Cyclophosphamide, Doxorubicin, Vincristine, And Prednisone Chemotherapy Research Articles

Mosunetuzumab in combination with CHOP in previously untreated DLBCL: safety and efficacy results from a phase 2 study

AbstractUp to 40% of patients with diffuse large B-cell lymphoma (DLBCL) are refractory to or relapse after first-line therapy, highlighting the need for better treatments. Mosunetuzumab is a CD20 × CD3 bispecific antibody that engages and redirects T cells to eliminate malignant B cells. In this phase 2, open-label study (NCT03677141), 40 patients (52.5% with international prognostic index ≥3) with previously untreated DLBCL initiated 6 cycles of IV mosunetuzumab with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Mosunetuzumab was administered in cycle 1 as step-up doses to mitigate cytokine release syndrome [CRS], and a dose of 30 mg was given on day 1 of cycles 2-6. Efficacy end points included objective and complete response rates, as determined by the investigator, via positron emission tomography–computed tomography, using Lugano 2014 criteria (87.5% and 85.0%, respectively). At a median follow-up of 32.0 months, the estimated 2-year progression-free survival and event-free survival rates were 65.4% (95% confidence interval [CI], 49.5-81.4) and 60.4% (95% CI, 44.7-76.1), respectively. CRS occurred in 60.0% of patients; all events were grade 1 (45.0%) or grade 2 (15.0%) and occurred primarily in cycle 1. Mosunetuzumab-related grade ≥3 neurologic adverse events (AEs) potentially consistent with immune effector cell–associated neurotoxicity syndrome occurred in 1 patient (2.5%). Grade 5 AEs were reported in 2 patients. Neutropenia occurred in 70.0% of patients, mostly during cycle 1 and was of short duration. These findings demonstrate promising activity and a manageable safety profile for mosunetuzumab-CHOP and warrant further investigation of mosunetuzumab in first-line combination regimens for DLBCL.

Serum thymidine kinase 1 activity as a prognostic biomarker in dogs with chemotherapy-treated diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is frequently treated with chemotherapy incorporating cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP), which induces remission in 80% to 95% of cases. However, not all dogs derive meaningful benefit from CHOP, and prognostic factors for dogs with DLBCL are poorly defined. Serum thymidine kinase 1 (TK1) activity, a marker of tumour cell proliferation, has shown promising initial results as a prognostic biomarker in dogs with multicentric lymphomas. The purpose of this study was to determine if baseline serum TK1 activity is associated with clinical outcome in dogs with CHOP-treated DLBCL. Baseline serum TK1 activity was measured in banked sera from 98 dogs with CHOP-treated DLBCL using a commercially available ELISA kit. Data on other potential prognostic factors were abstracted retrospectively from electronic medical records. Multivariable statistical methods were used to identify associations between TK1 and other potential prognostic factors with progression-free survival (PFS) and attainment of complete remission. TK1 activity at baseline was not associated with PFS (p=.299) or attainment of complete remission (p=.910) following CHOP chemotherapy. Of the other prognostic factors analysed, only purebred (vs. mixed breed) status (HR 8.81, 95% CI 1.68-46.30, p=.010), attainment of complete (vs. partial) remission (HR 0.09, 95% CI 0.02-0.49, p=.006), and baseline serum C-reactive protein concentration (HR 1.19, 95% CI 1.07-1.32, p=.001) were independently associated with PFS. Based on these findings, baseline serum TK1 activity does not appear to be a useful prognostic biomarker in dogs with CHOP-treated DLBCL.

Long-Term Outcomes of Patients Aged 65 Years or Older with Peripheral T-Cell Lymphoma, Not Otherwise Specified (PTCL-NOS) and T-Follicular Helper T-Cell Lymphoma (TFHTCL) Treated with Curative Intent CHOP(like) Chemotherapy

