Indolent Lymphoma Research Articles

Primary Cutaneous Multifocal Indolent CD8+ T-Cell Lymphoma: A Novel Primary Cutaneous CD8+ T-Cell Lymphoma

We report the case of a patient who was referred to our institution with a diagnosis of CD4+ small/medium-sized pleomorphic lymphoma. At the time, the patient showed a plethora of lesions mainly localizing to the legs; thus, we undertook studies to investigate the lineage and immunophenotype of the neoplastic clone. Immunohistochemistry (IHC) showed marked CD4 and CD8 positivity. Flow cytometry (FCM) showed two distinct T-cell populations, CD4+ and CD8+ (+/- PD1), with no CD4/CD8 co-expression and no loss of panT-cell markers in either T-cell subset. FCM, accompanied by cell-sorting (CS), permitted the physical separation of four populations, as follows: CD4+/PD1-, CD4+/PD1+, CD8+/PD1- and CD8+/PD1+. TCR gene rearrangement studies on each of the four populations (by next generation sequencing, NGS) showed that the neoplastic population was of T-cytotoxic cell lineage. IHC showed the CD8+ population to be TIA-1+, but perforin- and granzyme-negative. Moreover, histiocytic markers did not render the peculiar staining pattern, which is characteristic of acral CD8+ T-cell lymphoma (PCACD8). Compared to the entities described in the 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas, we found that the indolent lymphoma described herein differed from all of them. We submit that this case represents a hitherto-undescribed type of CTCL.

Multicolor flow cytometric assessment of Ki67 expression and its diagnostic value in mature B-cell neoplasms.

There is no unified standard data about the sensitivity and specificity regarding flow cytometry analysis of Ki67 expression during lymphoma diagnoses. This evaluated the efficacy of multicolor flow cytometry (MFC) in an estimate of the proliferative activity of B-cell non-Hodgkin lymphoma by comparing the expression of Ki67 using MFC and immunohistochemicals (IHC). A total of 559 patients with non-Hodgkin B-cell lymphoma were immunophenotyped using sensitive MFC, of which 517 were newly diagnosed and 42 were transformed lymphomas. Test samples include peripheral blood, bone marrow, various body fluids, and tissues. Through MFC multi-marker accurate gating, abnormal mature B lymphocytes with restricted expression of the light chain were screened. Ki67 was added to determine the proliferation index; the positive rate of Ki67 in tumor B cells was evaluated by cell grouping and internal control. For tissue specimens, MFC and IHC analyses were performed simultaneously to assess the Ki67 proliferation index. The positive rate of Ki67 by MFC was correlated with the subtype and aggressiveness of B-cell lymphoma. Ki67 could distinguish indolent lymphomas from aggressive subtypes with a cut-off value of 21.25%, and differentiate transformation from indolent lymphoma with a cut-off value of 7.65%. The expression of Ki67 by MFC (regardless of the type of samples)was highly agreement with the Ki67 proliferative index of tissue samples assessed by pathologic immunohistochemistry. MFC showed a fairly constant negative bias in evaluating tissue or bone marrow samples, compared with IHC. Ki67 is a valuable flow marker that can distinguish between indolent and aggressive types of lymphoma and assess whether indolent lymphomas are transformed. Using MFC to evaluate the positive rate of Ki67 is important in clinical settings. MFC has unique advantages in judging the aggressiveness of lymphoma in samples of bone marrow, peripheral blood, pleural and ascites, and cerebrospinal fluid. This is particularly important when tissue samples cannot be obtained, making it an important supplement for pathologic examination.

Management of Marginal Zone Lymphoma: A Canadian Perspective.

Marginal zone lymphomas (MZL) are a rare, heterogenous group of lymphomas, accounting for 5-17% of indolent non-Hodgkin lymphomas in the western world. They can be further divided into three subtypes: extranodal MZL, splenic MZL, and nodal MZL. These subtypes differ in clinical presentation and behavior, which influences how they are managed. There is currently no standard of care for the treatment of MZL, owing to the difficulty in conducting phase 3 randomized trials in MZL, and the fact that there are limited data on the efficacy of therapy in individual subtypes. Treatment practices are thus largely borrowed from other indolent lymphomas and are based on patient and disease characteristics, as well as access to therapy. This review summarizes the Canadian treatment landscape for MZL and how these therapies may be sequenced in practice.

