Thalidomide for systemic capillary leak syndrome.
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Capillary Leak Syndrome↗
Biomedical subjects
Andreas Josting
Publications and source records attributed to Andreas Josting.
Extramedullary acute myeloid leukemia (granulocytic sarcoma) with arm paresis, maculopapular exanthema and organ involvement.
Granulocytic sarcoma (extramedullary myelosarcoma, chloroma) is a rare extramedullary myeloid tumor which can occur at any anatomical site as isolated finding or associated with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). In this case, we describe a 71-year-old man who presented with incomplete paresis of the left arm, periorbital swelling, a maculopapular exanthema and organ involvement including testis and stomach. The tumors responded to combination chemotherapy and the patient fully recovered. However, after five months the patient relapsed and died quickly. This case confirms the importance of including granulocytic sarcoma in the differential diagnoses of a variety of diseases. In AML, the presence of granulocytic sarcoma is associated with worse overall survival. When diagnosed, it should be treated with intensive chemotherapy as soon as possible.
Aged↗
[New therapeutic strategies for Hodgkin lymphoma in cooperation of radiation oncology and medical oncology].
BACKGROUND: Between 1984 and 2002 more than 9500 pts. were enrolled in the multicentric randomized trials of the German Hodgkin Study Group (GHSG) and are evaluable for response, survival, recurrences, and toxicities. Actually the GHSG evaluates the efficacy of risk-adapted therapy composed of polychemotherapy (CT) and radiotherapy (RT). An extensive RT quality assurance program has been practiced during the study generations and will be continued. PATIENTS AND METHODS: The 4th study generation (1998-2002) includes the following trials: In the HD10 trial (early stages) 4x ABVD are tested against 2x ABVD followed by 20 Gy Involved Field (IF)-RT vs. 30 Gy IF-RT (4 arms). In order to optimize CT-regimen and IF-RT dose for pts. with intermediate stage, the HD11 trial compares 4x ABVD with 4x BEACOPP baseline followed by 20 Gy IF-RT vs. 30 Gy IF-RT in a 4 arm design. Concerning advanced stages (HD12), the BEACOPP regimen is to be optimized and the necessity of additive RT is tested. The standard arm (8x BEACOPP escalated) is compared with the toxicity reduced arm (4x BEACOPP escalated + 4x BEACOPP baseline) followed by 30 Gy RT on initial bulky disease and/or residual tumor vs. no RT (4 arms). RESULTS: Interim results (without arm comparisons) with a median follow-up of 18 months for HD10 and HD11 and 20 months for HD12 are as follows: Freedom from Treatment Failure (FFTF) at 18 months is in the HD10 trial (390 pts.) 96.4%, in the HD11 trial (480 pts.) 91.5% and in the HD12 trial (550 pts.) 90.2%.The overall survival (OS) at 18 months is in HD10 98.2%, in HD11 98.5%, in HD12 93.5%. In HD10, HD11 and HD12 respectively, 1.8%, 1.9% and 2.5% of pts. died and 1.0%, 2.5% and 2.2% suffered early progression. CONCLUSION/FURTHER STRATEGY: In order to reduce the relapse rate and toxicity and to improve the quality of life, the new HD13 trial for early stages (Fig. 1a) compares 2x ABVD, 2x ABV, 2x AVD und 2x AV, each followed by 30 Gy IF-RT. For the intermediate stages, the FFTF rate should be improved by intensifying the standard regimen. Therefore the new trial HD14 (Fig. 1b) compares 4x ABVD with 2x BEACOPP escalated + 2x ABVD, each followed by 30 Gy IF-RT. In the new trial for advanced stages HD15 (Fig. 1c),the FFTF/OS rates are to be maintained and the quality of life to be improved. 8x BEACOPP escalated, 6x BEACOPP escalated and 8x BEACOPP baseline with shortened 14-day cycle are compared. The use of PET to decide on additive RT will also be investigated.
Antineoplastic Combined Chemotherapy Protocols↗
[Hepatitis-C-virus-associated cryoglobulinemia. Pathogenesis, diagnosis and treatment].
BACKGROUND: Chronic hepatitis C-virus (HCV) infection is frequently associated with a variety of autoimmune phenomenons. Mixed cryoglobulins appear in up to 50% of chronic HCV-infected patients, mostly asymptomatic. PATHOGENESIS: Cryoprecipitates present IgM with rheumatoid factor activity and development of immunocomplexes deposited in small vessels responsible for resulting vasculitis. MANIFESTATIONS: Characteristic clinical findings are weakness, arthralgia and purpura with further complications including glomerulonephritis and neuropathic lesions. Several mechanisms for HCV-induced clinical lymphoproliferation are discussed, such as chronic B-cell stimulation and activation of the antiapoptotic oncogene bcl-2 leading to immunoglobulin synthesis and eventually evolving into B-cell non-Hodgkin's lymphoma (NHL). TREATMENT: Conventional treatment of HCV-associated mixed cryoglobulinemia aimes at reducing circulating immunocomplexes and causal therapy with interferon (IFN) and ribavirin. New approaches using the anti-CD20 antibody rituximab have been described recently.
Antiviral Agents↗
Rapidly alternating COPP/ABV/IMEP is not superior to conventional alternating COPP/ABVD in combination with extended-field radiotherapy in intermediate-stage Hodgkin's lymphoma: final results of the German Hodgkin's Lymphoma Study Group Trial HD5.
