Clinical Features and Therapeutic Outcomes Comparing Primary Mediastinal Large B-cell Lymphoma to Mediastinal Hodgkin Disease.

Currently, there is limited data available comparing Primary Mediastinal Large B-cell Lymphoma (PMBL) and mediastinal Hodgkin disease, nodular sclerosis type (HDNS). This is a retrospective cohort study that compares the clinical features, histology through immunohistochemistry (IHC) and treatment outcomes of 19 cases of PMBL and 39 cases of HDNS diagnosed over 13 years at a single institution in San Juan, PR. Superior Vena Cava syndrome (SVCS) and elevated Lactate Dehydrogenase (LDH) levels were more frequently seen in the PMBL cohort. At the median follow-up visit, of 74 months, no significant difference was seen in overall survival or progression free survival between PMBL and HDNS. Almost all of the relapses in the PMBL group occurred within 12 months of diagnosis. Our data suggests that PMBL and HDNS differ in their clinical presentation and have a favorable prognosis.

An Unexpected Presentation of a Maxillary Non-Hodgkin Lymphoma in an Elderly Hispanic Patient.

Extranodal NK/T-cell lymphoma (ENKTL), nasal type and aggressive NK cell leukemia are rare in Western World been less than 1% in USA to 8% in Asia among Non-Hodgkin's lymphomas. It is aggressive, with poor outcome and optimal treatment is unclear. A combination therapy that includes Peg-Asparaginase (SMILE) has been employed in young patients. An 85-year-old Puerto Rican male presented with anorexia, epistaxis, vertigo and involuntary facial movements. He was treated with injectable Onabotulinum toxin A due to suspicion of a hemifacial spasm. However, a CT scan demonstrated a left maxillary sinus lesion extending into the left middle turbinate with biopsy consistent with ENKTL. We adjusted therapy to patient's age and performance receiving Gemcitabine-Oxaliplatin (Gemox) with radiation obtaining a complete response with persistent negative Epstein Barr DNA titers. ENKTL is a rare disease initially misdiagnosed in our elderly patient, who demonstrated adequate response with a modified therapeutic regime.

Single-Arm, Open-Label Phase 2 Trial of Preemptive Methylprednisolone to Avert Progression to Respiratory Failure in High-Risk Patients with COVID-19.

Introduction: Covid-19 is a triphasic disorder first typified by a viral phase that lasts from the first onset of symptoms until seven days later. This is followed by a second and third phase, initially characterized by the appearance of lung infiltrates, followed in 20% by respiratory failure. The second phase is usually heralded by an elevation of serologic inflammatory markers including CRP, ferritin, IL-6, LDH as well as D-dimers. Approximately 20% proceed to the second phase and are usually then treated with dexamethasone, provided they are oxygen-dependent since these are the only cases that benefit from dexamethasone. If we had objective criteria to predict this 20% that develop severe illness, they could preemptively be treated with steroids. In this exploratory study we investigated the early use of preemptive steroids in the setting of early disease, in high-risk non-oxygen dependent cases. Methods: Eligible patients were those 21 years or older with a diagnosis of Covid-19 and oxygen saturation ≥91%. For patients to be classified as high-risk, they had to exhibit two or more of the following abnormalities 7-10 days after first symptom: IL-6 ≥ 10 pg/ml, ferritin > 500 ng/ml, D-dimer > 1 mg/L (1,000 ng/ml), CRP > 10 mg/dL (100 mg/L), LDH above normal range lymphopenia (absolute lymphocyte count <1,000 /µL), oxygen saturation between 91-94%, or CT chest with evidence of ground glass infiltrates. Primary endpoint was progression to respiratory failure. CALL score method was used to predict the expected number of cases of respiratory failure. High risk patients received methylprednisolone (MPS) 80 mg IV daily x 5 days starting no earlier than seven days from first onset of symptoms. The primary endpoint was progression to hypoxemic respiratory failure defined as PaO2 <60 mm Hg or oxygen saturation ≤90%. Secondary endpoints included survival at 28 days from registration, admission to intensive care and live discharge from the hospital. Change in levels of inflammatory markers and length of hospitalization were also assessed. Results: In 76 patients, the expected number with respiratory failure was 30 (39.5%), yet only 4 (5.3%) developed that complication (p=.00001). Survival at 28 days was 98.6%.Improvement in inflammatory markers correlated with favorable outcome. Conclusions: Our results are encouraging and suggest that this approach is both effective and safe.