Proteasome Inhibitors Interact Synergistically with BCL2, Histone Deacetylase, BET, and Jak Inhibitors against Cutaneous T-Cell Lymphoma Cells

Cutaneous T-cell lymphoma (CTCL) is often refractory to treatment at advanced stages with blood involvement ( Dummer et al., 2021 Dummer R. Vermeer M.H. Scarisbrick J.J. Kim Y.H. Stonesifer C. Tensen C.P. et al. Cutaneous T cell lymphoma. Nature Reviews Disease Primers. 2021; 7: 61 Crossref PubMed Scopus (22) Google Scholar ). We have previously revealed the synergistic cytotoxic effects of inhibiting BCL2, HDAC, BET, and/or JAK in patient-derived CTCL cells and CTCL cell lines, suggesting potential advantages of a spectrum of combination treatment strategies for this disease ( Cyrenne et al., 2017 Cyrenne B.M. Lewis J.M. Weed J.G. Carlson K.R. Mirza F.N. Foss F.M. et al. Synergy of BCL2 and histone deacetylase inhibition against leukemic cells from cutaneous T-cell lymphoma patients. Blood. 2017; 130: 2073-2083 Crossref PubMed Scopus (36) Google Scholar , Kim et al., 2018 Kim S.R. Lewis J.M. Cyrenne B.M. Monico P.F. Mirza F.N. Carlson K.R. et al. BET inhibition in advanced cutaneous T cell lymphoma is synergistically potentiated by BCL2 inhibition or HDAC inhibition. Oncotarget. 2018; 9: 29193-29207 Crossref PubMed Scopus (35) Google Scholar , Yumeen et al., 2020 Yumeen S. Mirza F.N. Lewis J.M. King A.L.O. Kim S.R. Carlson K.R. et al. JAK inhibition synergistically potentiates BCL2, BET, HDAC, and proteasome inhibition in advanced CTCL. Blood Adv. 2020; 4: 2213-2226 Crossref PubMed Scopus (19) Google Scholar ). Proteasome inhibitors target multiple pathways including protein degradation to cause cytotoxicity and have been utilized in other hematologic malignancies. They have demonstrated efficacy as a single agent in a small phase II trial of patients with relapsed or refractory CTCL ( Zinzani et al., 2007 Zinzani P.L. Musuraca G. Tani M. Stefoni V. Marchi E. Fina M. et al. Phase II Trial of Proteasome Inhibitor Bortezomib in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma. Journal of Clinical Oncology. 2007; 25: 4293-4297 Crossref PubMed Scopus (236) Google Scholar ), as well as in limited combinations during preclinical studies ( Yumeen et al., 2020 Yumeen S. Mirza F.N. Lewis J.M. King A.L.O. Kim S.R. Carlson K.R. et al. JAK inhibition synergistically potentiates BCL2, BET, HDAC, and proteasome inhibition in advanced CTCL. Blood Adv. 2020; 4: 2213-2226 Crossref PubMed Scopus (19) Google Scholar ) and early clinical trials ( Holkova et al., 2017 Holkova B. Yazbeck V. Kmieciak M. Bose P. Ma S. Kimball A. et al. A phase 1 study of bortezomib and romidepsin in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, indolent B-cell lymphoma, peripheral T-cell lymphoma, or cutaneous T-cell lymphoma. Leuk Lymphoma. 2017; 58: 1349-1357 Crossref PubMed Scopus (15) Google Scholar ). Herein, we share our expanded preclinical assessment of the synergistic activity of proteasome inhibitors when used with the BCL2 inhibitor venetoclax, HDAC inhibitor vorinostat, BET inhibitor mivebresib, or JAK inhibitor fedratinib. We reveal that the cytotoxic effects from combination treatment were greater than additive when assessed in patient-derived CTCL cells. Furthermore, we demonstrate an increase in apoptosis pathway activation with combination treatment and explore the gene expression changes underlying these synergistic effects.

