Biomedical subjects

Andreas Josting

Publications and source records attributed to Andreas Josting.

At least 19 recordsLinked to original sources

PubMed2006

Rituximab added to an intensified salvage chemotherapy program followed by autologous stem cell transplantation improved the outcome in relapsed and refractory aggressive non-Hodgkin lymphoma.

We investigated the addition of rituximab to an intensified salvage program followed by a myeloablative course with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory aggressive non-Hodgkin lymphoma (NHL). Patients with relapsed or progressive aggressive NHL were treated with two cycles of conventional salvage chemotherapy (DHAP) followed by high-dose sequential chemotherapy (cyclophosphamide, methotrexate with vincristine and etoposide) and a final myeloablative course (BEAM) with ASCT. Rituximab (375 mg/m(2)) was administered at each treatment cycle. This cohort was compared with a historical control group of patients treated with the same chemotherapy but without rituximab. Patients from both groups were matched by duration of first remission and lactate dehydrogenase serum levels. Forty-five patients were treated with chemotherapy and 22 with immunochemotherapy. The overall response rates (ORR) at the final evaluation were 63% for the immunochemotherapy group and 42% for the chemotherapy group (p = 0.330). In the historical controlled analysis freedom from second failure (FF2F) at 2 years in the immunochemotherapy group was 57% and overall survival (OS) was 77%. FF2F in the chemotherapy group was 18% (p = 0.0051) and OS was 37% (p = 0.0051). In the matched-pair analysis, FF2F was 58% in the immunochemotherapy group compared to 16% in the chemotherapy group (p = 0.0517); OS was 74 vs 33%, respectively (p = 0.0424). The toxicity was tolerable and comparable in both groups. The addition of rituximab to an intensified salvage chemotherapy regimen seems to improve the prognosis. However, only prospective randomized trial can offer sufficient data of the value of rituximab in relapsed and refractory aggressive NHL.

Adult↗

PubMed2006

Advances in biology, diagnostics, and treatment of Hodgkin's disease.

Hodgkin and Reed-Sternberg cells are derived from germinal center B cells. Amplification of identical rearranged and mutated immunoglobulin genes from different Hodgkin and Reed-Sternberg cells from the same patient also answered the question of the malignant nature because the clonality-the key criterion of malignancy-of Hodgkin and Reed-Sternberg cells was hereby shown. In addition, it could be demonstrated that Hodgkin and Reed-Sternberg cells do not only expand clonally within 1 affected lymph node, but also clonally disseminate in advanced-stage disease and relapse even after clinical complete remission. Recent publications demonstrate that a probably small subset of Hodgkin disease exists with T-cell derivation of the respective Hodgkin and Reed-Sternberg cells. The management of Hodgkin's disease is undergoing a paradigm shift as a result of very effective drug regimens that are capable of inducing high remission rates, the use of combined chemoradiotherapy with involved-field irradiation in early stages, the introduction of effective salvage chemotherapy of relapsed Hodgkin's disease with peripheral stem cell transplantation, a better understanding of prognostic factors, economic constraints, and a more sensitive realization of the magnitude of late treatment mortality.

Combined Modality Therapy↗

PubMed2006

Relapse in common lymphoma subtypes: salvage treatment options for follicular lymphoma, diffuse large cell lymphoma and Hodgkin disease.

Over the last decade diagnostic techniques such as immunophenotyping as well as cytogenetic and molecular profiling gave new insights into the pathogenesis of malignant lymphoma and helped to establish the WHO classification. The recognition of well-defined biological entities with distinct response and relapse patterns led to the development of more specific treatment strategies for individual lymphoma subtypes. New treatment modalities such as the monoclonal antibody rituximab have improved the results of first-line treatment of patients with certain B-cell lymphoma subtypes substantially. Furthermore, new prognostic factors were described for different lymphoma entities leading to further differentiation of treatment. As a consequence, the quality of relapse after first-line therapy has changed and treatment strategies for relapsed disease need to be redefined. This review summarises current salvage treatment options for common lymphoma subtypes taking into account variables which should be considered before an individual patient is treated. We focus on follicular lymphoma, diffuse large B-cell lymphoma and Hodgkin disease since these are most frequent and evidence-based salvage strategies are beginning to emerge.

