Impaired Humoral Immunity to SARS-CoV-2 Vaccination in Non-Hodgkin Lymphoma and CLL Patients.

Patients with hematologic malignancies are a high priority for SARS-CoV-2 vaccination, yet the benefit they will derive is uncertain. We investigated the humoral response to vaccination in 53 non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), or CLL patients. Peripheral blood was obtained 2 weeks after first vaccination and 6 weeks after second vaccination for antibody profiling using the multiplex bead-binding assay. Serum IgG, IgA, and IgM antibody levels to the spike specific receptor binding domain (RBD) were evaluated as a measure of response. Subsequently, antibody-positive serum were assayed for neutralization capacity against authentic SARS-CoV-2. Histology was 68% lymphoma and 32% CLL; groups were: patients receiving anti-CD20-based therapy (45%), monitored with disease (28%), receiving BTK inhibitors (19%), or chemotherapy (all HL) (8%). SARS-CoV-2 specific RBD IgG antibody response was decreased across all NHL and CLL groups: 25%, 73%, and 40%, respectively. Antibody IgG titers were significantly reduced (p < 0.001) for CD20 treated and targeted therapy patients, and (p = 0.003) for monitored patients. In 94% of patients evaluated after first and second vaccination, antibody titers did not significantly boost after second vaccination. Only 13% of CD20 treated and 13% of monitored patients generated neutralizing antibodies to SARS-CoV-2 with ICD50s 135 to 1767, and 445 and > 10240. This data has profound implications given the current guidance relaxing masking restrictions and for timing of vaccinations. Unless immunity is confirmed with laboratory testing, these patients should continue to mask, socially distance, and to avoid close contact with non-vaccinated individuals. STATEMENT OF TRANSLATIONAL RELEVANCE: Non Hodgkin lymphoma (NHL) and Chronic Lymphocytic leukemia (CLL) patients who are treated with anti-CD20 antibody therapy, BTK inhibitor therapy, or who are monitored with active disease, have decreased antibody response to SARS-CoV-2 vaccination and decreased antibody titers compared to healthy controls. Antibody titers do not boost following second vaccination, and very few patients generate neutralizing antibodies against SARS-CoV-2. This data is of particular importance, given the recent guidance from the CDC that vaccinated patients no longer need to be masked indoors as well as outdoors. Patients with NHL or CLL who fall into these categories should not consider their immunity from vaccination to be assured. If infected with SARS-CoV-2, they should be a high priority for monoclonal antibody directed therapy. Unless immune response to vaccination is confirmed with laboratory testing, they should continue to mask, socially distance, and to avoid close contact with non-vaccinated individuals.

Microbial dysbiosis is associated with aggressive histology and adverse clinical outcome in B-cell non-Hodgkin lymphoma.

B-cell non-Hodgkin lymphoma cell survival depends on poorly understood immune evasion mechanisms. In melanoma, the composition of the gut microbiota (GMB) is associated with immune system regulation and response to immunotherapy. We investigated the association of GMB composition and diversity with lymphoma biology and treatment outcome. Patients with diffuse large B-cell lymphoma (DLBCL), marginal zone (MZL), and follicular lymphoma (FL) were recruited at Mayo Clinic, Minnesota, and Perlmutter Cancer Center, NYU Langone Health. The pretreatment GMB was analyzed using 16S ribosomal RNA gene sequencing. We examined GMB compositions in 3 contexts: lymphoma patients (51) compared with healthy controls (58), aggressive (DLBCL) (8) compared with indolent (FL, MZL) (18), and the association of GMB with immunochemotherapy treatment outcomes (8 responders, 6 nonresponders). Respectively, we found that the pretreatment GMB in lymphoma patients had a distinct composition compared with healthy controls (P < .001); GMB compositions in DLBCL patients were significantly different than indolent patients (P = .01) with a trend toward reduced microbial diversity in DLBCL patients (P = .08); and pretreatment GMB diversity and composition were significant predictors of treatment responses (P = .01). The impact of these pilot results is limited by our small sample size, and should be considered a proof of principle. If validated, our results could lead toward improved treatment outcomes by improving medication stewardship and informing which GMB-targeted therapies should be tested to improve patient outcomes.

Non-Hodgkin Lymphoma with Synovial Involvement of the Knee.

Musculoskeletal involvement occurs in approximately 25% of patients diagnosed with non-Hodgkin lymphoma (NHL). Skeletal involvement is typically secondary, with primary lymphoma of the bone being much rarer. We describe a case in which a 52-year-old man initially presented features suggestive of Lyme arthritis in his left knee. A synovial biopsy performed as part of a synovectomy procedure revealed a proliferative synovium with dense lymphoplasmacytic B cell infiltrate, suggestive of NHL. An inguinal lymph node biopsy was also performed but did not produce results pathologically similar to those of the left knee synovial biopsy.

A Rare Case of Composite Dural Extranodal Marginal Zone Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

BACKGROUND: Primary extranodal marginal zone lymphoma (MZL) of the dura is a rare neoplastic entity in the central nervous system (CNS). METHODS: We used literature searches to identify previously reported cases of primary dural MZL. We also reviewed clinical, pathologic, and radiographic data of an adult patient with concurrent dural MZL and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). RESULTS: We identified 104 cases of dural MZL in the literature. None of them presented concurrently with another type of non-Hodgkin lymphoma. This is the first report of composite lymphoma consisting of dural MZL and CLL/SLL in the bone marrow and lymph nodes. CONCLUSION: Primary dural MZL is a rare, indolent low-grade CNS lymphoma, with a relatively good prognosis. Its treatment is multidisciplinary and often requires surgical intervention due to brain compression, along with low to moderate doses of radiotherapy and/or systemic chemotherapy.

Rapid and robust reversion to essential thrombocythemia on treatment with Decitabine in a case of hydroxyurea-induced t-MDS/AML.

Rapid remission of MDS/AML may be induced with Decitabine; however, significant megakaryocyte expansion and subsequent thrombocytosis may occur. Decitabine-mediated reversion of the MDS to benign ET via hypomethylation of JAK/STAT pathway repressors is one potential mechanism to explain this observed phenomenon.

B-cell lymphoma of the vagina occurring after treatment for classic Hodgkin lymphoma: a case report and literature review.

Malignant lymphomas of the female genital tract are very uncommon, and the development of a diffuse large B-cell lymphoma involving the vagina following treatment for classic Hodgkin lymphoma is extremely rare. Clinically and morphologically, this entity represents a challenge. We herein report such a case with liquid-based Pap test and tissue biopsy findings.

Postchemotherapy histiocyte-rich pseudotumor involving the spleen.

We report 2 cases of splenic postchemotherapy histiocyte-rich pseudotumor. Each patient had a history of diffuse large B-cell lymphoma, treated with multiagent chemotherapy. Computed tomography scans performed on both patients showed splenic masses. A positron emission tomography scan performed on 1 patient showed increased metabolic activity. The preoperative diagnosis in both patients was recurrent lymphoma, prompting splenectomy. The splenectomy specimens showed multiple, tan-white, firm nodules, up to 3.5 cm in diameter, that were histologically composed of central necrotic B cells (CD20+/CD3-), consistent with necrotic lymphoma, surrounded by numerous lipid-laden (xanthomatous) histiocytes. Clinical staging studies at the time of splenectomy showed no other sites of disease. We conclude that these histologic and immunophenotypic findings represent chemotherapy-induced tumor necrosis with a florid histiocytic reaction mimicking residual viable lymphoma. Others have used descriptive terminology or the term xanthomatous pseudotumor for these lesions that have been only rarely reported in the spleen previously.