Patients with indolent lymphomas are at high risk of infections: experience from a German outpatient clinic

BackgroundPatients with indolent B-cell non-Hodgkin lymphomas (B-NHLs) have an increased risk of infections which is caused by pathomechanisms of the diseases itself but also as a result of anti-tumor therapy. Especially the effects of anti-CD20 antibodies are well understood as these lead to decreased antibody production. Most studies regarding immunodeficiency in B-NHLs were conducted with multiple myeloma and chronic lymphocytic leukemia patients. As these studies not always represent the general population we collected and analyzed real world data from patients with indolent lymphomas and a control group (CG).ResultsPatients with B-NHLs undergoing therapy or who were regularly monitored in a watch and wait approach had, over the time of one year, an increased rate of infections compared to the CG of 145 healthy volunteers (mean: 11.66 vs. 7.13 infections per 1000 days). Consistent with this finding B-NHL patients received more antibiotic treatment (mean: 11.17 vs. 6.27 days) and were more often hospitalized than persons from the CG (mean: 5.19 vs. 0.99 days per 1000 days). Lymphoma patients without immunodeficiency had a lower infection rate than patients with non-symptomatic and symptomatic immunodeficiency (mean: 10.91 vs. 12.07 and 12.36 per 1000 days). The number of infections differed statistically significant for the subgroups and CG (7.13 per 1000 days). Patients with symptomatic immunodeficiency were mostly treated with regular immunoglobulin substitutions and infection rates were comparable to those of patients with asymptomatic immunodeficiency.ConclusionsOur data suggest the use of an approach with regular immune monitoring including the measurement of immunoglobulin levels and regular appointments for clinical assessment of all indolent lymphoma patients in order to identify patients with increased risk of infections. It also raises the question if patients with immunodeficiency should be treated more often with regular immunoglobulin substitution, but so far more studies are necessary to answer this question.

Safety and efficacy of dual PI3K-δ, γ inhibitor, duvelisib in patients with relapsed or refractory lymphoid neoplasms: A systematic review and meta-analysis of prospective clinical trials.

Duvelisib is the first FDA-approved oral dual inhibitor of phosphatidylinositol-3-kinase PI3K-delta (PI3K-δ) and PI3K-gamma (PI3K-γ). Although many clinical studies support the efficacy of duvelisib, the safety of duvelisib remains with great attention. This systematic review and meta-analysis aimed to evaluate the safety and efficacy of duvelisib in treating different relapsed or refractory (RR) lymphoid neoplasm types. We searched prospective clinical trials from PUBMED, EMBASE, Cochrane Library, and ClinicalTrials.gov. For efficacy analysis, Overall response rate (ORR), complete response rate (CR), partial response rate (PR), rate of stable disease (SDR), rate of progressive disease (PDR), median progression-free survival (mPFS), 12-/24-month PFS, and 12-month overall survival (OS) were assessed. For safety analysis, the incidences of any grade and grade ≥3 adverse events (AEs), serious AEs, and treatment-related discontinuation and death were evaluated. Subgroup analysis based on the disease type was performed. We included 11 studies and 683 patients, including 305 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 187 B-cell indolent non-Hodgkin lymphoma (iNHL), 39 B-cell aggressive non-Hodgkin lymphoma (aNHL), and 152 T-cell non-Hodgkin lymphoma (T-NHL) patients. The pooled ORR in CLL/SLL, iNHL, aNHL and T-NHL was 70%, 70%, 28% and 47%, respectively. Additionally, the pooled ORR in CLL/SLL patients with or without TP53 mutation/17p-deletion (62% vs. 74%, p=0.45) and in follicular lymphoma (FL) or other iNHL (69% vs. 57%, p=0.38) had no significant differences. Mantle cell lymphoma (MCL) patients had higher pooled ORR than other aNHL (68% vs. 17%, p=0.04). Angioimmunoblastic TCL (AITL) patients had higher pooled ORR than other PTCL patients (67% vs. 42%, p=0.01). The pooled incidence of any grade, grade ≥3, serious AEs, treatment-related discontinuation and death was 99%, 79%, 63%, 33% and 3%, respectively. The most frequent any-grade AEs were diarrhea (47%), ALT/AST increase (39%), and neutropenia (38%). The most frequent grade ≥3 AEs were neutropenia (25%), ALT/AST increased (16%), diarrhea (12%), and anemia (12%). Generally, duvelisib could offer favorable efficacy in patients with RR CLL/SLL, iNHL, MCL, and AITL. Risk and severity in duvelisib treatment may be mitigated through proper identification and management.

