Chemotherapy For non-Hodgkin Lymphoma Research Articles

Effect of Coenzym Q10 on Doxorubicin-induced Cardiotoxicity in Non Hodgkin's Lymphoma Patients

BACKGROUND : Non-Hodgkin's Lymphoma is a primary malignancy in the Lymph Nodes and lymphoid tissue originating from B lymphocytes, T lymphocytes and Natural Killer (NK) cells. Therapy for Non-Hodgkin's Lymphoma chemotherapy can be given alone or combined with radioactive therapy. Doxorubicin is a chemotherapy drug used for lymphoma with side effects, one of which is cardiotoxic effects. AIMS : To prove that coenzyme Q10 can reduce the cardiotoxic effect of doxorubicin chemotherapy in non-Hodgkin's lymphoma patients METHOD : Intervention study with a randomized pre and post test double blind control group design with 34 NHL patients undergoing chemotherapy. The treatment group received additional therapy with coenzyme Q10 300mg/day for 12 weeks while the controls received placebo. The cardiotoxic effects examined were assessed based on the results of Electrocardiography and Echocardiography. RESULT : The treatment group with coenzyme Q10 supplementation after the 4th chemotherapy showed a decrease in echocardiography results in 3 patients (18%) and in the control group 17 patients (100%). There was a significant difference in the echocardiography results of the treatment and control groups (p=0.001). There were no drug side effects in both groups CONCLUSION : Coenzyme Q10 supplementation provides an improvement in the cardiotoxic effects of doxorubicin in non-Hodgkin's lymphoma patients, on echocardiography, but not on Electrocardiography.

Hepatitis Virus-associated Non-hodgkin Lymphoma: Pathogenesis and Treatment Strategies.

Over the last decade, epidemiological studies have discovered a link between hepatitis C virus (HCV) and hepatitis B virus (HBV) infection and non-Hodgkin lymphoma (NHL). The regression of HCV-associated NHL after HCV eradication is the most compelling proof supporting HCV infection's role in lymphoproliferative diseases. HBV infection was found to significantly enhance the incidence of NHL, according to the epidemiological data. The exact mechanism of HCV leading to NHL has not been fully clarified, and there are mainly the following possible mechanisms: (1) Indirect mechanisms: stimulation of B lymphocytes by extracellular HCV and cytokines; (2) Direct mechanisms: oncogenic effects mediated by intracellular HCV proteins; (3) hit-and-run mechanism: permanent genetic B lymphocytes damage by the transitional entry of HCV. The specific role of HBV in the occurrence of NHL is still unclear, and the research on its mechanism is less extensively explored than HCV, and there are mainly the following possible mechanisms: (1) Indirect mechanisms: stimulation of B lymphocytes by extracellular HBV; (2) Direct mechanisms: oncogenic effects mediated by intracellular HBV DNA. In fact, it is reasonable to consider direct-acting antivirals (DAAs) as first-line therapy for indolent HCV-associated B-NHL patients who do not require immediate chemotherapy. Chemotherapy for NHL is affected by HBV infection and replication. At the same time, chemotherapy can also activate HBV replication. Following recent guidelines, all patients with HBsAg positive/HBV DNA≥2,000 IU/mL should be treated for HBV. The data on epidemiology, interventional studies, and molecular mechanisms of HCV and HBV-associated B-NHL are systematically summarized in this review.

Synchronous breast cancer and non-Hodgkin lymphoma: A case report.

IntroductionAmong women, breast cancer (BC) is the most prevalent type of cancer and the top cause of cancer deaths. Although non-Hodgkin lymphoma (NHL) is the most prevalent hematological cancer, it is rarely reported synchronous with BC. Moreover, which malignancy appears first can rarely be explained because they are usually detected incidentally while diagnosing and treating other malignancies. This paper reports a case of invasive ductal carcinoma (IDC) concomitant with NHL.Presentation of caseA 35-year-old woman presented with simultaneous IDC in the left breast and NHL in a lymph node in the neck. The patient underwent a modified radical mastectomy for stage IIIA IDC and received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy for stage I NHL.Clinical discussionTreating BC and NHL remains challenging due to their significantly different management, the lack of guidelines for treating BC and lymphoma simultaneously, and uncertainty about whether synchronous tumors should be treated separately as distinct clinical entities or as one disease with treatment covering both. Therefore, the best approach continues to be focusing on the most biologically aggressive malignancies.ConclusionThe enlargement of lymph nodes not in the lymphatic drainage of the primary tumor should be suspected of indicating multiple primary malignancies until proven otherwise. For patients with luminal-B BC, NHL chemotherapy can involve receiving the R-CHOP regimen, including doxorubicin and cyclophosphamide, which can help to mitigate BC.

