Immune checkpoint inhibitors targeting PD-1/PD-L1 in the treatment of human lymphomas.

Non-Hodgkin lymphomas (NHLs) encompass a diverse group of malignancies arising from B cells, T cells, and natural killer (NK) cells at various stages of differentiation. Conversely, classical Hodgkin lymphomas (cHLs) primarily feature Reed-Sternberg cells (RSCs) amid a background of reactive immune cells. Immunomodulatory pathways, notably the PD-1/PD-L1 axis, play pivotal roles in tumor immune evasion across both NHLs and cHLs. Elevated expression of PD-1 and PD-L1 is observed in a spectrum of lymphomas, influencing prognosis and treatment response. Therapeutically, immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have revolutionized lymphoma management, particularly in relapsed/refractory cases. Nivolumab and pembrolizumab, among others, have demonstrated efficacy in various B-cell lymphomas, with promising outcomes in cHL. Combination strategies incorporating ICIs with conventional chemotherapy or targeted agents show enhanced efficacy and are being explored extensively. In this review we discuss the most important features of the tumor microenvironment of NHLs and cHLs, address the therapeutic approaches with ICIs and try to outline future perspectives.

Remission With Radiation Therapy in Primary Tongue Mucosa-Associated Lymphoid Tissue Lymphoma: A Case Report.

Mucosa-associated lymphoid tissue (MALT) lymphoma arising from the tongue is a rare pathologic condition for which a standard treatment mode has not been established. This disease represents a low-grade lymphoma frequently found in the stomach but rarely in the lymphoid tissue of the tongue. Only six cases that have been reported could be retrieved. We present the case of a 79-year-old woman who manifested with a mass on her tongue. A biopsy of the mass confirmed a diagnosis of MALT lymphoma. Radiation therapy of 30.6 Gy in 17 fractions was performed, and a complete metabolic response was achieved.

Secular trends in incidence and mortality of non-Hodgkin's lymphoma in China, 1990-2019, and predictions to 2030: Outlook for the future burden of disease.

BACKGROUND: The aim of this study was to analyze the trend of non-Hodgkin's lymphoma incidence and mortality in China from 1990 to 2019, along with assessing the effects of age, period, and cohort, as well as to predict future trends. MATERIAL AND METHODS: Using data from the Global Burden of Disease Study 2019 we calculated the estimated annual percentage changes in the incidence and mortality of non-Hodgkin's lymphoma. Age-period-cohort analysis was used to assess the independent effects of these elements. Incidence and mortality until 2030 were predicted using a Bayesian age-period-cohort approach. RESULTS: During 1990-2019, there was a significant increase in the age-standardized incidence and mortality rate in non-Hodgkin's lymphoma. Strong effects of birth cohort and period on non-Hodgkin's lymphoma incidence and mortality were observed. In terms of prediction, future non-Hodgkin's lymphoma incidence and mortality in China will continue to increase, while the mortality rate will decrease; for women, both the rates are projected to rise, but they will remain lower than men. CONCLUSIONS: Currently, the non-Hodgkin's lymphoma burden is high in China, and it is expected to continue increasing in the future. Policymakers need to prioritize addressing the factors contributing to sex differences in disease burden, including variations in environmental exposures and lifestyles among men and women.

Clinical Outcome of Patients Receiving Rituximab in Combination with Bendamustine in Indolent B-cell Lymphomas: A Single-center Institutional Study.