Whole-body diffusion-weighted imaging with background body signal suppression and quantitative apparent diffusion coefficient in the detection, staging, and grading of non-Hodgkin lymphoma.

Assess reproducibility of detection, staging, and grading of non-Hodgkin lymphoma (NHL) using whole-body diffusion-weighted imaging with background body signal suppression (WB-DWIBS). Thirty NHL patients underwent WB-DWIBS, divided into 2 groups according to staging and grading. Image analysis and apparent diffusion coefficient (ADC) measurement of the largest lymph node in each group were performed by 2 observers. Inter-observer agreement was performed. Overall inter-observer agreement for detection of NHL was excellent (k = 0.843; 92.05%) with excellent inter-observer agreement of nodal disease (cervical, thoracic and abdominal) (k = 0.783, 0.769, and 0.856; 96.67%, 90.0%, and 93.3% respectively), extra-nodal disease (k = 1; 100%), and splenic involvement (k = 0.67; 83.3%). The overall inter-observer agreement of DWIBS in staging of NHL was excellent (k = 0.90; 94.9%) with excellent inter-observer agreement for stage I (k = 0.93; 96.4%), stage II (k = 0.90; 94.8%), stage III (k = 0.89; 94.6%), and stage IV (k = 0.88; 94.0%). There was significant difference between ADC in stage I, II (0.77 ± 0.13, 0.85 ± 0.09 × 10-3 mm2/s), and stage III, IV (0.63 ± 0.08, 0.64 ± 0.11 × 10-3 mm2/s, p < 0.002, < 0.001). Interclass correlation showed almost perfect agreement for ADC measurement in staging and grading groups (r = 0.96 and r = 0.85, respectively, p < 0.001). There was significant difference between ADC in aggressive lymphoma (0.65 ± 0.1, 0.67 ± 0.13 × 10-3 mm2/s) and indolent lymphoma (0.76 ± 0.14, 0.84 ± 0.09 × 10-3 mm2/s, p < 0.028, < 0.001). DWIBS is reproducible for detection and staging of nodal and extra-nodal involvement in patients with NHL. ADC can quantitatively participate in the staging and grading of NHL.

Survival trends in young patients with Waldenström macroglobulinemia: Over five decades of experience.

Waldenström macroglobulinemia (WM) is a rare, indolent lymphoma, that predominately affects the elderly. We report the outcomes of young WM patients, evaluated over five decades, compared to their older counterparts, matched for the time of diagnosis. Between January 1, 1960 and October 31, 2013, 140 (11.8%) WM patients were ≤50 years of age at diagnosis in our database, and their estimated 10-year overall survival (OS) was 74%, with death attributable to WM in a higher proportion of patients compared to their older (≥65 years) counterparts (91% vs. 58%, p= .0001). Young patients were grouped into three cohorts based on the timing of the initiation of therapy: Group 1 (1960-1977, n= 12), Group 2 (1978-1995, n= 48), and Group 3 (1996-2013, n= 74). Among young patients, there was no disease-specific survival (DSS) difference across the three periods, [median DSS at 13 years (95% CI 5-23), 16 years (95% CI 14-22), and 15 years (95% CI 10-NR; p= .41), respectively]. However, DSS for the older cohort incrementally improved (Group 1, median 5.2 years, Group 2: 9.6 years, Group 3: 12 years; p= .05) over these periods. The estimated average years-of-life lost for the young cohort was 11.2 years from diagnosis, based on the expected survival for a normal age- and sex-matched population. Despite a protracted disease course, nearly all young patients succumb to their disease. In contrast to the improved survival of the elderly patient population, the evolving treatment strategies in WM have not impacted the outcome of young patients; however, the impact of Bruton tyrosine kinase inhibitors on this unique patient population remains to be determined.