Risk Factors for Neutropenia after the First Cycle of Chemotherapy for Non-Hodgkin Lymphoma

Background and Objective: Neutropenia that occurs after the first cycle of chemotherapy for non-Hodgkin’s Lymphoma (NHL) may predict its recurrence in the subsequent cycles. Moreover, it has also been reported to be a poor prognostic factor for the treatment outcome. Therefore, we aimed to observe the incidence of first cycle neutropenia and identify the potential risk factors for its occurrence among patients with NHL underwent chemotherapy. Methods: A retrospective cohort was conducted in Sardjito General Hospital, Yogyakarta, Indonesia to analyze 466 subjects during 2012-2018, confirmed NHL, age 17 or older, treatment-naïve, underwent first-line chemotherapy without any previous primary GCSF prophylaxis. Relevant clinical conditions, pre-treatment laboratory parameters and treatment factors were obtained from medical records. Univariate and multivariate analysis were done using logistic regression to determine the significant factors. Results: Among 466 NHL subjects, 241 (51.7%) received rituximab-containing regiment, with DLBCL as predominant subtype in 196 subjects (41.8%). Neutropenia occurred in 119 (25.5%; 95% CI 21.7-29.6%) of the cases, with 87 (73.2%) of them had moderate-severe neutropenia. Age older than 50 years old, use of rituximab-containing regiment, ANC ≤ 4.83×103 cells/mm3, and WBC ≤ 7.26×103 cells/mm3 were significant predisposing factors for first cycle neutropenia. A multivariate analysis showed two significant prognostic factors i.e., rituximab-containing regiment and ANC level ≤ 4.83×103 cells/mm3 with OR 2.18 (95% CI 1.38–3.43) and 2.30 (95%CI 1.49–3.57), respectively. Conclusion: The administration of rituximab-based regimen and pre-treatment ANC ≤ 4.83×103 cells/mm3 in NHL require more attention to anticipate the occurrence of neutropenia after the first chemotherapy cycle. Further investigation is required to validate risk model and identify subgroup who benefits from early use of growth factor.

Constructing a Predictive Model of Depression in Chemotherapy Patients with Non-Hodgkin's Lymphoma to Improve Medical Staffs' Psychiatric Care.

Objectives Depression is highly prevalent in non-Hodgkin's lymphoma (NHL) patients undergoing chemotherapy. The social stress associated with malignancy induces neurovascular pathology promoting clinical levels of depressive symptomatology. The purpose of this study was to establish an effective depressive symptomatology risk prediction model to those patients. Methods This study included 238 NHL patients receiving chemotherapy, 80 of whom developed depressive symptomatology. Different types of variables (sociodemographic, medical, and psychosocial) were entered in the models. Three prediction models (support vector machine-recursive feature elimination model, random forest model, and nomogram prediction model based on logistic regression analysis) were compared in order to select the one with the best predictive power. The selected model was then evaluated using calibration plots, ROC curves, and C-index. The clinical utility of the nomogram was assessed by the decision curve analysis (DCA). Results The nomogram prediction has the most efficient predictive ability when 10 predictors are included (AUC = 0.938). A nomogram prediction model was constructed based on the logistic regression analysis with the best predictive accuracy. Sex, age, medical insurance, marital status, education level, per capita monthly household income, pathological stage, SSRS, PSQI, and QLQ-C30 were included in the nomogram. The C-index was 0.944, the AUC value was 0.972, and the calibration curve also showed the good predictive ability of the nomogram. The DCA curve suggested that the nomogram had a strong clinical utility. Conclusions We constructed a depressive symptomatology risk prediction model for NHL chemotherapy patients with good predictive power and clinical utility.

Full Uncapped Doses Of Chemotherapy In Non-Hodgkin's Lymphoma Patients With a High Body Surface Area Are Well Tolerated With No Increase In Toxicity, and a Trend Towards Improved Survival In Obese Patients

