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Canadian Medical Association Journal Aug 1985Most patients with early-stage Hodgkin's disease can now be cured by one of several therapeutic approaches. This review highlights the developments in the diagnosis and... (Review)
Review
Most patients with early-stage Hodgkin's disease can now be cured by one of several therapeutic approaches. This review highlights the developments in the diagnosis and treatment of the disease that have led to long-term survival rates greater than 90%. Past and present radio-therapy (RT) planning and treatment practices are discussed in the context of both clinical and pathological staging. The role of initial bimodal therapy (RT and chemotherapy [CT]) and the use of CT in patients who suffer relapse after initial treatment with RT alone are reviewed. On the basis of prognostic factors, subgroups of patients for whom bimodal therapy is recommended, including those with a bulky mediastinal mass, have now been identified. Although treatment is highly successful, debilitating consequences of RT and CT, such as infertility, infection and second malignant diseases, remain. Newer treatment regimens may reduce morbidity and have similar or better long-term results with respect to survival and quality of life.
Topics: Acute Disease; Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Hodgkin Disease; Humans; Infertility; Leukemia; Lymphoma; Male; Mechlorethamine; Menstruation Disturbances; Neoplasm Staging; Prednisone; Procarbazine; Prognosis; Vincristine
PubMed: 3893668
DOI: No ID Found -
Annals of Oncology : Official Journal... Nov 1995The optimal number of chemotherapy courses in responding patients with advanced-stage Hodgkin's disease (HD) is unknown. (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
The optimal number of chemotherapy courses in responding patients with advanced-stage Hodgkin's disease (HD) is unknown.
PATIENTS AND METHODS
With minimizing chemotherapy and thereby reducing late complications as the objective, patients with advanced HD were randomized to receive either 4 full MOPP/ABVD courses or treatment up to complete remission (CR). Forty-seven patients were given the fixed (FT) and 41 patients the individual treatment (IT). The two groups were balanced according to age, histopathology and sex, although stage IVB dominated in the IT group (20 vs. 8).
RESULTS
Sixty-six of 88 patients (75%) achieved CR. No difference between the two treatment groups in the proportion of stage IVB patients was seen when those achieving CR, i.e., the efficacy population were compared. The mean number of single chemotherapy courses given was 3.7 of MOPP and 3.5 of ABVD in the FT group, compared to 2.6 of MOPP and 2.5 of ABVD in the IT group (p < 0.001). The predicted progression-free survival at 10 years was 81% in the FT and 68% on the IT arm, respectively (p < 0.05). No statistically significant difference in cause-specific 10 year survival was observed (82% and 83%, respectively; p = 0.18). Long-standing CRs were achieved following minimal chemotherapy.
CONCLUSIONS
Since there are no available methods to identify long-term disease-free survivors among CR patients following a limited induction treatment, we suggest that the policy of giving 3-4 full MOPP/ABVD courses should continue. The price for such an approach is the overtreatment of a subset of already cured patients.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Dacarbazine; Disease-Free Survival; Doxorubicin; Drug Administration Schedule; Female; Hodgkin Disease; Humans; Male; Mechlorethamine; Middle Aged; Neoplasm Staging; Prednisone; Procarbazine; Prognosis; Prospective Studies; Survival Rate; Treatment Outcome; Vinblastine; Vincristine
PubMed: 8624292
DOI: 10.1093/oxfordjournals.annonc.a059356 -
Annals of Oncology : Official Journal... Feb 1995In patients with advanced Hodgkin's disease (HD), the alternation of MOPP with ABVD or hybrid MOPP/ABVD are associated with a high CR rate and a high probability of...
BACKGROUND
In patients with advanced Hodgkin's disease (HD), the alternation of MOPP with ABVD or hybrid MOPP/ABVD are associated with a high CR rate and a high probability of 5-year survival. However, even after effective chemotherapy the risk of nodal relapse is not negligible, and not only in initial bulky site(s) of disease. For this reason, in an attempt to prevent relapses after combination chemotherapy alone, we performed a prospective study to evaluate the efficacy and toxic effects of 6 courses of hybrid MOPP/ABVD followed by radiotherapy (RT) in stages II A bulky, II B, III and also in stage IV with bulky disease of residual after chemotherapy.