Introduction CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the standard treatment for older adults with non-anaplastic large cell lymphoma (ALCL), nodal peripheral T-cell lymphomas (PTCLs). However, recent studies suggest that patients (pts) > 75 years (y) have similar outcomes with CHOP compared to those receiving palliative regimens (Ellin et al. Hematological Oncology 2017). In addition, with studies demonstrating sensitivity of PTCLs to epigenetic therapies, especially in the T-follicular helper (TFH) subtypes, there are emerging clinical trials evaluating these agents in newly diagnosed PTCL patients > 60 y (NCT02232516). We evaluated the long-term outcomes of pts aged 65 y or older with PTCLs, a group generally not transplant eligible, treated with systemic therapy with a focus on those treated with curative intent CHOP(like) chemotherapy. Methods The BC Cancer Lymphoid Cancer Database was reviewed and pts > 65 years with PTCL, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL) as well as other T-Follicular Helper PTCL (collectively referred to as TFH T-cell lymphoma [TFHTCL]) diagnosed between 2000-2021 and who received front-line chemotherapy were included. Diagnoses were based on the World Health Organization (WHO) classifications of 2001, 2008, and 2017, depending on the era of diagnosis. Time to progression (TTP) was measured from the date of pathologic diagnosis to the date of relapse/progression, death due to treatment toxicity or lymphoma. Results 152 pts were initially identified, of which 5 were excluded: stage IA/IAE (n=3); CNS involvement only (n=2). Of the remaining 147 pts, 67 (46%) had PTCL-NOS and 80 (54%) had TFHTCL. The median age was 74 y (range 65-90) and the majority of pts had high risk features: International Prognostic Index (IPI) score of > 3 (n=113, 76%), stage III/IV disease (n=136, 93%) and PS of > 2 (n=85, 58%). Most pts (n=127, 86%) received multi-agent chemotherapy with curative intent. All pts received CHOP/CHOP-like chemotherapy (including five pts treated with CHP-brentuximab vedotin)Over half of these patients (n=66, 52%) received attenuated doses of chemotherapy starting from cycle 1, typically 50-75% dose intensity. Only two patients received consolidative autologous stem cell transplant. The remaining 20 patients received chemotherapy with palliative treatment intent, the majority (n=18, 90%) receiving cyclophosphamide alone or with the CVP (cyclophosphamide, vincristine, and prednisone) regimen. The median follow-up of all pts using the reverse Kaplan-Meier method was 9.2 y (range 0.9 to 12.5). The estimated 5-y TTP and overall survival (OS) for all patients were 21%, and 26%, respectively. Outcomes were similar in PTCL-NOS and TFHTCL (5-y TTP 17% vs 25%; p = 0.26). Curative intent chemotherapy was used more frequently in the 65-74 y vs > 75 y age group (70% vs 36%, p = 0.004). As expected, outcomes were superior in those treated with curative intent (Table 1): Median TTP of 11.3 months (m) vs 3.0 m; median OS of 24 m vs 4.5 m. Improvements in TTP and OS extended to those > 75 y (p < 0.001 for both). Considering the curative intent cohort, 91% of the relapse/progression events occurred within the first 3 y, and there was no significant difference in outcomes (5-y TTP/OS) with increasing age: 65-75 (19%/25%), >75 (34%/35%) (p = 0.08/0.6). Further, the outcomes of pts who received attenuated doses of CHOP-like chemotherapy were not inferior compared to full dose chemotherapy (5-y TTP/OS 32%/37% vs. 17%/21% p= 0.2/0.3). 5-y TTP/OS by the IPI ranged from 30%/52% for IPI of 1-2 to 12%/14% for IPI 4-5. The prognostic index for T-cell lymphoma (PIT) was more effective at identifying a lower risk group: 5-y TTP/ OS (PIT 1 40%/57%; PIT 2 21%/28%; PIT 3 21%/20% PIT 4 9%/10%, p = 0.002/0.001). Both models were prognostic in PTCL-NOS and TFHTCL. (Table 1) Conclusion With mature follow-up, ~ 30% of all older pts treated with curative intent CHOP-like chemotherapy remain progression-free and are alive at 5 y. Although results remain suboptimal, robust older patients can still be considered for curative intent CHOP chemotherapy with tailored doses to mitigate toxicity. Those with low risk IPI/PIT scores have a more favourable outcome with this approach, with a 5-y OS of > 50%, suggesting a benefit of subsequent therapies. In contrast, higher risk disease have poor outcomes and novel therapeutic approaches should be considered. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

KIR2DS1–HLA-C status as a predictive marker for benefit from rituximab: a post-hoc analysis of the RICOVER-60 and CLL8 trials