Introduction: Indolent non-Hodgkin's lymphomas (NHLs) are a diverse category of malignancies characterized by a chronic relapsing-remitting disease course. In the modern era, patients usually receive a combination of bendamustine plus rituximab as the initial therapy, otherwise known as an R-Benda regimen. While clinical trials have demonstrated R-Benda to be superior to other regimens, our study aims to provide insight into real-world outcomes of R-Benda therapy. Materials and Methods: We conducted a retrospective study for January 2015-July 2022 among patients receiving R-Benda for indolent NHLs at the Aga Khan University Hospital, Karachi, Pakistan. All patients underwent pre- and post-treatment assessment through positron emission tomography scan and computed tomography (CT) imaging. The response to treatment was assessed, and the overall survival (OS) and progression-free survival (PFS) were assessed using a Kaplan-Meier survival analysis. Results: We enrolled 118 patients, out of which the majority were elderly males (64%). The 2-year follow-up rate was 76.3% (n = 90), and the median follow-up time was 29 months. The most common histopathology encountered was follicular lymphoma (52%) presenting with stage IV disease (56%). Approximately 73% experienced a complete metabolic response to the treatment. Of these, 31.4% subsequently experienced a relapse. In addition, 17.7% of patients underwent a partial response, while 7% had refractory disease. The mean OS was 140 months (95% CI: 120-160), while the lower quartile value was 50 months. On the other hand, the median PFS was 80 months (95% CI: 43-N/A). Conclusion: Our study demonstrated that patients on R-Benda had good clinical outcomes, with the vast majority living beyond 50 months. Moreover, 76.1% had no disease progression for the first 2 years. It adds to the existing body of literature that demonstrates that in real-world experience, the outcomes of R-Benda treatment are better than those reported by earlier randomized-control trials.

Toward Inclusive Oncology: Challenges in the Therapy of Pediatric Non-B Non-Hodgkin Lymphomas.

BACKGROUND/AIM: Non-B non-Hodgkin lymphomas (NHL) represent over 30 T/NK lymphoma types. The majority of them are T-cell lymphoblastic lymphomas (TLL) and anaplastic large cell lymphomas (ALCL). Other rare non-B NHLs represent a diverse group of neoplasms, usually excluded from clinical trials. This study analyzed outcomes in pediatric patients with non-B NHL in a single oncology center with particular emphasis on patients with rare NHLs. PATIENTS AND METHODS: We retrospectively analyzed data from patients <18 years with newly diagnosed non-B NHL treated at the Department of Pediatric Hematology and Oncology in Bydgoszcz between 2002 and 2022. The probability of 5-year overall survival (pOS) and event-free survival (pEFS) were calculated for the entire cohort and patients with TLL and ALCL. The clinical course for patients with rare non-B NHL was described in detail. RESULTS: Twenty-six children were eligible for analysis. Fourteen patients were diagnosed with ALCL, nine with TLL, and three with rare NHL types (subcutaneous panniculitis-like T-cell lymphoma, extranodal NK/T-cell lymphoma and hydroa vacciniforme-like lymphoproliferative disease associated lymphoma). For the entire group, the 5-year pOS was 83.7% and the 5-year pEFS was 72.4%. For TLL and ALCL, the outcomes were comparable with those achieved in clinical trials. Patients with rare NHL were treated according to individualized therapy recommendations based on physicians' expertise and available case report descriptions. CONCLUSION: There is a lack of knowledge on optimal therapeutic strategies for rare NHLs. It is crucial to create trials dedicated to uncommon NHLs and establish therapy guidelines for these patients.

Multiantigen T-Cell Hybridizers: A Two-Component T-Cell-Activating Therapy.

Multispecific T-cell-engaging scaffolds have emerged as effective anticancer therapies for the treatment of hematological malignancies. Approaches that modulate cancer cell targeting and provide personalized, multispecific immunotherapeutics are needed. Here, we report on a modular, split antibody-like approach consisting of Fab' fragments modified with complementary morpholino oligonucleotides (MORFs). We synthesized a library of B-cell-targeting Fab'-MORF1 conjugates that self-assemble, via a Watson-Crick base pairing hybridization, with a complementary T-cell-engaging Fab'-MORF2 conjugate. We aptly titled our technology multiantigen T-cell hybridizers (MATCH). Using MATCH, cancer-specific T-cell recruitment was achieved utilizing four B-cell antigen targets: CD20, CD38, BCMA, and SLAMF7. The antigen expression profiles of various malignant B-cell lines were produced, and using these distinct profiles, cell-specific T-cell activation was attained on lymphoma, leukemia, and multiple myeloma cell lines in vitro. T-cell rechallenge experiments demonstrated the modular approach of MATCH by sequentially activating the same T-cell cohort against three different cancers using cancer antigen-specific Fab'-MORF1 conjugates. Furthermore, MATCH's efficacy was demonstrated in vivo by treating xenograft mouse models of human non-Hodgkin's lymphoma with CD20-directed MATCH therapy. In the pilot study, a single dose of MATCH allowed for long-term survival of all treated mice compared to saline control. In a second in vivo model, insights regarding optimal T-cell-to-target cell ratio were gleaned when a ratio of 5:1 T-cell-to-target cell MATCH-treated mice significantly delayed the onset of disease compared to higher and lower ratios.

