Clinical outcomes in patients diagnosed with extra-nodal Hodgkin lymphoma: a 20-year retrospective analysis of the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database

Background:Hodgkin lymphoma refers to a malignancy of the lymphatic tissue.Extra-nodal Hodgkin lymphoma(ENHL)is a rare variant consisting of Hodgkin lymphoma occurring outside the lymphatic system.Studies investigating the epidemiology associated with ENHL are rare.Methods:618 ENHL cases were analyzed using the National Cancer Institute’s Surveillance,Epidemiology,and End Results(SEER)database(2000–2020).Demographics including sex,race/ethnicity,rural-urban continuum,age group(categorized as adolescent and young adult(AYA)if between years of 15 and 39,and adult if over the age of 40),and living status(alive/deceased)were examined,with survival status as the main outcome.Results:This study included 335 males(54.2%)and 283 females(45.8%).Of this total,47.9%were in the AYA group.In terms of ethnicity the distribution was 12.5%non-Hispanic Black,67.5%non-Hispanic White,5.2%non-Hispanic Asian/Pacific Islander,and 14.9%Hispanic.Bivariate analyses evidenced significant differences in survival by age group with 91.6%in AYA vs.72.4%in adults(P<0.001)alive by the end of the study period.Multivariable analyses identified age as a key predictor of survival,as the AYA patients had a lower odds ratio for death(odds ratio=0.25,P<0.001).In addition,survival outcomes were also impacted by race,with non-Hispanic Blacks showing higher survival probabilities.Regarding treatment,27.0%of patients underwent surgery,with 10.2%receiving post-surgery radiation,reducing odds of mortality(odds ratio=0.32,P=0.046).Conclusion:The background research as such,tends to affirm that these two factors–age and race are quite crucial in the prognosis as well as management of ENHL.Compared to adults,AYA patients had significantly lower odds of death,while non-Hispanic Black individuals exhibited reduced survival probabilities.It should be noted that 27.0%of patients underwent surgery with 10.2%receiving post-operative radiation which led to decrease in mortality rates.Thus,these results reiterate the necessity for tailor-made treatment methods according to demographic characteristics to boost patient outcomes effectively.For better ENHL care,future studies could shed light on these disparities and improve treatment regimens as needed.

The role of radiotherapy in patients with refractory Hodgkin’s lymphoma after treatment with brentuximab vedotin and/or immune checkpoint inhibitors

Background:Approximately 10%–30%of patients with Hodgkin’s lymphoma(HL)experience relapse or refractory(R/R)disease after first-line standard therapy.Brentuximab vedotin(BV)and immune checkpoint inhibitors(ICIs)have important roles in the salvage treatment of R/R HL.However,subsequent treatment for HL refractory to BV and/or ICI treatment is challenging.Methods:We retrospectively analyzed patients in two institutions who had R/R HL,experienced BV or ICI treatment failure,and received radiotherapy(RT)thereafter.The overall response rate(ORR),duration of response(DOR),progression-free survival(PFS),and overall survival(OS)were analyzed.Results:Overall,19 patients were enrolled.First-line systemic therapy comprised doxorubicin,bleomycin,vinblastine,and dacarbazine(ABVD,84.2%);AVD plus ICIs(10.5%);and bleomycin,etoposide,doxorubicin,cyclophosphamide,vincristine,procarbazine,and prednisone(BEACOPP,5.3%).After first-line therapy,15(78.9%)and four patients(21.1%)had refractory disease and relapsed,respectively.After R/R HL diagnosis,six(31.6%),two(10.5%),and 11(57.9%)patients received BV and ICIs concurrently,BV monotherapy,and ICI monotherapy,respectively.All patients received intensity-modulated RT(n=12,63.2%)or volumetric modulated arc therapy(VMAT;n=7,36.8%).The ORR as well as the complete response(CR)rate was 100%;the median DOR to RT was 17.2 months(range,7.9–46.7 months).Two patients showed progression outside the radiation field;one patient had extensive in-field,out-of-field,nodal,and extranodal relapse.With a median follow-up time of 16.2 months(range,9.2–23.2 months),the 1-year PFS and OS were 84.4%and 100%,respectively.PFS was associated with extranodal involvement(P=0.019)and gross tumor volume(P=0.044).All patients tolerated RT well without adverse events of grade≥3.Conclusion:RT is effective and safe for treating HL refractory to BV or ICIs and has the potential to be part of a comprehensive strategy for HL.

