Adriamycin, Bleomycin, Vinblastine And Dacarbazine Research Articles

On the challenges of predicting treatment response in Hodgkin’s Lymphoma using transcriptomic data

BackgroundDespite the advancements in multiagent chemotherapy in the past years, up to 10% of Hodgkin’s Lymphoma (HL) cases are refractory to treatment and, after remission, patients experience an elevated risk of death from all causes. These complications are dependent on the treatment and therefore an increase in the prognostic accuracy of HL can help improve these outcomes and control treatment-related toxicity. Due to the low incidence of this cancer, there is a lack of works comprehensively assessing the predictability of treatment response, especially by resorting to machine learning (ML) advances and high-throughput technologies.MethodsWe present a methodology for predicting treatment response after two courses of Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) chemotherapy, through the analysis of gene expression profiles using state-of-the-art ML algorithms. We work with expression levels of tumor samples of Classical Hodgkin’s Lymphoma patients, obtained through the NanoString’s nCounter platform. The presented approach combines dimensionality reduction procedures and hyperparameter optimization of various elected classifiers to retrieve reference predictability levels of refractory response to ABVD treatment using the regulatory profile of diagnostic tumor samples. In addition, we propose a data transformation procedure to map the original data space into a more discriminative one using biclustering, where features correspond to discriminative putative regulatory modules.ResultsThrough an ensemble of feature selection procedures, we identify a set of 14 genes highly representative of the result of an fuorodeoxyglucose Positron Emission Tomography (FDG-PET) after two courses of ABVD chemotherapy. The proposed methodology further presents an increased performance against reference levels, with the proposed space transformation yielding improvements in the majority of the tested predictive models (e.g. Decision Trees show an improvement of 20pp in both precision and recall).ConclusionsTaken together, the results reveal improvements for predicting treatment response in HL disease by resorting to sophisticated statistical and ML principles. This work further consolidates the current hypothesis on the structural difficulty of this prognostic task, showing that there is still a considerable gap to be bridged for these technologies to reach the necessary maturity for clinical practice.

Effects of ABVD chemotherapy on ovarian function: epidemiology, hormonal dosages and ultrasound morphologic analyses in 270 patients with Hodgkin's disease.

Classical Hodgkin Lymphoma (HL) is a lymphoproliferative disease typically diagnosed in the young. The excellent results obtained with current treatment lead to long survival with age-related complications affecting patients' survival and quality of life. One issue affecting HL patients is infertility. This problem can be easily overcome in males with seminal liquid cryopreservation, however, in females it is more complex either in terms of the quality of the cryopreserved material or the patients' age at diagnosis. Moreover, not all chemo- or radio-therapies have the same negative impact on fertility.The main objectives of this study was to collect epidemiological information on HL patients involved in fertility preservation counseling and to analyze the impact of ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine), the standard treatment for HL, on ovarian function, hormonal levels and ovarian and uterine tissue morphologies. Patterns of fertility preservation were also reported. Data were obtained from 270 female patients at HL onset who were interested in fertility counseling prior to therapy initiation. Each patient was assessed at HL diagnosis for levels of Anti-Mullerian Hormone (AMH), Follicle Stimulating Hormone (FSH), and 17β-oestradiol (17β-oe), with additional assessments at 6 and 12 months after chemotherapy. Patients were evaluated with ultrasound scans to study the number of ovarian follicles and the degree of uterine thickness at the same timepoints. The average patient AMH level showed a statistically significant reduction at 6 months after chemotherapy (p=0.05) and by the 12 month time point returned to near pre-chemotherapy values. FSH and 17β-oe levels did not significantly vary throughout the study period. ABVD chemotherapy was associated with a significant reduction of both ovarian follicles and endometrial thickness at the 6 month time point followed by a recovery at the 12 time point in both ovaries. Different results were observed when patients changed treatment to a more intensive one. Based on the results from the hormonal measurements and the follicle echography, it appears that the toxic effect of ABVD on fertility is transient, whereas, in contrast, more intensive therapies may potentially be more harmful and long-lasting.