Warthin tumor concomitant with mantle cell lymphoma: a case report and review of literature.

RATIONALE: Warthin tumor (WT) is the second most common benign tumor in salivary gland. It has a slow growth rate and most frequently occurs in the parotid gland. Most patients present with an incidental finding of a painless mass inferior/anterior to the ear. Besides the epithelial component of the tumor, WT is characteristically associated with lymphoid stroma that is considered benign. While there have been a few reports of malignant transformation of the lymphoid components in WT, cases of WT concomitant with mantle cell lymphoma (MCL) are extremely rare. To the best of our knowledge, two cases have been described in the English literature. Herein, we report a case of WT concomitant with MCL in a 70-year-old female patient, and emphasize the importance of careful examination of lymphoid stroma in WT so that concurrent lymphoma is not missed. PATIENT CONCERNS: A 70-year-old Chinese woman with a 40-year history of cigarette smoking presented with a one year history of a right submaxillary mass with recent enlargement. DIAGNOSIS: Cervical ultrasound (US) and computed tomography (CT) scans of the neck revealed a well-circumscribed mass in the right parotid with a maximum diameter of 3.1 cm. Surgical resection of the mass was performed. Histopathological examination revealed a characteristic double-layer of neoplastic epithelium with prominent lymphoid stroma, suggesting WT. In addition, morphology and immunohistochemistry studies confirmed the coexistence of MCL. Thereafter, the final diagnosis of this case was WT concomitant with MCL. INTERVENTIONS: The patient was staged as stage I after clinical assessment. Due to the slow growth of parotid lesions, close observation was decided with periodic clinical and radiological monitoring. OUTCOMES: Currently, the patient demonstrates a stable disease by clinical evaluation. LESSONS: To the best of our knowledge, reported cases of WT concomitant with MCL are very rare. This case highlights the importance of a comprehensive assessment of the lymphoid stroma of WT to avoid missed diagnosis of a lymphoma component in a collision tumor.

Non-Hodgkin lymphoma incidence, mortality, and survival trends in Brunei Darussalam from 2011 to 2020.

BACKGROUND: Non-Hodgkin lymphoma (NHL) has been identified as a significant contributor to the cancer burden. This study investigates the incidence, mortality, and survival trends of NHL cancer in Brunei Darussalam from 2011 to 2020. METHODS: This is a registry-based retrospective study using de-identified data from the Brunei Darussalam Cancer Registry on patients diagnosed with NHL from 2011 to 2020 based on the ICD-10 codes C82-86. Statistical methods include descriptive statistics, age-specific and age-standardised incidence (ASIR) and mortality rates (ASMR), and joinpoint regression for trend analysis. Survival analysis was conducted using Kaplan-Meier plots, log-rank test, and Cox Proportional Hazards regression. RESULTS: From 2011 to 2020, 330 patients were diagnosed with NHL. The majority of patients were males (51.8%) and of Malay descent (82.7%). The age group most diagnosed was 55-74 years (42.3%), with a mean age at diagnosis being 55.1 years. The ASIRs were 12.12 for males and 10.39 per 100,000 for females; ASMRs were 6.11 for males and 4.76 per 100,000 for females. Diffuse large B-cell lymphoma was the most prevalent subtype, accounting for 39.1% of cases. The overall 5-year survival rate was 61.2%, with lower rates observed in older patients and those diagnosed at distant metastasis stage. Furthermore, older age and advanced stage diagnosis significantly increased mortality risk. NHL incidence and mortality rates in Brunei Darussalam remain stable over the period of 10 years, but highlights significant disparities in gender and age. CONCLUSIONS: The findings emphasize the importance of early detection and tailored treatments, especially for high-risk groups, in managing NHL's burden. These insights underline the need for focused healthcare strategies and continued research to address NHL's challenges.