Metachronous mixed cellularity classical Hodgkin’s lymphoma and T-cell leukemia/lymphoma: A case report

BACKGROUND The development of peripheral T-cell lymphoma(PTCL)after chemotherapy for Hodgkin’s lymphoma(HL)is rare,and highly aggressive TCL/leukemia has not been reported to date.The relationship between HL and PTCL needs further exploration to understand the pathogenesis of metachronous lymphoma(ML)and find effective treatment options.We report a patient with ML,whose biopsy of a right cervical lymph node initially confirmed classical HL(CHL).CASE SUMMARY We report a patient with ML,whose biopsy of a right cervical lymph node initially confirmed CHL,with typical reed–sternberg cells expressing CD30 and PAX-5.T-cell leukemia/lymphoma occurred 3 years after treatment,and a lymph node biopsy at the onset confirmed PTCL,nonspecific type,expressing CD3,CD4 and CD8.The patient was treated with standard doses of chemotherapy,programmed cell death-ligand 1 monoclonal antibody,and chidamide,all of which failed to achieve complete remission.The patient was diagnosed with refractory state,and eventually died of leukocyte stasis.CONCLUSION The accuracy of the diagnosis needs to be confirmed when chemotherapeutic drugs are not effective.

Febrile cholestatic disease as an initial presentation of nodular lymphocyte-predominant Hodgkin lymphoma

Febrile cholestatic liver disease is an extremely unusual presentation of Hodgkin lymphoma(HL).The liver biopsy of a 40-year-old man with febrile episodes and cholestatic laboratory pattern disclosed an uncommon subtype of HL,a nodular lymphocyte-predominant HL(NLPHL).Liver involvement in the early stage of the usually indolent NLPHL's clinical course suggests an aggressiveness and unfavorable outcome.Emphasizing a liver biopsy early in the diagnostic algorithm enables accurate diagnosis and appropriate treatment.Although rare,HL should be considered in the differential diagnosis of cholestasis.

Hepatitis C virus-related B cell subtypes in non Hodgkin's lymphoma

AIM:To evaluate if indolent B cell-non Hodgkin's lymphoma(B-NHL) and diffuse large B-cell lymphoma(DLBCL) in hepatitis C virus(HCV) positive patients could have different biological and clinical characteristics requiring different management strategies.METHODS:A group of 24 HCV related B-NHL patients(11 indolent,13 DLBCL) in whom the biological and clinical characteristics were described and confronted.Patients with DLBCL were managed with the standard of care of treatment.Patients with indolent HCV-related B-NHL were managed with antiviral treatment pegylated interferon plus ribavirin and their course observed.The outcomes of the different approaches were compared.RESULTS:Patients with DLBCL had a shorter duration of HCV infection and a higher prevalence of HCV genotype 1 compared to patients with indolent B-NHL in which HCV genotype 2 was the more frequent genotype.Five of the 9 patients with indolent HCV-relatedB-NHL treated with only antiviral therapy,achieved a complete response of their onco-haematological disease(55%).Seven of the 13 DLBCL patients treated with immunochemotheraphy obtained a complete response(54%).CONCLUSION:HCV genotypes and duration of HCV infection differed between B-NHL subtypes.Indolent lymphomas can be managed with antiviral treatment,while DLBCL is not affected by the HCV infection.

