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Summary: Data on non‐Hodgkin lymphoma (NHL) after classical Hodgkin lymphoma (cHL) are scarce. We therefore performed a retrospective analysis comprising 11·841 cHL patients who had first‐line treatment within the randomized German Hodgkin Study Group (GHSG) HD7–HD15 studies. After a median follow‐up of 106 months, 175 patients (1·5%) had developed NHL. The median time to NHL was 44 months, the median age at NHL diagnosis was 54 years. The five‐year event‐free survival and overall survival estimates from the diagnosis of NHL were 36·9% and 44·2%, respectively. Thus, NHL after cHL is a rare event primarily affecting older individuals and often resulting in the patient´s death. [ABSTRACT FROM AUTHOR]

What is it that we actually see when looking at PET (positron emission tomography)-positive signals in Hodgkin lymphoma (HL)? Thus, the question of how to manage PET-positive lesions at the end of frontline therapy in HL is indeed crucial, because undertreating a disease that can be cured with firstline treatment in 80-90% of cases must definitely be avoided. As a result the authors concluded that it may not always be decisive to perform a biopsy for PET-positive residual mediastinal tissue after frontline therapy and that it was safe and appropriate to first closely observe asymptomatic patients instead of directly intensifying treatment. In the GHSG HD15 trial Engert et al. assessed whether administering RT only to patients with persistent PET-positive residues after chemotherapy was justifiable compared to earlier trials where irradiation was given to all initial bulky findings and all residual disease. [Extracted from the article]

Genome-wide association studies (GWASs) have identified several, mainly co-dominantly acting, single-nucleotide polymorphisms (SNPs) associated with Hodgkin lymphoma (HL). We searched for recessively acting disease loci by performing an analysis of runs of homozygosity (ROH) based on windows of homozygous SNP-blocks and by calculating genomic inbreeding coefficients on a SNP-wise basis. We used data from a previous GWAS with 906 cases and 1217 controls from a population with a long history of no matings between relatives. Ten recurrent ROHs were identified among 25 055 ROHs across all individuals but their association with HL was not genome-wide significant. All recurrent ROHs showed significant evidence for natural selection. As a novel finding genomic inbreeding among cases was significantly higher than among controls (P = 2.11*10−14) even after correcting for covariates. Higher inbreeding among the cases was mainly based on a group of individuals with a higher average length of ROHs per person. This result suggests a correlation of higher levels of inbreeding with higher cancer incidence and might reflect the existence of recessive alleles causing HL. Genomic inbreeding may result in a higher expression of deleterious recessive genes within a population. [ABSTRACT FROM AUTHOR]

Background. Hodgkin lymphoma (HL) is a lymphoid malignancy characterized by the production of various cytokines possibly involved in immune deregulation. Interleukin-10 (IL-10) serum levels have been associated with clinical outcome inpatients with HL. Because host genetic variations are known to alter the expression and function of cytokines and their receptors, we investigated whether genetic variations influence clinical outcome of patients with HL. Methods. A total of 301 patients with HL who were treated within randomized trials by the German Hodgkin Study Group were included in this exploratory retrospective study. Gene variations of IL-10 (IL-10-597AC, rs1800872; IL-10-824CT, rs1800871; IL-10-1087AG, rs1800896; IL-10-3538AT, rs1800890; IL-10-6208CG, rs10494879; IL-10-6752AT, rs6676671; IL-10-7400InDel), IL-13 (IL-13-1069CT, rs1800925; IL-13Q144R, rs20541), and IL-4R (IL-4RI75V, rs1805010; IL-4RQ576R, rs1801275) were genotyped. Results. Inferior freedom from treatment failure (FFTF) was found in patients harboring the IL-10-597AA, IL-10-824TT, or the IL-10-1087AA genotype. In contrast, the IL-10-1087G-824C-597C haplotype present in about 48% of analyzed HL patients is nominally significant for a better FFTF in a Cox-Regression model accounting for stage and treatment. No associations were observed between the other IL-10 gene variations, IL-13-1069CT, IL-13Q144R, IL-4RI75V, IL-4RQ576R and the clinical outcome of patients with HL. Conclusions. Our study provides further evidence that proximal IL-10 promoter gene variations are associated with clinical course of patients with HL. However, treatment success and survival rates are already at a very high rate, supporting the need to design studies focusing on identification of predictors to reduce the side effects of therapy. [ABSTRACT FROM AUTHOR]