Hodgkin Disease↗

PubMed2005

Role of hematotoxicity and sex in patients with Hodgkin's lymphoma: an analysis from the German Hodgkin Study Group.

PURPOSE: Several scores have described sex as a prognostic factor in patients with Hodgkin's lymphoma (HL). However, little is known how sex-specific factors influence treatment outcome. We systematically investigated sex differences with regard to pretreatment characteristics and therapy-related variables, and examined their influence on the outcome of HL patients. PATIENTS AND METHODS: This analysis comprises 4,626 HL patients of all prognostic risk groups who were enrolled onto the multicenter studies HD4 to HD9 of the German Hodgkin Study Group. At 5.5 years, 2,050 female and 2,576 male patients were analyzed. RESULTS: Male and female patients had similar prognostic factors. There was more acute chemotherapy-related hematotoxicity in women, especially more severe leucopenia (WHO grade 3/4, 69.9% female and 55.2% male; P < .0001). Importantly, this did not translate into more infections. Female patients had similar response rates but fewer relapses and deaths, leading to a significantly better freedom from treatment failure (FFTF; at 66 months, 81% female [95% CI, 79% to 82%] and 74% male [95% CI, 72% to 76%]). Severe leucopenia during chemotherapy was strongly associated with better FFTF, both for males and females. In addition, when only those patients who developed severe leucopenia within the first two cycles of chemotherapy were included, the factor maintained its protective role. CONCLUSION: The protective role of severe leucopenia suggests the testing of a more individualized therapy. In future trials, this therapy may be tailored in a response-adapted manner depending on the individual toxicity profile within the first cycles.

Adolescent↗

PubMed2005

Fludarabine in combination with alemtuzumab is effective and feasible in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: results of a phase II trial.

PURPOSE: To determine the efficacy and safety of a newly developed concomitant administration of fludarabine and alemtuzumab (FluCam) in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). PATIENTS AND METHODS: A total of 36 patients were treated in this phase II study (median age, 61.47 years; mean number of prior chemotherapies, 2.6; Binet stage C, n = 28). After an initial dose escalation of alemtuzumab over 3 days, alemtuzumab 30 mg and fludarabine 30 mg/m2 were administered on 3 consecutive days. Treatment was repeated after 28 days for up to six cycles. Restaging (following National Cancer Institute criteria) was carried out after cycles 2 and 4 and 1 month after the end of treatment. RESULTS: The overall response rate was 83% (11 complete responses, 19 partial responses, one stable disease, and five progressive diseases). Two patients with progressive disease developed fungal pneumonias, and one patient died as a result of Escherichia coli sepsis. Two subclinical cytomegalovirus reactivations occurred. CONCLUSION: The new FluCam regimen is effective and feasible in patients with relapsed and refractory B-CLL.

Adult↗

PubMed2005

Lymphocyte-rich classical Hodgkin's lymphoma: clinical presentation and treatment outcome in 100 patients treated within German Hodgkin's Study Group trials.