Relapsed/refractory classical Hodgkin lymphoma effectively treated with low-dose decitabine plus tislelizumab:A case report

BACKGROUND Academic studies have proved that anti-programmed death-1(PD-1)monoclonal antibodies demonstrated remarkable activity in relapsed/refractory classical Hodgkin lymphoma(cHL).However,most patients ultimately experienced failure or resistance.It is urgent and necessary to develop a novel strategy for relapsed/refractory cHL.The aim of this case report is to evaluate the combination approach of low-dose decitabine plus a PD-1 inhibitor in relapsed/refractory cHL patients with prior PD-1 inhibitor exposure.CASE SUMMARY The patient was a 27-year-old man who complained of enlarged right-sided cervical lymph nodes and progressive pain aggravation of the right shoulder over the past 3 mo before admission.Histological analysis of lymph node biopsy was suggestive of cHL.The patient experienced failure of eight lines of therapy,including multiple cycles of chemotherapy,PD-1 blockade,and anti-CD47 antibody therapy.Contrast-enhanced CT showed that the tumors of the chest and abdomen significantly shrunk or disappeared after three cycles of treatment with decitabine plus tislelizumab.The patient had been followed for 11.5 mo until March 2,2021,and no progressive enlargement of the tumor was observed.CONCLUSION The strategy of combining low-dose decitabine with tislelizumab could reverse the resistance to PD-1 inhibitors in patients with heavily pretreated relapsed/refractory cHL.The therapeutic effect of this strategy needs to be further assessed.

Non Hodgkin’s Lymphoma with Right Atrial Intra Cardiac Metastases

Background: Diffuse Large B-Cell Lymphoma (DLBCL) is the most variant of Non-Hodgkin’s Lymphoma (NHL) and also the most common variant with secondary intracardiac masses. Case summary: 7 years old child presented to emergency with acute decompensated cardiac failure, ascites and tender hepatomegaly. 2D echo evaluation was suggestive of large intracardiac mass in the right atrium almost completely obstructing Tricuspid valve orifice, gross pericardial effusion and dilated Inferior Vena Cava (IVC). Emergency tumor excision surgery was performed which revealed 4 × 4 cm pinkish firm mass arising from anterior Tricuspid annulus which was completely excised. Child was extubated on postoperative day (POD) 0 and was on minimal inotropic support. Ascites reduced significantly on POD1 allowing abdominal palpation which revealed a mass in the epigastric region. This prompted evaluation by pediatrician and oncology workup suggestive of increased 18-Flouro Deoxy Glucose (18-FDG) uptake in the mediastinum, abdomen, bilateral proximal thighs, all mediastinal lymph nodal stations, bilateral lung hilar stations 10R, 10L involving all encasing the heart and great vessels with pleural deposits, Celiac trunk, superior Mesenteric Artery (SMA), Portal vein, IVC and abdominal aorta. Histo pathology Examination (HPE) and Immuno Histo Chemistry (IHC) of intracardiac mass revealed DLBCL which is metastatic in nature. Chemotherapy was started as per (French American British Lymphomes Malins B) FAB LMB-96 protocol with the child currently in the Induction phase having poor prognosis and less survival interval. Conclusion: Surgery can be considered a treatment option for metastatic intracardiac masses during emergency scenarios like cardiogenic shock to relieve obstruction along the pathway of blood flow in the heart even though we may not be able to completely excise the tumor surgically.

Composite diffuse large B-cell lymphoma and classical Hodgkin's lymphoma of the stomach:Case report and literature review

The combination of classical Hodgkin’s lymphoma(cHL)and non-Hodgkin lymphoma coexisting in the same patient is not common,especially in one extranodal location.Here we present a rare case of composite diffuse large B-cell lymphoma(DLBCL)and cHL occurring simultaneously in the stomach of a 53-year-old female who presented with upper abdominal discomfort and gas pain.Surgery was performed and the disease was diagnosed pathologically as composite lymphoma of DLBCL and cHL using hematoxylin-eosin and immunohistochemical staining.Epstein-Barr virus(EBV)infection was not detected by in situ hybridization for EBV-encoded RNA or immunohistochemistry for EBV latent membrane protein-1.Polymerase chain reaction analysis from the two distinct components of the tumor demonstrated clonal immunoglobulinκlight chain gene rearrangements.The patient died approximately 11 mo after diagnosis in spite of receiving eight courses of the CHOP and two courses of the rituximab-CHOP(RCHOP) chemotherapy regimen.This case report showed that the two distinct components,DLBCL and cHL,appeared to originate from the same clonal progenitor cell,and that EBV infection was not essential for transformation during the course of tumorigenesis.

