Web-based cognitive rehabilitation intervention for cancer-related cognitive impairment following chemotherapy for aggressive lymphoma: protocol for a randomised pilot trial.

INTRODUCTION: Cancer-related cognitive impairment is common among people diagnosed with and treated for cancer. This can be a distressing and disabling side effect for impacted individuals. Interventions to mitigate cognitive dysfunction are available, but, to date, most have been trialled in samples that are largely or exclusively composed of people with solid tumours. Intervention strategies to support cognitive functioning are needed, but there is a paucity of research in this area. The main aim of this study is to test the feasibility and acceptability of methods and procedures intended for use in a definitive trial of a web-based cognitive rehabilitation programme, Responding to Cognitive Concerns (eReCog), in people who have received chemotherapy for aggressive lymphoma. METHODS AND ANALYSIS: The proposed study is a single-site, parallel-group, pilot randomised controlled trial, with one baseline and one follow-up (or postintervention) assessment. 38 people from the target population with low perceived cognitive function based on the Cognitive Change Screen will be recruited from a specialist cancer centre between July 2023 and June 2024. After baseline assessment, participants will be randomised one-to-one to receive usual care only (a factsheet about changes in memory and thinking for people with cancer) or eReCog plus usual care. The 4-week eReCog intervention consists of four online modules offering psychoeducation on cognitive impairment associated with cancer and its treatment, skills training for improving memory, and attention and relaxation training. Study outcomes will include the feasibility of recruitment and retention at follow-up assessment (primary outcomes), as well as adherence to, usability of and intrinsic motivation to engage with eReCog, and compliance with study measures. The potential efficacy of eReCog will also be evaluated. ETHICS AND DISSEMINATION: Ethical approval was granted by the Peter MacCallum Cancer Centre Human Research Ethics Committee in Victoria, Australia (HREC/97384/PMCC). Study findings will be disseminated via peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry, ACTRN12623000705684.

Cancer-related cognitive impairment and wellbeing in patients with newly diagnosed aggressive lymphoma compared to population norms and healthy controls: an exploratory study.

PURPOSE: There has been little dedicated research on cancer-related cognitive impairment in patients with aggressive lymphoma. We describe and compare patients' cognitive function with that of healthy controls and patients' wellbeing and distress with general population values. We also explore associations between patients' neuropsychological test performance and self-reported cognitive function and distress. METHODS: Secondary analysis of data from a feasibility study of 30 patients with newly diagnosed aggressive lymphoma and 72 healthy controls. Patients completed neuropsychological tests and self-report measures before and 6-8 weeks after chemotherapy. Healthy controls completed neuropsychological tests and the FACT-Cog at enrolment and 6 months later. Mixed models were used to analyze neuropsychological test and FACT-Cog scores. One-sample t-tests were used to compare patients' self-reported wellbeing and distress with population norms. Associations were explored with Kendall's Tau b. RESULTS: Patients and healthy controls were well matched on socio-demographics. Differences between neuropsychological test scores were mostly large-sized; on average, patients' scores on measures of information processing speed, executive function, and learning and memory were worse both before and after chemotherapy (all p ≤ 0.003). The same pattern was observed for impact of perceived cognitive impairment on quality-of-life (both p < 0.001). Patients' physical and emotional wellbeing scores were lower than population norms both before and after chemotherapy (all p ≤ 0.018). Associations between neuropsychological performance and other measures were mostly trivial (all p > 0.10). CONCLUSION: For many patients with aggressive lymphoma, impaired neuropsychological test performance and impact of perceived impairments on quality-of-life precede chemotherapy and are sustained after chemotherapy. Findings support the need for large-scale longitudinal studies with this population to better understand targets for interventions to address cognitive impairments.

Jaundice caused by primary common bile duct lymphoma of a cat.

