Burkitt Lymphoma International Prognostic Index.

PURPOSE: Burkitt lymphoma (BL) has unique biology and clinical course but lacks a standardized prognostic model. We developed and validated a novel prognostic index specific for BL to aid risk stratification, interpretation of clinical trials, and targeted development of novel treatment approaches. METHODS: We derived the BL International Prognostic Index (BL-IPI) from a real-world data set of adult patients with BL treated with immunochemotherapy in the United States between 2009 and 2018, identifying candidate variables that showed the strongest prognostic association with progression-free survival (PFS). The index was validated in an external data set of patients treated in Europe, Canada, and Australia between 2004 and 2019. RESULTS: In the derivation cohort of 633 patients with BL, age ≥ 40 years, performance status ≥ 2, serum lactate dehydrogenase > 3× upper limit of normal, and CNS involvement were selected as equally weighted factors with an independent prognostic value. The resulting BL-IPI identified groups with low (zero risk factors, 18% of patients), intermediate (one factor, 36% of patients), and high risk (≥ 2 factors, 46% of patients) with 3-year PFS estimates of 92%, 72%, and 53%, respectively, and 3-year overall survival estimates of 96%, 76%, and 59%, respectively. The index discriminated outcomes regardless of HIV status, stage, or first-line chemotherapy regimen. Patient characteristics, relative size of the BL-IPI groupings, and outcome discrimination were consistent in the validation cohort of 457 patients, with 3-year PFS estimates of 96%, 82%, and 63% for low-, intermediate-, and high-risk BL-IPI, respectively. CONCLUSION: The BL-IPI provides robust discrimination of survival in adult BL, suitable for use as prognostication and stratification in trials. The high-risk group has suboptimal outcomes with standard therapy and should be considered for innovative treatment approaches.

Combinations or sequences of targeted agents in CLL: is the whole greater than the sum of its parts (Aristotle, 360 BC)?

The treatment landscape for chronic lymphocytic leukemia (CLL) is rapidly evolving. Targeted agents (TAs) have demonstrated impressive single agent activity and therefore have been replacing chemoimmunotherapy (CIT). Despite their efficacy, the optimal use of the current TAs remains challenging. Perhaps the major dilemma is whether these drugs are best used in sequence or in combinations. Most patients tolerate TA well, notably early during treatment; however, a substantial number discontinue therapy because of toxicities. Therefore, the reasons for discontinuation and, subsequently, the preferred sequence of these agents become critical issues. Although TA monotherapy has revolutionized the treatment of CLL, residual disease, acquired resistance, suboptimal durability of response in patients with high-risk disease, indefinite treatment duration, and decreased compliance over time are issues of concern. To address these challenges, an increasing number of studies are evaluating different combinations of TAs; however, these studies have been mostly small single arm trials in heterogeneous patient populations using different methods for response assessment. A number of questions remain regarding the predictive value of minimal residual disease (MRD) status, durability of response, fixed treatment durations, and importantly, criteria for selection of patients for the optimal combinations. Medical comorbidities, performance status, prior therapies, and disease risk profile are fundamental in determining the treatment plan for each individual patient. Furthermore, utilizing prognostic and predictive markers along with monitoring MRD can guide the development of individualized, better-tolerated, time-limited, and potentially curative chemo-free treatment regimens.

Determining the sequence of novel therapies in the treatment of relapsed Hodgkin's lymphoma.

INTRODUCTION: Hodgkin's lymphoma (HL) accounts for about 10% of all lymphomas in the U.S.A. Exceptional progress has been made in the treatment of HL with complete response (CR) rates up to 94% in limited stage and 88% in advanced stage disease with regimens such as adriamycin, bleomycin, vinblastine, and dacarbazine in the frontline setting. Nevertheless, up to 10% of patients with limited stage disease and 20-30% of those with advanced stage HL relapse. In the last decade, newer agents such as brentuximab vedotin (BV) and checkpoint inhibitors have been approved by the FDA for treatment of patients with relapsed or refractory HL. As these newer agents are increasingly incorporated in both the frontline and relapsed settings, their optimal sequence becomes challenging for clinicians. Areas covered: This review will discuss the evidence behind the approval of BV and checkpoint inhibitors in HL and the appropriate sequence for using them in relapsed HL. Expert commentary: The appropriate sequence of BV and/or checkpoint inhibitors in the relapsed setting depends on the regimen used in the frontline setting.