Pixantrone is a potentially more effective, less cardiotoxic alternative to doxorubicin for patients with aggressive non-Hodgkin lymphoma (aNHL). This phase I/II non-comparative study evaluated pixantrone in place of doxorubicin in the standard CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone), i.e. CPOP (cyclophosphamide, pixantrone, vincristine, and prednisone), in patients with relapsed aNHL who had previously received CHOP ±± rituximab. Patients were administered pixantrone on day 1 of each 21-day cycle. Phase I ( n == 35) dose escalation from 80 mg/m2 to 180 mg/m2 established the phase II ( n == 30) dose as 150 mg/m2. In phase II, 20 patients (67%%) received all six planned cycles. The objective response rate was 73%%, complete response/complete response unconfirmed (CR/CRu) rate was 47%%, and median overall survival was 17.9 months. Myelosuppression was nearly universal. Six patients (20%%) developed febrile neutropenia. Overall, left ventricular ejection fraction (LVEF) declines ≥≥10%% occurred in 14 patients; declines seemed transient and unrelated to dose. Symptomatic cardiac failure occurred in four patients; however, pre-existing conditions confounded causality. [ABSTRACT FROM AUTHOR]

Meta-analyses have followed some of the most important advances in the treatment of early-stage Hodgkin lymphoma (HL). In this review, details on all meta-analyses of patients with early-stage HL are discussed. In 1990, the first meta-analysis addressing patients with early-stage HL compared radiotherapy alone to combined-modality treatment (CMT). It was followed in 1998 by an individual-patient meta-analysis examining the role of radiotherapy with and without chemotherapy. In 2006, a comprehensive meta-analysis focusing on the risk of secondary malignancies, including most of the treatment regimens analyzed in clinical trials, was issued. The final analysis was published 2010 and provides important information for the ongoing discussion concerning the role of CMT compared to chemotherapy alone and is therefore discussed in more detail. In addition, the methodology and reporting of meta-analyses have improved over time. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background Addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy (R-chemo) has been shown to improve response rates and progression-free survival in patients with indolent or mantle cell lymphoma. However, the impact of R-chemo on overall survival is unclear. We performed a comprehensive systematic review and meta-analysis to examine the efficacy of combined immunochemotherapy using R-chemo compared with the identical chemotherapy alone with respect to overall survival in patients with advanced indolent lymphoma or mantle cell lymphoma. Methods Medical databases and conference proceedings were searched for randomized controlled trials published from January 1990 through December 2005 that compared R-chemo with chemotherapy alone in patients with newly diagnosed or relapsed indolent lymphoma or mantle cell lymphoma. We included full-text and abstract publications. Endpoints were overall survival, disease control, overall response, and toxicity. A fixed-effects model was assumed in all meta-analyses. For binary data, the relative risk was used as an indicator of treatment effect, and the Mantel-Haenszel method was used to pool relative risks. Statistical tests for heterogeneity were one-sided; statistical tests for effect estimates were two-sided. Results Seven randomized controlled trials involving 1943 patients with follicular lymphoma, mantle cell lymphoma, or other indolent lymphomas were included in the meta-analysis. Five studies were published as full-text articles, and two were in abstract form. Patients treated with R-chemo had better overall survival (hazard ratio [HR] for mortality = 0.65; 95% confidence interval [CI] = 0.54 to 0.78), overall response (relative risk of tumor response = 1.21; 95% CI = 1.16 to 1.27), and disease control (HR of disease event = 0.62; 95% CI = 0.55 to 0.71) than patients treated with chemotherapy alone. R-chemo improved overall survival in patients with follicular lymphoma (HR for mortality = 0.63; 95% CI = 0.51 to 0.79) and in patients with mantle cell lymphoma (HR for mortality = 0.60; 95% CI = 0.37 to 0.98). However, in the latter case, there was heterogeneity among the trials (P= .07), making the survival benefit less reliable. Conclusion In patients with indolent or mantle cell lymphoma, R-chemo is superior to chemotherapy alone with respect to overall survival. [ABSTRACT FROM AUTHOR]