Home-based management of COVID-19 by identification of low-risk features.

BACKGROUND: Covid-19 is a triphasic disorder characterized by a viral phase lasting 7-10 days from first onset of symptoms. In approximately 20% it is followed by a second stage heralded by elevation of pro-inflammatory markers such as ferritin, IL-6, CRP, LDH and D-dimers. We hypothesized that those with few abnormalities would have a low risk for progression to respiratory insufficiency and could be monitored at home without treatment. METHODS: Inclusion criteria included age >21, O2 saturation >90%. To be observed without treatment patients could not have >1 of the following: CRP > 10 mg/dL, high LDH, ferritin > 500 ng/ml, D-dimer > 1 mg/L, IL-6 > 10 pg/ml, absolute lymphocyte count <1,000, O2 sat <94%, or CT chest evidence of pneumonia. Primary endpoint: progression to respiratory failure. Secondary endpoint: 28-day survival. RESULTS: Of 208 entered, 132 were monitored without therapy. None progressed to respiratory failure or died. CONCLUSIONS: We have shown that our approach can identify cases who can safely be observed without treatment, thus avoiding expensive, potentially toxic therapies, and circumventing unnecessary, costly hospitalizations. These results support our hypothesis that after applying our criteria, 64% of Covid-19 cases can be monitored as outpatients without therapy.

Prevalence of Complementary/Alternative Medicine use in Cancer Patients in a Tertiary Hospital in Puerto Rico.

OBJECTIVE: We conducted a study in a tertiary hospital to investigate complementary and alternative medicine (CAM) prevalence in a Puerto Rican population. The study also evaluated demographic and clinical factors in order to correlate them with CAM use. METHODS: Spanish speaking residents with a known diagnosis of cancer being followed in the outpatient facilities at Auxilio Mutuo Cancer Center were invited to participate in the study. Patients who read and signed a consent form were given a questionnaire inquiring, among various things, on their use of any CAM treatment, education level, gender, place of residence and whether they had consulted their oncologist. The questionnaire also asked about their expectations for use of CAM. RESULTS: 215 patients were approached to participate out of which 200 signed the consent and accepted to participate. A total of 95 of 200 patients (47.5%) mentioned that they utilized at least one CAM treatment. Six factors were then analyzed for their correlation with CAM usage and three yielded statistically significant results at p<.05: age group, education level, and area of residence. After multivariate analysis all of these three factors behaved as independent variables. Gender, tumor type and stage were not significantly associated with use of CAM. CONCLUSION: Our data show that CAM use is significantly more common in those with higher education, younger age, and those living in non-metropolitan areas. Vitamin C and soursop (Graviola or guanábana) proved to be the two most common CAM treatments, respectively.

Gastric MALT Lymphoma with Biclonal Gammopathy and Bone Marrow Involvement Mimicking Multiple Myeloma.

Mucosa-associated lymphoid tissue (MALT) lymphomas are B-cell neoplasms that commonly affect the gastrointestinal (GI) tract, usually the stomach. In most cases, extranodal marginal zone lymphoma (ENMZL) is an indolent disease. Bone marrow involvement is common with MALT lymphoma accompanied by paraproteinemia; such involvement impels disease progression. Here, we present the case of an 82-year-old Hispanic patient with long-standing ENMZL in whom the gastric site responded to antibiotic treatment and Helicobacter pylori eradication, but the disease progressed over the years, with a biclonal gammopathy and bone marrow involvement with marked plasmacytic differentiation. In view of this, we suggest the routine evaluation of paraprotein in patients with ENMZL.

Evaluation of the MD Anderson tumor score for diffuse large B-cell lymphoma in the rituximab era.