PATIENTS AND METHODS
From January 1985 to August 1993, 133 patients with HD (128 newly diagnosed, stage II A bulky-IV, 5 in first relapse after RT) were treated according to the following program: 6 courses of the hybrid MOPP/ABVD regimen followed by RT (STNI + spleen in stages II A, II B, III without pelvic lymph node involvement, TNI + spleen in stage III with pelvic lymph node involvement, involved field in stage IV with bulky disease or residual after chemotherapy). The total dose of RT was 4000 cGy to the sites of bulky or residual disease and 2000 cGy to the other sites.
RESULTS
After hybrid MOPP/ABVD, 107 of 130 (82.3%) fully evaluable patients were classified as in CR or CR(U). After completion of RT, 108 patients were in CR and 3 were in PR, for an overall response rate of 85%. With a median follow-up duration of 45 months, the actuarial 5-year survival is 76% and the progression-free survival 68.6%. So far, only 14 patients have relapsed (6 within the irradiation field) and the 5-year relapse-free survival is 82.5%.
CONCLUSION
Six courses of hybrid MOPP/ABVD followed by RT in stages II A bulky, II B, III and in stage IV with bulky disease or residual after chemotherapy produced a high CR rate with low risk of relapse. However, a longer follow-up is necessary to evaluate the late effects of combined therapy.
Topics: Actuarial Analysis; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Diseases; Combined Modality Therapy; Dacarbazine; Doxorubicin; Female; Hodgkin Disease; Humans; Lymphatic Irradiation; Male; Mechlorethamine; Middle Aged; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Patient Compliance; Prednisone; Procarbazine; Prognosis; Prospective Studies; Survival Analysis; Treatment Outcome; Vinblastine; Vincristine
PubMed: 7540419
DOI: 10.1093/oxfordjournals.annonc.a059113 -
Cancer Mar 2002Lymphocyte-predominant Hodgkin disease (LPHD) is rare and has a natural history different from that of classic Hodgkin disease. There is little information in the... (Clinical Trial)
Clinical Trial
European Organization for Research and Treatment of Cancer and Groupe d'Etude des Lymphomes de l'Adulte very favorable and favorable, lymphocyte-predominant Hodgkin disease.
BACKGROUND
Lymphocyte-predominant Hodgkin disease (LPHD) is rare and has a natural history different from that of classic Hodgkin disease. There is little information in the literature regarding the role of chemotherapy in patients with early-stage LPHD. The objective of this study was to examine recurrence free survival (RFS), overall survival (OS), and patterns of first recurrence in patients with LPHD who were treated with radiotherapy alone or with chemotherapy followed by radiotherapy.
METHODS
From 1963 to 1996, 48 consecutive patients ages 16-49 years (median, 28 years) with Ann Arbor Stage I (n = 30 patients) or Stage II (n = 18 patients), very favorable (VF; n = 5 patients) or favorable (F; n = 43 patients) LPHD, according to the European Organization for Research and Treatment of Cancer and Groupe d'Etude des Lymphomes de l'Adulte (EORTC-GELA) criteria, received radiotherapy alone (n = 37 patients) or received chemotherapy followed by radiotherapy (n = 11 patients). The percentages of patients with VF disease (11% vs. 9% in the radiotherapy group vs. the chemotherapy plus radiotherapy group, respectively) or F disease (89% vs. 91%, respectively) within the two treatment groups were similar (P = 1.00). A median of three cycles of chemotherapy with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or with mitoxantrone, vincristine, vinblastine, and prednisone (NOVP) was given initially to six patients and five patients, respectively. A median total radiotherapy dose of 40 grays (Gy) given in daily fractions of 2.0 Gy was delivered to both treatment groups.
RESULTS
The median follow-up was 9.3 years, and 98% of patients were observed for > or = 3.0 years. RFS was similar for patients who were treated with radiotherapy alone and patients who were treated with chemotherapy followed by radiotherapy (10-year survival rates: 77% and 68%, respectively; P = 0.89). The OS rate also was similar for the two groups (10-year survival rates: 90% and 100%, respectively; P = 0.43). MOPP or NOVP chemotherapy did not reduce the risk of recurrence outside of the radiotherapy fields.