A 10-year-old American Shorthair cat presented with anorexia and jaundice, and echogenic evaluation revealed diffuse thickening of the common bile duct (CBD) wall. An exploratory laparotomy was conducted, the lesion was evaluated as difficult to remove, and the cat was euthanized and autopsied. Histologically, round neoplastic cells proliferated in the mucosa of the CBD and infiltrated the hepatic lobe, pancreas, and duodenum. Immunohistochemistry revealed that the neoplastic cells were positive for cytoplasmic-CD3 and granzyme B, and TCR-gamma clonal rearrangement was detected. Based on these findings, the neoplasia was diagnosed as a primary CBD lymphoma originating from cytotoxic T or natural killer cells. To the best of our knowledge, this is the first reported case of feline primary CBD lymphoma. Although rare, lymphoma of the CBD should be considered in cats with jaundice and thickening of the CBD.

A Scoping Review of Otologic Manifestations of Hematologic Malignancies.

OBJECTIVE: To examine the otologic and neurotologic symptoms, physical examination findings, and imaging features secondary to hematologic malignancies. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, databases, including PubMed, Scopus, and CINAHL, were searched for articles including patients with otologic manifestations of leukemia, lymphoma and multiple myeloma. Data collected included patient and study demographics, specific hematologic malignancy, timing and classification of otologic symptoms, physical examination findings, imaging features and methods of diagnosis. Pooled descriptive analysis was performed. RESULTS: Two hundred seventy-two articles, of which 255 (93.8%) were case reports and 17 (6.2%) were case series, reporting on 553 patients were identified. Otologic manifestations were reported on 307 patients with leukemia, 204 patients with lymphoma and 42 patients with multiple myeloma. Hearing loss and unilateral facial palsy were the most common presenting symptoms for 111 reported subjects with leukemia (n = 46, 41.4%; n = 43, 38.7%) and 90 with lymphoma (n = 38, 42.2%; n = 39, 43.3%). Hearing loss and otalgia were the most common presenting symptoms for 21 subjects with multiple myeloma (n = 10, 47.6%; n = 6, 28.6%). Hearing loss and unilateral facial palsy were the most common otologic symptoms indicative of relapse in subjects with leukemia (n = 14, 43.8%) and lymphoma (n = 5, 50%). CONCLUSION: Hearing loss, facial palsy, and otalgia might be the first indication of a new diagnosis or relapse of leukemia, lymphoma, or multiple myeloma. Clinicians should have a heightened level of suspicion of malignant etiologies of otologic symptoms in patients with current or medical histories of these malignancies.

Hypercalcaemia of malignancy: a case of vitamin-D-mediated hypercalcaemia in lymphoma.

Hypercalcaemia of malignancy (HCM) is a paraneoplastic syndrome that often portends a poor prognosis. We present an extremely rare (<1%) case of HCM due to extrarenal calcitriol (1,25-(OH)2D) production in a patient with splenic marginal zone lymphoma. A man in his 80s presented with a 3-week history of fatigue, unsteadiness and abdominal pain, and new findings of anaemia, kidney injury and hypercalcaemia. Laboratory evaluation, bone marrow biopsy and positron emission tomography/computed tomography (PET/CT) confirmed the diagnosis of splenic marginal zone lymphoma which produced calcitriol (1,25-(OH)2D3), causing the patient's hypercalcaemia.

COVID-19 in Pediatric Patients With Acute Lymphoblastic Leukemia or Lymphoma.