▪ IntroductionThe World Health Organisation estimated that in 2008 11% of the world adults population were obese, as defined by a body mass index (BMI) >30kg/m2. In this patient group, the appropriate dosing of chemotherapy has been contentious. Many clinicians prefer to cap the dose if the patients' body surface area (BSA), as calculated by the square root of height x weight divided by 3600, is above 2m2 due to concerns about the potential toxicity of high doses of chemotherapy. However, recent published data in patients receiving therapy for solid malignancies show no increase in toxicity amongst patients with high BSA receiving uncapped doses of chemotherapy. Furthermore, there is evidence that obese patients with aggressive non-Hodgkin's lymphoma (NHL) have better survival outcomes. The purpose of this study is to analyse whether patients with BSA of more than 2m2 who received uncapped doses of chemotherapy for NHL experienced higher rates of treatment-related toxicities and to assess whether this has any impact on clinical outcomes. MethodsA retrospective analysis of consecutive patients who received standard CHOP-like chemotherapy with or without rituximab for NHL between October 2006 and February 2013 was performed. Baseline characteristics were recorded. Treatment related adverse events (TRAEs) were categorised in accordance with Common Terminology Criteria for Adverse Events Version 4.0. Acute TRAEs were compared using a negative binomial regression model, and Fisher's exact test was used to compare delayed toxicities. Multivariable analysis was used to identify potential risk factors of treatment-related toxicity. Kaplan-Meier curves and log rank tests were used for survival analysis. ResultsIn total, 180 newly diagnosed NHL patients were included in the analysis with a median follow-up of 31.3 months (CI: 27.1 – 35.3 months). Fifty nine (32.8%) of these patients had a BSA of more than 2m2 and 50 (27.8%) were classified as obese. The group with a BSA of more than 2m2 was generally younger and had a lower International Prognostic Index (IPI) score. All patients received full uncapped doses of chemotherapy according to BSA calculated using actual body weight. The median number of acute TRAEs was 2 events per patient, with no clear relationship to BSA (Figure 1). In a covariate analysis, only IPI score was found to be significant. After adjusting for IPI score, there was a trend towards lower acute TRAEs in patients with a BSA of more than 2m2, although this was not statistically significant. There was no difference in the proportion of delayed toxicity between the two groups. The overall response rates were higher in the obese patients, 94.0% vs 86.2%, but that difference was not statistically significant (p = 0.1984). Obese patients had a trend towards better progression-free and overall survivals. This was seen in both the low and high grade B-cell NHL groups (Figure 2). [Display omitted] [Display omitted] ConclusionOur study demonstrates that NHL patients with high BSA receiving uncapped doses of chemotherapy do not experience more acute or delayed treatment-related toxicities. Similar to recently published data, the survival outcomes are comparable between the obese and non-obese patient groups. Our results do not support the common practice of capping chemotherapy doses at a BSA of 2 m2 and suggest that the historically inferior outcomes in obese patients with NHL could be due to relative under-dosing of chemotherapy in this group of patients. Disclosures:No relevant conflicts of interest to declare.

Chemotherapy for non-Hodgkin lymphoma in the hemodialysis patient: A comprehensive review.

Chemotherapy for non‐Hodgkin lymphoma (NHL) in the hemodialysis (HD) patient is a challenging situation. Because many drugs are predominantly eliminated by the kidneys, chemotherapy in the HD patient requires special considerations concerning dose adjustments to avoid overdose and toxicities. Conversely, some drugs are removed by HD and may expose the patient to undertreatment, therefore the timing of drug administration in relation to HD sessions must be carefully planned. Also, the metabolites of some drugs show different toxicities and dialysability as compared with the parent drug, therefore this must also be catered for. However, the pharmacokinetics of many chemotherapeutics and their metabolites in HD patients are unknown, and the fact that NHL patients are often treated with distinct multiagent chemotherapy regimens makes the situation more complicated. In a realm where uncertainty prevails, case reports and case series reporting on actual treatment and outcomes are extremely valuable and can aid physicians in decision making from drug selection to dosing. We carried out an exhaustive review of the literature and adopted 48 manuscripts consisting of 66 HD patients undergoing 71 chemotherapy regimens for NHL, summarized the data, and provide recommendations concerning dose adjustments and timing of administration for individual chemotherapeutics where possible. The chemotherapy regimens studied in this review include, but are not limited to, rituximab, cyclophosphamide + vincristine + prednisolone (CVP) and cyclophosphamide + doxorubicin + vincristine + prednisolone (CHOP)‐like regimens, chlorambucil, ibrutinib, bendamustine, methotrexate, platinum compounds, cytarabine, gemcitabine, etoposide, ifosfamide, melphalan, busulfan, fludarabine, mogamulizumab, brentuximab vedotin, and 90Y‐ibritumomab tiuxetan.

Abstract 4910: Neurocognitive effects of central nervous system directed chemotherapy in Non Hodgkin Lymphoma diseased children

Abstract Background and Purpose. Because the blood-brain barrier serves as a pharmacological barrier, malignant cells can remain in the central nervous system (CNS) despite systemic chemotherapy. Consequently, CNS-directed treatment is an essential part of therapy for Non-Hodgkin lymphoma (NHL). We aimed in this analysis to determine the neurocognitive effects of CNS-directed chemotherapy in children with NHL. Methods. In a cross-sectional study 20 NHL diseased children and 10 healthy controls were tested for neurocognitive functions. The selection criteria were: 3 years or more after the end of NHL chemotherapy only regimen, no anaemia, no CNS or systemic diseases. Both patients and healthy controls were examined for global intelligence quotient (IQ), verbal IQ, performance IQ, attention measures, auditory tests, long and short memory, math skills and academic achievement. Results. No decline in global IQ in NHL children compared to healthy controls but there was a significant decline of attention, verbal comprehension and performance IQ. Among 20 NHL diseased children 18 had poor recent and immediate memories while remote memory was normal in 16 children. Young age at diagnosis and treatment intensity were the commonest risk factors. Conclusion. In absence of cranial irradiation, childhood survivors of NHL experience long-term neurocognitive deficits after chemotherapy treatment. Global IQ is not a sufficiently sensitive measure to detect specific CNS deficits in NHL diseased children. The deficits are mainly present in basic neurophysiologic processes of attention and executive functioning. Note: This abstract was not presented at the meeting. Citation Format: Abeer Abd Elmoneim, Ahlam Eladawy, Mona Abu Elkasem, Soumaya Hadhood. Neurocognitive effects of central nervous system directed chemotherapy in Non Hodgkin Lymphoma diseased children [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4910.