OBJECTIVES: Diffuse large B-cell lymphoma (DLBCL) is an aggressive heterogeneous lymphoma with standard treatment. However, 30%-40% of patients still fail, so we should know which patients are candidates for alternative therapies. IPI is the main prognostic score but, in the rituximab era, it cannot identify a very high-risk (HR) subset. The MD Anderson Cancer Center reported a score in the prerituximab era exclusively considering tumor-related variables: Tumor Score (TS). We aim to validate TS in the rituximab era and to analyze its current potential role. METHODS: From GELTAMO DLBCL registry, we selected those patients homogeneously treated with R-CHOP (n = 1327). RESULTS: Five-years PFS and OS were 62% and 74%. All variables retained an independent prognostic role in the revised TS (R-TS), identifying four different risk groups, with 5-years PFS of 86%, 71%, 50%, and very HR (28%). With a further categorization of three variables of the original TS (Ann Arbor Stage, LDH and B2M), we generated a new index that allowed an improvement in HR assessment. CONCLUSIONS: (a) All variables of the original TS retain an independent prognostic role, and R-TS remains predictive in the rituximab era; (b) R-TS and additional categorization of LDH, B2M, and AA stage (enhanced TS) increased the ability to identify HR subsets.

A New Salvage Regimen for Aggressive Lymphomas Based on Gemcitabine, Rituximab, and Oxaliplatin Followed by Lenalidomide (GROC-Rev).

PURPOSE: To evaluate the impact of lenalidomide in patients with aggressive lymphoma who experienced less than complete response (CR) or as maintenance therapy after CR after gemcitabine, rituximab, and oxaliplatin salvage chemotherapy (GROC-Rev regimen). PATIENTS AND METHODS: Patients with relapsed/refractory non-Hodgkin lymphoma received up to 6 GROC-Rev courses: rituximab (375 mg/m2 provided intravenously) on day 1, oxaliplatin (100 mg/m2 provided intravenously; 2 hours), gemcitabine (provided 1250 mg/m2 intravenously; 30 minutes) on day 2, and pegfilgrastim (6 mg provided subcutaneously) on day 3. Patients switched to lenalidomide if they did not experience at least partial response (PR) after their second GROC-Rev course, or if they experienced less than a CR after 6 courses. RESULTS: In 33 patients, overall response was 61% (CR = 39%). Of 17 patients with PR who continued to 6 courses, 10 (59%) experienced CR and 7 PR as maximum response; of these 7, 1 died before receiving lenalidomide, 1 experienced CR while receiving lenalidomide (17%), and 2 experienced a further PR (33%). Of 16 with disease that failed to respond to GROC-Rev after their second course, 2 died before lenalidomide could be administered, and 2 experienced CR (14%) and 1 PR (7%) after lenalidomide. Overall survival and progression-free survival were 47% and 33% at 2 years. Grade 3/4 adverse events included neutropenia, thrombocytopenia, and/or anemia (n = 5), neutropenic infection (n = 3), urinary tract infection (n = 3), pneumonia (n = 2), cellulitis (n = 2), and seizure (n = 1). Eight went on to receive transplants. CONCLUSION: GROC-Rev is an effective and well-tolerated salvage regimen consisting of chemotherapy followed by lenalidomide maintenance in patients with relapsed/refractory non-Hodgkin lymphoma. Simultaneous administration of these agents is worth exploring in future studies.

Incidence and Risk Factors for Developing Herpes Zoster Among a Cohort of Patients Diagnosed With Lymphoma at a Community Cancer Center.