Importance: COVID-19 in pediatric patients with acute lymphoblastic leukemia or lymphoma (ALL/LLy) has not been described in detail and may affect chemotherapy administration and long-term outcomes. Objective: To describe the clinical presentation of COVID-19 and chemotherapy modifications in pediatric patients with ALL/LLy. Design, Setting, and Participants: This is a retrospective case series of patients at St Jude Children's Research Hospital and its affiliate sites with newly diagnosed ALL/LLy who were treated on the Total XVII protocol (NCT03117751) between March 30, 2020, and June 20, 2022. Participants included patients aged 1 to 18 years who were receiving protocol chemotherapy. Acute symptoms and chemotherapy modifications were evaluated for 60 days after the COVID-19 diagnosis, and viral clearance, adverse events, and second SARS-CoV-2 infections were followed up during the 27-month study period. Exposures: SARS-CoV-2; all patients were screened at least weekly and at symptom onset and/or after known exposure to SARS-CoV-2. Main Outcomes and Measures: Description of the spectrum of COVID-19 illness and chemotherapy modifications. Results: Of 308 pediatric patients, 110 (36%) developed COVID-19 at a median age of 8.2 (IQR, 5.3-14.5) years. Sixty-eight patients (62%) were male. Most patients were in the continuation/maintenance phase of chemotherapy (101 [92%]). Severe disease was rare (7 [6%]) but was associated with older age, higher white blood cell counts at ALL/LLy diagnosis, lower absolute lymphocyte counts at COVID-19 diagnosis, abnormal chest imaging findings, and SARS-CoV-2 reinfection. Rare but serious thrombotic events included pulmonary embolism and cerebral venous sinus thrombosis (n = 1 for each). No multisystem inflammatory syndrome in children or death was seen. SARS-CoV-2 reinfection occurred in 11 patients (10%) and was associated with older age and with receiving standard or high-risk vs low-risk ALL/LLy therapy. Chemotherapy interruptions occurred in 96 patients (87%) and were longer for patients with severe disease, SARS-CoV-2 reinfection, and/or a COVID-19 diagnosis during the pre-Omicron variant period vs the post-Omicron period (after December 27, 2021). Conclusions and Relevance: In this case series of COVID-19 in pediatric patients with ALL/LLy, severe COVID-19 was rare, but chemotherapy administration was affected in most patients. Long-term studies are needed to establish the outcomes of COVID-19 in this population.

Association of a decreased platelet count with poor survival in patients with adult secondary hemophagocytic lymphohistiocytosis.

We aimed to examine the association between baseline platelet count (PLT) and the prognosis of adult secondary hemophagocytic lymphohistiocytosis (sHLH). Data from 292 patients with pretreatment platelet counts were retrospectively analysed from January 2016 to December 2020. We categorized platelet count into quartiles. Multivariable Cox proportional hazards models and restricted cubic splines (RCS) were used to evaluate the relationship between platelet count and mortality. During a median follow-up of 53 (interquartile ranges, 17-223) days, a total of 208 deaths occurred. After adjusting for multiple variables, a non-linear and inverse relationship was observed between platelet count and mortality in sHLH patient (P for nonlinearity=0.002). For non- lymphoma-associated haemophagocytic lymphohistiocytosis (non-LHLH), a similar curve was also observed (P for nonlinearity =0.028). Decreased PLT (PLT Q4) was associated with an increased risk of mortality (adjusted hazard ratio: 1.97; 95% confidence interval: 1.28-3.04; Ptrend =0.005). Similar results were observed in the LHLH subgroup (adjusted hazard ratio: 1.84; 95% confidence interval: 1.05-3.24; Ptrend =0.024) but not in the non-LHLH subgroup (Ptrend =0.266). Baseline platelet count demonstrated a nonlinear and inverse association with an increased risk of mortality among adult sHLH patients. This method is used to identify sHLH patients with inferior overall survival due to its low cost and universal availability.

Clinical Utility of Stepwise Bronchoalveolar Lavage Fluid Analysis in Diagnosing and Managing Lung Infiltrates in Leukemia/Lymphoma Patients With Febrile Neutropenia.