Background: Randomized controlled trials (RCTs) are the best tool to evaluate the effectiveness of clinical interventions. The Consolidated Standards for Reporting Trials (CONSORT) statement was introduced in 1996 to improve reporting of RCTs. We aimed to determine the extent of ambiguity and reporting quality as assessed by adherence to the CONSORT statement in published reports of RCTs involving patients with Hodgkin lymphoma from 1966 through 2002. Methods: We analyzed 242 published full-text reports of RCTs in patients with Hodgkin lymphoma. Quality of reporting was assessed using a 14-item questionnaire based on the CONSORT checklist. Reporting was studied in two pre-CONSORT periods (1966–1988 and 1989–1995) and one post-CONSORT period (1996–2002). Results: Only six of the 14 items were addressed in 75% or more of the studies in all three time periods. Most items that are necessary to assess the methodologic quality of a study were reported by fewer than 20% of the studies. Improvements over time were seen for some items, including the description of statistics methods used, reporting of primary research outcomes, performance of power calculations, method of randomization and concealment allocation, and having performed intention-to-treat analysis. Conclusions: Despite recent improvements, reporting levels of CONSORT items in RCTs involving patients with Hodgkin lymphoma remain unsatisfactory. Further concerted action by journal editors, learned societies, and medical schools is necessary to make authors even more aware of the need to improve the reporting RCTs in medical journals to allow assessment of validity of published clinical research. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the feasibility and efficacy of the intensified induction chemotherapy regimen ACOMED for patients with aggressive non-Hodgkin's lymphoma (NHL). Untreated adult patients with aggressive NHL, presenting with Ann Arbour stage II–IV disease or stage I with bulky disease, and with at least one of the following risk factors: age > 60 years, advanced disease, elevated serum lactate dehydrogenase level, Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2, presence of extranodal sites of disease and bulky disease, were treated with the ACOMED regimen consisting of 4–6 cycles of adriamycin 25 mg/m 2 i.v. on days 4–5, cyclophosphamide 250 mg/m 2 i.v. on days 1–5, vincristine 2 mg i.v. absolute on day 1, methotrexate 500 mg/m 2 i.v. on day 1 with leucovorin-rescue after 24 h 30 mg/m 2 i.v. and 3 × 15 mg p.o., etoposide 100 mg/m 2 i.v. on days 3–5, dexamethasone 10 mg/m 2 p.o. on days 1–5 and granulocyte colony-stimualting factor support, repeated on day 21. Twenty-two patients were treated within this study at a single center. After 4–6 cycles of ACOMED followed by additional involved field radiotherapy in 18 patients, the complete and overall response rates were 86% (19 of 22 patients) and 95% (21 of 22 patients), respectively. After a median observation time of 10 years and 2 months, 16/22 (73%) patients are alive in continuous complete reponse without evidence of any late toxicities. ACOMED followed by involved field radiation presents a highly effective regimen for remission induction and long-term survival in patients with aggressive NHL, and merits further investigation. [ABSTRACT FROM AUTHOR]

Patients with primary progressive or refractory Hodgkin’s disease (HD) or aggressive non-Hodgkin’s lymphoma (NHL) have a particularly poor prognosis. Here we report the results of autologous tandem transplantation in these patients. Patients aged 18–55 years with primary progressive or refractory relapsed HD and aggressive NHL were included. Patients received high-dose etoposide (2000 mg/m2) followed by peripheral blood stem cell harvest (PBSC). The first high-dose chemotherapy (TMC) consisted of thiotepa (750 mg/m2), mitoxantrone (40 mg/m2), and carboplatin (990 mg/m2). Patients with no change (NC), partial remission (PR), or complete remission (CR) after TMC then received BEAM with carmustine (300 mg/m2), etoposide (1200 mg/m2), cytarabine (1600 mg/m2), and melphalan (140 mg/m2). Patients with bulky disease (>5 cm) or residual lymphoma received involved field radiotherapy. Twenty-five patients were included (HD=10, NHL=15, median age 34 years). Two patients with HD achieved a CR and five patients a PR [response rate (RR) 70%]. Three patients (30%) experienced treatment failure including two deaths due to peritransplant complications. Five patients with aggressive NHL were in CR and two patients in PR (RR 46%). Of the eight patients (56%) with treatment failure, three had progressive disease and five died from peritransplant complications. Freedom from treatment failure (FFTF) and overall survival (OS) for all patients after 12 months was 28% and 40%, respectively. Tandem HDCT followed by autologous stem cell transplantation (ASCT) offers a chance of cure in these poor prognostic patients, but is associated with risks. [ABSTRACT FROM AUTHOR]