A Rare Case of Hodgkin’s Lymphoma Presenting as Hypereosinophilia

Although eosinophilia is a recognised associated feature of Hodgkin’s Lymphoma, hypereosinophilia is seldom the presenting feature in the patient. Here, the authors report an unusual case of a 21-year-old male patient who presented to the General Medicine outpatient department of the hospital with a history of multiple episodes of left-sided pleural effusion in addition to mediastinal and cervical lymphadenopathy. Baseline investigations revealed hypereosinophilia which was persistent despite Diethylcarbamazine (DEC) and steroid therapy. Computer Tomography (CT) guided biopsy of an anterior mediastinal mass, likely to be thymus, led to the diagnosis of Hodgkin's Lymphoma. The patient was transferred to the Haematology department where he was started on Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) chemotherapy regimen. Despite the fact that blood eosinophilia is an associated finding, it is rare for a patient to present with it. The authors also discuss the discrepancies related to the credibility of eosinophilia as a prognostic marker for Hodgkin’s disease.

PMON84 A Unique Case of Diabetes Insipidus Revealing Hodgkin's lymphoma

Abstract Introduction While diabetes insipidus rarely presents as a symptom of non-Hodgkin's lymphoma, it is very rarely a revealing symptom of Hodgkin's lymphoma. We present a case of this unique association. Case presentation We report a case of a 25-year-old previously healthy male with no significant past medical history who presented with complaints of polydipsia, polyuria, and nocturia. A water deprivation test confirmed central diabetes insipidus. He started therapy with oral desmopressin and had clinical improvement. Magnetic resonance imaging (MRI) of his head showed thickened infundibulum and a lack of posterior pituitary bright spot, consistent with infundibulo-neurohypophysitis. There were no obvious masses within the anterior or posterior lobe, nor were suprasellar soft tissue masses noted. Diabetes mellitus (DM), autoimmune diseases, and infectious diseases were excluded. A chest x-ray revealed a superior mediastinal mass and a CT scan confirmed multiple mediastinal lymphadenopathies. A biopsy of pre-tracheal lymph node revealed nodular sclerosing Hodgkin's lymphoma. The patient received six cycles of chemotherapy with Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) and achieved a complete remission. A follow up MRI head scan showed a decreasing in the thickness of infundibulum along with non-visualization of the posterior pituitary bright spot. Finally, his symptoms resolved with DDAVP therapy. Conclusions Diabetes insipidus involving the pituitary gland of Hodgkin's lymphoma is an extremely rare presentation of endocrine deficiency and malignancy. The literature describes only a few such cases. Clinicians should be aware diabetes insipidus might rarely present as a symptom of Hodgkin's lymphoma without obvious metastatic involvement of the neurohypophysial system. Continuing to report anecdotal experiences in managing similar complex scenarios is essential and remains the only reference for clinicians who handle patients with a similar presentation. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Interim FDG-PET/CT for therapy monitoring and prognostication in Hodgkin’s Lymphoma

The aim of the study was to assess the predictive value of interim FDG-PET/CT (iPET) in patients with Hodgkin’s lymphoma (HL) treated with Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy. A total of 245 consecutive patients with de novo HL between 12/2013 and 12/2017 were evaluated retrospectively. All patients were treated with upfront ABVD, performed PET/CT scans at baseline, after 2 cycles (interim PET, iPET2) or 4 cycles (iPET4) and at the end of therapy, and followed up for at least 6 months after therapy. The response status on iPET was defined according to the standard five-point Deauville scores (DS) as follows: complete metabolic response (CMR, DS 1–3) and non-complete metabolic response (nCMR) (DS 4 and 5). End-of-treatment (EoT) response was assessed by FDG-PET/CT and if needed biopsy confirmation of PET-positive findings. The association between iPET and EoT response was investigated using logistic regression analysis. Survival analysis was performed using the Cox regression hazard model and Kaplan–Meier methods. Sixty-nine patients underwent iPET-2 and 176 iPET-4. No association was found between the timing of iPET and iPET response status (P-value = 0.71). Two hundred and one patients (82%) had iPET-CMR and 44 (18%) iPET -nCMR. iPET was strongly associated with EoT response status: 194/201 (96 .5%) of iPET-CMR had a complete response at the EoT while only 21/44 (47.7%) of patients with iPET-nCMR presented a complete response at EoT (P-value < 0.0001). The median follow-up was 32 months (range 6–81). Patients with iPET-CMR presented a better outcome with 91% 3 y event-free-survival (EFS) and 95% 3 y overall survival (OS) than those with iPET-nCMR (41 and 86%, respectively, P-value < 0.0001). In multivariable analyses, iPET retained an independent prognostic factor of EFS and OS (P-value < 0.0001 and P-value = 0.002, respectively). iPET is highly predictive of outcome of HL patients treated with ABVD and allows to tailor therapy to the individual patient.