Development of Hepatic Steatosis After Chemotherapy for Non‐Hodgkin Lymphoma

Nonalcoholic fatty liver disease is the most common liver disorder in the developed world. Although typically reflecting caloric overload, it can also be secondary to drug toxicity. We aimed to describe the incidence and risk factors for de novo steatosis during chemotherapy for non‐Hodgkin lymphoma (NHL). In this retrospective case‐control study, adult patients with NHL were treated with rituximab, cyclophosphamide, doxorubicin, prednisone, and vincristine (R‐CHOP) or R‐CHOP + etoposide (EPOCH‐R). Patients with liver disease or steatosis were excluded. Abdominal computed tomography was performed pretreatment and at 3‐ to 6‐month intervals and reviewed for steatosis. Patients with de novo steatosis were matched 1:1 to controls by age, sex, and ethnicity. Of 251 treated patients (median follow‐up 53 months), 25 (10%) developed de novo steatosis, with the vast majority (23 of 25; 92%) developing it after chemotherapy. Of those, 14 (61%) developed steatosis within the first 18 months posttreatment and 20 (87%) within 36 months. Cases had higher baseline body mass index (BMI; mean ± SD, 29.0 ± 6.5 versus 26.0 ± 5.2 kg/m2; P = 0.014) and hyperlipidemia (12% versus 2%; P = 0.035). Although their weights did not change during chemotherapy, BMI in cases increased by 2.4 ± 2 kg/m2 (mean ± SD) from end of treatment to steatosis compared to 0.68 ± 1.4 in controls (P = 0.003). Etoposide‐containing regimens were associated with a shorter time to steatosis (median 34 weeks versus 154 weeks; P < 0.001) despite similar baseline risk factors. Conclusion: The recovery period from NHL chemotherapy appears to be a “hot spot” for development of fatty liver, driven by early posttreatment weight gain, especially in subjects with baseline risk factors.

The use of metaphors in non-Hodgkin's lymphoma patients undergoing chemotherapy.

The aim of this study was to explore the use of metaphors by non-Hodgkin's lymphoma (NHL) patients undergoing chemotherapy in a haematology ward setting. There is a dearth of literature exploring the use of metaphors in people with cancer undergoing aggressive treatment. Hence, this study aims to explore the use of metaphors in NHL patients undergoing chemotherapy and additionally, examining whether the use of such metaphors has an empowering/disempowering effect. A qualitative design was used. The participants were six adult patients diagnosed with NHL and undergoing chemotherapy. Data collection was undertaken between July 2016-December 2016. Each participant was interviewed twice using semi-structured interviews. The data were analysed using Pragglejaz method for finding metaphors. The participants used metaphors 17 times per 1,000 words to describe their experience of undergoing chemotherapy for NHL. The metaphors cited focused on aspects relating to "war", "prison" and a "journey". The findings demonstrate that certain metaphors used by the study participants, such as those pertaining to "war" or a "journey", concur with those described in narratives of people with cancer in general. However, the use of the "prison" metaphor by NHL patients undergoing chemotherapy relates particularly to their context of being isolated while undergoing treatment for fear of infection. Consequently, there is the need to interpret metaphors in relation to the specific type of illness and context. Furthermore, the findings of this study suggest that the impact of metaphors in empowering/disempowering people with cancer depends on the unique interpretation of the individual patient.

Observation of therapeutic effects of point application at Shenque (CV 8) plus moxa-salt hot compress for prevention of gastrointestinal adverse reactions after chemotherapy for non-Hodgkin lymphoma

To observe the clinical efficacy of point application with Da Huang (Rhizoma Rhei Cruda) powder at Shenque (CV 8) plus moxa-salt hot compress on the umbilicus for preventing gastrointestinal adverse reactions after chemotherapy for non-Hodgkin lymphoma (NHL). A total of 60 cases with NHL under chemotherapy were divided into two groups by hospitalization order, with 30 cases in each group. The control group was treated with routine nursing and the observation group was additionally given point application with Da Huang (Rhizoma Rhei Cruda) powder plus moxa-salt hot compress on the umbilicus, to compare the effect in preventing gastrointestinal adverse reactions after chemotherapy between the two groups. The occurrence rates of constipation, nausea, vomiting and poor appetite on the second day and fifth day after chemotherapy were obviously lower in the observation group than those in the control group, with statistically significant differences between the two groups (all P<0.05). The point application with Da Huang (Rhizoma Rhei Cruda) powder at Shenque (CV 8) plus maxa-salt hot compress on the umbilicus can produce more significant efficacy in preventing the gastrointestinal adverse reactions after chemotherapy for NHL than routine nursing. Moreover, it is simple and easy to be used and popularized.