Lymphoplasmacytic lymphoma with anemia and lymphadenopathy: a case report

Background: An uncommon, indolent mature B-cell lymphoma called lymphoplasmacytic lymphoma (LPL) secretes monoclonal immunoglobulin M (IgM) protein in 90%-95% of cases. Non-IgM monoclonal proteins are secreted by a very tiny percentage of LPL. Patient Concerns: 67-year-old Chadi female, who was admitted to our hospital with a history of altered level of consciousness, decreased oral intake for 2 days, headache, fatigue, and palpitation for 3 years. Case Presentation: According to the histology and immunohistochemistry of the lymph node excisional biopsy, the patient was diagnosed with malignant lymphoma consistent with LPL or Waldenstrom macroglobulinemia. Due to the high expense, the patient refused target therapy and chemotherapy in favor of merely receiving occasional transfusions as supportive care. The patient is pursuing supportive care and elective hospitalizations. Conclusion: LPL is an extremely uncommon, sluggish illness. To further understand the clinical consequences, more research involving more patients is necessary.

Follicular lymphoma microenvironment: insights provided by single-cell analysis.

Follicular lymphoma (FL) is the most frequent indolent lymphoma and is characterized by the abundant infiltration of tumor microenvironment (TME) cells. The activity of TME cells reportedly plays an important role in the biology of FL. TME cells that reside within neoplastic follicles, such as T-follicular helper cells and follicular dendritic cells, have been shown to aid in FL development and progression through interactions with malignant B cells, whereas regulatory T cells have unexpectedly shown an apparently favorable prognostic impact in FL. Unfortunately, the understanding of the FL TME, particularly regarding minor cell subsets, has been hampered by unknown cell heterogeneity. As with other solid and hematologic cancers, novel single-cell analysis technologies have recently been applied to FL research and have uncovered previously unrecognized heterogeneities, not only in malignant B cells but also in TME cells. These reports have greatly increased the resolution of our understanding of the FL TME and, at the same time, raised questions about newly identified TME cells. This review provides an overview of the unique aspects of FL TME cells with a clinical viewpoint and highlights recent discoveries from single-cell analysis, while also suggesting potential future directions.

Advances in the multi-omics landscape of follicular lymphoma

Follicular lymphoma (FL) is the most common indolent lymphoma originating from germinal center B cells. FL represents a clinically and biologically heterogeneous disease. Most patients have favorable outcomes, but a subset of patients experiences early progression or transformation and has a poor prognosis. Abnormalities in FL cells and tumor microenvironment have been revealed using multi-omics techniques, including genomic, epigenomic, transcriptomic and proteomic analysis. Recurrent somatic gene aberrations mainly involve epigenetic modifiers, transcription factors, oncogenic pathways and microenvironment modulators. Single-cell transcriptomic analysis show marked inter- and intra-patient FL subclone heterogeneity. In addition, a comprehensive profile of microenvironmental components is provided, unveiling the crosstalk between tumor and microenvironment that induce FL progression and facilitate immune escape. Together, these studies provide insights into the mechanisms and biomarkers of high-risk FL populations, as well as the potential targeted and immunotherapy options. Future research should focus on integrating multi-omics aberrations to optimize therapeutic strategies in FL.

Composite Lymphoma Comprising Follicular Lymphoma with In-situ Mantle Cell Neoplasia: A Case Report and Review of the Literature

A 55-year-old gentleman presented to our hospital with a single inguinal adenopathy, and no other clinical symptoms or signs. An excisional lymph node biopsy was performed. Pathologic evaluation demonstrated follicular center site which stained positive for CD20, CD10, Bcl-2, Bcl-6, and mantle zone cells which demonstrated Cyclin D1 (CCND1) positivity, partial SOX11 positivity and no expression of CD5, suggesting the diagnosis of composite lymphoma comprising follicular lymphoma (FL) with in situ mantle cell neoplasia (ISMCN), the latter previously referred as in situ mantle cell lymphoma (MCLIS). FL is known as indolent non-Hodgkin lymphoma; however, the clinical significance of a coexisting ISMCN continues to be elusive, and optimal management of these patients remains largely unknown. This paper reports a new case of this extremely uncommon condition and also discusses reviews of the literature including advances in molecular pathogenesis and lymphoma genomics with the aim to offer novel insights into this rare hematological malignancy.