Comparisons of treatment outcomes of epcoritamab versus chemoimmunotherapy, polatuzumab-based regimens, tafasitamab-based regimens, or chimeric antigen receptor T-cell therapy, in third-line or later relapsed/refractory large B-cell lymphoma.

Many therapies are available for the treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after ≥ 2 lines of therapy, albeit with scant evidence on the comparative effectiveness of these therapies. This study used inverse probability of treatment weighting to indirectly compare treatment outcomes of epcoritamab from the EPCORE NHL-1 trial with individual patient data from clinical practice cohorts treated with chemoimmunotherapy (CIT) and novel therapies (polatuzumab-based regimens, tafasitamab-based regimens, and chimeric antigen receptor T-cell [CAR T] therapies) for third-line or later R/R large B-cell lymphoma (LBCL) and DLBCL. In this analysis, epcoritamab demonstrated significantly better response rates and overall survival rates than CIT, polatuzumab-based regimens, and tafasitamab-based regimens. No statistically significant differences in response rates or survival were found for epcoritamab compared with CAR T in R/R LBCL.

Melanoma as Subsequent Primary Malignancy in Hematologic Cancer Survivors-A Literature Review.

The occurrence of second primary malignancies is becoming increasingly important among cancer survivors. Melanoma, an aggressive neoplasm originating from the melanocytes, is responsible for most skin cancer-related deaths. This review aims to explore the risk of melanoma occurrence as a second primary cancer after the most common subtypes of hematologic neoplasia, a malignant disease originating from myeloid or lymphocytic cell lineages. Chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) are among the most associated subtypes with melanoma development. We also discuss the underlying hypotheses that may explain the associations between these malignancies and the impact of melanoma on survival. The review emphasizes the importance of increasing awareness of melanoma risk in hematologic cancer survivors, as it can lead to prompt recognition, improved skin surveillance, and better survival outcomes.

Multiple primary diffuse large B-cell lymphoma masquerading as meningioma.

Background: Primary non-Hodgkin's lymphoma with multiple extra- and intra-calvarial extensions without systemic spread in an immunocompetent patient is extremely rare. They masquerade commonly as meningioma and can present as mass lesions with raised intracranial pressure. Case Description: We report one such case of primary diffuse large B-cell lymphoma (DLBCL) in a young female involving the scalp, dural involvement in the right frontal region, left parietal, and posterior fossa and mimicking both clinically and radiologically as meningioma. She was managed surgically. Histological examination showed features suggestive of DLBCL (germinal center type). She was planned for adjuvant therapy. However, at 2 months following surgery, she succumbed due to systemic involvement of the disease. Conclusion: DLBCL is seen rarely in neurosurgical practice. They can present as tumors with adjacent extra- and intra-cranial masses. They pose a diagnostic challenge as it can be easily confused with meningioma. Tumor resection is performed to confirm diagnosis and in patients who present with raised intracranial pressure. Chemotherapy is the preferred treatment, and adjuvant therapy should be started early.

Coexistence of non-Hodgkin lymphoma and multisystem hydatid cysts; successful albendazole therapy for muscular hydatid cysts: A case report.

INTRODUCTION: "Hydatid cyst" or cystic Echinococcosis is a parasitic infection caused by the larval stage of Echinococcus granulosus. The liver and lungs are the most common sites to occur. Incidence in muscles is exceptionally rare. Surgery has been the traditional approach for treatment of cystic echinococcusis. PRESENTATION OF CASE: We report a rare case of 44 years old man with multiple hydatid cysts; liver, lungs, paraspinal muscles. The muscular cyst had manifested as a swelling in his back and was the principal clinical presentation as it caused pain and discomfort. He was treated with Albendazole, and a thoracic surgery for the management of the lung cysts had been performed. On admission and after his surgery, lymphadenopathy had manifested and following adequate diagnostic modalities he was diagnosed with Non-Hodgkin lymphoma. Then, after three months, physical examination revealed significant reduction in the size of his back cyst that was no longer visible. DISCUSSION: Here we present a successful treatment for muscular hydatid cysts. While prior reports have managed it surgically; albendazole has played a significant role in our case, in addition to the diagnosis of the NHL in the course of managing multiple hydatid cysts. CONCLUSION: The presence of non-Hodgkin lymphoma alongside hepatic cystic disease is rare, and the coexistence of NHL and muscular hydatidosis is unprecedented in medical literature.