The addition of rituximab to chemotherapy has substantially improved outcomes for patients with B-cell malignancies. The mechanisms of action of rituximab include activation of natural killer cells. Killer-cell immunoglobulin-like receptors (KIRs) mediate natural killer cell function through interaction with HLA. We evaluated the clinical impact of KIR-HLA genotypes on rituximab-containing therapy. For this post-hoc analysis, we used data from the RICOVER-60 trial (NCT00052936) as the discovery cohort and the CLL8 trial (NCT00281918) as the validation cohort. RICOVER-60 included patients aged 61-80 years with aggressive B-cell lymphoma treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with or without rituximab. CLL8 included patients aged 30-81 years with chronic lymphocytic leukaemia treated with chemotherapy (fludarabine and cyclophosphamide; FC) with or without rituximab. We evaluated the KIR and HLA-C status of 519 patients with available blood samples in the RICOVER-60 trial and the KIR2DS1 and HLA-C status of 549 patients with available blood samples in the CLL8 trial, and evaluated their associations with event-free survival (RICOVER-60), progression-free survival, and overall survival (RICOVER-60 and CLL8). In the RICOVER-60 trial, 201 (39%) patients were positive for KIR2DS1, 79 (15%) were homozygous for HLA-C2, and 36 (7%) were positive for KIR2DS1 and homozygous for HLA-C2. In the CLL8 trial, 206 (38%) patients were positive for KIR2DS1, 75 (14%) were homozygous for HLA-C2, and 26 (5%) were positive for KIR2DS1 and homozygous for HLA-C2. In the RICOVER-60 trial, both KIR2DS1 and HLA-C status were identified as independent risk factors for survival. KIR2DS1 positivity, homozygosity for HLA-C2, and subsequent KIR2DS1-HLA-C status were associated with adverse clinical outcome in patients receiving rituximab-containing therapy (event-free survival for patients with KIR2DS1-HLA-C2/C2 vs all other patients, HR 2·6 [95% CI 1·4-4·7], p=0·0015; progression-free survival, 2·7 [1·5-5·1], p=0·0013; overall survival, 2·8 [1·5-5·4], p=0·0016) but not in patients receiving CHOP chemotherapy only (event-free survival, 0·9 [0·5-1·7], p=0·85; progression-free survival, 1·1 [0·6-2·0], p=0·81; overall survival, 1·2 [0·6-2·4], p=0·53). A significant interaction between KIR2DS1-HLA-C status and rituximab was observed (p=0·018 for event-free survival and p=0·034 for progression-free survival). In contrast to all other patients, those positive for KIR2DS1 and homozygous for HLA-C2 did not benefit from adding rituximab to CHOP chemotherapy (event-free survival, 1·9 [0·8-4·6], p=0·16; progression-free survival, 1·4 [0·6-3·4], p=0·48; overall survival, 1·6 [0·6-4·3], p=0·33). In the CLL8 trial, KIR2DS1-HLA-C status was confirmed as a predictive marker for benefit from rituximab therapy (p=0·024 for the interaction of KIR2DS1-HLA-C status and rituximab regarding progression-free survival). In contrast to all other patients, those positive for KIR2DS1 and homozygous for HLA-C2 did not benefit from adding rituximab to FC chemotherapy (progression-free survival, 2·1 [0·9-4·9], p=0·094; overall survival, 2·6 [0·5-12·7], p=0·21). Assessment of KIR2DS1 and HLA-C genotype might identify patients who would not benefit from rituximab, thereby allowing alternative therapies to be given. Further validation of these findings in prospective clinical trials is needed. F Hoffman La Roche.

Concentração de proteínas de fase aguda e vitamina D em cães com linfoma multicêntrico

Abstract This study aimed to evaluate the serum concentration of vitamin D (25-Hydroxyvitamin D) and acute phase proteins (APPs; alpha-1 acid glycoprotein, haptoglobin, transferrin, ceruloplasmin, albumin, IgA, IgG and alpha-1 - antitrypsin) as potential biomarkers for prognostic and therapy response in dogs with multicentric lymphoma submitted to the CHOP (Cyclophosphamide, Doxorubicin, Vincristine and Prednisone) chemotherapy protocol. Thirteen dogs with multicentric lymphoma classified as high grade by cytology were included in the treatment group (GL), while ten healthy dogs were included in the control group (GC). Serum was collected in the weeks T0, T5 and T10 of CHOP chemotherapy protocol, for the GL group, and in a single collection, for the GC group. All the collected samples were evaluated for the APPs and vitamin D concentrations through electrophoresis and chemiluminescence methods, respectively. Diagnostic and staging tests were performed for all the dogs in the GL group, and included cytopathology, histopathology and immunohistochemistry of the affected lymph node. Of these dogs, 9 achieved a complete response and 4 a partial response to the treatment. Data analysis was performed with the R software. The results demonstrated that serum concentrations of IgA, haptoglobin and α1-acid glycoprotein were significantly different between the groups and also between the different chemotherapy times analyzed (p&lt;0.05), indicating that these proteins can be considered as sensitive biomarkers for lymphoma in dogs. Furthermore, the α1-acid glycoprotein showed prognostic value for the disease, with 63% specificity. However, vitamin D concentration was not correlated with prognosis of the dogs with lymphoma.

Glycemic Control of Non-Hodgkin Lymphoma (NHL) Non-Diabetes Mellitus (DM) Patient in the First CHOP Chemotherapy

Non-Hodgkin’s lymphoma (NHL) chemotherapy is cyclophosphamide, doxorubicin, vincristine, andprednisone (CHOP) have hyperglycemia side effects that affect the success of chemotherapy. Improvedglycemic control decreases morbidity and mortality. Determine the glycemic control changes in non-DMNHL patients before and the sixth day after the first CHOP chemotherapy.Method: Prospective longitudinal observational analytic study in the Internal Medicine Inpatient Unit Dr.Soetomo Teaching Hospital Surabaya, involved all the first CHOP chemotherapy NHL patients duringNovember 2019-February 2020. A total of 21 patients met chemotherapy requirements and were not DM.The glycemic control check uses the hexokinase method and a glucometer (Easy Touch®). Data analysisusing the Wilcoxon test was considered significant if p <0.05.Results: Total research subjects were 21 people, female domination (66.7%), mean age 49.24 ± 13.96 years,clinical stage 3 dominance (52.38%), mean HbA1C 5.75 ± 0.49%, average FBG 90.86 ± 13.13 mg/dL, themean PPBG 114.33 ± 20.16 mg/dL. Daily blood glucose levels during chemotherapy were highest on thefirst day’s pre-dinner. There were significant differences in FBG and PPBG before chemotherapy and thesixth day after chemotherapy (p-values 0.032 and 0.002). The incidence of new-onset DM on the sixth dayafter the first CHOP chemotherapy was 2 subjects (9.53%).Conclusion: There was an increase in FBG and PPBG of NHL non-DM patients before and the sixth dayafter the first CHOP chemotherapy

Chidamide combined with cyclophosphamide, doxorubicin, vincristine and prednisone in previously untreated patients with peripheral T-cell lymphoma.