Das Hodgkin-Lymphom in fortgeschrittenen Stadien

BackgroundIn recent years, positron emission tomography (PET)-adapted protocols and new agents such as brentuximab vedotin are increasingly used as part of first-line protocols of advanced-stage Hodgkin lymphoma (HL).ObjectivesThis manuscript reviews guideline-based therapy and available trial data in advanced-stage HL.Materials and methodsThis is a narrative review.ResultsThe German HL guideline recommends interim PET2-guided (PET after 2 cycles) chemotherapy using 4 cycles of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone) for PET2-negative patients up to 60 years of age with advanced HL and 6 cycles eBEACOPP for PET2-positive patients. Furthermore, patients with PET-positive residual lymphoma should receive consolidation radiotherapy with 30 Gy. This is based on effective tumor control and short duration of therapy of 3 months in most patients. For elderly patients, treatment with 2 cycles of ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) followed by 4 cycles of AVD and irradiation of PET-positive residuals is recommended.ConclusionsAdvanced-stage HL is curable in more than 90% of cases. The goal of current scientific efforts is to reduce toxicity while maintaining efficacy by including immune checkpoint inhibitors.

Is the integration of lymphocyte/monocyte ratio and international prognostic score effective in predicting prognosis for hodgkin's lymphoma in the modern era? A prospective cohort study

BACKGROUND: Determining the prognosis of Hodgkin's Lymphoma (HL) is crucial to avoid overtreatment and undertreatment, both of which have dangerous effects on the patient's health. This justifies the many studies to find prognostic factors, which in turn contribute to making the appropriate therapeutic decision. International Prognostic Score (IPS) and lymphocyte/monocyte ratio (LMR) are the most common prognostic indicator in HL, but they have some limitations in their application at some stages of the disease. The aim of this research was to study the efficiency of combining IPS and LMR to predict prognosis at both stages of the disease (early and advanced).METHODS: This study included 84 newly classical HL patients treated by ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) with radiotherapy.RESULTS: IPS showed a poor ability to predict 18-month progression-free survival (PFS) in both early-stage disease (P = 0.162) and advanced-stage disease (P = 0.191); LMR showed high performance in predicting 18-month PFS in early-stage patients treated with ABVD (HR = 5.456, confidence interval [CI] =1.04–28.715, P = 0.045). The combination of IPS and LMR was able to predict 18-month PFS in both early- and advanced-stage disease (HR = 12.21, CI = 1.24–120.1, P = 0.032) (HR = 2.84, CI = 1.04–5.04, P = 0.041), respectively.CONCLUSIONS: The combination of IPS and LMR defines two important risk groups: the high-risk group (IPS ≥3 and LMR <2.9) and the low-risk group (IPS <3 and LMR ≥2.9); it can therefore be used to predict prognosis and adapt treatment to suit each patient's condition.

Prognostic Role of the Expression of Latent-Membrane Protein 1 of Epstein-Barr Virus in Classical Hodgkin Lymphoma.

The prognostic impact of the presence of Epstein–Barr virus (EBV) in classical Hodgkin lymphoma (cHL) is controversial. Previous studies reported heterogeneous results, rendering difficult the clinical validation of EBV as a prognostic biomarker in this lymphoma. The objective of this study was to evaluate the survival impact of the expression of EBV Latent-Membrane Protein 1 (EBV-LMP1) in tumoral Hodgkin–Reed–Sternberg (HRS) cells of primary diagnostic samples of cHL. Formalin-Fixed Paraffin-Embedded (FFPE) lymph node samples from 88 patients with cHL were analyzed. Patients were treated with the standard first-line chemotherapy (CT) with Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) followed by radiotherapy. The Kaplan–Meier method and the Cox proportional hazards model were used for carrying out the survival analysis. In order to investigate whether the influence of EBV was age-dependent, analyses were performed both for patients of all ages and for age-stratified subgroups. In bivariate analysis, the expression of EBV was associated with older age (p = 0.011), mixed cellularity subtype cHL (p < 0.001) and high risk International Prognostic Score (IPS) (p = 0.023). Overall survival (OS) and progression-free survival (PFS) were associated with the presence of bulky disease (p = 0.009) and advanced disease at diagnosis (p = 0.016). EBV-positive cases did not present a significantly lower OS and PFS in comparison with EBV-negative cases, for all ages and when stratifying for age. When adjusted for covariates, absence of bulky disease at diagnosis (HR: 0.102, 95% CI: 0.02–0.48, p = 0.004) and limited disease stages (I–II) (HR: 0.074, 95% CI: 0.01–0.47, p = 0.006) were associated with a significant better OS. For PFS, limited-disease stages also retained prognostic impact in the multivariate Cox regression (HR: 0.145, 95% CI: 0.04–0.57, p = 0.006). These results are of importance as the early identification of prognostic biomarkers in cHL is critical for guiding and personalizing therapeutic decisions. The prognostic role of EBV in cHL could be modulated by the type of CT protocol employed and interact with the rest of presenting features.