Bendamustine and rituximab is well-tolerated and efficient in the treatment of indolent non-Hodgkin's lymphoma and mantle cell lymphoma in elderly: A single center observational study.

Bendamustine and rituximab (BR) is a preferred first-line therapy for indolent non-Hodgkin's lymphoma (iNHL) and mantle cell lymphoma (MCL); however, few reports on BR performance in elderly patients are available to date. We compared safety and efficacy of BR in patients ≥70 years (elderly) vs <70 years (younger) treated at our institution. Among 201 patients, 113 were elderly (median age: 77 years), including 38 patients ≥80 years, and 88 were younger (median age: 62 years). Elderly patients had more bone marrow involvement by lymphoma, anemia, ECOG status 3 and high-risk disease follicular lymphoma (P < .05 for all). Fifty-four percent of elderly received full dose of bendamustine vs 79.5% of younger patients. More elderly patients (54%) vs younger (43.2%) experienced treatment delay. Less elderly proceeded to rituximab maintenance. Overall, the number of adverse events per patient and transformed B-Cell lymphoma/secondary malignancies were similar between groups. Elderly patients had less febrile neutropenia, rituximab-associated infusion reactions, but more herpes zoster reactivation. There were more deaths in the elderly (37.2%) vs younger (10.2%) groups (P < .001), mainly due to non-lymphoma-related causes. With median follow-up of 42 months [4.0-97.0] disease-free survival for the elderly was similar to younger patients. There was no difference between patients <80 and ≥80 years (P=.274). In conclusion, the real-world elderly patients have more advanced disease and higher ECOG status. BR is well-tolerated; elderly patients had lower incidence of febrile neutropenia. Dose reduction and treatment delays are common, but BR efficacy was not affected even in very old patients (≥80 years).

Bendamustine in the treatment of patients with indolent non-Hodgkin lymphoma refractory or relapse to rituximab treatment: An open-label, single-agent, multicenter study in China.

The optimal treatment strategy for refractory or relapse (R/R) indolent non-Hodgkin lymphoma (iNHL) has not been fully identified. This study aims to investigate the efficacy and tolerance of bendamustine hydrochloride developed in native Chinese corporation in the treatment of patients with R/R iNHL. A total of 101 patients from 19 centers were enrolled in this study from July 2016 to February 2019. Bendamustine hydrochloride (120mg/m2 ) was given on days 1 and 2 of each 21-day treatment cycle for six planned cycles or up to eight cycles if tolerated. Parameters of efficacy and safety were analyzed. The median age of the patients was 53.44 (range, 24.4-74.6) years old. A total of 56 (55.44%) patients completed at least six treatment cycles, and the relative dose intensity was 93.78%. The overall response rate was 72.28%, and the median duration of response was 15.84months (95% confidence interval [CI], 13.77-27.48months). Median progression-free survival was 16.52months (95% CI, 14.72-23.41months), and the median overall survival was not reached. Grade 3 or 4 hematologic toxicities included neutropenia (77.22%), thrombocytopenia (29.70%), and anemia (15.84%). The most frequent nonhematologic adverse events (any grade) included nausea, vomiting, fatigue, fever, decreased appetite, and weight loss. Seven patients died during the trial, and four cases may be related to the investigational drug. This study reveals that bendamustine hydrochloride is a feasible treatment option for the indolent B-cell non-Hodgkin lymphoma patient who has not remitted or relapsed after treatment with rituximab. All adverse events were predictable and manageable.