Single gene mutations and prognosis in limited-stage follicular lymphoma treated with radiation therapy.

Radiotherapy is routinely used for management of limited-stage follicular lymphoma (FL), yet half of patients ultimately relapse. We hypothesized that the presence of specific gene mutations may predict outcomes. We performed targeted sequencing of a 69-gene panel in 117 limited-stage FL patients treated with radiotherapy and identified recurrently mutated genes. CREBBP was most frequently mutated, and mutated CREBBP was associated with inferior progression-free survival, though not after false discovery rate adjustment. This association failed to validate in an independent cohort. We conclude that recurrent gene mutations do not predict outcomes in this setting. Alternative biomarkers may offer better prognostic insight.

Tazemetostat for relapsed/refractory B-cell non-Hodgkin lymphoma with EZH2 mutation in Japan: 3-year follow-up for a phase II study.

Previously, we reported the efficacy and safety of tazemetostat in Japanese patients with relapsed/refractory follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) harboring the EZH2 mutation in a multicenter, open-label, phase II study. Here, we present a follow-up analysis of tazemetostat at a long-term median follow-up of 35.0 months. Twenty patients were enrolled: 17 in the FL cohort and three in the DLBCL cohort. In the FL cohort, the objective response rate was 70.6%, consistent with the primary analysis, and the median progression-free survival (PFS) was not reached. The 24-month and 36-month PFS rates were 72.1% (95% confidence interval [CI] 41.5%-88.6%) and 64.1% (95% CI 33.7%-83.4%), respectively. The median duration of treatment was 30.2 months. After the primary analysis at a median follow-up of 12.9 months, grade 1-2 urinary tract infection, peripheral motor neuropathy, and hypogammaglobulinemia newly emerged, but the incidence of adverse events (AEs) did not increase notably during this follow-up period. No unexpected grade ≥ 3 treatment-related AEs were reported. Long-term oral monotherapy with tazemetostat showed favorable efficacy and safety profiles, indicating that it may be a useful third-line or later treatment option for patients with relapsed/refractory FL harboring the EZH2 mutation. Trial registration: ClinicalTrials.gov: NCT03456726.

Clinical and Biomarker Characteristic of Lymphoma Patients in Hasan Sadikin Lymphoma Registry.

Background: No specific data have been systematically collected regarding lymphoma patient characteristics, while non-Hodgkin lymphoma (NHL) is identified as the 7th most common cancer and Hodgkin lymphoma (HL) is the 28th. Inflammation plays an important role in the pathogenesis and progression of lymphoma. Malnutrition is an adverse prognostic factor in lymphoma. Systemic Inflammatory Index (SII), Prognostic Nutritional Index (PNI), and Advanced Lung Cancer Inflammation Index (ALI) were biomarkers depicting inflammation and nutritional status. This study aims to describe the clinical and biomarker characteristics of both HL and NHL patients. Methods: This descriptive study used a cross-sectional design, and data were collected from Hasan Sadikin Hospital lymphoma registry from January 2020 to November 2023. Demographic, staging, and histopathological data were extracted. Three biomarkers were evaluated. Survival curves were drawn using Kaplan-Meier curve analysis, and the log rank test was used for comparison of survival between early and advanced stage. Results: A total of 271 patients were recruited as participants, and the majority (80.5%) had NHL, with diffuse large B-cell lymphoma (DLBCL) being the most common histopathological type (50.5%). Early disease was observed in two-thirds of patients, and low-risk International Prognostic Index (IPI) score was the most common prognostic score found (95%). SII was slightly higher in early compared to advanced stages. Treatment response was evaluated from 101 patients, and complete response was observed in 44.5%. Two-year overall survival (OS) was 93.1%, with median survival 22.7 (95% CI 21.9-23.5) months. In early stage, the median survival was slightly longer than in advanced stage [23.0 (95% CI 22.2-23.8) vs 21.6 (95% CI 19.3-23.8) months, P=0.09]. Conclusion: Hodgkin lymphoma and DLBCL had similar clinical and biomarker characteristics. There were slight differences between the three biomarkers SII, ALI, and PNI based on the disease stage. Almost all patients still survived at 2-year follow-up.

