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This randomized study assessed if intravenous iron improves hemoglobin (Hb) response and permits decreased epoetin dose in anemic (Hb 9-11 g/dl), transfusion-independent patients with stainable iron in the bone marrow and lymphoproliferative malignancies not receiving chemotherapy. Patients (n=67) were randomized to subcutaneous epoetin beta 30 000 IU once weekly for 16 weeks with or without concomitant intravenous iron supplementation. There was a significantly (P<0.05) greater increase in mean Hb from week 8 onwards in the iron group and the percentage of patients with Hb increase >or=2 g/dl was significantly higher in the iron group (93%) than in the no-iron group (53%) (per-protocol population; P=0.001). Higher serum ferritin and transferrin saturation in the iron group indicated that iron availability accounted for the Hb response difference. The mean weekly patient epoetin dose was significantly lower after 13 weeks of therapy (P=0.029) and after 15 weeks approximately 10 000 IU (>25%) lower in the iron group, as was the total epoetin dose (P=0.051). In conclusion, the Hb increase and response rate were significantly greater with the addition of intravenous iron to epoetin treatment in iron-replete patients and a lower dose of epoetin was required.

Standard prophylaxis and treatment of malignancy-associated hyperuricemia in the USA has been allopurinol with vigorous hydration, urinary alkalinization and osmotic diuresis. Urate oxidase, the enzyme that converts uric acid to allantoin (a readily excreted metabolite that has 5- to 10-fold higher solubility than uric acid), is an alternative therapy; however, few published findings support this practice. Between February 1994 and December 1996, we administered non-recombinant urate oxidase (Uricozyme) to 126 children with newly diagnosed non-B cell acute lymphoblastic leukemia (ALL) during the first 5 days of chemotherapy with methotrexate, 6-mercaptopurine or both. Their blood levels of uric acid and other indicators of tumor lysis were measured at diagnosis and during treatment and then compared with findings in 129 similarly treated historical controls who had received allopurinol to control hyperuricemia. Clinical responses to urate oxidase were also determined in eight patients with newly diagnosed B cell ALL or advanced-stage non-Hodgkin lymphoma. Patients treated with urate oxidase had rapid and significantly greater decreases in their blood uric acid levels than did the historical controls (median maximal level during treatment, 2.3 vs 3.9 mg/dl, P < 0.001). They also had lower creatinine (0.6 vs 0.7 mg/dl, P = 0.01) and blood urea nitrogen (11 vs 24 mg/dl, P < 0.001) levels. Similar findings were made in the eight cases of B cell ALL or non-Hodgkin lymphoma. None of the patients required dialysis for acute renal failure. Six (4.5%) of the 134 children given urate oxidase had allergic reactions, manifested primarily by urticaria, bronchospasm and hypoxemia. Thus, non-recombinant urate oxidase is a more effective uricolytic agent than allopurinol but is associated with acute hypersensitivity reactions, even in patients without a history of allergy.

Patients with indolent non-Hodgkin lymphoma treated with bendamustine have an increased risk of common infections such as bacterial pneumonia and opportunistic infections such as Pneumocystis jirovecii pneumonia, cytomegalovirus, varicella zoster virus, and histoplasmosis, compared with patients receiving other chemotherapy regimens. Abstract Background Bendamustine is a potent chemotherapy agent increasingly used to treat indolent non-Hodgkin lymphoma (iNHL). While effective, it causes significant T-cell lymphopenia, which may increase risk of infection. We examined infectious complications associated with bendamustine-containing regimens among older patients with iNHL. Methods For this Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort study, we identified 9395 patients with iNHL (follicular, marginal zone, Waldenström macroglobulinemia) treated with chemotherapy from 2006 to 2013. Thirteen percent received bendamustine-containing regimens. We compared baseline characteristics and infection incidence rates between patients treated with and without bendamustine. We conducted multivariate Cox proportional hazards regression (adjusting for demographics, comorbidities, disease and treatment characteristics, risk factors for infection, and antimicrobial prophylaxis) to determine infectious risks associated with bendamustine. Results Bendamustine was associated with an increased risk of both common infections such as bacterial pneumonia (hazard ratio [HR], 1.50 [95% confidence interval {CI}, 1.21-4.85]) and opportunistic infections such as cytomegalovirus (HR, 3.98 [95% CI, 1.40-11.26]), varicella zoster virus (HR, 1.49 [95% CI, 1.18-1.89]), histoplasmosis (HR, 3.55 [95% CI, 1.10-11.42]), and Pneumocystis jirovecii pneumonia (when administered as third-line therapy: HR, 3.32 [95% CI, 1.00-11.11]). Risk of infections was more prominent in patients receiving bendamustine as part of later (third-line and above) regimens, and independently associated with well-established factors such as neutropenia and corticosteroid exposure. Conclusions Bendamustine is associated with an increased risk of common and opportunistic infections in patients with iNHL. Further prospective investigation into the potential role of antimicrobial prophylaxis is needed in these patients.