Richter transformation of chronic lymphocytic leukaemia: a British Society for Haematology Good Practice Paper.

Richter transformation of chronic lymphocytic leukaemia: a British Society for Haematology Good Practice Paper.

Comparison of Outcome of Adolescents with Newly Diagnosed Hodgkin Lymphoma (HL) in Argentina, Treated within a Pediatric Vs an Adults Clinical Trial : Experience of the Gatla Group

Introduction: There are no prospective clinicaltrials directly comparing results of pediatric and adult treatment approaches in adolescents with HL. We report a comparison of clinical outcomes in adolescents (14-18 years)treated within the GATLA adult clinical trial (LH05) during 2005 to 2012 due to the lack of a pediatric clinical trial in Argentina, and within the pediatric clinical trial 11-EHP-12 since 2012. In LH05 all patients (pts) were treated with ABVD and re-evaluated with PET-CT after the 3rd cycle (PET-3). Pts with Deauville Score 1-2 were considered in Complete Remission (CR) and received no further therapy. Pts with Partial Remission (PR) and PET-3 Deauville Score 3-5 continued with ABVD plus Involved Field Radiotherapy (IFRT). Pts with Stable Disease (SD) or Progressive Disease (PD) were treated with salvage chemotherapy. In 11-EHP-12 High Risk (HR) pts were treated with OEPA (vincristine, etoposide, prednisone, and doxorubicin)/COPDAC (cyclophosphamide, vincristine, prednisone, and dacarbazine) plus IFRT (20Gy:CR/25Gy:PR). Intermediate (IR) and Low Risk (LR) pts were treated with 6 or 4 cycles of ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) respectively +/- IFRT according response. Unlike the adult trial LH05, the pediatric trial 11-EHP-12 involved a more intensive therapy with dose dense chemotherapy and radiotherapy in all HR pts and IR and LR in PR.Progression-free survival (PFS) was defined as time from treatment to relapse or death from any cause. Overall survival (OS) was defined as time from treatment to death from any cause. Risk assignment: 11-EHP-12 according Stanford/Danna Farber/SJCRH Consortium classification where HR include Stages IIB, IIB and IV. LH05: Risk assigned according the International Prognostic Score (HR pts: IPS >2).Patients and Methods : We retrospectively searched in the GATLA data base all patients with age 14-18 years treated for HL within any of the two mentioned clinical trials. Twenty pts from the LH-05 and 47 pts from the 11-EHP-12 met the inclusion criteria for this analysis.Results: In the LH05 the EFS at 3 years was 75% vs 85% in the 11-EHP-12 with an OS at 3 years of 90% vs 93% respectively. In both groups of patients, the EFS at 3 years was lower than that of the rest the patients in the same clinical trial. In LH 05 the 3y EFS for the 377-pts analyzed was 82 % (90% for PET-3 negative and 65% for PET-3 positive) and the 3y OS was 97% (98% for PET-3 negative and 92% for PET-3 positive). In 11-EHP-12 all 120-pts analyzed had a 3y EFS: 88,5% (85% for HR, 87,7% for IR and 100% for LR) and a 3y OS of 97,4% (95,5% for HR, 100% for IR and LR). The 5 events in the Adult Trial: 4 HR pts. and 1 LR pt. 5/5 PET-3 positive.Conclusion: Patients 14-18 years old in both clinical trials had an inferior outcome than the rest of the age groups. The EFS was superior in this group of pts treated with 11-EHP-12, although the percentage of high risk patients was higher than in the trial LH05 (68% vs 45% respectively). There was no difference in the OS. Future randomized clinical trials are needed to evaluate efficacy and safety of treating this age group with a more aggressive chemotherapy regimen and the inclusion of RT vs a conservative approach. [Display omitted] DisclosuresPavlovsky:TAKEDA: Speakers Bureau.