Epstein Barr virus-positive mucocutaneous ulcer of thecolon associated Hodgkin lymphoma in Crohn＇s disease

Epstein Barr virus （EBV） positive mucocutaneous ulcers（EBVMCU） form part of a spectrum of EBV-associatedlymphoproliferative disease. They have been reportedin the setting of immunosenescence and iatrogenicimmunosuppression, affecting the oropharyngeal mucosa,skin and gastrointestinal tract （GIT）. Case reports andseries to date suggest a benign natural history respondingto conservative management, particularly in the GIT. Wereport an unusual case of EBVMCU in the colon, arisingin the setting of immunosuppression in the treatment ofCrohn＇s disease, with progression to Hodgkin lymphoma18 mo after cessation of infliximab. The patient presentedwith multiple areas of segmental colonic ulceration,histologically showing a polymorphous infiltrate withEBV positive Reed-Sternberg-like cells. A diagnosisof EBVMCU was made. The ulcers failed to regressupon cessation of infliximab and methotrexate for 18mo. Following commencement of prednisolone for herCrohn＇s disease, the patient developed widespreadHodgkin lymphoma which ultimately presented as alife-threatening lower GIT bleed requiring emergencycolectomy. This is the first report of progression ofEBVMCU to Hodgkin lymphoma, in the setting of ongoingiatrogenic immunosuppression and inflammatory boweldisease.

Sternal Hodgkin’s lymphoma: A case report and review of literature

BACKGROUND Sternal tumors are difficult to diagnose, and usually need to be differentiated from other diseases such as tuberculosis, osteosarcoma, intrathoracic thyroid and thymoma. The sternum is a rare site of Hodgkin’s lymphoma, which is often misdiagnosed as tuberculosis on routine histopathology.CASE SUMMARY We reported a 47-year-old female patient with chest pain in the upper sternum for 1 mo. Chest computed tomography found a mass in the upper sternum.Pathology and immunohistochemistry of the biopsy confirmed the diagnosis of typical Hodgkin’s lymphoma(mixed cellularity subtype). Patient was diagnosed with primary sternal Hodgkin’s lymphoma and administered 6 cycles of adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy. Patient had no tumor recurrence and progression at a follow-up visit 2 years later.CONCLUSION This study highlights the rarity of primary sternal Hodgkin’s lymphoma and the challenges of its diagnosis. A Pub Med and Web of Science search revealed 10 reported cases of sternal involvement in Hodgkin’s lymphoma.

Color Doppler sonography and angioscintigraphy in hepatic Hodgkin's lymphoma

AIM： To estimate the characteristics of Color Doppler findings and the results of hepatic radionuclide angiography （HRA） in secondary Hodgkin＇s hepatic lymphoma. METHODS： The research included patients with a diagnosis of Hodgkin＇s lymphoma with metastatic focal lesions in the liver and controls. Morphologic characteristics of focal liver lesions and hemodynamic parameters were examined by pulsed and Color Doppler in the portal, hepatic and splenic veins were examined. Hepatic perfusion index （HPI） estimated by HRA was calculated. was observed. Lesions were mostly hypoechoic and mixed, solitary or multiple. Some of the patients presented with dilated splenic veins and hepatofugal blood flow. A pulse wave was registered in the centre and at the margins of lymphoma. The average velocity of the pulse wave was higher at the margins （P 〉 0.05）. A continuous venous wave was found only at the margins of lymphoma. There was no linear correlation between lymphoma size and velocity of pulse and continuous wave （r = 390, P 〈 0.01）. HPI was significantly lower in patients with lymphomas than in controls （P 〈 0.05）, pointing out increased arterial perfusion in comparison to portal perfusion. CONCLUSION： Color Doppler ultrasonography is a sensitive method for the detection of neovascularization in Hodgkin＇s hepatic lymphoma and estimation of its intensity. Hepatic radionuclide angiography can additionally help in the assesment of vascularisation of liver lesions.