BACKGROUND: Although most cases of herpes zoster (HZ) are self-limited, lymphoma patients are at greater risk for recurrences and more serious and atypical complications that can delay scheduled anti-lymphoma treatment or prevent its continuation. PATIENTS AND METHODS: This is a cohort study with a retrospective chart review of 415 patients diagnosed with lymphoma to determine the incidence and risk factors for developing HZ among this population. Data collected included date of diagnosis, patient's age, last follow-up or death, stage and presentation of lymphoma, treatment type, baseline laboratory tests, and comorbidities. Patients with a diagnosis of HZ at any time during their course of illness were identified. Patients were divided into various subgroups to analyze their risk of developing HZ individually. The frequencies of each categorical variable were compared with χ2 tests. Relative risks were calculated using 95% confidence intervals (CIs). RESULTS: During a median follow-up of 8.9 years, 46 cases of HZ were identified, with an overall incidence density of 11.1%. Higher rates of HZ were associated with lymphocytopenia (P = .038), presentation (P = .030), stage (P = .034), autologous stem cell transplant (P = .019), multiple courses of chemotherapy (P = .035), and fludarabine therapy (P = .002). Those who received what we labeled as 'highly immunosuppressive chemotherapy' had 2.9 times the risk to develop HZ than those who did not receive this therapy (95% CI, 1.47-5.623; P < .001). CONCLUSIONS: Receiving highly immunosuppressive chemotherapy is an independent risk factor for developing HZ. Patients with the risk factors described here might benefit from antiviral prophylaxis against HZ.

Advances in Diagnosis and Management of Diffuse Large B-cell Lymphoma.

The management of diffuse large B-cell lymphoma (DLBCL) has been gradually evolving since the discovery of its 2 major forms, the germinal center B-like (GCB) and activated B-cell (ABC) types. Although the reference standard for the identification of these cell types is considered gene expression profiling (GEP), currently the only method commercially available is immunohistochemistry (IHC). The application of various IHC-based algorithms and their correlation with GEP and clinical outcome are discussed. Because of the adverse prognostic implications of the non-GCB type and its potential effects on treatment selection, the recently revised World Health Organization classification has included these biologic cell types. The management of double hit lymphomas, which almost exclusively fall under the GCB category, is discussed, together with the double expresser phenotype, which is usually grouped under the non-GCB type. The role of lenalidomide and ibrutinib in the management of the non-GCB type is examined. We also discuss the front-line management of primary mediastinal large cell lymphoma using the EPOCH (etoposide, prednisolone, Oncovin [vincristine], cyclophosphamide, hydroxydaunorubicin [doxorubicin]) regimen and examine new salvage data on immune checkpoint inhibitors for this clinical subtype. The prognosis, clinical features, and management of de novo CD5+ DLBCL are discussed, and newer and promising developments in the management of primary central nervous system lymphomas are presented in detail. The most popular salvage regimens and the application of high-dose chemotherapy with stem cell transplantation are assessed in detail. Finally, data on new treatment tactics such as CART (chimeric antigen receptor T-cell) cells and promising new drugs, including blinatumomab and venetoclax, are presented.

Results of Upfront Therapy for Marginal Zone Lymphoma.

BACKGROUND: Marginal zone lymphomas (MZLs) are indolent disorders composed of 3 subtypes: extranodal marginal zone lymphoma (MALT), splenic marginal zone lymphoma (SMZL), and nodal marginal zone lymphoma (NMZL). Early-stage MALT is treated with radiotherapy or antibiotics, and advanced MALT and NMZL are managed with either watch and wait or chemotherapy. SMZLs are treated with splenectomy or rituximab. However, because these approaches have failed to cure patients with SMZL and NMZL, we have systematically used upfront chemotherapy for them, as well as for advanced MALT. We report the outcomes of this approach. PATIENTS AND METHODS: A total of 44 patients with MZL were identified from our database and divided into 2 groups. Group 1 (22 with early-stage MALT) patients received either radiotherapy (n = 17) or antibiotics with or without surgery (n = 5). Group 2 included 9 patients with advanced MALT, 9 with SMZL, and 4 with NMZL. Group 2 was treated with FND-R (fludarabine 25 mg/m2 on days 1 to 3, mitoxantrone 10 mg/m2 on day 1, dexamethasone 20 mg on days 1 to 5, and rituximab 375 mg/m2 on day 1; n = 14) or CHOP-R (cyclophosphamide 750 mg/m2 on day 1, doxorubicin 50 mg/m2 on day 1, vincristine 2 mg intravenous push on day 1, prednisone 100 mg/m2 orally on days 1 to 5, rituximab 375 mg/m2 on day 1; n = 8), followed by maintenance rituximab for 70%. RESULTS: All patients achieved complete remission, and only 2 patients in group 1 had developed a relapse at 70 and 75 months. Both relapses were stage I MALT that had initially been treated with radiotherapy. Both were salvaged with FND-R and remained free of disease at 27 and 39 months after the relapse. At 10 years, the failure-free survival for the 44 patients was 80% and the overall survival was 100%. None of the patients in group 2 developed a relapse. The long-term toxicities have been acceptable. CONCLUSIONS: The excellent responses using upfront chemotherapy for MZL suggests that this disorder is curable. Our results should be confirmed in a prospective trial.