Effect of body mass index on the prognosis of children and adolescents with high-grade mature B-cell non-Hodgkin lymphoma.

BACKGROUND: Little progress has been made in determining the prognostic factors for children and adolescents with high-grade mature B-cell non-Hodgkin lymphoma (HG B-NHL). Based on the important role of body mass index (BMI) in cancer, this study explored the effect of BMI on the prognosis of patients with HG B-NHL. METHODS: Patients aged <18 years with newly diagnosed HG B-NHL were enrolled. Patients were divided into normal, overweight, obese, and emaciated BMI groups according to the growth criteria for children and adolescents. RESULTS: In total, 435 patients were enrolled in this study. There were 329 (75.6%), 46 (10.6%), 13 (3.0%), and 47 (10.8%) patients stratified into the normal, overweight, obese, and emaciated BMI groups, respectively. The event-free survival and overall survival rates of the entire cohort were 89.3% and 92.4%, respectively. The 5-year event-free survival rate for the patients with obese BMI was worse than those with overweight BMI (76.2% vs. 95.6%, p = .04). The 5-year overall survival rate for the patients with emaciated BMI was worse than those with normal (84.5% vs. 93.1%, p = .04) or overweight BMI (84.5% vs. 97.7%, p = .03). Cox multivariate analysis showed that obese or emaciated BMI at diagnosis was associated with an increased risk of death (p = 0.04; HR, 2.26) and was identified as an independent adverse prognostic factor in pediatric HG B-NHL. CONCLUSION: Obese or emaciated BMI at diagnosis is associated with poor prognosis in pediatric HG B-NHL and can be used for risk stratification.

A Rare Case of Refractory Nodal Marginal Zone Lymphoma in a Child, Successfully Cured by Allogeneic Stem Cell Transplant: A Case Report.

BACKGROUND: Nodal marginal zone lymphoma (NMZL) is a rare form of non-Hodgkin lymphoma (NHL), accounting for around 2% of all NHL in pediatrics and adults. It is considered the least common subtype of marginal zone lymphoma, which is rarely seen in pediatrics and is usually viewed as a mild disease. In adults, its presentation varies from mild to aggressive disease with multiple lymph node enlargement and systemic symptoms. CASE REPORT: Here, we report an interesting case of a 31-month-old boy who developed refractory EBV-positive NMZL with extensive disease. The tumor did not respond well to conventional chemotherapy and Rituximab. Therefore, we manage the disease with second-line chemotherapy, including bortezomib, followed by an allogeneic hematopoietic stem cell transplant (HSCT) with an excellent outcome. CONCLUSION: Very few cases have been reported for aggressive NMZL children. The tumor was refractory to first line chemotherapy. However, the successful outcome was achieved by allogeneic stem cell transplant with myeloablative conditioning chemotherapy. The significance of this particular case is that this is the first reported case from pediatrics for refractory NMZL, which responded well to allogeneic stem cell transplant.

Hematological malignancy-associated pyoderma gangrenosum: evaluating the magnitude of the association.