PURPOSE: Febrile neutropenia (FN) is a serious complication in hematologic malignancies, and lung infiltrates (LIs) remain a significant concern. An accurate microbiological diagnosis is crucial but difficult to establish. To address this, we analyzed the utility of a standardized method for performing bronchoalveolar lavage (BAL) along with a two-step strategy for the analysis of BAL fluid. PATIENTS AND METHODS: This prospective observational study was conducted at a tertiary cancer center from November 2018 to June 2020. Patients age 15 years and older with confirmed leukemia or lymphomas undergoing chemotherapy, with presence of FN, and LIs observed on imaging were enrolled. RESULTS: Among the 122 enrolled patients, successful BAL was performed in 83.6% of cases. The study used a two-step analysis of BAL fluid, resulting in a diagnostic yield of 74.5%. Furthermore, antimicrobial therapy was modified in 63.9% of patients on the basis of BAL reports, and this population demonstrated a higher response rate (63% v 45%; P = .063). CONCLUSION: Our study demonstrates that a two-step BAL fluid analysis is safe and clinically beneficial to establish an accurate microbiological diagnosis. Given the crucial impact of diagnostic delays on mortality in hematologic malignancy patients with FN, early BAL studies should be performed to enable prompt and specific diagnosis, allowing for appropriate treatment modifications.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): contemporary advances and current controversies.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory syndrome with characteristic clinical, radiological, and pathological features, and can be effectively treated with corticosteroid-based immunotherapies. The exact pathogenesis of CLIPPERS remains unclear, and specific diagnostic biomarkers are not available. According to the 2017 diagnostic criteria, probable CLIPPERS should be considered in middle-aged patients with subacute onset of pontocerebellar symptoms and typical punctuate and curvilinear gadolinium enhancement lesions ("salt-and-pepper" appearance) located in the hindbrain (especially pons) on magnetic resonance imaging. In addition, CLIPPERS-mimics, such as central nervous system (CNS) lymphoma, and several antibody-associated autoimmune CNS diseases (e.g., myelin oligodendrocyte glycoprotein antibody-associated disease, autoimmune glial fibrillary acidic protein astrocytopathy, and anti-N-methyl-D-aspartate receptor encephalitis), should be extensively excluded. The prerequisite for definite CLIPPERS is the perivascular T-cell-predominant inflammatory infiltration observed on pathological analysis. A biopsy is strongly suggested when clinical/radiological red flags are present. Most patients with CLIPPERS respond well to corticosteroids and have a good prognosis. Long-term low-dose corticosteroid maintenance therapy or corticosteroids coupled with immunosuppressants are recommended to prevent the recurrence of the syndrome. The potential progression of CLIPPERS to lymphoma has been suggested in some cases; therefore, at least 2-year clinical and radiological follow-up is essential. Here, we critically review the recent developments and provided an update on the clinical characteristics, diagnostic criteria, differential diagnoses, and therapeutic management of CLIPPERS. We also discuss the current controversies in this context that can be resolved in future research studies.

Lifetime risks of second primary malignancies after pediatric Hodgkin lymphoma and non-Hodgkin lymphoma.

OBJECTIVES: Survivors after pediatric Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) are with lifetime risk for second primary malignancy (SPM). This necessitates a thorough analysis to better understand the potential long-term health implications for these individuals. METHODS: We used a US-wide population-based cancer registry data to quantify the SPM risk and identify its incidence patterns among pediatric lymphoma patients. RESULTS: We observed 4.74-fold (95% CI 4.27-5.25) and 3.40-fold (95% CI 2.78-4.10) increased risks of SPM in survivors after pediatric HL and NHL, respectively. Through over 40 years' follow-up, the cumulative incidence of SPM for pediatric lymphoma was persistently increasing, and here we firstly report the high 40-year cumulative incidence rates of SPM, 22.2% for HL and 12.6% for NHL, suggesting that SPM accounts for a great proportion of deaths among survivors. Of 6805 pediatric lymphomas, 462 (6.36%) developed a SPM, especially second breast and thyroid cancer, followed by hematologic neoplasms including leukemia and NHL. The competing risk analysis demonstrated gender, lymphoma subtype and radiotherapy were significantly associated with SPM. Different risk patterns of SPM were identified between pediatric HL and NHL. Chemotherapy accelerated SPM development but did not increase its incidence risk. CONCLUSION: Overall, patients after pediatric lymphoma can be with high lifetime risk of SPM, and more attention should be paid to SPM-related signs for early detection and intervention.

Lymphoma-associated hemophagocytic lymphohistiocytosis (LA-HLH): a scoping review unveils clinical and diagnostic patterns of a lymphoma subgroup with poor prognosis.

Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome driven by pathologic activation of cytotoxic T-lymphocytes and macrophages. Despite advances in diagnostics and management, adult patients with lymphoma-associated HLH (LA-HLH) harbor particularly poor prognosis and optimal treatment remains challenging. As systematic data on LA-HLH are scarce, we aimed to synthesize research evidence by thorough analysis of the published literature in PubMed (MEDLINE-database) within the context of a scoping review. Of 595 search results, 132 articles providing information on 542 patients were reviewed and analyzed. Median patient age was 60 years (range, 18-98) with male predominance (62.7%). B- and T-NHL were equally represented (45.6% and 45.2%), Hodgkin's lymphoma was reported in 8.9% of the cases. The majority of patients (91.6%) presented in Ann-Arbor-Stages III and IV, and bone marrow infiltration was observed in a significant proportion of patients (61.5%). Soluble CD25 levels were markedly elevated (median 10,000 U/ml), with levels beyond 10,000 U/ml indicating unfavorable prognosis for 30-day and overall survival. 66.8% of the patients died after median 5.1 months. LA-HLH remains a clinical challenge requiring specialized management. Timely diagnosis and appropriate lymphoma-specific treatment are of utmost importance to enhance patient outcomes.

Allogeneic Hematopoietic Cell Transplantation for Juvenile Myelomonocytic Leukemia with a Busulfan, Fludarabine, and Melphalan Regimen: JPLSG JMML-11.

Juvenile myelomonocytic leukemia (JMML), which is classified as a myelodysplastic/myeloproliferative neoplasm, is a rare hematologic malignancy of childhood. Most patients with JMML require allogeneic hematopoietic cell transplantation (HCT) as a curative therapy. A Japanese retrospective analysis demonstrated favorable outcomes for a busulfan (BU) + fludarabine (FLU) + melphalan (MEL) regimen, with an overall survival (OS) of 72% and an event-free survival (EFS) of 53%. To further validate the efficacy and safety of this regimen, the Japan Pediatric Leukemia/Lymphoma Study Group (JPLSG) conducted a nationwide prospective study, JMML-11. Between July 2011 and June 2017, 28 patients with newly diagnosed JMML were enrolled in JMML11. Low-dose chemotherapy for tumor control before HCT was recommended, and patients treated with AML-type chemotherapy and azacitidine were excluded. The conditioning regimen comprised i.v. BU, 16 doses administered every 6 h, with dose adjustment based on pharmacokinetic (PK) studies on days -11 to -8; FLU, 30 mg/m2/day or 1 mg/kg/day for patients <10 kg or age <1 year on days -7 to -4; and MEL, 90 mg/m2/day or 3 mg/kg/day for patients <10 kg or <1 year on days -3 to -2. The donor was selected by the physician in charge. A family donor was available for 7 patients (3 HLA-matched siblings, 3 HLA-1-antigen mismatched parents, and 1 haploidentical father). Overall, 21 patients received grafts from unrelated donors, including 8 HLA-matched donors and 13 HLA-mismatched donors. The graft source was related bone marrow (BM) for 7 patients, unrelated BM for 14 patients, and unrelated cord blood for 7 patients. Neutrophil engraftment was achieved in 21 of 28 patients (75%), with a median of 20.5 days (range, 11 to 39 days) after transplantation. The 3-year OS, 3-year EFS, 3-year relapse rate, and 3-year transplantation-related mortality were 63% (95% confidence interval [CI], 42% to 78%), 52% (95% CI, 32% to 69%), 18% (95% CI, 6% to 34%), and 21% (95% CI, 9% to 38%), respectively. WBC count before the conditioning regimen (≥7.0 × 109/L) was significantly associated with inferior EFS and OS. Body surface area ≥.5 m2, spleen size <4 cm before conditioning, and HLA-matched unrelated BM donors were significantly associated with better OS. Adverse effects related to the conditioning regimen included febrile neutropenia (86%), diarrhea (39%), hypoxemia (21%), and mucositis (18%). BU-associated toxicity, including sinusoidal obstruction syndrome (SOS) and thrombotic microangiopathy (TMA), occurred in 7 patients (25%; SOS, n = 6; TMA, n = 2). Retrospective analysis of PK data after the first BU dose in 23 patients, including 6 with SOS and 17 without SOS, did not show significant differences between groups. The JMML-11 study confirms the positive results of previous retrospective analyses. BU+FLU+MEL might become a standard conditioning regimen for patients with JMML.