PURPOSE: To investigate whether treatment results in intermediate-stage Hodgkin's lymphoma can be improved by rapid application of non-cross-resistant drugs, the 10-drug regimen cyclophosphamide, vincristine, procarbazine, and prednisone (COPP), doxorubicin, bleomycin, and vinblastine (ABV), and ifosfamide, methotrexate, etoposide, and prednisone (IMEP), repeated every 6 weeks, was compared with conventional alternating COPP/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) administered every 8 weeks. PATIENTS AND METHODS: From January 1988 to January 1993, 996 patients in stage I or II Hodgkin's lymphoma with at least one risk factor (massive mediastinal tumor, massive spleen involvement, extranodal disease, elevated ESR, or more than two lymph node areas involved) and all patients in stage IIIA Hodgkin's lymphoma were randomized to receive two cycles of COPP/ABVD or COPP/ABV/IMEP followed by extended-field radiotherapy. RESULTS: Both regimens produced similar rates for treatment responses (complete remission, 93% v 94%), freedom from treatment failure (80% v 79%), and overall survival (88% for both regimens) at a median follow-up time of 7 years. Most serious toxicities during chemotherapy were similar in both regimens. However, World Health Organization grade 3 and 4 leukocytopenia occurred significantly more frequently in the COPP/ABV/IMEP arm (53% v 44% of patients; P =.010). There were no differences in the number of serious infections and toxic deaths during therapy. The number of second malignancies was also the same in both arms (22 each). CONCLUSION: Alternating COPP/ABVD and rapid alternating COPP/ABV/IMEP in combination with extended-field radiotherapy are equally effective in intermediate-stage Hodgkin's lymphoma and produce excellent long-term treatment results.
Adolescent↗
New prognostic score based on treatment outcome of patients with relapsed Hodgkin's lymphoma registered in the database of the German Hodgkin's lymphoma study group.
PURPOSE: To evaluate salvage treatment outcome of patients with relapsed Hodgkin's disease (HD) and to distinguish different risk groups using identified prognostic factors. PATIENTS AND METHODS: From 4,754 patients registered in the German Hodgkin's Lymphoma Study Group (GHSG) database between 1988 and 1999, 422 patients with early (n = 170) or late (n = 252) relapsed HD were identified. One hundred seven patients (25%) relapsed after radiotherapy (RT) for early stages, 133 patients (32%) after combined-modality therapy for intermediate stages, and 182 patients (43%) after chemotherapy (CT) and RT to initial bulky disease or residual lymphoma for advanced stages. At relapse, characteristics of these 422 patients (median age, 38 years; range, 17 to 77) were stage III/IV, 45%; B symptoms, 24%; elevated erythrocyte sedimentation rate, 29%; anemia, 13%; and Karnofsky performance score, less than 90 in 13%. At first relapse, salvage treatment was RT in 13%, CT in 54%, and high-dose chemotherapy (HDCT) with autologous stem-cell transplantation (ASCT) in 33%. RESULTS: Median follow-up time after relapse was 45 months. Freedom from second failure (FF2F) and overall survival (OS) were 81% and 89% for relapse after RT, 33% and 46% for early relapse after CT, and 43% and 71% for late relapse after CT, respectively. In multivariate analysis, independent risk factors were time to relapse, clinical stage at relapse, and anemia at relapse. Four subgroups with significantly different FF2F and OS were identified. The prognostic score was predictive for patients who relapsed after RT, CT with conventional CT salvage, and CT with HDCT/ASCT. CONCLUSION: In the GHSG database, time to relapse and clinical stage and anemia at relapse are relevant factors and can be used to form a prognostic score for HD patients at relapse.
Actuarial Analysis↗
New treatments for Hodgkin's disease.
Four of five patients with Hodgkin's disease (HD) will be cured with modern treatment strategies, depending on stage and risk factor profile. In early stage favorable HD, cure rates are greater than 90% with extended field (EF) irradiation, the standard treatment. However, the concept of EF irradiation therapy is being abandoned by most study groups because of the recognition of fatal long-term effects, especially the high rates of second solid tumors. Newer approaches include mild chemotherapy combined with involved field (IF) irradiation to control occult disease. Combined modality is the treatment of choice in early stages unfavorable (intermediate) HD, in which EF irradiation is substituted by IF irradiation. In the last three decades, because of the high relapse rates (30%-50%) after first-line polychemotherapy, the standard regimens were often modified. However, until recently, these efforts could not change the relatively poor outcome for patients with advanced stage disease. The introduction of a new dose-intensified regimen (BEACOPP) has significantly improved the prognosis for patients with advanced HD. Patients who relapse after radiation therapy alone for early stage HD have satisfactory results with combination chemotherapy and are not considered as candidates for high-dose chemotherapy with autologous stem cell transplantation. For patients with relapsed HD after combination chemotherapy, the data support the use of high-dose chemotherapy with autologous stem cell transplantation.
Antineoplastic Agents↗
Carboxypeptidase-G2 rescue in cancer patients with delayed methotrexate elimination after high-dose methotrexate therapy.
High-dose methotrexate (HDMTX) is a component of many cancer treatment regimens. Despite careful management, delayed renal clearance, followed by extremely high serum levels with potentially life-threatening toxicity can occur. In the present study, we report our results of carboxypeptidase-G2 (CPDG2) rescue in 8 patients with delayed methotrexate elimination and renal impairment after HDMTX therapy for lymphoma or osteosarcoma. A dose of 50 U/kg CPDG2 was administered. MTX plasma levels decreased rapidly and recovery of renal function was observed in all patients. No patient developed severe WHO grade 4 MTX toxicity. CPDG2 provides an alternative route of MTX elimination by converting it to inactive and non-toxic metabolites. CPDG2 rescue was well tolerated, safe and very effective in preventing severe or life-threatening MTX toxicity.
Adult↗