Extended Follow-up of Patients Treated With Bendamustine for Lymphoid Malignancies.

INTRODUCTION: Bendamustine, typically in combination with rituximab, is an effective treatment for chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma. Despite its acceptable short-term toxicity profile, long-term toxicities are less well established. This study investigated the long-term adverse effects of bendamustine and responses to subsequent treatments. PATIENTS AND METHODS: Charts of 194 patients were retrospectively reviewed; 54% had received prior treatment (76% attained complete response [CR] or partial response [PR]). RESULTS: Patients who did not achieve a CR or PR did not respond well to subsequent treatments. Malignancies following bendamustine were diagnosed in 11% (21) of patients (first line [7] and salvage [14]), including squamous (8) or basal cell (4) skin cancers; prostate cancer (3), renal cancer (3), bladder cancer (2), melanoma (2), lung cancer (1), and histiocytic sarcoma (1). There were no occurrences of therapy-related myelodysplastic syndrome or acute myelogenous leukemia reported. Infections occurred in 63% of patients; however, no deaths were attributable to bendamustine. CONCLUSION: Bendamustine is an effective therapy with limited long-term sequelae in patients with lymphoid malignancies.

Impact of obinutuzumab alone and in combination for follicular lymphoma.

Although rituximab-based chemoimmunotherapy prolongs the survival of patients with follicular lymphoma (FL), this disease is considered incurable in most patients. Thus, new therapies are needed not only for those in the relapsed/refractory setting, but also for initial treatment. Obinutuzumab (G, GA101) is a third-generation, fully humanized type II glycoengineered, anti-CD20 monoclonal antibody that results in increased direct cell death and antibody-dependent, cell-mediated cytotoxicity/phagocytosis compared to rituximab. Obinutuzumab has significant antitumor activity when used alone or in combinations in untreated or relapsed refractory FL patients. Studies have demonstrated its ability to prolong progression-free survival and, in some cases, overall survival, and to eliminate minimal residual disease. Several ongoing trials are investigating combinations with chemotherapy, immunomodulators, targeted drugs, and immunotherapy agents. G is generally well tolerated, with associated adverse effects including infusion-related reactions, neutropenia, thrombocytopenia, and reactivation of hepatitis B virus. Future studies with this antibody should focus on identifying predictive markers and developing chemotherapy-free combinations that will improve the outcome of patients with FL.

Allergic contact dermatitis to metal allergens in Iran.

BACKGROUND: Metallic allergens such as nickel are among the most common causes of allergic contact dermatitis (ACD), but frequencies of contact dermatitis to these allergens may vary in different areas. OBJECTIVES: This study aimed to determine the frequencies of ACD caused by three common metallic allergens: nickel sulfate; potassium dichromate; and cobalt chloride. METHODS: Data for 1137 patients with clinical diagnoses of contact dermatitis and/or atopic dermatitis evaluated by patch testing in Iran during a 5-year period were retrospectively studied to establish the frequencies of hypersensitivity to these metallic allergens. RESULTS: A total of 313 patients (27.5%) gave positive patch test results for at least one metallic allergen. Allergy to nickel (229 cases, 20.0%) was the most commonly observed, followed by allergy to cobalt (90 cases, 8.0%) and allergy to chromium (70 cases, 6.2%). Nickel allergy was significantly more frequent in females and in subjects aged <40 years, whereas chromium hypersensitivity was more common in males and in subjects aged >40 years. Sensitivity to nickel or chromium was a risk factor for cobalt allergy. CONCLUSIONS: Nickel was most commonly identified as a metallic allergen in Iran and tended to affect women aged <40 years. Regulations pertaining to nickel release may decrease the frequency of nickel hypersensitivity in Iran.