Abstract Primary central nervous system lymphomas (PCNSL) are aggressive non-Hodgkin lymphomas affecting the central nervous system (CNS). Although immunophenotyping studies suggested an uniform activated B-cell (ABC) origin, more recently a spectrum of ABC and germinal center B-cell (GC) cases has been proposed, with the molecular subtypes of PCNSL still being a matter of debate. With the emergence of novel therapies demonstrating different efficacy between the ABC and GC patient groups, precise assignment of molecular subtype is becoming indispensable. To determine the molecular subtype of 77 PCNSL and 17 secondary CNS lymphoma patients, we used the NanoString Lymphoma Subtyping Test (LST), a gene expression-based assay representing a more accurate technique of subtyping compared with standard immunohistochemical (IHC) algorithms. Mutational landscapes of 14 target genes were determined using ultra-deep next-generation sequencing. Using the LST-assay, a significantly lower proportion (80% vs 95%) of PCNSL cases displayed ABC phenotype compared with the IHC-based characterization. The most frequently mutated genes included MYD88, PIM1, and KMT2D. In summary, we successfully applied the LST-assay for molecular classification of PCNSL, reporting higher proportion of cases with GC phenotype compared with IHC analyses, leading to a more precise patient stratification potentially applicable in the diagnostic algorithm of PCNSL.

ObjectivesSurvivors 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.MethodsWe used a US-wide population-based cancer registry data to quantify the SPM risk and identify its incidence patterns among pediatric lymphoma patients.ResultsWe 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.ConclusionOverall, 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.

Background Primary gastrointestinal non-Hodgkin’s lymphoma (PGINHL) of small and large intestines is a group of heterogeneous, rare malignancies. Optimal treatment practices remain undefined. Methods A systematic review (2003–2015) was performed to assess tumor characteristics, treatment practices, and treatment outcomes of PGINHL of small and large intestines. Results Twenty-eight studies (1658 patients) were included; five focused on follicular lymphoma subtype. Of the non-follicular patients, 59.3 % presented with abdominal pain, 37.2 % were located in ileocecum, and 53.6 % were diffuse large B cell lymphoma subtype. The majority of patients (60.7 %) were treated with a combination of surgery and chemotherapy. Forty-three percent of studies concluded an overall survival benefit with surgery; none reported increased postoperative morbidity or mortality. Survival outcomes were not typically stratified by emergent versus elective surgery. Multivariate analysis within individual studies associated B cell lymphoma and ileocecum location with higher survival, while advanced stage and B symptoms were associated with poorer survival. Patients with asymptomatic follicular lymphoma had no progression with a watchful waiting approach. Conclusions The majority of patients with non-follicular small and large intestinal PGINHLs are treated with both chemotherapy and surgery. Although surgery appears to be an important part of the treatment algorithm, definitive statements regarding its survival benefit remain limited due to lack of patient stratification based on timing and indication for surgery.