Gossmann A, Eich HT, Engert A, Josting A, Müller R-P, Diehl V, Lackner K-J. CT and MR imaging in Hodgkin's disease– present and future.Eur J Haematol 2005: 75 (Suppl. 66): 83–89.© Blackwell Munksgaard 2005.Initial staging of Hodgkin's disease is crucial to determine the location and extent of disease, and is the hallmark for the choice of treatment. At present, the established radiological technique for staging Hodgkin's disease is computed tomography (CT). Modern multidetector row CT scanners allow fast imaging from the scull base to the groins during a single breath hold with a spatial resolution of approximately 1 mm. Both, nodal and extranodal involvement of Hodgkin's disease can be diagnosed with CT. Magnetic resonance (MR) imaging is another useful cross-sectional imaging modality for staging Hodgkin's disease. The development of fast MR imaging techniques has considerably reduced imaging time without compromising the quality of MR images. As a consequence, MR imaging is now considered to be as diagnostic as CT for staging Hodgkin's disease. The excellent soft-tissue contrast and the lack of exposure to ionizing radiation are the main advantages of MR imaging. For the detection of extranodal Hodgkin's disease, MR imaging is superior to assess involvement of the brain, the spinal cord and bone marrow; while CT allows excellent evaluation of lung disease. Common major problems in staging Hodgkin's disease are still the detection of nodal involvement in normal sized lymph nodes and residual tumor masses after therapy. In the future, newly developed lymphotropic contrast agents for MR imaging might be helpful to answer these questions. [ABSTRACT FROM AUTHOR]

Nogová L, Reineke T, Josting A, Müller-Hermelink HK, Eich HT, Behringer K, Müller R-P, Diehl V, Engert A. Lymphocyte-predominant and classical Hodgkin's lymphoma– comparison of outcomes.Eur J Haematol 2005: 75 (Suppl. 66): 106–110.© Blackwell Munksgaard 2005.Introduction: Lymphocyte predominant Hodgkin's lymphoma (LPHL) differs in histological and clinical presentation from classical Hodgkin's lymphoma (cHL). Treatment of LPHL patients using standard Hodgkin's lymphoma (HL) protocols leads to complete remission (CR) in more than 95% of patients. However, differences in terms of relapse rates, survival and freedom from treatment failure (FFTF) between LPHL and cHL patients were suggested by a recent intergroup analysis. To obtain a more comprehensive picture, we reviewed all LPHL-cases registered in the GHSG database and compared patient characteristics and treatment outcome with cHL patients.Patients and methods: We retrospectively analyzed 8298 HL patients treated within the GHSG trials (HD4–HD12): 394 LPHL patients and 7904 cHL patients. From 394 LPHL patients 63% were in early stage, 16% in intermediate and 21% in advanced stage of disease. Of the 7904 cHL patients analyzed, 22% were in early, 39% in intermediate and 39% in advanced stages. About 9% of LPHL patients had B symptoms compared to 40% in cHL patients.Results: About 91% LPHL vs. 86% cHL patients in early stages, 86% vs. 83% in intermediate and 79% vs. 75% in advanced stages reached CR/CRu. Additional analysis for LPHL IA patients showed 98% CR/CRu after extended field, 100% after involved field (IF) and 98% CR/CRu after combined modality treatment. About 0.3% LPHL patients developed progressive disease (PD) compared to 3.7% cHL patients. The relapse rate of LPHL patients was very similar to cHL (8.1% vs. 7.9%). There were 2.5% secondary malignancies in LPHL and 3.7% in cHL patients. About 4.3% LPHL patients and 8.8% cHL patients died. The FFTF rates for LPHL and cHL patients at a median observation of 41 or 48 months were 92% and 84%, respectively. The OS for LPHL and cHL patients was 96% and 92%, respectively.Conclusion: The cHL patients present more frequently with advanced stages and B symptoms compared to LPHL patients. There was no difference in treatment outcome in terms of CR/CRu, PD and mortality between LPHL and HL. Surprisingly, there were also no differences in patients with relapse. [ABSTRACT FROM AUTHOR]