Clinical features and prognosis of eight patients with splenic diffuse red pulp small B-cell lymphoma

Objective: To investigate the clinical characteristics, response, and prognosis of splenic diffuse red pulp small B-cell lymphoma (SDRPL) . Methods: Eight cases of SDRPL were diagnosed and treated at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, between May 2017 and April 2022. Data on the clinical features, laboratory results, bone marrow and spleen biopsy results, response, and prognosis were collected and analyzed. Results: The median age at diagnosis was 54 (42-69) years. Splenomegaly and lymphocytosis were present in all cases, and PET/CT revealed normal to slightly elevated splenic FDG uptake. All cases were in stage Ⅳ, with spleen, peripheral blood, and bone marrow but no proximal lymph nodes involved. The cytoplasm of neoplastic villous cells was abundant, and splenic pathology showed that small homogenous lymphocytes permeated the splenic sinus and splenic cord, and the white pulp atrophied. Immunohistochemistry was not typical, and B-cell markers including CD19, CD20 and CD79α were positive. After a median follow up of 35.5 (4-60) months, 7 cases were alive after splenectomy with or without chemoimmunotherapy. The patient with CCND3 P284A and MYC S146L mutation developed to B-cell prolymphocytic leukemia (B-PLL) 1 month after splenectomy and died at 16 months of follow-up. Conclusion: A rare indolent B-cell lymphoma that primarily affects the elderly, SDRPL. Most patients achieved long-term survival, but the prognosis of patients who progress to B-PLL was poor.

Lymphoplasmacytic Lymphoma with Paraprotein IgG

Lymphoplasmacytic lymphoma (LPL) is a rare indolent mature B-cell lymphoma. LPL secreting immunoglobulins other than IgM are rare. There are very few case series on non-IgM LPL, and little is known about the clinical features and outcomes of patients with this disease. We report the case of a 65-year-old-male who was referred to our hospital for further investigations of persistent chronic anaemia and was diagnosed with IgG-LPL based on the presence of M protein from serum electrophoresis. Bone marrow morphology exhibit a spectrum of B-cell differentiation ranging from small mature lymphocytes to plasma cells. The patient underwent treatment with a combination of bortezomib, dexamethasone and rituximab and showed positive response. LPL with paraprotein IgG is a rare indolent disease and has a heterogeneous clinicopathological presentation with limited literature reviews. Our case report and literature review provide insights and knowledge in the description of the clinicopathological features of IgG LPL.

Indolent extranodal B-NHL CD20 positive MALT lymphoma in a patient with primary Sjögren’s syndrome with a good response to rituximab treatment

Indolent extranodal B-NHL CD20 positive MALT lymphoma in a patient with primary Sjögren’s syndrome with a good response to rituximab treatment

High local control and low ocular toxicity using ultra-low-dose "boom-boom" radiotherapy for indolent orbital lymphoma.

The first line definitive treatment for early-stage indolent B-cell lymphoma is radiation therapy (RT). Due to the sensitivity of orbital structures to radiation, ultra-low-dose RT (4 Gy in 2 fractions, "boom-boom") has and been utilized as an attractive option for orbital lymphoma. In this retrospective study, we evaluated the outcome and toxicity of "boom-boom" RT for indolent orbital lymphoma with an emphasis on ophthalmologic toxicity. This is a retrospective case series with 17 patients with orbital lymphoma who received boom-boom RT at a single tertiary referral center between January 2017 and June 2022. Medical records, imaging and radiation treatment plans were reviewed. Endpoints included response rate, progression, and ocular toxicity per oncologist and ophthalmology reports. A total of 17 patients (12 female and 5 male) with 19 indolent orbital lymphomas were included. Median follow-up was 39 months. Complete, partial, and stable response was achieved in 65%, 24%, and 12% of patients, respectively. Only 1 patient developed local recurrent 47 month after radiation treatment, and was successfully salvaged with standard dose radiation (24 Gy). Five-year distant progression rate is 18%. Oncologist-reported Common Terminology Criteria for Adverse Events (CTCAE) toxicity rates were 6% grade 1 and 0% grade 2+. Ophthalmologist reported 33.3% new post-RT toxicities including dry eye, cataract, and chorioretinal atrophy. There is no significant vision acuity change after RT. "Boom-Boom" RT (4 Gy in 2 fractions) provides excellent control for indolent orbital lymphoma. While minimal toxicity was documented by radiation oncologists, higher rates were noted by ophthalmologists, highlighting the radiosensitivity of orbital structures and potentially underreported ocular toxicity in "boom-boom" and standard regimens. Further prospective randomized studies are needed to better define the outcome and toxicity of ultra-low-dose (4 Gy) RT for ocular lymphoma.