Vanishing bile duct syndrome in Hodgkin's lymphoma: A case report and literature review

Vanishing bile duct syndrome (VBDS) has been described in different pathologic conditions including infection, ischemia, adverse drug reactions, autoimmune diseases, allograft rejection, and humoral factors associated with malignancy. It is an acquired condition characterized by progressive destruction and loss of the intra-hepatic bile ducts leading to cholestasis. Prognosis is variable and partially dependent upon the etiology of bile duct injury. Irreversible bile duct loss leads to significant ductopenia, biliary cirrhosis, liver failure, and death. If biliary epithelial regeneration occurs, clinical recovery may occur over a period of months to years. VBDS has been described in a number of cases of patients with Hodgkin&#x02019;s lymphoma (HL) where it is thought to be a paraneoplastic phenomenon. This case describes a 25-year-old man found on liver biopsy to have VBDS. Given poor response to medical treatment, the patient underwent transplant evaluation at that time and was found to have classical stage IIB HL. Early recognition of this underlying cause or association of VBDS, including laboratory screening, and physical exam for lymphadenopathy are paramount to identifying potential underlying VBDS-associated malignancy. Here we review the literature of HL-associated VBDS and report a case of diagnosed HL with biopsy proven VBDS.

Epidemiology of hodgkin’s lymphoma

The epidemiology of Hodgkin’s Lymphoma (HL) varies with age at clinical onset. In developing countries, the disorder appears predominantly during childhood and its incidence decreases with age, while in industrialized countries, the incidence rate increase with age. There has long been a view that the differences in descriptive epidemiology of Hodgkin’s Lymphoma around the world, and also between children, young adults and older adults may reflect differences in etiology between them. Hodgkin’s Lymphoma has long been suspected to have an infectious precursor, and indirect evidence has implicated Epstein-Barr virus (EBV), as a causal agent. The etiology of EBV-negative cases remains obscure. Epidemiological investigation of the etiology of Hodgkin’s Lymphoma is making steady progress, and it leads to a better understanding and hence prevention. This review considers in detail the descriptive and the etiological epidemiology of Hodgkin’s Lymphoma.

Clinical features of AIDS patients with Hodgkin's lymphoma with isolated bone marrow involvement:report of 12 cases at a single institution

Objective： To study the main clinical and histopathological features of 12 patients with Hodgkin＇s lymphoma （HL） diagnosed primarily from bone marrow （BM） involvement. Methods： We included 12 acquired immunodeficiency syndrome （AIDS） patients with HL assisted in the F. J. Mufiiz Infectious Diseases Hospital since January 2002 to December 2013. The diagnosis of ilL with primary BM involvement in patients was confirmed by clinical, histopathological, and immunohistochemical findings. Results： All patients presented ＂B＂ symptoms and pancytopenia. All of them had stage IV neoplasm disease because of BM infiltration. The median of CD4＋ T-cell counts was 114 cells/μL, and mixed cellularity （MC） was the most frequent histopathological subtype of 92% cases. Conclusion： When other causes are excluded, BM biopsy should be performed in AIDS patients with ＂B＂ symptoms and pancytopenia to evaluate BM infiltration by atypical lymphocytes.