ObjectiveChidamide is an oral histone deacetylase subtype-selective inhibitor approved for relapsed or refractory peripheral T-cell lymphoma (PTCL). This phase 1b study evaluated the safety, pharmacokinetics, and preliminary efficacy of chidamide in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) for treatment-naïve PTCL patients.MethodsThis study was an open-label, multicenter trial composed of dose escalation and dose expansion. Patients received CHOP for six 21-d cycles and chidamide on d 1, 4, 8 and 11 in each cycle. Four dose levels of chidamide (20, 25, 30 and 35 mg) were evaluated. The primary objective was to evaluate the safety and tolerability of the combination regimen.ResultsA total of 30 patients were evaluated in this study: 15 in the dose-escalation part and 15 in the dose-expansion part. In the dose-escalation study, three patients were enrolled in the 35 mg chidamide cohort. One had dose-limiting toxicity with grade 3 vascular access complications, and one had grade 2 neutropenia with a sustained temperature >38 °C. Dose escalation was stopped at this chidamide dose level. The most common (≥10%) grade 3 or 4 adverse events (AEs) were leukopenia (90.0%), neutropenia (83.3%), vomiting (13.3%), thrombocytopenia (10.0%) and febrile neutropenia (10.0%). No significant changes in chidamide pharmacokinetic properties were observed before and after combination treatment. The objective response rate for the 28 patients evaluable for preliminary efficacy was 89.3% (25/28), with 16 (57.1%) achieving complete response or unconfirmed complete response. The estimated median progression-free survival was 14.0 months. In summary, we chose chidamide 30 mg as the recommended dose for phase 2.ConclusionsThe addition of chidamide to standard CHOP chemotherapy was tolerable with promising preliminary efficacy in previously untreated PTCL patients, which supports further clinical studies with this combination regimen for the frontline treatment of PTCL.

The adhesion molecule ICAM-1 in diffuse large B-cell lymphoma post-rituximab era: relationship with prognostic importance and rituximab resistance.

Intercellular adhesion molecule-1 (ICAM-1) is a cell-surface receptor contributing to lymphocyte homing, adhesion and activation. The prognostic significance of the protein is unknown in diffuse large B-cell lymphoma (DLBCL) in post-rituximab era. We detected expression of ICAM-1 immunohistochemically in 102 DLBCL tissue samples. Overexpression of ICAM-1 was found in 28 (27.5%) cases. In patients with low ICAM-1 expression levels, the addition of rituximab to CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy resulted in an improved overall response rate, progression-free survival (PFS) and overall survival (OS) (P=0.019, 0.01, 0.02). In pre-clinical models, we found that chronic exposure of cell lines to rituximab led to downregulation of ICAM-1 and acquirement of a rituximab resistant phenotype. In vitro exposure of rituximab resulted in rapid aggregation of B-cells regardless of the ICAM-1 expression levels. MTT assay showed knockdown of ICAM-1 could cause rituximab resistance. Neutralization of ICAM-1 did not affect rituximab activity in vitro and in vivo. Our data illustrated that in post-rituximab era, R-CHOP significantly improved the ORR, PFS and OS in ICAM-1 negative subset patients. Downregulation of ICAM-1 may contribute to rituximab resistance, and that rituximab, by promoting cell-cell aggregation, may sensitize cells to the cytotoxic effects of chemotherapy agents.

High Sensitivity Troponin T as Complementary Modality for Determining Doxorubicin Regimen Cardiotoxicity in Non-Hodgkin Lymphoma Patients.

Purpose: This study aims to evaluate the role of high-sensitivity troponin T (hsTnT) as a complementary tool for determining cardiotoxicity in non-Hodgkin lymphoma (NHL) patients receiving cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen chemotherapy. Methods: We included 35 patients diagnosed with NHL who received CHOP chemotherapy. Left ventricular ejection fraction (LVEF) and hsTnT were measured at two time points: before the first cycle (pre-test) and after the fourth cycle (post-test). The LVEF and hsTnT were analysed using IBM SPSS version 24 through the paired-sample T-test, Wilcoxon signed-rank test, Pearson’s correlation and Spearman’s correlation. Results: There was a significant difference in both LVEF and hsTnT between pre-chemotherapy and post-4th chemotherapy cycles (P = 0.001). However, more contrast difference from the baseline value of hsTnT compared to LVEF could be observed. LVEF did not detect any deterioration in myocardial function. However, 10 out of 35 subjects exhibit hsTnT higher than the 99th percentile of the population (>14 pg/ml), suggesting that myocardial injury (MI) could be detected. There was no correlation between LVEF and hsTnT (P > 0.05). Conclusion: HsTnT, together with LVEF, could complement each other and offer better coverage for detecting cardiotoxicity during the administration of CHOP in NHL patients. An insignificant correlation between hsTnT and LVEF showed that cardiotoxicity existed in a broad spectrum including cellular damage and functional impairment, as hsTnT represents cellular damage, and LVEF reflects heart functional capacity.