Anti-spike antibody response to the COVID vaccine in lymphoma patients.

Patients with hematologic malignancies have poor outcomes from COVID infection and are less likely to mount an antibody response after COVID infection. This is a retrospective study of adult lymphoma patients who received the COVID vaccine between 12/1/2020 and 11/30/2021. The primary endpoint was a positive anti-COVID spike protein antibody level following the primary COVID vaccination series. The primary vaccination series was defined as 2 doses of the COVID mRNA vaccines or 1 dose of the COVID adenovirus vaccine. Subgroups were compared using Fisher's exact test, and unadjusted and adjusted logistic regression models were used for univariate and multivariate analyses. A total of 243 patients were included in this study; 72 patients (30%) with indolent lymphomas; 56 patients (23%) with Burkitt's, diffuse large B-cell lymphoma (DLBCL), and primary mediastinal B-cell lymphoma (PMBL) combined; 55 patients (22%) with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL); 44 patients (18%) with Hodgkin and T-cell lymphomas (HL/TCL) combined; 12 patients (5%) with mantle cell lymphoma; and 4 patients (2%) with other lymphoma types. One-hundred fifty-eight patients (65%) developed anti-COVID spike protein antibodies after completing the primary COVID vaccination series. Thirty-eight of 46 (83%) patients who received an additional primary shot and had resultant levels produced anti-COVID spike protein antibodies. When compared to other lymphoma types, patients with CLL/SLL had a numerically lower seroconversion rate of 51% following the primary vaccination series whereas patients with HL/TCL appeared to have a robust antibody response with a seropositivity rate of 77% (p = 0.04). Lymphoma patients are capable of mounting a humoral response to the COVID vaccines. Further studies are required to confirm our findings, including whether T-cell immunity would be of clinical relevance in this patient population.

Clinical Characteristics and Treatment Outcomes of Patients with Primary Ocular Adnexal Lymphoma at Siriraj Hospital

Objective: Malignant lymphoma represents the most common primary orbital malignant neoplasm.&#x0D; Materials and Methods: We retrospectively reviewed data and analyzed clinical characteristics and treatment outcomes of patients with primary ocular adnexal lymphoma at Siriraj Hospital, a tertiary health-care and teaching center in Bangkok, Thailand between January 2004 and June 2017.&#x0D; Results: From the total of 94 patients with primary ocular adnexal lymphoma, 77 cases (81.9%) were indolent, of which extranodal marginal zone lymphoma (EMZL) was the most common (76.6%). Aggressive subtype accounted for 17 cases (18.1%), consisting of diffuse large B-cell lymphoma (9.6%), mantle cell lymphoma (4.3%), and extranodal NK/T cell lymphoma (3.2%). Plasmacytic differentiation was found in half of EMZL and 4 cases of EMZL had association with IgG4-related disease. Most of the patients presented with proptosis (54.3%), followed by a palpable mass (42.6%). Most patients had Ann Arbor stage I (66.3%) with zero ECOG performance status (91.1%). Chemotherapy was the main treatment for both indolent and aggressive lymphomas. The overall response rate and complete response rate were 88.6% and 68.7%, respectively. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 60.1% and 84.2%, respectively. The indolent group had better overall (92.4% vs 69.2%) (P=0.01) and complete response rates (73.1% vs 50%) (P=0.01) than the aggressive group.&#x0D; Conclusion: Histopathological subtypes and clinical stages of lymphoma are the best indicators of prognosis and treatment outcomes. Chemotherapy was an effective treatment modality for both indolent and aggressive lymphoma subtypes with better treatment outcomes in the indolent group.