Klimm B, Diehl V, Pfistner B, Engert A. Current treatment strategies of the German Hodgkin Study Group (GHSG).Eur J Haematol 2005: 75 (Suppl. 66): 125–134.© Blackwell Munksgaard 2005.Hodgkin's Lymphoma (HL) has developed to one of the best curable human cancers and overall about 80% of patients experience long-term disease free survival. Therefore, current treatment strategies aim at further improving treatment outcome, thereby trying to by minimize therapy-induced complications, such as infertility, cardiopulmonary toxicity, and secondary malignancies. Ongoing trials investigate a reduction of chemotherapy in terms of dose or cycles given, and the application of lower radiation doses and smaller radiation fields. For patients with a specific high-risk profile, new approaches with more intense drug combinations are currently being investigated. Moreover, the advent of effective salvage high-dose therapy for relapsed disease and a better understanding of prognostic factors have further improved the management of HL. Here, we summarize current strategies of the German Hodgkin Study Group (GHSG) in diagnostics and treatment of primary and relapsed HL, together with recent approaches for specific subgroups of HL patients. [ABSTRACT FROM AUTHOR]

Summary. The granulopoiesis-stimulating factors, granulocyte colony-stimulating factor (G-CSF) and granulocyte–macrophage colony-stimulating factor (GM-CSF), are used to prevent neutropenia and febrile neutropenia in patients with malignant lymphoma. The question as to whether G-CSF/GM-CSF improves dose-intensity, tumour response and overall survival (OS) has not yet been answered. As the results from single studies are inconclusive, a systematic review was performed to determine the effectiveness of G-CSF/GM-CSF. Randomized controlled trials comparing prophylaxis with G-CSF/GM-CSF versus no prophylaxis in adult patients with malignant lymphoma undergoing conventional chemotherapy were included. Medical databases (Cochrane Library, Medline, Embase) and conference proceedings were searched. All authors were contacted to obtain missing data. We included 11 studies making a total of 1434 patients. Compared with no prophylaxis, G-CSF/GM-CSF significantly reduced the relative risk (RR) for neutropenia {RR 0·64 [95% confidence interval (CI) 0·55–0·75]} febrile neutropenia (RR 0·74 [95% CI 0·62–0·89]) and infection (RR 0·74 [95% CI 0·64–0·85]). G-CSF/GM-CSF did not decrease infection-related mortality (RR 2·07 [95% CI 0·81–5·34]), improve complete remission (CR) (RR 1·06 [95% CI 0·96–1·16]) or OS (HR 0·98 [95% CI 0·81–1·18]). In conclusion, G-CSF/GM-CSF given during conventional chemotherapy in malignant lymphoma patients reduced the RR of neutropenia, febrile neutropenia and infection. However, there is no evidence that G-CSF/GM-CSF improved CR and OS in this clinical setting. [ABSTRACT FROM AUTHOR]

Recombinant DNA technology makes it possible to genetitally fuse V genes or cytokines to toxin domains, resulting in immunotherapeutics for selective destruction of tumor cells. Since recombinant immunotoxins can be easily manipulated in terms of affinity or cytotoxic potency and produced in large quantities, we have developed a new CD30 ligand-based fusion toxin (CD3OL-ETA'). Human CD30L cDNA was ligated into a pET-based expression plasmid and thereby fused to a modified Pseudomonas aeruginosa exotoxin A (ETA') lacking its cell-binding domain I. After IPTG-indiced expression in E. coli strain BL21(DE3), the 60 kDa His-tagged fusion protein (CD3OL-ETA') was isolated from inclusion bodies. Denatured protein was renatured in the presence of 0.4 M arginine and a glutathione redox system. Refolded protein was purified and concentrated by ion-exchange chromatography on a HiTrap Q column. The binding properties of CD3OL-ETA' were evaluated by competitive ELISA, immunohistochemical staining, and FACS analysis on CD30-expressing cells. The in vitro toxicity of the fusion protein was then tested on the CD30[sup +] Hodgkin-derived cell line L540cy and the Burkitt's lymphoma cell line BL38. CD30L-ETA' exhibited specific cytotoxicity against L540cy cells (IC[sub 50] = 24 ng/ml) as determined by [[sup 3]H]leucine uptake assays. This is the first report on the specificity and cytotoxic potency of a chimeric CD30L fusion toxin against Hodgkin's disease-derived cells. [ABSTRACT FROM AUTHOR]

The article reports on research which was conducted to investigate the outcome and risk factors of patients with Hodgkin lymphoma (HL) who relapse or progress after autologous stem cell transplant (ASCT). Researchers evaluated 149 patients. They found that 75% died within 65 months after recurrence of HL following ASCT and that nearly 40% died within one year.