PURPOSE: To investigate the clinical characteristics and treatment outcome of patients with lymphocyte-rich classical Hodgkin's lymphoma (LRCHL) compared with other histologic subtypes of Hodgkin's lymphoma (HL). PATIENTS AND METHODS: From a total of 2,715 patients with biopsy-proven HL treated within the trials HD7 to HD12 of the German Hodgkin's Study Group, 100 patients (4%) with LRCHL, 145 patients (5%) with lymphocyte-predominant HL (LPHL), 1,688 patients (62%) with nodular sclerosis, 731 patients (27%) with mixed cellularity, and 23 patients (1%) with lymphocyte depletion were identified. Patients with LRCHL had a median age of 38 years (range, 16 to 74 years). RESULTS: Compared with other histologic subtypes, patients with LRCHL are, on average, older and usually present with early stages of disease (stage I, 34%; stage II, 46%). The median time of follow-up was 32.2 months (95% CI, 28.2 to 37.0 months). Complete and partial remission was achieved in 96 patients (96%) and four patients (4%), respectively, with LRCHL. The event-free and overall survival rates were 97% (95% CI, 93% [corrected] to 100% [corrected]) and 97% (95% CI, 93% [corrected] to 100% [corrected]), respectively, at 30 months. Only three patients died; all of the deaths were caused by treatment-related toxicities. CONCLUSION: LRCHL is a distinct subtype of CHL, with features of CHL and LPHL, and is a rare entity accounting for only 4% of HLs. LRCHL has a different pattern of clinical presentation and age and sex distribution than other CHLs. It is associated with an excellent prognosis if treated with current treatment regimens. When treating patients with LRCHL, great attention should be paid to avoid acute toxicities.

Adolescent↗

PubMed2005

Hodgkin's lymphoma in elderly patients: a comprehensive retrospective analysis from the German Hodgkin's Study Group.

PURPOSE: With improved prognosis for patients with Hodgkin's lymphoma (HL), interest increasingly focuses on high-risk groups such as elderly patients. We thus performed a retrospective analysis using the German Hodgkin's Study Group (GHSG) database to determine clinical risk factors, course of treatment, and outcome in elderly HL patients in comparison with younger adults. PATIENTS AND METHODS: A total of 4,251 patients included in the GHSG studies HD5 to HD9 were analyzed, of whom 372 (8.8%) were 60 years or older and 3,879 (91.2%) were younger than 60 years. Patient characteristics, treatment results, toxicity, freedom from treatment failure (FFTF), and overall survival (OS) were compared. RESULTS: Elderly patients more often had mixed cellularity subtype, "B" symptoms, elevated erythrocyte sedimentation rate, and poorer performance status. Less frequently observed were nodular sclerosis subtype, large mediastinal mass, and bulky disease. Acute toxicity during chemotherapy was generally higher in elderly patients. This was most obvious for severe infections (grade 3 or 4; 15% v 6%) correlating with more severe leukopenia in elderly patients (grade 4; 38% v 23%). As a result, significantly fewer elderly patients received the intended full chemotherapy dose (75% v 91%). The survival analysis showed a significantly poorer treatment outcome for elderly patients in terms of 5-year OS (65% v 90%), FFTF (60% v 80%), and HL-specific FFTF (73% v 82%). CONCLUSION: Elderly patients have a poorer risk profile compared with younger HL patients and experience more severe treatment-associated toxicity. Higher mortality during treatment as well as lower dose-intensity are the major factors explaining the poorer overall outcome of elderly HL patients.

Age Factors↗

PubMed2005

Autologous tandem transplantation in patients with primary progressive or relapsed/refractory lymphoma.

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/m(2)) followed by peripheral blood stem cell harvest (PBSC). The first high-dose chemotherapy (TMC) consisted of thiotepa (750 mg/m(2)), mitoxantrone (40 mg/m(2)), and carboplatin (990 mg/m(2)). Patients with no change (NC), partial remission (PR), or complete remission (CR) after TMC then received BEAM with carmustine (300 mg/m(2)), etoposide (1200 mg/m(2)), cytarabine (1600 mg/m(2)), and melphalan (140 mg/m(2)). 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.

Adult↗

PubMed2005

Salvage radiotherapy in patients with relapsed and refractory Hodgkin's lymphoma: a retrospective analysis from the German Hodgkin Lymphoma Study Group.