Long-term outcomes, secondary malignancies and stem cell collection following bendamustine in patients with previously treated non-Hodgkin lymphoma.

Despite the long history of bendamustine as treatment for indolent non-Hodgkin lymphoma, long-term efficacy and toxicity data are minimal. We reviewed long-term data from three clinical trials to characterize the toxicity and efficacy of patients receiving bendamustine. Data were available for 149 subjects at 21 sites. The median age was 60 years at the start of bendamustine (range 39-84), and patients had received a median of 3 prior therapies. The histologies included grades 1-2 follicular lymphoma (FL; n = 73), grade 3 FL (n = 23), small lymphocytic lymphoma (n = 20), marginal zone lymphoma (n = 15), mantle cell lymphoma (n = 9), transformed lymphomas (n = 5), lymphoplasmacytic lymphoma (n = 2) and not reported (n = 2). The median event-free survival was 14·1 months. Nine of 12 attempted stem cell collections were successful. With a median follow-up of 8·9 years, 23 patients developed 25 cancers, including 8 patients with myelodysplastic syndrome/acute myeloid leukaemia. These data provide important information regarding the long-term toxicity of bendamustine in previously treated patients. A small but meaningful number of patients achieved durable remissions following bendamustine. These rigorously collected, patient-level, long-term follow-up data provide reassurance that bendamustine or bendamustine plus rituximab is associated with efficacy and safety for patients with relapsed or refractory indolent non-Hodgkin lymphoma.

High ten-year remission rates following rituximab, fludarabine, mitoxantrone and dexamethasone (R-FND) with interferon maintenance in indolent lymphoma: Results of a randomized Study.

We report a single-centre, randomized study evaluating the efficacy and safety of concurrent fludarabine, mitoxantrone, dexamethasone (FND) and rituximab versus sequential FND followed by rituximab in 158 patients with advanced stage, previously untreated indolent lymphoma, enrolled between 1997 and 2002. Patients were randomized to 6-8 cycles of FND followed by 6 monthly doses of rituximab or 6 doses of rituximab given concurrently with FND. All patients who achieved at least a partial response received 12 months of interferon (IFN) maintenance. Median ages were 54 and 55 years. The two groups were comparable with the exception of a higher percentage of females (65% vs. 43%) and baseline anaemia (23% vs. 11%) in the FND followed by rituximab group. Complete response/unconfirmed complete response rates were 89% and 93%. The most frequent grade ≥ 3 toxicity was neutropenia (86% vs. 96%). Neutropenic fever occurred in 21% and 16%. Late toxicity included myelodysplastic syndrome (n = 3) and acute myeloid leukaemia (n = 5). With 12·5 years of follow-up, no significant differences based on treatment schedule were observed. 10-year overall survival estimates were 76% and 73%. 10-year progression-free survival estimates were 52% and 51%. FND with concurrent or sequential rituximab, and IFN maintenance in indolent lymphoma demonstrated high response rates and robust survival.

Indolent Lymphomas That Present With Clinically Aggressive Features: A Subset of Low-Grade Lymphomas With a Behavior Inconsistent With the Histologic Diagnosis.