CONCLUSIONS
MOPP or NOVP chemotherapy did not improve RFS or OS significantly in patients with VF or F LPHD, although the statistical power was limited. Ongoing clinical trials will help to clarify the role of a watch-and-wait strategy or systemic therapy, including anthracycline (epirubicin or doxorubicin), bleomycin, and vinblastine-based chemotherapy or antibody-based approaches, in the treatment of these patients.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Disease-Free Survival; Female; Hodgkin Disease; Humans; Male; Mechlorethamine; Middle Aged; Mitoxantrone; Neoplasm Recurrence, Local; Neoplasm Staging; Prednisone; Procarbazine; Prognosis; Retrospective Studies; Treatment Outcome; Vinblastine; Vincristine
PubMed: 11920535
DOI: 10.1002/cncr.10404 -
Blood May 1996In the Working Formulation (WF), non-Hodgkin's lymphomas (NHL) are grouped according to their clinical behavior. These disorders are listed as entities defined by... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial Review
Clinical analysis of 670 cases in two trials of the European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group subtyped according to the Revised European-American Classification of Lymphoid Neoplasms: a comparison with the Working Formulation.
In the Working Formulation (WF), non-Hodgkin's lymphomas (NHL) are grouped according to their clinical behavior. These disorders are listed as entities defined by morphology, phenotype, and cytogenetics in the proposed Revised European-American Classification of Lymphoid Neoplasms (REAL), the clinical relevance of which is still debated. We analyzed 670 NHL cases included in two randomized clinical trials (EORTC 20855 WF-intermediate/high-grade and 20856 WF-low-grade malignancy) with histologic material available for review. Based on hematoxylin-eosin-stained sections, 77% of cases could be subtyped. Immunophenotyping was considered to be mandatory only in diagnosing T-cell lymphoma and anaplastic large-cell lymphoma. Of 522 cases subtyped, 11% were mantle cell lymphoma (MCL), 5% were marginal zone B-cell lymphoma (MZBCL), 46% were follicle center lymphoma, and 32% were diffuse large B-cell lymphoma. Statistical analysis and comparisons between classifications were made only within each trial and treatment group. MCL and MZBCL were characterized by a shorter median survival (3.4 and 4.1 years, respectively) in comparison with low- and intermediate-grade WF groups (> 9.3 and 5.8 years, respectively). In terms of progression-free survival, MCL showed a behavior similar to the low-grade group, with frequent relapses. Follicle center cell lymphomas behaved as low-grade lymphomas as defined by the WF and diffuse large B-cell lymphomas as the WF-intermediate grade group. Because several NHL entities have a clinical behavior of their own, their recognition by the REAL classification offers clinicians additional information that is not obtained when the WF is used.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow; Combined Modality Therapy; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Etoposide; Humans; Immunologic Factors; Immunophenotyping; Interferon alpha-2; Interferon-alpha; Life Tables; Lymphoma, Non-Hodgkin; Mechlorethamine; Methotrexate; Prednisone; Procarbazine; Prognosis; Recombinant Proteins; Survival Analysis; Survival Rate; Vincristine
PubMed: 8639796
DOI: No ID Found -
Blood May 1981
Review
Topics: Antineoplastic Combined Chemotherapy Protocols; Cell Transformation, Neoplastic; Giant Cell Tumors; Hodgkin Disease; Humans; Immunity, Cellular; Mechlorethamine; Prednisone; Procarbazine; Prognosis; Spleen; Vincristine
PubMed: 7011441
DOI: No ID Found -
Journal of Clinical Oncology : Official... Feb 2013To assess therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) risk in patients treated for Hodgkin lymphoma (HL) on successive generations of...
PURPOSE
To assess therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) risk in patients treated for Hodgkin lymphoma (HL) on successive generations of Stanford clinical trials.
PATIENTS AND METHODS
Patients with HL treated at Stanford with at least 5 years of follow-up after completing therapy were identified from our database. Records were reviewed for outcome and development of t-AML/MDS.