Pre-operative assessment of basal cell carcinoma dimensions using high frequency ultrasonography and its correlation with histopathology.

INTRODUCTION: High frequency ultrasonography (HFUS) is a non-invasive, low risk method which can provide real-time visual information regarding different processes in cutaneous tissue. The goal of this study is to compare the accuracy of HFUS in determining depth and width of basal cell carcinoma (BCC) lesions compared with histopathology as a reference standard. METHODS: The depth and width of 56 primary BCCs in various locations were measured in vivo using the ultrasound system device Digital Taberna Promedica (Luneburg, FRG DUB 20 Ultrasound Scanner), with a 50-MHz hand-held transducer and compared with the depth and width reported in histopathologic examination of these lesions after complete excision. The intraclass correlation coefficient (ICC) was calculated using a one-way ANOVA table to compare measured dimensions for the same tumors with the two diagnostic methods. RESULTS: The mean depth of tumor in HFUS (1353.68 ± 656.456 microns) was lower than the amount measured by the dermatopathologist (1560.71 ± 1044.323 microns). However, the difference was not statistically significant (P > 0.05). The means of largest diameter of tumors in HFUS and pathology were 5996.77 ± 2271.783 and 3891.07 ± 1995.452 microns, respectively (P < 0.001). There was a low correlation in diameter (r = 0.27, P < 0.05) and a moderate correlation in depth (r = 0.45, P < 0.001) of BCCs between these two methods. CONCLUSION: HFUS may be a useful method to assess the dimensions of BCC prior to surgery.

Variation of biophysical parameters of the skin with age, gender, and body region.

BACKGROUND: Understanding the physiological, chemical, and biophysical characteristics of the skin helps us to arrange a proper approach to the management of skin diseases. OBJECTIVE: The aim of this study was to measure 6 biophysical characteristics of normal skin (sebum content, hydration, transepidermal water loss (TEWL), erythema index, melanin index, and elasticity) in a normal population and assess the effect of sex, age, and body location on them. METHODS: Fifty healthy volunteers in 5 age groups (5 males and females in each) were enrolled in this study. A multifunctional skin physiology monitor (Courage & Khazaka electronic GmbH, Germany) was used to measure skin sebum content, hydration, TEWL, erythema index, melanin index, and elasticity in 8 different locations of the body. RESULTS: There were significant differences between the hydration, melanin index, and elasticity of different age groups. Regarding the locations, forehead had the highest melanin index, where as palm had the lowest value. The mean values of erythema index and melanin index and TEWL were significantly higher in males and anatomic location was a significant independent factor for all of 6 measured parameters. CONCLUSION: Several biophysical properties of the skin vary among different gender, age groups, and body locations.

Oral and jaw lymphoma in an Iranian population.

INTRODUCTION: Lymphoma is the second most common malignancy of head and neck. Many studies have been carried out in different population groups to detect the subtypes of oral and jaw lymphoma, but such research has not been conducted in Iran. The purpose of this study was to determine the subtypes of oral and jaw lymphoma by immunohistochemistry. MATERIALS AND METHODS: A total of 36 paraffin-embedded blocks (25 males and 11 females) with primary diagnosis of non-Hodgkin lymphoma were studied by immunohistochemical markers according to cellular morphology. RESULTS: The frequencies were diffuse large B-cell (41.1%), low-grade B-cell (35.2%), peripheral T-cell (11.7%), Burkitt (5.8%), and Hodgkin lymphomas (5.8%). The involved sites were salivary gland (26.4%), maxillary bone (23.5%), mandibular soft tissues (17.6%), maxillary sinus (14.7%), mandibular bone (8.8%), tonsils and tongue (5.7%), and lip and vestibule (2.9%), and 2 cases (5.5%) turned out to be undifferentiated carcinomas. The most common lymphomas in male and females were diffuse large B-cell and low-grade B-cell lymphomas, respectively. CONCLUSIONS: The epidemiology of different types of oral lymphoma in a sample of Iranian population was not similar with other populations of the world. Immunohistochemistry and molecular methods are required to prove the diagnosis in addition to typing of lymphoma.