BACKGROUND: The expected presentation for low-grade lymphomas consists of disseminated lymphadenopathy with no constitutional symptomsk, and with bone marrow involvement, normal lactate dehydrogenase (LDH), low proliferative rate as determined by Ki-67, and positron emission tomography (PET) scan with low standardized uptake values (SUVs) < 14. However, it is not unusual for some cases to present with 1 or more clinically aggressive features. Because the clinical behavior of such patients has not been investigated, there are no data regarding their expected outcome. PATIENTS AND METHODS: For these cases, we use the term "clinically discordant indolent histology" (CDIH), which we define as any follicular grade 1-2, grade 3-A, or small lymphocytic lymphoma that meets at least 1 or more of the following conditions at the time of diagnosis: constitutional symptoms, LDH elevation, PET SUV > 14, unusual areas of involvement for indolent non-Hodgkin lymphoma (NHL) (bone, pleura, central nervous system, soft tissue, lung), Ki-67 > 30%, necrotic areas seen on computed tomography scan, or discrete space-occupying lesions in the liver or spleen. We have reviewed our NHL database with the objective of identifying such cases so we could compare them with those with the expected presentation of indolent NHLs. RESULTS: Patients with CDIH have a less favorable overall survival and failure-free survival, and a higher rate of transformation to a higher-grade histology. CONCLUSIONS: CDIH functionally behaves as aggressive NHL despite the fact that under the microscope the lymphomas resemble typical indolent NHLs. These cases seem to fare better when treated with a regimen containing doxorubicin-rituximab.

Prognostic significance of baseline peripheral absolute neutrophil, monocyte and serum ß2-microglobulin level in patients with diffuse large b-cell lymphoma: a new prognostic model.

There are limited reports that baseline peripheral absolute neutrophil count (ANC), absolute monocyte count (AMC), absolute lymphocyte count (ALC) and serum ß2-microglobulin level independently predict survival in patients with diffuse large B-cell lymphoma (DLBCL). To confirm these findings, we analysed these parameters together with components of the International Prognostic Index (IPI) in patients with newly-diagnosed DLBCL. We evaluated baseline clinical features for their ability to predict survival in 817 newly diagnosed, previously untreated patients with DLBCL who received frontline treatments between October 2001 and December 2011. The median age at diagnosis was 58 years. Multivariate analysis identified elevated baseline ANC (P = 0·036), AMC (P = 0·028) and serum ß2-microglobulin level (P < 0·001), poor performance status (P < 0·001) and high number of extranodal disease sites (P = 0·0497) as independent unfavourable predictors of OS; serum ß2-microglobulin level was the strongest predictor of survival outcomes among all the parameters. High baseline serum ß2-microglobulin, ANC and AMC levels are independent prognostic factors for short overall survival in patients with newly diagnosed DLBCL. Our new model, based on the above five parameters, better stratifies patients into various risk categories than the IPI for newly diagnosed DLBCL.

Rituximab plus hyper-CVAD alternating with MTX/Ara-C in patients with newly diagnosed mantle cell lymphoma: 15-year follow-up of a phase II study from the MD Anderson Cancer Center.

Intensive chemotherapy regimens containing cytarabine have substantially improved remission durability and overall survival in younger adults with mantle cell lymphoma (MCL). However, there have been no long-term follow-up results for patients treated with these regimens. We present long-term survival outcomes from a pivotal phase II trial of rituximab, hyper-fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with methotrexate and cytarabine (R-HCVAD/MA). At 15 years of follow-up (median: 13·4 years), the median failure-free survival (FFS) and overall survival (OS) for all patients was 4·8 years and 10·7 years, respectively. The FFS seems to have plateaued after 10 years, with an estimated 15-year FFS of 30% in younger patients (≤65 years). Patients who achieved complete response (CR) after 2 cycles had a favourable median FFS of 8·8 years. Six patients developed myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML) whilst in first CR. The 10-year cumulative incidence of MDS/AML of patients in first remission was 6·2% (95% confidence interval: 2·5-12·2%). In patients with newly diagnosed MCL, R-HCVAD/MA showed sustained efficacy, with a median OS exceeding 10 years in all patients and freedom from disease recurrence of nearly 15 years in almost one-third of the younger patients (≤65 years).