A case of severe left main isolated stenosis in a young woman with previous history of non-Hodgkin lymphoma

We report the case of a 34-year-old female treated with radiotherapy and chemotherapy for non-Hodgkin lymphoma at the age of 16. The patient came to our attention because of progressive dyspnea on effort and a positive result on a pharmacologic stress echo test. Coronary angiography revealed focal critical ostial stenosis of the left main coronary artery. Considering the high surgical risk due to possible post-radiation thoracic adherence and the young patient age, she underwent successful stenting of the left main stenosis with drug-eluting stent, followed by an intravascular ultrasound-guided post-dilation and final kissing balloon inflation. The procedure was uncomplicated.Heart diseases are among the frequently seen long-term effects of chemo/radiotherapy used for lymphoma treatment. The pathogenesis of radiation-induced coronary artery disease is complex and not yet fully understood, the mechanism is multifactorial and likely involves direct damage from radiation exposure or mediated by inflammatory cytokine secretion. Surgery management is often challenging due to radiation sequences, and a percutaneous approach is therefore used. The risk of long-term radiotherapy damage depends on radiation dose and the field of exposure. Modern techniques with lower radiation exposure and smaller treatment volumes may reduce these risks in future.

Abstract LB-236: Risk of tMDS/AML after chemotherapy for first primary lymphoid malignancy, 2000-2013

Abstract Previous studies have demonstrated elevated risks for tMDS/AML after chemotherapy for non-Hodgkin lymphoma, Hodgkin lymphoma, and plasma cell neoplasms, but current treatment practices have changed considerably. We utilized large-scale, population-based cancer registry data from the United States to quantify for the first time tMDS/AML risks after chemotherapy for lymphoid malignancies in the current treatment era, including analysis for specific non-Hodgkin lymphoma subtypes. In 17 registries, we identified 121,840 adults without HIV infection who survived ≥1 year following a first primary lymphoid malignancy diagnosis during 2000-2013 and were initially treated with chemotherapy. tMDS/AML risk was compared with that expected in the general population using SIRs. tMDS/AML risk was significantly increased 5- to 9-fold after chemotherapy for the most common lymphoid malignancies, including DLBCL, plasma cell neoplasms, follicular lymphoma, Hodgkin lymphoma, and CLL/SLL (Table 1). Approximately 5-fold increased risks were observed after chemotherapy for marginal zone lymphoma, LPL/WM, and other/unspecified lymphomas. In contrast, risks were strikingly elevated (&amp;gt;10-fold) after chemotherapy for precursor leukemia/lymphoma, Burkitt lymphoma/leukemia, peripheral T-cell lymphoma, and mantle cell lymphoma. Only chemotherapy for hairy cell leukemia was not associated with increased tMDS/AML risk (SIR=1.4), albeit based on small numbers. tMDS/AML risks were higher &amp;lt;5 years after diagnosis compared with ≥5 years for Hodgkin lymphoma, precursor leukemia/lymphoma, Burkitt lymphoma/leukemia, and peripheral T-cell lymphoma. In contrast risks were persistently elevated ≥5 years after diagnosis for other lymphoid malignancies. In summary, tMDS/AML risk remains elevated in the modern era following chemotherapy for nearly all lymphoid malignancies. With ongoing introduction of new treatment approaches, continued consideration of risks and benefits of specific agents (and combinations), doses, and duration of therapy is critical. By time since lymphoid neoplasm diagnosisOverall1.0-4.9 years≥5 yearsFirst primary lymphoid malignancyTotal (N)Mean age at diagnosis (y)NSIR(95%CI)NSIR(95%CI)NSIR(95%CI)Hodgkin lymphoma16,74840.3659.0(6.9, 11.4)4310.7(7.8, 14.5)226.8(4.3, 10.3)CLL/SLL8,47864.31129.4(7.7, 11.3)729.2(7.2, 11.6)409.8(7.0, 13.3)DLBCL31,69259.72045.6(4.8, 6.4)1265.6(4.7, 6.7)785.5(4.4, 6.9)Follicular lymphoma15,65659.51457.8(6.6, 9.2)867.9(6.3, 9.8)597.7(5.8, 9.9)Marginal zone lymphoma4,22362.8295.5(3.7, 7.8)195.7(3.4, 8.9)105.1(2.4, 9.4)Plasma cell neoplasms22,75363.21176.1(5.0, 7.3)795.4(4.3, 6.8)388.2(5.8, 11.2)Precursor leukemia/lymphoma3,53042.73237.3(25.5, 52.7)2852.6(35.0, 76.1)412.3(3.3, 31.4)Mantle cell lymphoma3,52163.44010.1(7.3, 13.8)279.9(6.5, 14.4)1310.7(5.7, 18.3)LPL/WM1,95466.0134.3(2.3, 7.3)105.0(2.4, 9.2)32.8(0.6, 8.2)Peripheral T-cell lymphoma3,15655.73012.7(8.6, 18.1)2315.5(9.8, 23.2)78.0(3.2, 16.5)Burkitt lymphoma/leukemia1,18048.41924.3(14.6, 37.9)1328.6(15.2, 48.9)618.3(6.7, 39.8)Hairy cell leukemia1,70554.631.4(0.3, 4.2)~~Other, unspecified7,24462.0535.7(4.3, 7.4)386.6(4.7, 9.1)154.2(2.3, 6.9) Abbreviations: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL); confidence interval (CI); diffuse large B-cell lymphoma (DLBCL); lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM); standardized incidence ratio (SIR); Surveillance, Epidemiology, and End Results (SEER); treatment-related myelodysplastic syndrome/acute myeloid leukemia (tMDS/AML). Citation Format: Lindsay M. Morton, Graca M. Dores, Megan M. Herr, Martha S. Linet, Margaret A. Tucker, Rochelle E. Curtis. Risk of tMDS/AML after chemotherapy for first primary lymphoid malignancy, 2000-2013 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-236. doi:10.1158/1538-7445.AM2017-LB-236