Background: Hematologic malignancies (HMs) are well-known underlying comorbidities of pyoderma gangrenosum (PG). However, studies quantifying the likelihood of PG after HMs are yet to be performed. Objective: To investigate the bidirectional association between PG and several HMs, namely acute leukemia, chronic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, and multiple myeloma. Methods: A population-based retrospective cohort study was conducted to study the risk of HMs in patients with PG (n = 302) as compared to age-, sex-and ethnicity-matched control subjects (n = 1,799). A case-control design was used to estimate the likelihood of PG in individuals with a preexisting history of HMs. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were estimated by Cox regression and logistic regression, respectively. Results: The prevalence of preexisting HM was higher in patients with PG than in controls (6.7% vs. 0.9%, respectively). The likelihood of having PG was significantly greater among patients with a history of HM (adjusted OR, 7.88; 95% CI, 3.85-16.15; p < 0.001), particularly during the first year following the diagnosis. This association was significant for acute leukemia, chronic leukemia, non-Hodgkin lymphoma, and multiple myeloma but not for Hodgkin lymphoma. The incidence rate of HM was 3.3 (95% CI, 1.2-7.4) and 1.6 (95% CI, 0.9-2.6)/1,000 person-years among patients with PG and controls, respectively. Relative to controls, patients with PG were not more likely to develop subsequent HM (adjusted HR, 2.22; 95%CI, 0.77-6.45; p = 0.142). Compared to other patients with PG, those with HM-associated PG experienced an increased all-cause mortality rate (adjusted HR, 2.19; 95%CI, 1.09-4.40; p = 0.028). Conclusion: HM, particularly acute leukemia and multiple myeloma, are associated with an elevated likelihood of provoking PG.

Maxillary Diffuse Large B-Cell Lymphoma Enshrouded as Osteomyelitis: A Case Report.

Extranodal non-Hodgkin's lymphoma (NHL) afflicting the head and neck region is rare, accounting for only about 5%. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL affecting the oral cavity. Due to its variable clinical presentation and non-pathognomic course, it can be easily misdiagnosed with overlapping characteristics to common oral pathologies. In the present case, the authors report an unusual presentation of DLBCL and highlight the significant diagnostic challenge encountered by the clinician. In our case, osteonecrosis of the maxilla with soft tissue swelling misleads the diagnosis of chronic osteomyelitis. However, further, work-up was pursued, and the patient was managed successfully with chemotherapy and is currently disease-free for the past 1 year. An accurate clinico-radiological diagnosis with histopathological confirmation is emphasized to deliver a potentially curative treatment in a timely manner.

Sex-based Differences in Risk for Therapy-related Myeloid Neoplasms.

BACKGROUND: Therapy-related myeloid neoplasm (t-MN) is a life-threatening complication of autologous peripheral blood stem cell (PBSC) transplantation for non-Hodgkin lymphoma (NHL). Prior studies report an association between clonal hematopoiesis (CH) in PBSC and risk of t-MN, but small samples precluded examination of risk within specific sub-populations. METHODS: Targeted DNA sequencing was performed to identify CH mutations in PBSC from a retrospective cohort of 984 NHL patients (median age at transplant 57y; range: 18-78). Fine-Gray proportional subdistribution hazard regression models estimated association between number of CH mutations and t-MN, adjusting for demographic, clinical, and therapeutic variables. Secondary analyses evaluated association between CH and t-MN among males and females. RESULTS: CH was identified in PBSC from 366 patients (37.2%). t-MN developed in 60 patients after median follow-up of 5y. Presence of ≥2 mutations conferred increased t-MN risk (adjusted hazard ratio [aHR]=2.10, 95% confidence interval [CI]=1.08-4.11, p=0.029). CH was associated with increased t-MN risk among males (aHR=1.83, 95%CI=1.01-3.31) but not females (aHR=0.56, 95%CI=0.15-2.09). Although prevalence and type of CH mutations in PBSC was comparable, the 8y cumulative incidence of t-MN was higher among males vs. females with CH (12.4% vs. 3.6%) but was similar between males and females without CH (4.9% vs. 3.9%). Expansion of CH clones from PBSC to t-MN was seen only among males. CONCLUSIONS: Presence of CH mutations in PBSC confers increased risk of t-MN after autologous transplantation in male but not female patients with NHL. Factors underlying sex-based differences in risk of CH progression to t-MN merit further investigation.