in young patients, therapy intensification is associated with organ toxicity and the development of secondary malignant neoplasms. At the same time, in elderly patients, the results of generally accepted antitumor treatment protocols should be considered suboptimal. In the last decade, the treatment of refractory cHL has improved significantly due to the use of immune checkpoint inhibitors.Taking into account the above, the priority issue in modern clinical hematology is to improve cHL treatment strategies not only in elderly but also in young patients by maintaining a balance between high efficacy and low toxicity. Moreover, the inclusion of nivolumab in first-line therapy is not only pathogenetically justified and effective, but also safe. The article presents data from clinical observations of the successful nivolumab use in combination with chemotherapy in patients with newly diagnosed cHL.

Investigating the influence of germline ATM variants in chronic lymphocytic leukemia on cancer vulnerability.

Chronic lymphocytic leukemia (CLL) patients have an increased risk of secondary cancers, along with predisposition to CLL in their relatives. We have previously identified germline ATM variants as associated with CLL risk; here, we present their impact on predisposition to secondary neoplasms in CLL patients and their relatives. Patients enrolled in our tissue bank who had germline ATM status available were mailed a questionnaire between April 2022 and May 2023. Of the 333 patients who replied to the questionnaire, 283 patients (85%) reported at least one relative with a cancer history. The prevalence of family history of B-cell lymphoproliferative disorders was significantly higher (p=0.02) in patients with germline ATM variants (32%) compared to those without germline ATM variants (21%) including familial CLL (25% vs 18%) (p=0.04). No significant difference in the prevalence of secondary cancers was found between patients with and without germline ATM variants (p=0.73), although the role for individual ATM variants in other malignancies could not be excluded given the small sample size. Time to first CLL treatment (TTFT) was shorter in patients harboring somatic ATM events while no difference was observed in patients with germline ATM variants. In conclusion, we demonstrate a higher prevalence of B-cell lymphoproliferative disorders, including familial CLL, in relatives of CLL patients carrying germline ATM variants. The presence of these germline variants did not impact TTFT compared to patients harboring somatic ATM mutations.

Risk and survival outcomes of secondary pelvic neoplasm after radiotherapy in female patients with genital neoplasms: A large Population-Based cohort study

Background and purposeTo investigate the impact of radiotherapy (RT) on the risk of secondary pelvic neoplasms (SPN) and the survival outcomes of patients following a diagnosis of female patients with genital neoplasm(FGN). Materials and MethodsUtilizing SEER databases, this study involved 102,895 patients from nine oncology centers, spanning 1990 to 2015. We employed the Fine-Gray competing risks regression methodology to chart the trajectory of SPN development and used the Kaplan–Meier method to calculate the 10-year overall survival rates. ResultsThis study included 25,774 patients in the RT group and 77,121 in the non-radiotherapy (NRT) group. The cumulative incidence rate of SPN was 5.10 % in the RT group and 3.42 % in the NRT group. The RT group showed a significantly higher incidence of bladder cancer (adjusted hazard ratio [HR]: 1.75; 95 % confidence interval [CI]: 1.43–2.14; P < 0.05), colon cancer (adjusted HR: 1.32; 95 % CI: 1.16–1.49; P < 0.05), and rectal cancer (adjusted HR: 1.34; 95 % CI: 1.10–1.65; P < 0.05) compared to the NRT group. After propensity score matching, patients in the RT group who developed bladder cancer had significantly reduced 10-year survival rates compared to patients with primary pelvic tumors (P = 0.01). ConclusionRT is identified as an independent risk factor for the development of SPN in patients with FGN. Patients with FGN who undergo RT demonstrate a significant increase in the risk of developing secondary neoplasms, specifically bladder cancers, and experience a reduction in 10-year survival rates.

Obesity and risk for liver disease: a two-sample Mendelian randomisation study.

The associations between obesity and liver diseases are complex and diverse. To explore the causal relationships between obesity and liver diseases, we applied two-sample Mendelian randomisation (MR) and multivariable MR analysis. The data of exposures (BMI and WHRadjBMI) and outcomes (liver diseases and liver function biomarker) were obtained from the open genome-wide association study database. A two-sample MR study revealed that the genetically predicted BMI and WHRadjBMI were associated with non-alcoholic fatty liver disease, liver fibrosis and autoimmune hepatitis. Obesity was not associated with primary biliary cholangitis, liver failure, liver cell carcinoma, viral hepatitis and secondary malignant neoplasm of liver. A higher WHRadjBMI was associated with higher levels of biomarkers of lipid accumulation and metabolic disorders. These findings indicated independent causal roles of obesity in non-alcoholic fatty liver disease, liver fibrosis and impaired liver metabolic function rather than in viral or autoimmune liver disease.