The article offers information on the effectiveness of lenalidomide in treating patients with refractory or multiple relapsed Hodgkin lymphoma (HL). It reports that lenalidomide is a derivative of thalidomide and is categorized in the class of immunodulatory drugs. It discusses the clinical trial conducted on patients with refractory or multiple relapsed Hodgkin lymphoma. It concludes that lenalidomide is easily tolerated within patients and high toxicity is also not observed.

No abstract available [ABSTRACT FROM AUTHOR]

This sixteenth biannual report of the Cochrane Haematological Malignancies Group highlights recently published randomized controlled trials (RCTs) in the field of hemato-oncology, with special focus on non-Hodgkin’s lymphoma. The report covers the publication period June 2012 to July 2013. Trials are selected regarding their methodology and implication for clinical practice. Studies were identified by electronic search of MEDLINE using a broad search filter that covers all topics in hemato-oncology combined with a highly sensitive search filter for randomized trials (Cochrane Handbook for Systematic Reviews of Interventions). Four RCTs are presented in detail, followed by two further RCTs of high importance in a short version. The report is finalized with an overview of new and updated Cochrane Reviews. [ABSTRACT FROM PUBLISHER]

Purpose: The role of radiotherapy (RT) after intensive chemotherapy in patients with advanced stage Hodgkin's lymphoma (HL) is still unclear. The German Hodgkin Study Group (GHSG) randomized HD12 trial was designed to test whether consolidative RT in the region of initial bulky disease and of residual disease is necessary after effective chemotherapy. A quality control program based on a multidisciplinary panel of radiation oncologists, radiologists, and medical oncologists who reviewed all patients' staging and restaging imaging was initiated. Methods and Materials: A total of 1661 patients aged 16 to 65 years with HL in Stage IIB (large mediastinal mass and/or E-lesions) or Stage III to IV were randomized from January 1999 to January 2003 according to a factorial design between: 8 esc.BEACOPP + RT (arm A), 8 esc.BEACOPP non-RT (arm B), 4+4BEACOPP + RT (arm C), 4+4BEACOPP non-RT (arm D). Results: In the fifth interim analysis, 1449 patients were eligible for the arm comparison with regard to RT. After a median observation time of 48 months the FFTF rate was 86% and the OS 92%. The FFTF was 95% in the RT arms A+C and 88% in the non-RT arms B+D: no sequential significant difference. One thousand and eighty four patients were evaluated by the panel. The panel defined initial bulky disease in 800 patients and residual disease in 600 patients. The panel recommended continuation of therapy according to the randomization for 934 of 1084 patients and additive RT independently from the randomization arm for 145 of 1084 patients. Conclusions: The study showed that RT can be reduced substantially after effective chemotherapy. However, because of the irradiation of 10% of patients in the non-RT arms, equivalent effectiveness of a non-RT strategy cannot be proved. A substantial limitation of consolidative RT according to expert panel recommendations appears to be possible without reducing effectiveness. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of radiotherapy on the severe pulmonary toxicity observed in the pilot study of BAGCOPP (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, and gemcitabine) for advanced-stage Hodgkin''s lymphoma. Methods and Materials: Patients with Stage III or IV Hodgkin''s lymphoma or Stage IIB with risk factors participated in this single-arm, multicenter pilot study. Results: Twenty-seven patients were enrolled on the study before its premature closure as a result of the development of serious pulmonary toxicity in 8 patients. The pulmonary toxicity occurred either during or immediately after the BAGCOPP chemotherapy course. Pulmonary toxicity contributed to one early fatality but resolved in the other 7 patients after cessation of gemcitabine and bleomycin, allowing continuation of therapy. Fifteen patients received consolidative radiotherapy, including 4 who previously had pulmonary toxicity. There were no reported cases of radiation pneumonitis and no exacerbation of pulmonary symptoms in the 4 patients who had had previous pulmonary toxicity. Conclusions: The severe pulmonary toxicity observed in this study has been attributed to an interaction between gemcitabine and bleomycin. Gemcitabine (when administered without bleomycin) remains of interest in Hodgkin''s lymphoma and is being incorporated into a new German Hodgkin''s Lymphoma Study Group protocol that also includes consolidative radiotherapy. This study supports the concept of the integration of radiotherapy in gemcitabine-containing regimens in Hodgkin''s lymphoma if there is an interval of at least 4 weeks between the two modalities and with a schedule whereby radiotherapy follows the chemotherapy. [Copyright &y& Elsevier]