Adult Lymphomas in a Tertiary Hospital in South – South Nigeria: A Review of Clinicopathologic Features and Treatment Outcome

Background: There has been an increase in the prevalence of Lymphomas in our environment lately. Thorough literature search reveals a limited number of reports on the prevalence of Lymphoma and no information on the clinicopathologic pattern and outcome of treatment of this disease in our centre. Data on the burden of Lymphoma across different regions are important, as there may be variation in incidence in different locations even within the same country. This will keep healthcare providers informed about the current trend of Lymphomas in the region and facilitate prompt and appropriate diagnosis and treatment as well as assist Government agencies in better healthcare planning.&#x0D; Aim: To determine the burden, clinicopathologic characteristics and treatment outcome of Lymphoma among a cohort of adult patients accessing care in a Referral Hospital in Southern Nigeria&#x0D; Methods: This was a longitudinal prospective study of all lymphoma cases managed in the Department of Haematology, University of Uyo Teaching Hospital, Uyo, between January 1, 2014 and December 31, 2018&#x0D; Results: There were 59 cases. Forty 40 (67.8%) were males and 19(32.2%)were females giving a male to female ratio of 4.4:1. Hodgkin Lymphoma(HL) accounted for 11(18.6%) of the cases while Non-Hodgkin Lymphoma(NHL) accounted for 48( 81.4%)of the cases , with the mean ages for HL and NHL patients being 32.09 +9.22 years and 40.88 + 12.21 years, respectively. The distribution of the different histologic subtypes of the malignancy were as follows: HL; Nodular Lymphocyte Predominant(7cases;63.6%), Nodular Sclerosis(2 cases;18.2%) and Lymphocyte Depleted(2 cases;18.2%). NHL; Small Lymphocytic Lymphoma(23cases;47.9%),Diffuse Large Cell Lymphoma(15 cases;31.3%),unspecified&#x0D; (4 cases;8.3%), Follicular Lymphoma(2 cases;4.2%),Lymphoblastic Lymphoma(2 cases;4.2%), Mantle Cell Lymphoma(1 case;2.1%) and Adult T-Cell Lymphoma(1 case;2.1%). Fourteen 14 (29.2%) out of all the NHL patients had immunohistochemistry and only nine 9 of them were CD20 positive. Relapse rate among the cohort was 11.9% (7/59), while 15.3% (9/59) were still in remission. The cure rate was 5.1%, loss to follow up was 22.0% and 37.3% of patients died in the course of therapy either from advanced disease, non -compliance to treatment or late presentation. All the HL patients received ABVD (Adriamycin, Bleomycin, Vinblastine and Dacarbazine) regimen alone. Majority of the NHL patients (91.7%, 44/48) received CHOP (Cyclophosphamide, Doxorubicin, Oncovin and Prednisolone) regimen alone, while 8.3% (4/48) received Rituximab with CHOP (R-CHOP).&#x0D; Conclusion: The clinicopathological profile, age and sex distribution of lymphoma in our study were comparable to those reported by other authors with nodular lymphocyte predominant being the most common HL histologic subtype and small lymphocytic lymphoma the predominant NHL histologic subtype in our environment. The general outcome was very poor with a high default rate and unsettling mortality figures.

Hodgkin Variant of Richter's Transformation (HvRT) Among Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) Patients in British Columbia (BC), Canada

Hodgkin Variant of Richter's Transformation (HvRT) Among Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) Patients in British Columbia (BC), Canada

Hodgkin Lymphoma in Adolescent and Young Adults: Real-World Data from a Single Tertiary Cancer Center in India.

Purpose: There is lack of consensus on management of adolescent and young adult (AYA) Hodgkin lymphoma with respect to chemotherapy approach (adult or pediatric). Hence we sought to evaluate the efficacy and safety of Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) chemotherapy in AYA Hodgkin lymphoma. Patients and Methods: It is a retrospective, observational, single-center study. From January 2013 to December 2016, all consecutive patients with AYA (15-25 years, all stages) were analyzed. The primary endpoint of the study was event-free survival (EFS). Secondary endpoints were complete response rates (CR) and overall survival (OS). Results: A total of 220 patients (70% men) with median age 20 years were evaluated. A significant proportion of patients had adverse features such as stage III/IV disease (63%), bulky disease (63%), extranodal involvement (37%), and marrow involvement (22%). After two cycles and end of therapy, 77% patients achieved complete response. Primary progressive disease was seen in 6% patients. With a median follow-up of 2.6 years, 19 (8.6%) patients relapsed, 1 patient developed second malignancy, and 6 patients died. Three-year EFS and OS were 81.3% and 97%, respectively. Bleomycin-induced lung injury was seen in 16% patients. On multivariate analysis stage at presentation, bone marrow involvement, partial response at interim positron emission tomography and International prognosis score (IPS) >3 were predictors of poor EFS. Conclusion: ABVD is an effective and safe regimen in AYA Hodgkin lymphoma. Advanced disease with high IPS (>3) score needs an early escalation approach to escBEACOPP regimen.