Impact of lung biomarker testing on out-of-pocket costs for metastatic non-small cell lung cancer

Biomarker testing in metastatic non-small lung cancer (NSCLC) is critical for appropriate treatment. Claims-based datasets offer real-world information on the use and cost of biomarker testing. We used 2013-2021 data from Optum's de-identified Clinformatics Data Mart Database. Eligible patients were adults with ≥ 2 NSCLC diagnosis codes and ≥ 2 claims of a secondary malignant neoplasm. We excluded patients with another primary or no continuous insurance coverage 12 months prior and 6 months after diagnosis. We assessed out-of-pocket (OOP) costs. Descriptive statistics were used to assess testing rates, and multivariable analyses (MVA) were performed to assess factors associated with testing. We identified 4377 patients with metastatic NSCLC (mean age 60 years (SD 8.33), 49.6% female, 76.7% former smokers). Testing rates within 2 months of diagnosis increased from 58.15% in 2013 to 69.96% in 2021. On MVA, biomarker testing was associated with younger age, nonsmokers, Mountain geographic region, and point-of-service insurance plans. Biomarker testing was associated with a median OOP cost of $98 (IQR: $43.87-$306.58). Patients who underwent biomarker testing had a median total OOP cost of all services within 6 months of diagnosis of $3560.20 (IQR: $1538.37-$6199.44) compared to $1979.58 (IQR: $725.75-$4003.06) for those who did not undergo biomarker testing. Using claims data, we find that most patients with metastatic NSCLC undergo biomarker testing early in their treatment course (0-60 days), suggesting that testing is appropriately being obtained early on in their treatment course, but this testing is associated with substantially higher overall OOP costs to patients.

Improving the Utility of a Cancer Gene Mutation Panel for Multiple Myeloma Patients

Abstract Multiple myeloma is a plasma cell malignancy that accounts for 1-2% of all cancer diagnoses and 10-15% of hematopoietic neoplasms. Clonal rearrangement of the IG locus suggests a monoclonal model for pathogenesis. The presence of cytogenetic abnormalities in &amp;gt;90% of cases suggests transformation by chromosomal instability and rearrangement. Classification and consensus guidelines by The International Myeloma Working Group (IMWG) and others reflect this by categorizing myeloma based on ploidy, translocations, and chromosomal abnormalities. Interestingly, a portion of Emory’s test volume for cancer gene mutation profiling by second generation short-read sequencing is for multiple myeloma cases. This suggests our 75-gene myeloid neoplasm panel (MMP75) is being utilized for medical purposes that are not met by cytogenetic and microarray characterizations performed during the diagnostic workup of multiple myeloma. Inspired by this observation, this study investigates providers motivations for ordering MMP75 and assesses the adequacy of our current implementation for their stated purposes. Anecdotes from ordering physicians indicate interest in MMP75 results when informing prognosis, selecting treatments, and evaluating for treatment associated secondary neoplasms. A more formal survey is underway that will statistically capture how the results of MMP75 testing were ultimately used: to inform diagnosis, determine prognosis, guide treatment, explain progression, identify/rule-out secondary neoplasia, or no effect on management. We also explore the variants called by MMP75 when performed using bone marrow from patients who received a cytogenetic workup for multiple myeloma at some point. A retrospective analysis of the 5-year interval between Jan 2019 and Jan 2024 identified 156 cases meeting this criterion. The number of pathogenic variants per case ranged between 1 and 8, with mutations detected across 42 genes. The genes most frequently identified with pathogenic mutations were TP53 (22.4%), DNMT3A (19.2%), TET2 (14.7%), and ASXL1 (12.2%). All four have been associated with adverse outcomes in patients with multiple myeloma. Activating events in therapeutic targets included mutations in the RAS/RAF pathway (16.7%), JAK/STAT signaling (2.6%), and the kinase KIT (0.6%). While these findings support the use of MMP75 for detection of relevant mutations, the genetic variants identified are not unique to multiple myeloma. Mutations detected in DNMT3A, TET2, and ASXL1 are common in clonal hematopoiesis of indeterminant potential (CHIP) and myeloid neoplasms. Hotspot mutations in TP53 and activating events in the RAS/RAF pathway also occur in various hematologic malignancies. This test therefore detects events that occur in both the plasma cell compartment and other cells of origin. This encumbers distinguishing variants that inform on a patient’s multiple myeloma from events that suggest a secondary neoplasm. Future directions include determining whether the effect of plasma cell enrichment on a mutations variant allele frequency (VAF) in repeat testing can help distinguish true multiple myeloma variants from events in other cells.