RESULTS
Seven hundred fifty-four patients treated from 1974 to 2003 were identified. Therapy varied across studies. Radiotherapy evolved from extended fields (S and C studies) to involved fields (G studies). Primary chemotherapy was mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or procarbazine, mechlorethamine, and vinblastine (PAVe) in S studies; MOPP, PAVe, vinblastine, bleomycin, and methotrexate (VBM), or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in C studies; and VbM (reduced dose of bleomycin compared with VBM) or mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone (Stanford V) in G studies. Cumulative exposure to alkylating agent (AA) was notably lower in the G studies compared with the S and C studies, with a 75% to 83% lower dose of nitrogen mustard in addition to omission of procarbazine and melphalan. Twenty-four (3.2%) of 754 patients developed t-AML/MDS, 15 after primary chemotherapy and nine after salvage chemotherapy for relapsed HL. The incidence of t-AML/MDS was significantly lower in the G studies (0.3%) compared with the S (5.7%) or C (5.2%) studies (P < .001). Additionally, in the G studies, no t-AML/MDS was noted after primary therapy, and the only patient who developed t-AML/MDS did so after second-line therapy.
CONCLUSION
Our data demonstrate the relationship between the cumulative AA dose and t-AML/MDS. Limiting the dose of AA and decreased need for secondary treatments have significantly reduced the incidence of t-AML/MDS, which was extremely rare in the G studies (Stanford V era).
Topics: Academic Medical Centers; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; California; Chemotherapy, Adjuvant; Clinical Trials as Topic; Dacarbazine; Databases, Factual; Doxorubicin; Drug Administration Schedule; Female; Hodgkin Disease; Humans; Incidence; Leukemia, Myeloid, Acute; Male; Mechlorethamine; Melphalan; Methotrexate; Myelodysplastic Syndromes; Neoplasm Staging; Neoplasms, Second Primary; Prednisone; Procarbazine; Radiotherapy Dosage; Radiotherapy, Adjuvant; Retrospective Studies; Risk; Vinblastine; Vincristine
PubMed: 23295809
DOI: 10.1200/JCO.2012.44.5791 -
Bulletin Du Cancer 2002Hodgkin's disease can be cured from 80 to 90% of cases with a regular improvement of therapeutic results since 1960. We detailed the remission criteria with a focus on... (Review)
Review
Hodgkin's disease can be cured from 80 to 90% of cases with a regular improvement of therapeutic results since 1960. We detailed the remission criteria with a focus on post therapeutic residual masses which did not influence the relapse rate. The follow-up of patients in remission is made as an outbasis care every 4 months during the first year than every 6 months with a routine bilan for 10 years. Some adverse events can occur with first, the acute leukemia arising before 10 years, this risk is decreasing with the disminished use of MOPP chemotherapy. The other solid tumors occur later and are related to the patient age, the type of treatment given and individual factors. Thyroid diseases are frequent but mostly benign needing only consumption of thyroid extracts. Fertility is directly related to chemotherapy (including alkylating agents) and to pelvic radiation therapy. With the current use of ABVD-type chemotherapy the preservation of fertility is good but there is a risk for long term cardiopulmonary toxicity almost for the older patients receiving together mediastinal radiation therapy. At the end most long-term survivors of Hodgkin's disease recover a normal socioprofessional life, while reporting a longer duration of fatigue and many children were born after treatments.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cause of Death; Dacarbazine; Doxorubicin; Fertility; Hodgkin Disease; Humans; Incidence; Mechlorethamine; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Prednisone; Procarbazine; Remission Induction; Risk Factors; Time Factors; Vinblastine; Vincristine
PubMed: 12206979
DOI: No ID Found -
Acta Oncologica (Stockholm, Sweden) Jan 2015Hodgkin lymphoma (HL) in children constitutes approximately 30% of all pediatric lymphomas in Sweden. The chance of cure is high, but the frequency of late effects has...
BACKGROUND
Hodgkin lymphoma (HL) in children constitutes approximately 30% of all pediatric lymphomas in Sweden. The chance of cure is high, but the frequency of late effects has been considerable. Over recent years, efforts have been made to reduce treatment with maintained survival.
MATERIAL AND METHODS
All patients 0-17 years, identified in the Swedish Childhood Cancer Register as diagnosed between 1985 and 2009, were included. The material was analyzed using descriptive statistics and for survival estimates the Kaplan-Meier method was used.