Relationship between Autoimmune Diseases and Imbalances in Helper/Suppressor T-cell Populations after Rituximab-containing Chemotherapyfor Non-Hodgkin Lymphoma

Immunologic abnormalities including autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP) have been described in patients with non-Hodgkin lymphoma. In some cases, anti-red cell or platelet antibodies are produced by lymphoma cells. However, cases of the occurrence of autoimmune diseases without recurrence of lymphomas have been also reported. The relationship between autoimmune diseases with post-bone marrow transplantation and Hodgkin disease may be attributed to immune dysfunctions, particularly those involving T cells. This autoimmune phenomenon may be related to imbalances in helper/suppressor T-cell populations. Imbalances in helper and suppressor T-cell populations have been reported after R-CHOP chemotherapy, and the recovery of serum IgG and CD4+ counts was observed more than 2 years after R-CHOP therapy in patients with B-cell lymphoma. In this report, we present a case of an 87-year-old man who was treated with rituximab-containing chemotherapy and maintained complete remission. However, the immunophenotyping of peripheral blood and bone mallow mononuclear cells revealed a reversed CD4/CD8 ratio. Two years later, he developed ITP. He was treated with intravenous immunoglobulin and eltrobopag, and thrombocytopenia improved. Five years later, he developed pneumonia and sudden Coombs-positive hemolytic anemia caused by autoantibodies against D antigen and thrombocytopenia without the recurrence of lymphoma. He was treated with prednisolone and a pulse dose of methylprednisolone; however, his response to therapy was poor and he subsequently died. We herein report a case who have been showed reversed imbalances in the helper/suppressor T cell populations over 2 years after R-CHOP therapy, developed AIHA and ITP without recurrence of lymphoma. The long-term monitoring of T-cell counts after rituximab containing chemotherapies is important, and careful attention to infection signs.

Salmonella enterica serovar Typhimurium combined with CHOP chemotherapy for non Hodgkin Lymphoma.

Salmonella enterica serovar Typhimurium combined with CHOP chemotherapy for non Hodgkin Lymphoma.

The ASH Practice Improvement Module in Non-Hodgkin Lymphoma: Assessing the Feasibility, Reliability and Usefulness of a New Quality Improvement Tool