Effect of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD)treatment on female mice reproductive function

Effect of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD)treatment on female mice reproductive function

Successful treatment of primary bone marrow Hodgkin lymphoma with brentuximab vedotin: a case report and review of the literature

BackgroundHodgkin lymphoma usually presents with sequential enlargement of peripheral lymph nodes, and bone marrow invasion rarely occurs (approximately 3–5%). However, several cases have been reported as “primary” bone marrow Hodgkin lymphoma, especially among patients with human immunodeficiency virus and the elderly. This type of Hodgkin lymphoma is characterized by no peripheral lymphadenopathies and has been reported to have poorer prognosis.Case presentationA 38-year-old Japanese man was admitted to our hospital because of fever of unknown origin and pancytopenia without lymphadenopathies. Bone marrow examination revealed Hodgkin cells mimicking abnormal cells. These were positive for CD30, EBER-1, CD15, PAX-5, and Bob-1 and negative for Oct-2, CD3, CD20, surface immunoglobulin, CD56. On the basis of systemic evaluation and bone marrow examination, he was diagnosed with primary bone marrow Hodgkin lymphoma. We initiated therapy with DeVIC (dexamethasone, etoposide, ifosfamide, and carboplatin) therapy, but remission was not achieved. Then, the patient was treated with brentuximab vedotin combined with systemic chemotherapy (Adriamycin, vinblastine and dacarbazine), which was effective.ConclusionsThere is no established treatment strategy for Hodgkin lymphoma, and therapeutic outcomes using ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine)-like or CHOP (cyclophosphamide, Adriamycin, vincristine, and prednisone)-like regimens are reportedly poor. Only a few patients have been reported to achieve long-term remission. Through this case report, we suggest an alternative therapeutic option for primary bone marrow Hodgkin lymphoma.

Brentuximab for Refactory Hodgkin’s Lymphoma: A Case Report

Hodgkin's lymphoma (HL) continues to be an intriguing, and fascinating lymphoma [1]. HL is expected to cure the majority of patients. Brentuximab vedotin is a CD30 antibody. We survey efficacy of brentuximab in patient with HL who was resistant to treatment. A 43 year old male referred with cough and right supraclavicular lymphadenopathy. His disease was HL, nodular sclerosis type (stage IIB and grade II) with megakaryocytosis in bone marrow aspiration (BMB). He was treated with 6 cycles of induction chemotherapy including adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) and achieved a complete remission by imaging assessment. Then he received ifosfamide, carboplatin, etoposide (ICE) plus brentuximab vedotin (1.8 mg/kg every 3 weeks) regimen for 6 courses. At the end of this time he been eligible for autologous bone marrow transplantation (BMT). Bone marrow was done and after 13 days with good engraftment the patient discharge hospital. Therapists should be try with a specific target when they need a new and potent treatment like BMT for an active disease. Brentuximab vendotin is a new drug in policy of recurrence that it used for a few of cases in Iran.

The role of F-18 FDG PET/CT in evaluating the impact of HIV infection on tumor burden and therapy outcome in patients with Hodgkin lymphoma

To evaluate the impact of HIV infection on tumor burden and therapy outcome following treatment with chemotherapy in patients with Hodgkin lymphoma. A total of 136 patients with classical Hodgkin lymphoma were studied (mean age±SD = 32.31±1.39years, male=86, female=50). Advanced disease (stage III and IV) was present in 64% of patients. HIV infection was present in 57 patients while 79 patients were HIV-negative. Baseline F-18 FDG PET/CT was obtained in all patients. SUVmax, MTV and TLG were determined on the baseline scan to evaluate for tumor burden. All patients completed a standard regimen of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). After a median period of 8weeks (range=6 to 17weeks), a repeat F-18 FDG PET/CT scan was obtained to evaluate response to therapy using Deauville 5-point scoring system. The HIV-positive and HIV-negative groups were similar with regards to age and disease stage. The groups were heterogeneous with respect to gender (p=0.029). The SUVmax, MTV and TLG of lesions were not significant different between the two groups. Complete response was seen in 72.8% of the study population. Presence of HIV infection was associated with higher rate of treatment failure with 40.4% of the HIV-positive patients having treatment failure while only 17.7% of the HIV-negative patients had treatment failure (p=0.0034). HIV infection was a significant predictor of response to chemotherapy. Effects of SUVmax, MTV, TLG and Ann Arbor stage of the disease were not statistically significant as predictors of therapy outcome. In a multiple logistic regression, presence of HIV infection still remained an independent predictor of therapy outcome in the presence of other factors such as SUVmax, MTV, TLG and the Ann Arbor stage of the disease. HIV infection is not associated with a higher tumor burden in patients with Hodgkin lymphoma. HIV infection is, however, a strong predictor of poor therapy outcome in patients treated with standard regimen of ABVD.

