Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of adjuvant radiation therapy (RT) in the management of advanced-stage Hodgkin's disease (HD) was analyzed in 222 patients who attained a complete remission (CR) with alternating chemotherapy combinations. Mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) or MOPP/ABV alternating with the lomustine, melphalan, and vindesine combination (MOPP/ABV/CAD) were similarly effective in inducing a CR in 222 of 270 (83%) patients. These patients were scheduled to receive consolidative RT to bulky disease or other critical sites of initial nodal involvement to a total dose of 2,000 cGy, with an optional additional boost of 1,000 cGy. However, only 125 (56%) patients received radiation to all initial nodal sites of disease. In 69 (31%) patients, only selected nodal sites were included in the radiation fields, and 28 (13%) did not receive any RT. Of the 222 CR patients, 42 (19%) relapsed during a median follow-up period of 6.5 years (range, 2 to 15 years). Of these, 26 (62%) patients relapsed exclusively in unirradiated nodal sites, six (14%) within irradiated sites, and 10 (24%) both within and outside irradiated fields. The actuarial 10-year relapse-free survival (RFS) and overall survival (OS) for patients receiving radiation to all initially involved nodal sites were 89% and 94%, respectively, compared with 68% and 71% (P less than .0001) for patients who had only partial or no RT. Cox proportional hazards regression analysis showed that RT to all sites of initial disease was the most significant independent covariate (P less than .005) affecting RFS and OS. These data demonstrate that residual microscopic disease is relatively frequent in patients with apparent CR after alternating combination chemotherapy, and that irradiation of all sites of initial nodal involvement decreases relapse and improves survival in advanced-stage HD.
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PMID:Impact of adjuvant radiation on the patterns and rate of relapse in advanced-stage Hodgkin's disease treated with alternating chemotherapy combinations. 196 May 60

Seventeen patients with advanced stage Hodgkin's disease who relapsed or failed to respond to multiple regimens of combination chemotherapy (mostly Mechlorethamine, Vincristine, Procarbarzine, Prednisone and Adriamycin, Bleomycin, Vinblastine, Dacarbazine) were treated with accelerated hyperfractionated total lymphoid irradiation (TLI) and high-dose chemotherapy followed by autologous bone marrow transplantation (AuBMT). Candidates for the protocol did not have prior radiation therapy and had no evidence of bone marrow involvement. Their bone marrow was initially harvested and cryopreserved. The treatment protocol consisted of reinduction with conventional doses of combination chemotherapy followed by boost local field irradiation to areas of residual disease (1500 cGy within 5 days) and total lymphoid irradiation (2004 cGy given in 12 fractions of 167 cGy each t.i.d. delivered within 4 days). The patients were treated with Etoposide (250 mg/m2/day I.V. X 3 days) and high-dose Cyclophosphamide (60 mg/kg/day I.V. X 2 days). Cryopreserved (unpurged) autologous bone marrow was infused 48 hr after completion of chemotherapy. Of the 17 patients treated, four were in relapse and 13 refractory to multiple regimens of combination chemotherapy. Four patients died during the immediate peritransplant period (2--septicemia, 2--pulmonary complications). Of the 13 surviving patients, 12 entered a complete remission and one had a partial remission and died of disease 6 months later. One patient relapsed 5 months after treatment and is currently alive with disease. Eleven patients (65%) are alive with no evidence of disease 4-35 months (median 20 months) following completion of therapy. Treatment with this protocol results in a high rate of complete remission and a potential for long-term disease-free survival in previously unirradiated patients with advanced stage refractory or relapsed Hodgkin's disease who have exhausted conventional modes of chemotherapy.
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PMID:Total lymphoid irradiation, high-dose chemotherapy and autologous bone marrow transplantation for chemotherapy-resistant Hodgkin's disease. 247 11

Mechlorethamine, when administered in massive doses (0.6-1.5 mg/kg) to cancer patients in several early studies, caused severe irreversible hearing loss. There have been no reports of ototoxicity with doses of 0.4 mg/kg or less. The authors describe a 36-year-old man who developed profound sensorineural hearing loss during his first cycle of MOPP chemotherapy for Hodgkin's disease. Cyclophosphamide was substituted for mechlorethamine in subsequent cycles and his hearing deficit resolved. This is the first reported case of reversible ototoxicity associated with currently recommended doses of mechlorethamine.
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PMID:Reversible mechlorethamine-associated hearing loss in a patient with Hodgkin's disease. 375 58