Response-adapted therapy with infusional EPOCH chemotherapy plus rituximab in HIV-associated, B-cell non-Hodgkin's lymphoma.

Four cycles of rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy is as effective as six cycles in low-risk diffuse large B-cell lymphoma (DLBCL). Here we report a post-hoc analysis of a prospective clinical trial in patients with human immunodeficiency virus-associated DLBCL and high-grade lymphoma treated with four to six cycles of EPOCH plus rituximab based on a response-adapted treatment strategy. One hundred and six evaluable patients with human immunodeficiency virus-associated DLBCL or highgrade CD20+ non-Hodgkin lymphoma were randomized to receive rituximab (375 mg/m2) given either concurrently prior to each infusional EPOCH cycle, or sequentially (weekly for 6 weeks) following completion of EPOCH. EPOCH consisted of a 96-hour intravenous infusion of etoposide, doxorubicin, and vincristine plus oral prednisone followed by an intravenous bolus of cyclophosphamide every 21 days for four to six cycles. Patients received two additional cycles of therapy after documentation of a complete response by computed tomography after cycles 2 and 4. Sixty-four of 106 evaluable patients (60%; 95% confidence interval [95% CI]: 50%-70%) in both treatment arms had a complete response. The 2-year event-free survival rates were similar in the 24 patients with complete response who received four or fewer cycles of EPOCH (78%; 95% CI: 55%-90%) due to having achieved a complete response after two cycles, compared with those who received five or six cycles of EPOCH (85%; 95% CI: 70%-93%) because a complete response was first documented after cycle 4. A response-adapted strategy may permit a shorter treatment duration without compromising therapeutic efficacy in patients with human immunodeficiency virus-associated lymphoma treated with EPOCH plus rituximab, which merits further evaluation in additional prospective trials. Clinical Trials.gov identifier NCT00049036.

WEE1 inhibition synergizes with CHOP chemotherapy and radiation therapy through induction of premature mitotic entry and DNA damage in diffuse large B-cell lymphoma.

Background:Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, characterized by high levels of genomic instability and the activation of DNA damage repair pathways. We previously found high expression of the cell cycle regulator WEE1 in DLBCL cell lines. Here, we investigated the combination of the WEE1 inhibitor, AZD1775, with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) and radiation therapy (RT), with the aim of improving first-line treatment.Methods:Cell viability experiments were performed to determine synergistic combinations. Levels of DNA damage were established using flow cytometry for γH2AX and protein analysis for DNA damage response proteins CHK1 and CHK2. Flow cytometry analysis for cell cycle and pH3 were performed to determine cell cycle distribution and premature mitotic entry.Results:Treatment with either RT or CHOP led to enhanced sensitivity to AZD1775 in several DLBCL cell lines. Treatment of cells with AZD1775 induced unscheduled mitotic progression, resulting in abnormal cell cycle distribution in combination with RT or CHOP treatment. In addition, a significant increase in DNA damage was observed compared with CHOP or RT alone. Of the single CHOP components, doxorubicin showed the strongest effect together with AZD1775, reducing viability and increasing DNA damage.Conclusion:In conclusion, the combination of RT or CHOP with AZD1775 enhances sensitivity to WEE1 inhibition through unscheduled G2/M progression, leading to increased DNA damage. Based on these results, WEE1 inhibition has great potential together with other G2/M arresting or DNA damaging (chemo) therapeutic compounds and should be further explored in clinical trials.

Lymphoid Neoplasms With Plasmablastic Differentiation: A Comprehensive Review and Diagnostic Approaches.

Plasmablastic neoplasms encompass several entities including plasmablastic lymphoma, plasmablastic plasmacytoma/multiple myeloma, primary effusion lymphoma and its extracavitary variant, anaplastic lymphoma kinase-positive large B-cell lymphoma, and Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 (HHV8)-positive diffuse large B-cell lymphoma, not otherwise specified. Morphologically, the tumor cells are large with eccentrically located nuclei, prominent nucleoli, and basophilic/amphophilic cytoplasm. Immunophenotypically, the tumor cells express plasma cell-related antigens including CD38, CD138, interferon regulatory factor-4 (IRF4)/MUM1, PR domain zinc finger protein-1 (PRDM1), and/or X-box binding protein-1 (XBP1), with frequent loss of CD20. These tumors are diagnostically challenging for general pathologists due to their overlapping morphology and immunophenotype, and due to their rarity, and particularly so when clinical and radiologic information is insufficient. We also discuss HHV8-negative effusion-based lymphoma due to its overlapping features with primary effusion lymphoma. In this review, we focus on the useful diagnostic markers and pertinent molecular findings in these distinct entities and propose a practical diagnostic algorithm using anaplastic lymphoma kinase, HHV8, in situ hybridization for Epstein-Barr virus-encoded small RNA, immunoglobulin M, light chain stains, and clinicoradiologic criteria to avoid misdiagnosis. At the molecular level, MYC protein overexpression with or without MYC rearrangement and PRDM1-inactivating mutations or deletions are noted in a subset of such tumors, especially in plasmablastic lymphoma. Prognosis in these entities is dismal with conventional CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Therefore, novel target therapies, such as anti-CD30 agents, and/or immune blockade therapy, are potential treatment options in the future.