PURPOSE: To evaluate treatment outcome and prognostic factors in patients with refractory or first relapsed Hodgkin's disease (HD) treated with salvage radiotherapy (SRT) alone. PATIENTS AND METHODS: From 4,754 patients registered in the database of the German Hodgkin Study Group from 1988 to 1999, 624 patients were identified with progressive disease (n = 202), or with early (n = 170) or late (n = 252) relapsed HD. At first treatment failure, SRT alone was given to 100 patients. Patient characteristics were: median age, 36 years; progressive disease, 47%; early relapse, 23%; late relapse, 30%; and "B" symptoms, 14%. Eighty-five percent of the patients relapsed after cyclophosphamide, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (COPP/ABVD) -like regimens; 8% after bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) regimens, 7% after first-line radiotherapy alone. RESULTS: The volume irradiated was mantle field in 43% of patients, inverted-Y in 8%, total nodal irradiation in 12%, and involved-field in 37%. The median SRT dose was 40 Gy (range, 15 to 50 Gy). Seventy-seven patients achieved a complete remission and four patients achieved a partial remission. The 5-year freedom from treatment failure and overall survival (OS) rates were 28% and 51%, respectively. In multivariate analysis, significant prognostic factors for OS were B symptoms (P = .018) and stage at relapse (P = .014). For freedom from second failure (FF2F) Karnofsky performance status (P = .0001) was significant. In patients with limited stage at progression/relapse, duration of first remission was significant (P = .04) for FF2F. CONCLUSION: SRT offers an effective treatment for selected subsets of patients with relapsed or refractory HD.

Adolescent↗

PubMed2005

Overview of the Sixth International Symposium on Hodgkin's disease--recent advances in basic and clinical trials.

The Sixth International Symposium on Hodgkin's disease was held in Cologne, Germany, between September 18 and 21, 2004, organized by the German Hodgkin Study Group (GHSG) and chaired by Volker Diehl. Since 1987 the international symposia were held at regular intervals in Cologne with the aim to facilitate international cooperation and to bring together new scientific and clinical results reached in the field of Hodgkin's disease. The expanding number of participants from about 300 attendees at the first symposium to almost 800 from 48 countries at the Sixth International Symposium indicates the increasing importance of this meeting. For the second time a patient seminar with more than 350 attendees has been organized. This sixth meeting was going to be unique, since the GHSG celebrated its 25th anniversary and honored Volker Diehl, the group's founder in recognition of his work during more than 25 yr. The symposium was held at the University of Cologne's main building, creating a special, scientific and familiar atmosphere. Throughout the symposia carried out by the GHSG, preclinical and clinical several topics have always been of basic interest and have provided a basis for discussion and scientific exchange.

Clinical Trials as Topic↗

PubMed2005

CT and MR imaging in Hodgkin's disease--present and future.

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.

Hodgkin Disease↗

PubMed2005

Lymphocyte-predominant and classical Hodgkin's lymphoma--comparison of outcomes.

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.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Autologous transplantation in relapsed and refractory Hodgkin's disease.

The current data support the use of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as standard procedure for the majority of patients with Hodgkin's disease (HD) relapsing or progressing after combination chemotherapy. Prognostic factors reflecting unfavourable prognostic features of the disease as well as resistance to conventional salvage therapy have been identified. Preliminary data suggests a high efficacy of high-dose sequential chemotherapies in these patients. An ongoing randomized trial is comparing standard HDCT versus sequential HDCT in patients with relapsed HD.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Severe pulmonary toxicity in patients with advanced-stage Hodgkin's disease treated with a modified bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, and gemcitabine (BEACOPP) regimen is probably related to the combination of gemcitabine and bleomycin: a report of the German Hodgkin's Lymphoma Study Group.

PURPOSE: To investigate a new effective, nonleukemogenic polychemotherapy regimen, BAGCOPP (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, gemcitabine) in a phase I/II dose-escalation study in patients with advanced-stage Hodgkin' s disease (HD). PATIENTS AND METHODS: Patients in clinical stages IIB with risk factors III and IV were enrolled in this nonrandomized, multicenter trial aimed at defining the maximum-tolerated dose of gemcitabine within a modified escalated BEACOPP regimen. Gemcitabine was given at a starting dose of 800 mg/m(2) on days 1 and 4 of each cycle. RESULTS: Twenty-seven patients (eight female, 19 male) were enrolled with a median age of 33 years (range, 19 to 65 years). Due to a higher than expected hematotoxicity, the day-4 application of gemcitabine was omitted after 14 patients were included and 59 cycles were given. A total of eight patients developed lung toxicity, mainly pneumonitis (six of eight), which led to the termination of the study. With a median follow-up of 27 months, 25 patients are in continuing complete remission. CONCLUSION: The substitution of etoposide by gemcitabine in the escalated BEACOPP schema is not feasible and leads to severe pulmonary toxicity. This toxicity is probably related to the concomittant application of gemcitabine and bleomycin.