Recently, the combination chemotherapy Novantrone, Oncovin, Velban, Prednisone [NOVP] was developed by The University of Texas M. D. Anderson Cancer Center for treatment of Hodgkin's disease [HD]. Preliminary clinical results show that NOVP is as effective as the traditional Mechlorethamine, Oncovin, Procarbazine, Prednisone [MOPP] regimen in achieving remission, but with fewer side-effects. To determine if NOVP is genotoxic, we studied the induction of chromosome breaks and sister chromatid exchanges [SCEs] in lymphocytes of 42 HD patients both before and during NOVP treatment. Furthermore, in vitro bleomycin treatment was used to unmask potential single-stranded DNA breaks inducted by the therapy. Our results showed that NOVP did not cause elevated levels of chromosome or single-stranded DNA breaks, or SCEs. These results together with previous findings that NOVP caused minimal acute and gonadal toxicities suggest that NOVP is less toxic than MOPP. Therefore, this new regimen shows promise as an effective and minimally toxic regimen for treatment of HD.
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PMID:A new chemotherapy regimen for treatment of Hodgkin's disease associated with minimal genotoxicity. 768 18

In treatment strategies adapted to the specific problems in children with Hodgkin's disease (HD) high priority has been given to the reduction of late effects caused by radio- and chemotherapy, without sacrificing high survival rates. Combined modality treatment, as a standard option, has enabled reduced doses and fields of radiotherapy and lower cumulative total doses of critical cytotoxic agents. In Germany and Austria 1242 children and adolescents with HD have been treated in five consecutive multicentre studies since 1978. The main general objectives were to determine the extent to which radio- and chemotherapy can be reduced within a combined modality treatment concept and to find an effective chemotherapy of low long-term toxicity. Mechlorethamine in MOPP was replaced by adriamycin (OPPA) in the first 2 cycles of CT and by cyclophosphamide (COPP) in the additional cycles. The total number of cycles was reduced for early and intermediate stages. From the second study (HD-82) onward, patients were allocated to three treatment groups (2, 4 or 6 cycles, respectively) according to disease stage, and involved-field instead of extended-field irradiation was given. With radiation doses of 35, 30 and 25 Gy, high rates for event-free survival (97, 92 and 85%, respectively) at 14 years were achieved, demonstrating that microfoci in adjacent fields are safely eradicated by the chemotherapy used. Late effects of OPPA and OPPA/COPP: the cumulative risk of secondary leukaemias in 686 patients after 15 years was 0.9% for all patients and 0.8% for those who remained in first remission. Cardiomyopathies have not been observed (cumulative total dose of adriamycin 160 mg/m2). Increased FSH-levels indicating impaired spermatogenesis were found in 40% of the male patients without relapse. The prevalence was related to the number of procarbazine containing cycles (29% after 2 cycles, 46% after 4, and 63% after 6). In study HD-90, procarbazine in OPPA was replaced by etoposide (OEPA) for the boys (cumulative dose 1000 mg/m2), whereas girls received OPPA again. In TGs 2 and 3, both boys and girls received an additional 2 or 4 COPP cycles. Standard doses of involved-field irradiation were reduced to 25, 25 and 20 Gy. The preliminary evaluation after nearly 5 years reveals that the reduction in radiation doses did not affect the results with OPPA and OPPA/COPP chemotherapy. In localized stages, 2 OEPA (boys) and 2 OPPA (girls) cycles produced identical results. An additional objective of the German-Austrian trials was to re-evaluate the relevance of exploratory laparotomy and splenectomy within a combined modality treatment concept for all patients. While all children were laparotomized and splenectomized in the first study, the frequency of splenectomy and laparotomy was reduced step by step on the basis of retrospective analyses of the study data regarding infra-diaphragmatic involvement. Splenectomy has been completely abandoned since 1990. In conclusion, the ratio of cure rates and late effects has been favourably balanced with OPPA and OPPA/COPP plus low-dose involved-field irradiation, especially in female patients. In boys, the risk of testicular dysfunction can be further reduced by substituting OEPA for OPPA. Age up to 18 years does not appear to bear any prognostic significance for the treatment results under the conditions of the therapy concept described.
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PMID:Treatment of children and adolescents with Hodgkin's disease: the experience of the German-Austrian Paediatric Study Group. 892 49