Detection of the Incidence of Infections and Acute Biochemical Changes in Diffused Large B-Cell Lymphoma Patients Treated with Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (CHOP) with and without Rituximab

Acute biochemical changes, hepatotoxicity, nephrotoxicity and frequency of infections are common in diffuse large B-cell Lymphoma patients undergoing Cyclophosphamide, Doxorubicin, Oncovin (Vincristine) Prednisone (CHOP) and Rituximab plus CHOP chemo cycles. Eventually, it leads to prolonging hospital stay and suspending the next chemotherapy cycles. The objectives of our study were to determine the changes in biochemical disturbances induced by CHOP or RCHOP and second objective was to compare the effect of CHOP with or without rituximab on the incidence of the infections such as (Cytomegalovirus, Herpes Simplex Virus and Varicella-Zoster virus), bacterial infections and tuberculosis. Files were prospectively reviewed during the tenure of 2014-2016. Participants aged greater than or equal to 18 years old with a known case of DLBCL undergoing CHOP or RCHOP chemotherapy were allowed to be included in the study. Baseline and posttreatment patients profile of blood chemistry, liver functions test was collected and compared with the Common Terminology Criteria for adverse events v3.0 2009 CTCAE 2009 and the data regarding infection of Cytomegalovirus, Herpes Simplex Virus and Vericella-Zoster virus, bacterial infections and tuberculosis were drawn from the participant's profile. Patients treated with CHOP therapy showed a significant difference of Alkaline Phosphatase (ALP) (p-value 0.009), direct bilirubin (p-value 0.034) and serum glutamic-pyruvic transaminase (SGPT) (p-value 0.004). Bacterial Pneumonia was only 1 (5%) and 1 (5%) CMV reported positive after the R-CHOP. We propose that liver profile including (bilirubin, SGOT and SGPT) Urea, Creatinine and electrolytes should strictly be considered if found deranged before every treatment cycle and suspend chemotherapy in case of moderate or severe toxicity.

Elevated serum interleukin-10 level and M2 macrophage infiltration are associated with poor survival in angioimmunoblastic T-cell lymphoma.

Interleukin-10 (IL-10) induces an immunosuppressive microenvironment including M2 macrophages, inhibiting anti-tumor immunity. The aim of this study was to evaluate whether serum IL-10 level at diagnosis and tissue infiltration of M2 macrophages could predict survival outcome of patients with angioimmunoblastic T-cell lymphoma (AITL).We measured serum levels of IL-5, IL-10, IL-12, and interferon-gamma (IFN-γ) at diagnosis in AITL and other common subtypes of nodal T-cell lymphoma including peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), ALK-negative anaplastic large cell lymphoma (ALCL) or ALK-positive ALCL between September 2008 and December 2014. We also analyzed the infiltration of CD68- and CD163-positive macrophages in tumor tissue of AITL. In total, 97 patients with AITL (n=37), PTCL-NOS (n=40), ALK-negative ALCL (n=11), or ALK-positive ALCL (n=9) were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). Among cytokines, only the serum level of IL-10 was significantly higher in AITL patients than in other subtypes (P < 0.05). Compared to other subtypes, the association of serum IL-10 with overall survival (OS) was only significant in AITL. Accordingly, the response to CHOP chemotherapy was significantly worse in the high IL-10 group, and infiltration of CD163-positive M2 macrophages was significantly associated with OS in AITL. In conclusion, this study demonstrated the prognostic relevance of serum IL-10 and tissue infiltration of M2 macrophages in AITL patients. Our results suggest the possible use of these variables as potential therapeutic targets and novel prognostic indicators in patients with AITL.