Clinical study of chemotherapy-related cognitive impairment in patients with non-Hodgkin lymphoma

BACKGROUND Chemotherapy for malignant tumors can cause brain changes and cognitive impairment,leading to chemotherapy-induced cognitive impairment(CICI).Current research on CICI has focused on breast cancer and Hodgkin’s lymphoma.Whether patients with non-Hodgkin’s lymphoma(NHL)undergoing chemo-therapy have cognitive impairment has not been fully investigated.therapy have cognitive impairment has not been fully investigated.AIM To investigate whether NHL patients undergoing chemotherapy had cognitive impairments.METHODS The study included 100 NHL patients who were required to complete a compre-hensive psychological scale including the Brief Psychiatric Examination Scale(MMSE)at two time points:before chemotherapy and within 2 wk of two chemo-therapy courses.A language proficiency test(VFT),Symbol Number Pattern Test(SDMT),Clock Drawing Test(CDT),Abbreviated Daily Cognition Scale(ECog-12),Prospective and Retrospective Memory Questionnaire,and Karnofsky Perfor-mance Status were used to assess cognitive changes before and after chemo-therapy.RESULTS The VFT scores for before treatment(BT)and after treatment(AT)groups were 45.20±15.62,and 42.30±17.53,respectively(t-2.16,P<0.05).The CDT scores were 8(3.5-9.25)for BT and 7(2.5-9)for AT groups(Z-2.1,P<0.05).Retrospective memory scores were 13.5(9-17)for BT and 15(13-18)for AT(Z-3.7,P<0.01).The prospective memory scores were 12.63±3.61 for BT and 14.43±4.32 for AT groups(t-4.97,P<0.01).The ECog-12 scores were 1.71(1.25-2.08)for BT and 1.79(1.42-2.08)for AT groups(Z-2.84,P<0.01).The SDMT and MMSE values did not show a significant difference between BT and AT groups.CONCLUSION Compared to the AT group,the BT group showed impaired language,memory,and subjective cognition,but objec-tive cognition and execution were not significantly affected.

Risks and diagnosis of coronary artery disease in Hodgkin lymphoma survivors

Higher mortality rates are reported because of cardiovascular diseases in individuals living in industrialized areas of the World.In cancer patients,cardiotoxic chemotherapeutic agents and/or mediastinal radiotherapy are additional risk factors for the development of coronary artery disease.An improved survival rate for patients with Hodgkin lymphoma was reported in recent decades.Determining and handling the long-term effects of cancer treatment have become more important nowadays,parallel to the good results reached in survival rates.Mediastinal radiotherapy and cardiotoxic chemotherapeutic agents are routinely used to treat Hodgkin lymphoma but are commonly associated with a variety of cardiovascular complications.Drugs used in cancer treatment and radiotherapy may cause deleterious effects on contractile capacity and conduction system of the heart.Approximately ten years after the completion of all therapies,the cardiovascular disease risk peaks in patients who survived from Hodgkin lymphoma.The value of coronary computed tomography angiography as a diagnostic tool in determining coronary artery disease as early as possible is underlined in this review,in patients who are in remission and carry the risk of coronary artery disease probably because of chemo/radiotherapy used in their treatment.Survivors of Hodgkin lymphoma especially treated with combined chemoradiotherapy at younger ages are candidates for coronary computed tomography angiography.

Atypical cutaneous lesions in advanced-stage Hodgkin lymphoma: A case report

BACKGROUND Cutaneous involvement in Hodgkin lymphoma (HL) is a rare finding.Few cases have been reported in literature,most describing paraneoplastic manifestations.Only very few papers have described primary HL skin infiltration,reporting a wide range of clinical presentations that frequently include ulcers;plaques,nodules and papules have also been noticed.CASE SUMMARY We report the case of a 56-year-old man who presented fever,multiple adenomegalies of neck and axilla and thick serpiginous skin lesions involving bilateral pectoral regions.After an initial diagnostic workup for a suspected active infectious disease,a lymph node biopsy was performed,which showed a neoplastic invasion from a mixed cellularity classical HL.The same histological pattern was described in a cutaneous biopsy of the chest lesions.The other staging procedures performed revealed an advanced disease,with unfavourable clinical prognostic features.The patient was prescribed 6 cycles of ABVD chemotherapy scheme (doxorubicin,bleomycin,vinblastine,dacarbazine),a regiment that requires demonstration of metabolic response achievement at the interim PET/CT scan to confirm continuation or to change therapeutic strategy.CONCLUSION Skin involvement in HL is a rare finding and may represent a challenging clinical presentation due to extremely various types of lesions observed.