The purpose was to verify the 5-year results of the MOPPEBVCAD chemotherapy regimen with limited radiotherapy in relation to the promising preliminary data. Mechlorethamine, vincristine, procarbazine, prednisone, epidoxorubicin, bleomycin, vinblastine, lomustine, melphalan, and vindesine were delivered according to a schedule derived through hybridization, intensification, and shortening of the corresponding alternating CAD/MOPP/ABV regimen. Radiotherapy was restricted to sites of bulky involvement or to areas that responded incompletely to chemotherapy. This multicenter, controlled, nonrandomized trial involved 145 eligible patients. Radiotherapy was administered to 47 patients, 46 of whom were in complete remission after chemotherapy. Remissions were complete in 137 patients (94%), partial in 4 (3%), and null in the remaining 4. Tumor-specific, overall, relapse-free, and failure-free survival at 5 years were 0.89, 0.86, 0.82, and 0.78, respectively. Hematologic toxicity was considerable, whereas nonhematologic side effects were fully acceptable. Most of the unfavorable prognostic factors lost their clinical weight. Only age and lymphocyte depletion histologic type were statistically correlated with major follow-up endpoints; performance status and bone marrow involvement were subordinate to age. Seven patients developed a second cancer (including 3 myelodysplasias). MOPPEBVCAD with selected radiotherapy is a highly effective regimen in advanced Hodgkin's disease. Early and late toxicity are no more severe than what would be expected with other alternating or hybrid regimens. A comparison with ABVD, which is currently considered the standard regimen for advanced Hodgkin's disease, is needed.
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PMID:Long-term results from MOPPEBVCAD chemotherapy with optional limited radiotherapy in advanced Hodgkin's disease. 953 79

Recommendations for the treatment of "poor prognosis" stages I and II Hodgkin's disease (HD) depend on the extent of staging. For centers that favor exploratory laparotomy and splenectomy, the standard treatment after negative surgical staging remains subtotal lymphoid irradiation. However, most centers recommend excluding selected patients from surgical staging. In particular, most specialists agree that patients with bulky mediastinal disease (large mediastinal adenopathy) should receive combined chemotherapy and radiotherapy without surgical staging. Centers that have eliminated staging laparotomy rely on clinical staging and have identified a number of poor prognostic factors that influence treatment recommendations. In 1995, the following factors were considered to be associated with an unfavorable prognosis in clinical stages (CS) I and II HD: advanced age, systemic symptoms, high erythrocyte sedimentation rate, large number of individual sites, and presence of bulky disease. For example, these factors have been used in the H7 and H8 European Organization for the Research and Treatment of Cancer trials and have been adopted by almost 100 participant groups. For CS I and II patients with unfavorable presentations, the literature suggests that the optimal treatment is a combination of chemotherapy and radiotherapy. Nevertheless, the optimal delivery of chemotherapy and radiotherapy is still debated and a number of the questions listed below are awaiting answers: 1. The chemotherapy schedule: Mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alone can no longer be recommended (for toxicity reasons) for the routine treatment of poor prognosis CS I and II HD. Many centers, on theoretical arguments, favor seven or eight drug combinations (MOPP/ABV hybrid), although the advantage of these combinations in toxicity and efficacy over doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone has not been demonstrated. 2. The number of chemotherapy courses: Most groups use six cycle regimens, but reduction to three to four cycles is currently being investigated both in pilot and randomized studies. 3. Timing of chemotherapy: Chemotherapy is given first in most instances. Whether or not a "sandwiched" scheme is better than all the chemotherapy given upfront remains to be answered. 4. Volumes to be irradiated: Data suggest that the irradiated volumes can be safely limited to initially involved lymph node regions after effective chemotherapy. The question is presently being addressed in a few ongoing randomized trials. 5. Radiation dose to be delivered: The decrease of the radiation dose to 35 to 36 Gy after effective chemotherapy has gained a wide acceptance. Further dose reduction is being investigated. In conclusion, except for selected CS I and II patients still referred for surgical staging, combined modality therapy appears to be the treatment of choice for poor prognosis CS I and II HD.
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PMID:Combined Modality Treatment for Poor Prognosis Stages I and II Hodgkin's Disease. 1071 77