HIV-infection has no prognostic impact on advanced-stage Hodgkin lymphoma.

Classical Hodgkin lymphoma (cHL) is a non-AIDS-defining cancer with a good response to chemotherapy in the combined antiretroviral therapy (cART) era. The aim of the present study was to compare the characteristics, the response to treatment and the survival of advanced-stage cHL treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) between cART-treated HIV-positive and HIV-negative patients. We retrospectively analyzed advanced-stage cHL patients from a single institution, uniformly treated with ABVD. All HIV-positive patients received cART concomitantly with ABVD. A total of 69 patients were included in the study: 21 were HIV-positive and 48 were HIV-negative. HIV-positive patients had more aggressive features at cHL diagnosis, such as worse performance status, more frequent bone marrow involvement and mixed cellularity histologic subtype. There were no differences in complete response rate (89% in HIV-positive vs. 91% in HIV-negative), P = 1; disease-free survival (DFS) [10-year DFS probability (95% CI) 70% (41-99%) vs. 74% (57-91%)], P = 0.907 and overall survival (OS) [10-year OS probability (95% CI) 73% (52-94%) vs. 68% (51-85%)], P = 0.904. On multivariate analysis, HIV infection did not correlate with worse OS. Although HIV-positive patients with cHL had more aggressive baseline features in this series, there were no differences in response rate or survival between HIV-positive and HIV-negative patients.

Non-growing follicle density is increased following adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy in the adult human ovary.

Do the chemotherapeutic regimens of ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) or OEPA-COPDAC (combined vincristine, etoposide, prednisone, doxorubicin (OEPA) and cyclophosphamide, vincristine, prednisone, dacarbazine (COPDAC)) used to treat Hodgkin lymphoma (HL), affect the density, morphology and in vitro developmental potential of human ovarian follicles? Ovarian tissue from women treated with ABVD contained a higher density of non-growing follicles (NGFs) per cubic millimetre and increased numbers of multiovular follicles but showed reduced in vitro growth compared with patients with lymphoma who had not received chemotherapy, patients treated with OEPA-COPDAC, age-matched healthy women and age-related model-predicted values. Chemotherapy regimens can cause a loss of follicles within the ovary, which depends on the drugs given. Early stage HL is commonly treated by ABVD, a non-alkylating regimen that apparently has ovarian sparing qualities; thus it is important to investigate the histological appearance and distribution of follicles within ABVD-treated ovarian tissue. Thirteen ovarian biopsies were obtained from HL patients (six adolescents and seven adults) and one biopsy from a non-HL patient. Two HL patients and the non-HL patient had received no treatment prior to biopsy collection. The remaining 11 HL patients received one of two regimens: ABVD or OEPA-COPDAC. Tissue was analysed histologically and compared to biopsies from healthy women, and in a subgroup of patients, tissue was cultured for 6 days in vitro. Ovarian biopsies were obtained from patients undergoing ovarian cryopreservation for fertility preservation and from healthy women at the time of Caesarian section ('obstetric tissue'). Follicle number and maturity were evaluated in sections of ovarian cortical tissue, and compared to an age-related model of mean follicle density and to age-matched contemporaneous biopsies. The developmental potential of follicles was investigated after 6 days of tissue culture. A total of 6877 follicles were analysed. ABVD-treated tissue contained a higher density of NGFs per cubic millimetre (230 ± 17) (mean ± SEM) than untreated (110 ± 54), OEPA-COPDAC-treated (50 ± 27) and obstetric (20 ± 4) tissue (P < 0.01), with follicle density 9-21 SD higher than predicted by an age-related model. Biovular and binucleated NGFs occurred frequently in ABVD-treated and in adolescent-untreated tissue but were not observed in OEPA-COPDAC-treated or obstetric tissue, although OEPA-COPDAC-treated tissue contained a high proportion of morphologically abnormal oocytes (52% versus 23% in untreated, 22% in ABVD-treated and 25% in obstetric tissue; P < 0.001). Activation of follicle growth in vitro occurred in all groups, but in ABVD-treated samples there was very limited development to the secondary stage, whereas in untreated samples from lymphoma patients growth was similar to that observed in obstetric tissue (untreated; P < 0.01 versus ABVD-treated, NS versus obstetric). N/A LIMITATIONS, REASONS FOR CAUTION: Although a large number of follicles were analysed, these data were derived from a small number of biopsies. The mechanisms underpinning these observations have yet to be determined and it is unclear how they relate to future fertility. This study confirms that the number of NGFs is not depleted following ABVD treatment, consistent with clinical data that female fertility is preserved. Our findings demonstrate that immature follicle density can increase as well as decrease following at least one chemotherapy treatment. This is the first report of morphological and follicle developmental similarities between ABVD-treated tissue and the immature human ovary. Further experiments will investigate the basis for the marked increase in follicle density in ABVD-treated tissue. Funded by UK Medical Research Council Grants G0901839 and MR/L00299X/1. The authors have no competing interests.