Myeloid sarcoma mimicking as recurrent squamous cell carcinoma: What is the etiology?

Abstract Introduction/Objective Myeloid sarcoma is an extramedullary malignancy of primitive myeloid cells and can occur during, preceding, or as a relapse of acute myeloid leukemia that occurs mostly in the soft tissue and skin. Methods/Case Report A 77-year-old white male with a history of oral squamous cell carcinoma status post resection (18 months ago) followed by radiation and chemotherapy (15 months prior), presented to the ear nose and throat clinic with increasing weakness and dizziness. He received two doses of Cisplatin and was currently on Pembrolizumab. On examination, there were two lesions in the oral cavity, one on the right gingivobuccal sulcus and a second on the left posterior mandibular ridge, suspicious for squamous cell carcinoma recurrence. Interestingly, the biopsy did not show evidence of recurrent squamous cell carcinoma but showed sheets of blasts that were positive for MPO, CD117, CD43, and CD68, consistent with myeloid sarcoma. Subsequent peripheral blood and bone marrow examinations showed acute myeloid leukemia. Results (if a Case Study enter NA) NA Conclusion Myeloid neoplasms post-cytotoxic therapy (MN-pCT) occur after radiation, alkylating agents, DNA topoisomerase II inhibitors, antimetabolites, and PARP1 inhibitors for a non-myeloid malignancy. Topoisomerase inhibitors are associated with MN-pCT after a latency period of 1 to 3 years; alkylating agents and radiation are associated with MN-pCT after a latency period of 5 to 7 years. Interestingly, this patient developed myeloid sarcoma in a previously irradiated area within 2 years. Cisplatin was discontinued after 2 doses due to side effect complications and is unlikely to be the culprit. Pembrolizumab is not considered to be a cytotoxic therapy and has not been reported to be associated with MN-pCT, however, the latency period for radiation-induced MN-pCT is unusually short in this patient and this raises the possibility of a Pembrolizumab-induced secondary myeloid neoplasm; additional investigation with other patients on this medication with second subsequent malignancies is required.

Comparing the Efficacy and Safety of First-Line Treatments for Chronic Lymphocytic Leukemia: A Network Meta-Analysis.

The Chronic Lymphocytic Leukemia (CLL) treatment strategies have transitioned from chemotherapy and chemoimmunotherapy to chemo-free regimens. Frequentist network meta-analysis allows for both direct and indirect comparisons between different treatments. Randomized controlled trials assessing first-line treatments were included. Outcomes were progression-free survival (PFS), overall survival, undetectable minimal residual disease (MRD), objective response rate, and adverse events. Studies with comparable characteristics also underwent subgroup analysis, stratifying by age, comorbidities, IGHV status, and cytogenetic abnormalities. 30 eligible trials involved 12,818 patients and 30 treatments were included. Acalabrutinib demonstrated a PFS advantage over ibrutinib and obinutuzumab-venetoclax (OV) in patients over 65 years old or with unmutated IGHV. In younger patients with comorbidities, Acalabrutinib-Obinutuzumab (AO) had superior PFS compared to Ibrutinib-Obinutuzumab (IO), Ibrutinib-Venetoclax (IV), and OV. For older patients with comorbidities, Acalabrutinib and AO both outperformed OV without significant difference between them. MRD-guided IV surpassed OV in patients without comorbidities. IO exhibited extended PFS benefits compared to OV in patients with mutated IGHV or with del(17p) and/or TP53 mutations. IV and IO have lower neutropenia rates than OV. IV have fewer infections than Acalabrutinib and AO. AO causes less diarrhea than IV but more headaches than IO and OV. OV has lower hypertension rates than IO. IV has fewer arthralgia than AO. For any grade secondary primary neoplasms, IV and OV is less than AO. Tailored chemo-free regimens can be selected based on age, comorbidities, IGHV status, and cytogenetic abnormalities to optimize treatment outcomes while considering different response spectra.