Do Fertility Preservation Outcomes in Patients Diagnosed with Lymphoma Differ Based on Cancer Stage?

Purpose: This study aims to investigate whether oocyte stimulation outcomes in fertility preservation (FP) vary in patients with different stages of lymphoma. Methods: This is a retrospective cohort study conducted at Northwestern Memorial Hospital (NMH). Between 2006 and 2017, 89 patients were identified with a diagnosis of lymphoma who contacted the FP navigator at NMH. Anti-müllerian hormone (AMH) levels and FP ovarian stimulation outcomes were collected for analysis. The data were analyzed using chi-squared and analysis of variance tests. A regression analysis was also done to adjust for potential confounding variables. Results: Of the 89 patients who contacted the FP navigator, there were 12 patients (13.5%) with stage 1 lymphoma, 43 patients (48.3%) with stage 2, 13 patients (14.6%) with stage 3, 13 patients (14.6%) with stage 4, and 8 patients (9.0%) where staging information was not available. Forty-five of the patients proceeded with ovarian stimulation before initiating cancer treatment. Patients who underwent ovarian stimulation had a mean AMH level of 2.62 and median peak estradiol levels of 1772.0 pg/mL. Median oocytes retrieved was 16.77, mature oocytes were 11.00 and median oocytes frozen after completing FP was 8.00. These measures were also stratified by stage of lymphoma. Conclusion: We found no significant difference in number of retrieved, mature or vitrified oocytes between different cancer stages. There was also no difference in AMH levels in the different cancer stage groups. This suggests that even in higher stages of lymphoma, many patients respond to ovarian stimulation techniques and have a successful stimulation cycle.

Lymphoma masquerading as jaw pain, headache, and syncope: A case report.

BACKGROUND: Lymphomas of parapharyngeal space often have complex manifestations, posing a diagnostic dilemma for clinicians. CASE DESCRIPTION: A 64-year-old man sought treatment for a 4-month history of unresolving right-sided headache and jaw pain associated with syncope, all of which started with a toothache. Since the onset of pain, the patient had undergone multiple diagnostic tests with various specialists, with no pain relief. A detailed clinical and radiologic examination by an orofacial pain specialist revealed diffuse large B-cell lymphoma in the parapharynx. PRACTICAL IMPLICATIONS: A thorough knowledge of the head and neck anatomy helps in identifying the pathophysiology of complex orofacial pain manifestations, which assists in early diagnosis and treatment.

Emergency laparotomy for abdominal catastrophes secondary to lymphoma: A systematic review.

Intestinal lymphomas can rarely present as abdominal catastrophes with perforation or small bowel obstruction. There is little data regarding their optimal surgical management and associated outcomes. We aimed to systematically review relevant published literature to assess the presentation, diagnosis, optimal surgical approach and associated post-operative outcomes. A systematic on-line literature search of Embase and Medline identified 1485 articles of which 34 relevant studies were selected, including 7 retrospective studies, 1 case series and 26 case reports. Selected articles were assessed by two reviewers to extract data. 95 patients with abdominal catastrophes secondary to lymphoma (predominately Burkitt (28 %) and Diffuse Large B-cell lymphoma (29 %)) were identified with a median age of 52 years, 40 % were female. Of the small bowel resections 25% (n = 18) suffered post-operative complications with a 13.8 % (n = 10) 30-day mortality. Ileocolonic resections had a 27 % complication rate with 18 % mortality and primary repair had a 25 % complications rate and 25 % mortality. Median follow-up was 8 days (range 1-96). Notable points of differences in the presentations between these different lymphomas included the majority of Burkitt's lymphoma were younger, had a known diagnosis, were on chemotherapy and presented with perforation in contrast to those with B cell lymphoma who were predominately older, had new diagnoses and presented with a balanced proportion of obstruction and perforation. Abdominal catastrophes secondary to intestinal lymphomas most commonly present with perforation. Aggressive surgical management, including small bowel resection, may offer similar remission rates for lymphoma patients presenting with abdominal catastrophes as those without such emergency complications.