Introduction Primary malignant lymphoma of the cervix is an extremely rare condition, accounting for only 0.008% of all cervical tumors and 2% of female extranodal lymphomas. The most common histological subtype is diffuse large B-cell lymphoma. This malignancy is often asymptomatic in its early stages, but advanced cases may include systemic symptoms, pelvic discomfort, and vaginal bleeding. Diagnosis is challenging due to its nonspecific clinical presentation and similarity to other gynecological conditions. Imaging and immunohistochemistry play essential roles in diagnosis and staging. Treatment typically involves chemotherapy, with the standard CHOP regimen for Non-Hodgkin’s lymphoma being the main treatment in most cases. To the best of our knowledge, this is the first case in the literature to describe acute kidney injury associated with the already rare entity of primary female genital tract lymphoma. Case presentation A 66-year-old multiparous woman presented with severe headache, nausea, vomiting, and dizziness lasting three days, alongside systemic symptoms such as weight loss, lethargy, and night sweats. Imaging indicated bilateral hydronephrosis, ascites, and an enlarged uterus with a suspected tumor. Biopsy confirmed diffuse large B-cell lymphoma with immunohistochemical positivity for CD20 and negative CD3. The patient was classified as stage IV according to the Ann Arbor system. Initial treatment included diuretics, hemodialysis, and chemotherapy with a dose-reduced CHOP regimen due to atrial fibrillation and reduced cardiac ejection fraction. Despite initial improvements, the patient developed tumor lysis syndrome and meningeal infiltration. Her condition deteriorated after the second chemotherapy cycle, culminating in neutropenic fever, massive hemorrhage, and ultimately death. Conclusion Our case highlights the diverse manifestations of the disease, including acute kidney injury secondary to bilateral hydronephrosis, a previously unreported complication. Early recognition is essential for optimal management. While chemotherapy remains the mainstay of treatment, the lack of standardized protocols underscores the need for further research. This case emphasizes the unpredictable nature of primary female genital tract lymphomas and their potential to cause systemic complications.

There are no definitive clinical practice guidelines regarding the necessity and dosage of trimethoprim–sulfamethoxazole (TMP/SMX) prophylaxis for Pneumocystis jirovecii pneumonia (PJP) in individuals undergoing rituximab therapy. This retrospective study evaluated the effectiveness and safety of various TMP–SMX prophylactic dosing regimens over a 1-year period in 690 patients with non-Hodgkin lymphoma treated with rituximab at a university hospital in Thailand from 2013 to 2022. Out of these patients, 622 (90.1%) received TMP/SMX, with a mean duration of prophylaxis of 265.7 days (SD 85.66). The overall incidence of PJP was 1% (7 patients), which was significantly higher in the non-prophylaxis group (5.8%, 4 patients) compared to the prophylaxis group (0.6%, 3 patients). No cases of PJP occurred among those receiving standard prophylaxis or a single-strength tablet every other day, three times a week. However, instances in the prophylaxis cohort were reported in patients who took two single-strength tablets twice daily, twice a week. Prophylaxis resulted in a significant reduction in the one-year incidence of PJP, with a hazard ratio of 0.105 (95% CI: 0.023–0.469). Mild adverse reactions were noted in 3.05% of patients, all of whom recovered. These findings suggest that TMP/SMX prophylaxis was associated with a lower incidence of PJP and was well tolerated. Future studies should explore optimal dosing strategies while considering patient selection bias and concurrent immunosuppressive therapy.

Older patients with cancer who may be more susceptible than younger patients to the myelosuppressive effects of chemotherapy undergo dose delays and reductions that can compromise treatment outcomes. Incidence of neutropenic complications and suboptimal chemotherapy delivery can be reduced with prophylactic colony-stimulating factors; however, their use in older patients with cancer has not been well studied. A randomized, multicenter, community-based trial was designed to compare prophylactic pegfilgrastim use (all cycles of chemotherapy) versus its more common reactive use (at clinicians' discretion) in patients aged 65 years or older with various cancers. Pegfilgrastim use in all cycles reduced the incidence of febrile neutropenia by about 60% and hospitalizations caused by neutropenia and febrile neutropenia by about 50% versus reactive pegfilgrastim use in later cycles. The study showed that older patients with cancer can be treated safely with optimal doses of chemotherapy with appropriate supportive care. Nurses, key collaborators in providing supportive care, can take an active role in identifying older patients who may benefit from pegfilgrastim in all cycles of chemotherapy.