Background:The American Society of Hematology Practice Improvement Modules (ASH PIMs) are online tools designed for clinicians to monitor the quality of care in their practice. The ASH PIM for non-Hodgkin lymphoma (NHL) was designed by a committee of NHL experts and was recently released in the ASH Academy. The ASH PIM for NHL defines quality metrics in six areas: pathological diagnosis, staging, Hepatitis B testing, use of growth factors, vaccination, and fertility counseling.Objectives:1) Use the ASH PIM for NHL to measure quality of care at 4 cancer centers in the Greater Toronto Area. 2) Assess the feasibility, reliability, and usefulness of the ASH PIM for NHL.Methods:To measure quality of care, 78 patients undergoing first line chemotherapy for NHL were reviewed at 4 cancer centers (3 academic centers and 1 community center) near Toronto, Canada. Two hematology fellows independently scored each patient chart for the 6 quality metrics in the ASH PIM. After data collection, interviews (using structured questionnaires) were conducted with the chart reviewers as well as with physicians experienced at treating NHL.Results: Three out of the 4 cancer centers had high performances (>90%) in pathological diagnosis and staging. Two of the 4 centers had high performances for Hepatitis B testing. Zero of the 4 centers had high performances for documenting growth factor use, vaccinations and fertility counseling.A feasibility questionnaire revealed that each chart required 15 minutes for review. Reviewers noted that the ASH PIM for NHL was clear for how to score pathological diagnosis, staging, and hepatitis B testing (mean score >4 out of 5 for clarity), but unclear for how to score the use of vaccinations (mean 2.3/5). Reviewers were able to accurately score pathological diagnosis, staging, and hepatitis B (mean >4/5 for perceived accuracy), but were unable to accurately score vaccination and fertility counseling (mean <3/5). Interviews revealed concern that practices around vaccination and fertility counseling were not being well documented in the medical record. Inter-rater reliability was high across all 6 metrics (Gwet’s first order agreement coefficient 0.81 – 0.97).Of the 6 metrics, experienced NHL physicians rated pathological diagnosis and staging as most important, with vaccination and growth factor use rated as least important. When provided with the performance data for their own center, the results were perceived to accurately reflect patient care in 5 out of 6 of the metrics. Performance on fertility counseling was thought to be under-estimated due to poor documentation. Overall, the ASH PIM for NHL was perceived to capture the quality of patient care moderately well. Areas not captured by the ASH PIM, but perceived to be important to NHL patient care included: the reduction of delays between lymphoma suspicion and first treatment, patient satisfaction, and advanced care planning.Conclusions: The ASH PIM for NHL is feasible, reliable, and measures a number of important aspects of patient care. Some metrics could be made clearer by including more explicit definitions. Performance on the metrics relying on clinical documentation was not as high as for those relying on objective testing. The performance of cancer centers in the Greater Toronto Area on the ASH PIM for NHL suggests specific areas for quality improvement at each center. DisclosuresHicks:Gilead: Research Funding.

Intestinal lymphoma--a review of the management of emergency presentations to the general surgeon.

Intestinal non-Hodgkin's lymphoma (NHL) is uncommon but not rare. This paper aims to review the recent evidence for the management of perforated NHL of the intestine, consider when chemotherapy should be commenced and examine the likely outcomes and prognosis for patients presenting as surgical emergencies with this condition. MEDLINE and Cochrane databases were searched using intestinal lymphoma, clinical presentation, perforation, management and prognosis. The full text of relevant articles was retrieved and reference lists checked for additional articles. Emergency surgery was required at disease presentation for between 11 and 64% of intestinal NHL cases. Perforation occurs in 1-25% of cases, and also occurs whilst on chemotherapy for NHL. Intestinal bleeding occurs in 2-22% of cases. Obstruction occurs more commonly in small bowel (5-39%) than large bowel NHL and intussusceptions occur in up to 46%. Prognosis is generally poor, especially for T cell lymphomas. There is a lack of quality evidence for the elective and emergency treatment of NHL involving the small and large intestine. There is a lack of information regarding the impact an emergency presentation has on the timing of postoperative chemotherapy and overall prognosis. It is proposed that in order to develop evidence-based treatment protocols, there should be an intestinal NHL registry.

Management of the HBV reactivation in isolated HBcAb positive patients affected with Non Hodgkin Lymphoma

BackgroundOccult HBV infection (OBI) is defined by the persistence of HBV in the liver without serum HBsAg and HBVDNA. It represents a life-threatening event during immunosuppressive chemotherapies. An OBI occurs in approximately 18% of HBcAb + patients. International guidelines suggest surveillance for HBV markers in immunosuppressed patients. In Non-Hodgkin Lymphoma (NHL), the prevalence of OBI reactivation remains to be established.MethodsIn order to determine the prevalence of occult HBV reactivation in a large cohort of patients during chemotherapy for NHL, we analysed 498 NHL patients in a centre of Southern Italy. We evaluated HBV markers, NHL type, treatment type and occurrence of HBV reactivation.ResultsForty % of patients were treated with monoclonal antibodies and 60.3% without. Ninety-six patients were HBcAb+, HBsAg-. HBV reactivation occurred in ten subjects of this subgroup. All of them were successfully treated with Lamivudine. None of the patients experienced liver-related death. The prevalence of OBI reactivation was of 10.42% in HBcAb + HBsAb- patients. This event occurred in 50% of patients treated with mild immunosuppressive therapies. Each reactivation was treated with Lamivudine.DiscussionThis report suggests that a strict surveillance is important and cost-effective in HBcAb + HBsAg- NHL patients treated with mild immunosuppressive therapies, in order to detect an occult HBV reactivation.