Waldenstrom's macroglobulinemia associated with Hodgkin's lymphoma:a case report

Waldenstrom＇s macroglobulinemia/lymphoplasmacytic lymphoma （WM/LPL） is a low-grade B-cell non- Hodgkin＇s lymphoma with an indolent clinical course. Higher-grade non-Hodgkin lymphoma （NHL） and therapy- related myelodysplasia/acute leukemia （t-MDS/AML） have been reported in patients with WM/LPL in previous studies. However, only two cases with WM/LPL were reported to develop to Hodgkin lymphoma （HL）. Here, we report the first case of WM/LPL who developed classical HL simultaneously 3 years after initial nucleoside analog-based chemotherapy.

Comparison of Dose-dense ABVD and Standard ABVD in the Treatment of Early Unfavorable and Advanced Hodgkin's Lymphoma: A Retrospective Analysis

This retrospective analysis compared standard regimen of doxorubicin, bleomycin, vin- blastine, and dacarbazine （ABVD） with the dose-dense ABVD regimen （ABVD-21） in terms of effi- cacy and toxicity. Patients who had early-stage unfavorable or advanced Hodgkin＇s lymphoma （HL） according to German Hodgkin Study Group criteria from March 1999 to February 2011 were ana- lyzed for treatment response, long-term survival and hematological toxicity. There were 85 patients in the ABVD-21 group and 118 patients in the ABVD group respectively. The complete remission rates aider completion of treatment were 92.9% and 90.7% for ABVD-21 and ABVD, respectively. During a median follow-up period of 62 months, no significant difference was found in projected 10-year progression-free survival （PFS） and overall survival （OS） rates （84.7% and 94.1% respectively for ABVD-21; 81.4% and 91.5% for ABVD）. Subgroup analyses showed that ABVD-21 was signifi- cantly better than ABVD for patients with IPS〉3 in terms of PFS and OS rates. Grade 3 to 4 leuko- penia （51.8% vs. 28.8%, P=0.001） and neutropenia （57.6% vs. 39.0%, P=0.009） were more common with ABVD-21. We were led to conclude that dose-dense ABVD did not result in better tumor con- trol and overall survival than did ABVD for early-stage unfavorable HL. However, patients at high risk, for example, with IPS〉3, may benefit from dose-dense ABVD.

Rejection of Experimental Hodgkins Lymphoma by T-Cells Engineered with a CD19 Chimeric Antigen Receptor

T cells engineered to express chimeric antigen receptors (CARs) combining an external antibody binding domain with the CD3ζ T cell receptor (TCR) signaling domain for triggering cell activation are being used for immunotherapeutic targeting of tumor cells in a non-HLA restricted manner. In this study we transduced T cells with a CD19-CAR construct containing a truncated CD34 gene (tCD34) marker and used these to target the B cell antigen CD19 on the surface of a Hodgkin’s lymphoma (HL) cell line (L591) both in vitro and in vivo. Levels of tCD34 expression in transduced peripheral blood mononuclear cells (PBMCs) ranged from 6% - 20% and this was increased to 82% after selection for transduced tCD34+ cells. In vitro cytotoxicity testing on a CD19+ HL cell line (L591) showed specific cell lysis initiated by the CD19-CAR transduced PBMCs. Importantly, CD19-CAR T cells prevented the growth of L591 HL tumor cells when co-injected subcutaneously (sc) in 6/6 severe combined immunodeficient (SCID) mice. There was no evidence of anti-tumor activity when CD19-CAR T cells were infused intravenously (iv) at the same time as L591 HL tumor cells were injected sc. However, 3/6 SCID mice showed tumor rejection within 83 days after iv infusion of CD19-CAR T cells 3 - 9 days after establishment of L591 HL tumors, while all control animals succumbed to tumors within 60 days. Interestingly, immuno-histochemical analysis of L591 HL tumors demonstrated that CD19-CAR T cells were detected not earlier than 11 days after infusion within the tumor mass. These results suggest that CD19 is a potentially attractive target for the immunotherapy of HL.