Efficacy of CHOP chemotherapy on unspecified peripheral T cell lymphoma in patients aged 80 years and over and its prognostic analysis

Objective To evaluate the efficacy of CHOP(cyclophosphamide, doxorubicin, vincristine, and prednisone)chemotherapy on peripheral T cell lymphomas-unspecified(PTCL-U)in patients aged 80 years and over, and investigate the chemotherapy adverse effects and its prognostic factors. Methods Clinical data of 57 patients with PTCL-U confirmed by pathology and immunohistochemistry in Guangzhou First People's Hospital from January 2008 to January 2015 were retrospectively analyzed. The efficacy and adverse effects of CHOP chemotherapy, and its prognostic factors were evaluated. Results Of 57 patients, 11(19.3%)achieved complete remission, 23(40.4%)had partial remission, 14(24.6%)had stable disease, and 9(15.8%)had progressive disease after CHOP chemotherapy, with a total effective rate of 59.6%(34 cases). The expected 1-year, 2-year and 3-year overall survival(OS)rate was 70.2%(40 cases), 36.8%(21 cases) and 17.5%(10 cases), respectively. The median survival time was 18.2 months. Among the 57 patients, 40(70.2%)had hypoplasia of bone marrow at degreeⅠ-Ⅱ, 17(29.8%)at degree Ⅲ-Ⅳ, 49(86.0%)had mild nausea and vomiting(degreeⅠ-Ⅱ), 8(14.0%)had severe nausea and vomiting(degree Ⅲ-Ⅳ), 7 had liver dysfunction, 2 had cardiac toxicity and 7 had disturbance of blood coagulation. Univariate analysis showed that the alkaline phosphatase, Ki-67 percentage, lymphoma international prognostic index(IPI)score, extranodal involved sites(>1), as well as the efficacy and course of chemotherapy were the prognostic factors for survival time in very elderly patients. Multivariate analysis indicated that IPI score>2(95%CI: 1.12~6.35, χ2=5.45, P 1)(95%CI: 2.58-15.32, χ2=16.42, P 4)(5%CI: 0.18~0.79, χ2=7.28, P<0.01)were the independent prognostic factors for the median survival time in very elderly patients. Conclusions PTCL-U patients aged 80 years and over have poor prognosis. CHOP chemotherapy has a certain effect on PTCL-U in very elderly patients, and chemotherapy side effects can be tolerated. IPI score>2 and extranodal involved sites(>1)are the important prognostic factors in very elderly PTCL-U patients. The completion of full course of chemotherapy with remission occurrence is important to prolong survival time in very elderly PTCL-U patients. Key words: Lymphoma, T-cell, Peripheral; Antineoplastic combined chemotherapy protocols; Elderly, aged over 80 years; Prognosis

Retrospective analysis for treatment of naïve canine multicentric lymphoma with a 15-week, maintenance-free CHOP protocol.

Standard of care treatment of dogs with multicentric lymphoma includes combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP); however, owners may be hesitant to commit the resources necessary to complete a lengthy, multi-drug protocol. One hundred thirty-four client-owned dogs with multicentric lymphoma were treated with a 15-week CHOP chemotherapy protocol. The overall response rate was 98% with 104 dogs experiencing a complete response (CR). The median progression-free survival (PFS) time for all dogs was 176 days, and the median disease-specific overall survival time was 311 days. Prognostic factors identified on multivariate analysis as significant for PFS included substage, immunophenotype, hospitalization for adverse events, need for dose reduction, presence of neutrophilia at diagnosis, presence of anemia and experiencing a CR as best response to therapy. In conclusion, this protocol may be a viable alternative to CHOP protocols using a larger number of treatments.

Long-term efficacy of CHOP-based chemotherapy alone or combined with radiotherapy for adolescent/childhood primary systemic anaplastic large-cell lymphoma

Objective To investigate the long-term efficacy of CHOP (cyclophosphamide,doxorubicin,vincristine,and prednisone)-based chemotherapy alone or combined with regional radiotherapy for adolescent/childhood primary systemic anaplastic large-cell lymphoma (ALCL).Methods A retrospective analysis was performed on the medical records of 28 patients not older than 21 years with a confirmed diagnosis of primary systemic ALCL,who were admitted to our hospital from January 1998 to December 2010.Of 12 stage Ⅰ / Ⅱ patients,2 received chemotherapy alone,and 10 received chemotherapy and radiotherapy;of 16 stage Ⅲ/Ⅳ patients,14 received chemotherapy alone,and 2 received chemotherapy and radiotherapy.CHOP regimen was adopted in 15 patients,and CHOP regimen combined with other highintensity regimens was adopted in 13 patients.There were 3-17 chemotherapy cycles (median:6 cycles).Radiotherapy was performed mainly by involved field radiation,with a dose of 39.6-50.0 Gy (median:45 Gy).Results After the first course of treatment,25 (89％) of all patients achieved a complete remission (CR),and 3 patients experienced disease progression.With a median follow-up of 45.3 months,the 5-year event-free survival (EFS) and overall survival (OS) for all patients were 80％ and 93％,respectively.The 5-year OS was 100％ for patients achieving a CR after treatment,versus 0％ for those not achieving a CR (P =0.000).The 5-year EFS was 38 ％ for patients with involvement of ≥ 2 extranodal organs,versus 85 ％ for those with involvement of ＜ 2 extranodal organs (P =0.010).Conclusions CHOP chemotherapy combined with regional radiotherapy (for patients with localized disease) is an effective treatment for adolescent/childhood primary systemic ALCL,but long-term follow-up is needed to investigate treatmentrelated toxicities. Key words: Lymphoma, anaplastic large cell; Lymphoma, adolescent; Lymphoma, childhood; Chemotherapy ; Radiotherapy; Prognosis