Adolescent↗

PubMed2004

Centralized radiation oncologic review of cross-sectional imaging of Hodgkin's disease leads to significant changes in required involved field-results of a quality assurance program of the German Hodgkin Study Group.

PURPOSE: To guarantee the treatment quality of involved-field radiotherapy (IF-RT) of patients in the Hodgkin's disease (HD)10 and HD11 trials of the German Hodgkin Study Group, with 460 participating study centers, a quality assurance program was conducted. It was based on a central prospective radiation oncologic review of all patients' entire diagnostic imaging and clinical findings. An individual RT prescription was provided for every study patient. The purpose of the present investigation was to assess the feasibility of such a procedure and its impact on the final definition of disease extension and patient treatment. METHODS AND MATERIALS: Between 1998 and 2002, 1371 patients were enrolled into the HD10 trial (early-stage disease) and 1570 patients into the HD11 trial (intermediate-stage disease). The HD10 trial tested four cycles of Adriamycin (doxorubicin), bleomycin, vinblastine, and dacarbazine (ABVD) against two cycles of ABVD followed by 20 Gy of IF-RT vs. 30 Gy of IF-RT (four study arms). The HD11 trial compared four cycles of ABVD with four cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) baseline followed by 20 Gy IF-RT vs. 30 Gy IF-RT in a four-arm design. All study centers were required to score disease involvement at a total of 34 possible anatomic sites on case report forms and send them, together with all diagnostic imaging, to the RT reference center in Cologne, Germany. Images were reviewed there by a panel of expert radiation oncologists and radiologists and compared with the case report form. Differences between the disease involvement documented by the participating center and the reference center were recorded. Subsequently, an individualized treatment proposal was compiled. Complete sets of documentation were submitted to the reference center for 89% of the patients in both HD10 and HD11. RESULTS: A considerable proportion of involved sites were incorrectly recorded on the corresponding case report form by the participating center. For patients with early-stage HD (HD10), there was a correction of disease involvement in 49% (593 of 1214 patients) and for patients with intermediate-stage HD (HD11) in 67% (936 of 1397 patients). Most discrepancies were seen in the lower mediastinum (23%), infraclavicular (17%), upper cervical (16%), supraclavicular (13%), and pulmonary hilar region (13%). This resulted in a change of disease stage in 41 of those 1,529 patients whose documented disease involvement had to be corrected (2.7%). Ninety-three patients had to be treated in a different protocol, because of changes in stage and risk factors. Owing to incorrect lymph node documentation of the participating centers, the RT treatment volume had to be enlarged in 891 (34%) and reduced in 82 (3%) of 2,611 patients. CONCLUSION: A central prospective review of patient data and consecutive prescription of individual RT treatment volume is feasible within large multicenter trials for HD. Such a procedure has a significant impact on the correctness of stage definition, allocation to treatment groups, and extent of the IF treatment volume.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin's lymphoma: results of the HD8 trial of the German Hodgkin's Lymphoma Study Group.