Synchronous Hodgkin's Lymphoma and Seminoma, a Rare Co-Existence and an Important Lesson

Introduction:Second malignancies, including lymphoma, occur at a higher incidence in men previously treated for germ cell tumors than in the general population (1). Synchronous presentation of seminoma and lymphoma is rare but has important ramifications for the treatment of both malignancies. Without clinical vigilance this situation may be easily missed, leading to inappropriate management of each cancer. We describe a patient found to have synchronous seminoma and Hodgkin Lymphoma and discuss the effects of the dual diagnoses on his evaluation and care.Case presentation:A 59 year old male with no significant medical history presented with progressive swelling and erythema of the right testis. Testicular cancer was suspected and he underwent a radical right inguinal orchiectomy. Pathology revealed a 5.7cm seminoma of the testis with lymphovascular invasion and without spermatic cord involvement (pT2) (Fig. 1). His tumor markers including AFP, LDH, and Beta-HCG were normal (S0). A CT scan of the chest, abdomen and pelvis followed by a PET/CT revealed enlarged, hypermetabolic mediastinal, hilar and periportal lymphadenopathy interpreted by the radiologist as concerning for metastatic disease. Given the atypical distribution for lymphadenopathy from testicular seminoma, an excisional biopsy of a left hilar node was performed and revealed Classical Hodgkin Lymphoma with IHC positive for CD15, CD30 and PAX-5 (Fig 2). He denied any B-symptoms and his bone marrow was uninvolved by lymphoma (stage IIIA). Adjuvant therapy for his germ cell tumor, otherwise an important consideration, was deferred and he began chemotherapy with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) for 6 cycles. Interim PET/CT after 2 cycles of ABVD showed a complete response. He has completed 6 cycles of ABVD and chose observation as opposed to single dose of adjuvant carboplatin for his seminoma and is currently under surveillance for both malignancies.Discussion:The unusual coexistence of Hodgkin Lymphoma and seminoma has rarely been documented in medical literature, with three other cases previously reported (2, 3). In each case a biopsy of lymphadenopathy, primarily outside the retroperitoneum, yielded a diagnosis of lymphoma. Both Hodgkin Lymphoma and germ cell tumors commonly involve lymph nodes and present in young men. Lymphadenopathy may understandably be assumed to represent metastatic disease in a young man with known testicular cancer. Clinical vigilance is necessary to question the nature of atypical sites of lymphadenopathy in such a patient, and to pursue the possibility of an alternate diagnosis with a lymph node biopsy. A missed diagnosis of lymphoma in such a patient would also mean harmful over-staging of the germ cell tumor. While these two cancers represent two of the most curable malignancies, their treatment is different and would be grossly wrong if each cancer is not correctly diagnosed and staged.Conclusion:Our report highlights the importance of clinical suspicion of a lymphoma in patients with another cancer and lymphadenopathy not typical of metastatic disease for that tumor type. In such situations a lymph node biopsy is crucial in order to proceed with the correct therapy of each malignancy. While the simultaneous presentation of Hodgkin Lymphoma and seminoma is rare, cases like ours highlight the importance of questioning metastatic disease when lymphoma seems to be a possibility.