Protease Inhibitor Vs. Non-Protease Inhibitor Based Antiretroviral Therapy In HIV-Infected Patients With Hodgkin and Non-Hodgkin Lymphoma Receiving Chemotherapy

▪HIV-infected individuals are at an increased risk of developing AIDS-defining cancers like high-grade B-cell non-Hodgkin lymphoma (NHL). Hodgkin lymphoma (HL), although not an AIDS-defining cancer, also occurs at increased frequency in HIV-infected patients. One of the main challenges that face clinicians is the high likelihood of Highly Active Antiretroviral Therapy (HAART) and chemotherapy drug-drug interactions. Antiretroviral agents that inhibit the metabolism of chemotherapy drugs may result in increasing the risk of adverse effects, which in turn could lead to life-threatening toxicities and treatment delays. On the other hand, antiretroviral agents that induce the metabolism of chemotherapy drugs may reduce their efficacy, and hence compromise treatment outcomes. Therefore, the choice of appropriate HAART regimen is essential when treating HIV-associated lymphomas.The aim of our study was to compare toxicities, response rates and survival outcomes in patients with HIV-associated lymphoma treated with chemotherapy according to whether patients received protease inhibitor (PI) or non-PI based HAART.This was a retrospective study, which included HIV-infected patients who were on HAART and treated with chemotherapy for NHL or HL from January 1st 2003 to December 31st2010 at a single institution. Patients were identified from the Haematology and Immunology departmental databases. All patients had biopsy proven lymphoma and were HIV positive at lymphoma diagnosis. We compared differences in adverse effects between patients on PI and non-PI based HAART. Univariate and multivariate logistic regression analyses were used to test for factors associated with grade 3-4 toxicities. Differences in response rates and overall survival (OS) between patients on PI vs. those on non-PI based HAART were also investigated.A total of 53 patients were included, n=37 with NHL and n=16 with HL. Of the 53 patients, 47% and 53% were on PI and non-PI based HAART, respectively. Median baseline CD4 cell count value for all 53 patients was 273 (range 14-970) cells/μL. Baseline HIV viral load (VL) was undetectable (<50 copies/mL) in 15 (28%) of 53 patients. By multivariate analysis, the use of PI-based cART was significantly associated with increased odds ratio (OR) of developing grade 3-4 neurotoxicity (OR= 11.42, 95% CI 1.7-76.49, p-value=0.012) and grade 3-4 infections (OR=14.08, 95% CI 2.13-93.07, p-value=0.006). By univariate analysis, the use of PI-based cART was significantly associated with decreased OR of completion of stage appropriate chemotherapy (OR=0.23, 95% CI 1.1-19.07, p-value=0.023). The complete remission (CR) or unconfirmed complete remission (CRu) rate at the end of treatment for 51 evaluable patients was 86%. The OS rate for all 53 patients was 77%, with a median OS of 53 (range, 3-121) months. There were no statistically significant differences in response rates or OS between patients receiving PI-based HAART and those receiving non-PI based HAART.This study demonstrated that PI-based HAART was significantly associated with more treatment related toxicities compared to non-PI based HAART in patients undergoing chemotherapy for HIV-associated lymphoma. However, there were no significant differences in survival outcomes or response rates between the two groups. If appropriate, non-PI based HAART should be considered during chemotherapy for HIV-associated lymphoma in order to minimize treatment-related toxicities. Disclosures:No relevant conflicts of interest to declare.

Concurrent Infection of Hepatitis B Virus Negatively Affects the Clinical Outcome and Prognosis of Patients with Non-Hodgkin’s Lymphoma after Chemotherapy

Hepatitis B virus (HBV) is hepatotropic and lymphotropic. HBV-infected individuals have an increased risk of developing malignant lymphoma, and the HBV infection rate in lymphoma patients is significantly higher than that in the general population. However, the exact mechanism and correlation between HBV infection and lymphoma onset and progression currently remain unclear. We retrospectively analyzed clinical data from non-Hodgkin’s lymphoma (NHL) patients with different HBV infection statuses. The results showed that the HBV infection rate was significantly higher in patients with B-cell type and late stage of NHL. The chemotherapy efficacy for NHL patients with chronic active HBV infection was significantly lower than that for the patients with chronic inactive HBV infection, the patients with HBV carriers and the patients without HBV infection. In addition, the NHL chemotherapy activated HBV replication and caused significant liver dysfunction, which could further reduce the chemotherapy efficacy. Through Kaplan-Meier survival curve and log-rank analysis, we found that the HBV infection status in NHL patients was significantly correlated with the patients’ progression-free survival (PFS) and overall survival (OS). Compared with the patients without HBV infection (PFS: 95% CI 47.915 to 55.640; OS: 95% CI 81.324 to 86.858), the PFS and OS of the patients with chronic active HBV infection were significantly shorter (PFS: 95% CI 9.424 to 42.589, P < 0.001; OS: 95% CI 42.840 to 82.259, P = 0.006). The study demonstrated that the sustained HBV replication in patients with chronic active HBV infection could be a key factor that influences the prognosis of NHL patients after chemotherapy, and thus may provide information for designing rational clinical treatments for NHL patients with different HBV infection statuses and improve the treatment efficacy and prognosis.