PURPOSE: To investigate whether radiotherapy can be reduced without loss of efficacy from extended field (EF) to involved field (IF) after four cycles of chemotherapy. PATIENTS AND METHODS: Between 1993 and 1998, patients with newly diagnosed early-stage unfavorable HD were enrolled onto this multicenter study. Patients were randomly assigned to receive cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) + doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for two cycles followed by radiotherapy of 30 Gy EF + 10 Gy to bulky disease (arm A) or 30 Gy IF + 10 Gy to bulky disease (arm B). RESULTS: Of 1,204 patients randomly assigned to treatment, 1,064 patients were informative and eligible for the arm comparison (532 patients in arm A; 532 patients in arm B). The median observation time was 54 months. Five years after random assignment, the overall survival (OSran) for all eligible patients was 91% and freedom from treatment failure (FFTFran) was 83%. Survival rates at 5 years after start of radiotherapy revealed no differences for arms A and B, respectively, in terms of FFTF (85.8% and 84.2%) and OS at 5 years (90.8% and 92.4%). There also were no differences between arms A and B, respectively, in terms of complete remission (98.5% and 97.2%), progressive disease (0.8% and 1.9%), relapse (6.4% and 7.7%), death (8.1% and 6.4%), and secondary neoplasia (4.5% and 2.8%). In contrast, acute side effects including leukopenia, thrombocytopenia, nausea, gastrointestinal toxicity, and pharyngeal toxicity were more frequent in the EF arm. CONCLUSION: Radiotherapy volume size reduction from EF to IF after COPP + ABVD chemotherapy for two cycles produces similar results and less toxicity in patients with early-stage unfavorable HD.

Adolescent↗

PubMed2003

Secondary myeloid leukemia and myelodysplastic syndromes in patients treated for Hodgkin's disease: a report from the German Hodgkin's Lymphoma Study Group.

PURPOSE: To assess the incidence and outcome of secondary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in patients with Hodgkin's disease (HD). PATIENTS AND METHODS: Between 1981 and 1998, the GHSG conducted three trial generations for early, intermediate, and advanced HD involving a total of 5,411 patients (called HD1 through HD9). RESULTS: A total of 46 patients with secondary AML/MDS were identified. The median age at diagnosis of leukemia was 47 years (range, 22 to 79 years). Primary therapy was as follows: radiotherapy alone (n = 4); doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD; n = 1); cyclophosphamide, vincristine, procarbazine, and prednisone (COPP)/ABVD or similar (n = 30); bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) baseline (n = 2); and BEACOPP escalated (n = 9). Twelve patients developed AML/MDS after salvage therapy, including four patients who developed AML/MDS after high-dose chemotherapy with autologous stem-cell transplantation. Thirty-six of the secondary malignancies were AML, and 10 malignancies were MDS. After a median observation time of 55 months, incidence of secondary AML/MDS was 1%. Treatment for secondary AML/MDS was as follows: cytarabine (Ara-C)-containing regimens (6-thioguanin, cytarabine, daunorubicin [TAD]/high-dose cytarabine, mitoxantrone [HAM], HAM, Ida-Ara-C (idarubicin + Ara-C), Ida-Flag (idarubicin, fludarabin, Ara-C, G-CSF), and idarubicin, cytarabine, etoposide [ICE]+HAM; n = 11), TAD-chemotherapy (n = 5), other regimens (n = 3), no treatment or supportive care (n = 24), palliative oral chemotherapy (n = 3), and allogeneic stem cell transplantation (n = 9). After 24 months of observation, no difference in freedom from treatment failure and overall survival (2% and 8%, respectively) was observed in patients who developed AML or MDS. CONCLUSION: The prognosis of patients with secondary AML/MDS after primary HD is poor. Thus, emphasis should be made to improve initial treatment in an attempt to prevent this complication.

Acute Disease↗

PubMed2003

Current treatment strategies in early stage Hodgkin's disease.

Treatment of Hodgkin's disease (HD) is strictly dependent on stage. Historically, early stage HD included the limited stages I, II, and IIIA (according to the Cotsworth modification of the Ann Arbor classification), whereas advanced HD included stage III with B symptoms and stage IV. It was observed that early stage HD with certain clinical risk factors had a significantly worse outcome. As a consequence, several studies defined these patients as suffering from early stage unfavorable (or intermediate stage) HD, demanding a more aggressive treatment.

Combined Modality Therapy↗