Survival and failure outcomes in PCNSL with WBRT followed by CHOP Chemotherapy: An alternative treatment approach in community settings in low resource countries

Introduction: Primary central nervous system lymphoma (PCNSL) is relatively uncommon malignancy with potentially aggressive behavior. The standard management of PCNSL is high-dose methotrexate (HD-MTX) based chemotherapy and whole brain radiotherapy (WBRT). This treatment is associated with toxicity and requires in-patient admission with intensive monitoring. An alternative approach with WBRT followed by systemic chemotherapy with standard cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen can be used in community settings in a cohort of patients who cannot receive the standard treatment due to logistic reasons. Materials and Methods: We retrospectively reviewed the patients of PCNSL treated in our institute from January 2004 to May 2010. A total of 39 patients of PCNSL were treated. All patients received WBRT followed by systemic chemotherapy with standard CHOP regimen. Survival analysis was done with Kaplan-Meier method using Statistical Package for Statistical Analysis (SPSS version 15). Prognostic factor influencing survival was evaluated using Cox regression analysis. Toxicity and overall treatment compliance analysis was also evaluated. Results: Overall compliance to RT and chemotherapy was excellent, 37 (94.9%) patients completed planned treatment within the stipulated time period. Grades II-III skin toxicity was seen in three patients and Grade II hematological toxicity was seen in two patients. At 1 month after completion of planned treatment, 15 patients had no symptoms and 20 patients had significant improvement while four patients deteriorated clinically while radiological imaging showed complete response, partial response, progression of disease in 22, 12 and 5 patients respectively. Mean overall survival (OS) was 36.34 months and median OS was 20.0 months with 3-year actuarial OS of 38%. Age of 50-year was a significant (P < 0.05) prognostic factor for survival. Conclusions: The standard of care in management of PCNSL is HD-MTX based chemotherapy. However, considering poor compliance and tolerability to treatment in low resource countries in routine clinical setting, WBRT followed by systemic chemotherapy with standard CHOP regimen for treatment of PCNSL demonstrate reasonably good outcome. This regimen is quite economic as well as simple to implement.

Gastric plasmablastic lymphoma in HIV-negative patient

An 82-year-old female patient presented with melena, epigastric pain, progressive abdomen fullness and weight loss (8 kg) in the past 2 months. During physical examination, cutaneous pallor was evident and a large abdominal mass in epigastrium was palpable. There was no peripheric lymphadenopathy or hepatosplenomegaly. Blood count showed microcytic anemia and ferropenia (Hb = 7.5 g/dl, VGM = 79 fL; ferritin = 21 g/l, iron saturation = 23 %). Differential leukocyte counts, hepatic transaminase and lactate dehydrogenate levels were within normal limits. Upper gastrointestinal endoscopy revealed large gastric body ulceration with areas of mucosal hyperemia and pallor (Fig. 1). Computed tomography of the abdomen (Fig. 2) showed diffuse wall thickening involving the gastric fundus, body and antrum. Histological examination of the biopsy specimens revealed a diffuse, monomorphous proliferation of the tumour cells with features of immunoblasts, CD138, MUM-1, and kappa light chains positive (Fig. 3). These plasmablast-like features of tumour cells and lack of CD45 and B-cell associated antigens, disclosed the diagnosis of plasmablastic lymphoma (PBL). Serology was negative for the human immunodeficiency virus (HIV), the electrophoretic pattern of serum proteins was normal and the bone marrow biopsy was free of lymphoma at histological evaluation. The patient started treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy, but died before the second cycle was given.

Clinical features of de novo CD25+ diffuse large B-cell lymphoma

CD25 (interluekin-2 receptor) expression in diffuse large B-cell lymphoma (DLBCL) cells has been not examined. To characterize CD25+ DLBCL, 123 patients, who were newly diagnosed with DLBCL, were analyzed by single-color flow cytometry (FCM). CD25-positivity was significantly higher in DLBCL patients (n = 123; mean ± SD, 27.8 ± 30.6%) than in those with reactive lymphadenopathy (n = 16; mean ± SD, 8.6 ± 4.3%) and follicular lymphoma (n = 60; mean ± SD, 12.7 ± 12.4%). By two-color FCM, CD25/CD19 or CD25/CD20 dual positivity in DLBCL patients was shown: mean ± SD, 63.7 ± 25.5% (n = 13) and 55.0 ± 28.1% (n = 14), respectively. Eighty-two percent of the patients with DLBCL received rituximab combined with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy. A cut-off value of 60% with CD25-positivity clearly divided patients with DLBCL into two groups: CD25-high or CD25-low DLBCL. Although clinical and immunophenotypic features were not significantly different in both groups, the former showed a significantly poorer response and more inferior progression-free survival than the latter. CD25 may be a new prognostic marker and could be a therapeutic target in DLBCL.