RESULTS
Three hundred and thirty-four patients were identified during this time period. The median age was 14 years. Male sex was over-represented, especially in lower age groups and in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). In nodular sclerosis and in age group 15-17 years, female sex dominated. Most of the cases presented in stages I or II. B-symptoms were present in 38% of cHL, but only in 7% of NLPHL. The number of patients receiving radiotherapy has been significantly reduced during the period studied. The relapse rate in cHL was 10 ± 2% and in NLPHL 16 ± 7%. The relapse rate was significantly higher in cHL stage IIB compared to other stages in the same therapy group. In cHL 6% died, and in NLPHL 0%. The 5-, 10- and 20-year overall survival estimates in cHL were 96 ± 1%, 95 ± 1% and 90 ± 3%, respectively, with no significant difference when comparing different treatment regimens and time periods. The 5- and 10-year overall survival after relapse in cHL was 81 ± 8% and 75 ± 10%, respectively.
CONCLUSION
During the period studied there is no indication of a decline in survival despite changes in treatment. Survival rates in Sweden are high, and even after relapse chances of cure are high. We were not able to identify any characteristics specific for the group of patients that did not survive.
Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Child; Child, Preschool; Dacarbazine; Doxorubicin; Female; Hodgkin Disease; Humans; Incidence; Infant; Infant, Newborn; Male; Mechlorethamine; Prednisone; Procarbazine; Recurrence; Sex Distribution; Survival Analysis; Sweden; Vinblastine; Vincristine
PubMed: 25203597
DOI: 10.3109/0284186X.2014.948058 -
Clinical Cancer Research : An Official... Jan 2006MOPPEBVCAD (mechlorethamine, vincristine, procarbazine, prednisone, epidoxirubicin, bleomycin, vinblastine, lomustine, doxorubicin, and vindesine) chemotherapy with... (Comparative Study)
Comparative Study Randomized Controlled Trial
PURPOSE
MOPPEBVCAD (mechlorethamine, vincristine, procarbazine, prednisone, epidoxirubicin, bleomycin, vinblastine, lomustine, doxorubicin, and vindesine) chemotherapy with limited radiotherapy was devised in 1987 to reduce late toxicity and second tumor incidence while trying to improve effectiveness through increases of dose intensity and dose density. Late results, toxicity, and second tumor incidence were reviewed in all the patients treated.
EXPERIMENTAL DESIGN
The drugs of three previous alternating regimens [CAD (lomustine, melphalan, and vindesine), MOPP (mechlorethamine, vincristine, procarbazine, and prednisone), and ABV (doxorubicin, bleomycin, and vinblastine)] were intensified and hybridized, the cumulative dose of mechlorethamine was lowered, and irradiation was delivered to no more than two sites either bulky or partially responding to chemotherapy.
RESULTS
A total of 307 previously untreated advanced-stage patients underwent MOPPEBVCAD chemotherapy. Radiotherapy was delivered to 118 of 307 patients (38%). Remission was complete in 290 patients (94%). With a median follow-up of 114 months, 10-year overall, disease-free, and failure-free survival rates were 79%, 84%, and 71%, respectively. Forty-two patients relapsed and 60 died. The causes of death were Hodgkin's lymphoma in 36 patients, second neoplasms in 12, cardiorespiratory diseases in 4, pulmonary diseases in 2, and unknown in 6. Sixteen second tumors (of which nine were myelodysplasia and/or acute leukemia) were diagnosed in all. Outside this series of 307 patients, MOPPEBVCAD obtained complete responses in 12 of 15 relapsed and 9 of 9 refractory patients who had previously been treated with other regimens.
CONCLUSIONS
Clinical response and long-term results are very satisfactory, whereas the second tumor incidence was lower than would have been expected with MOPP analogues. Given its response/late toxicity balance, MOPPEBVCAD does not undermine the leading role of ABVD as first-line regimen but can be indicated as a very effective second-line conventional therapy.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Disease-Free Survival; Doxorubicin; Drug-Related Side Effects and Adverse Reactions; Epirubicin; Female; Hodgkin Disease; Humans; Lomustine; Male; Mechlorethamine; Middle Aged; Neoplasms, Second Primary; Pilot Projects; Prednisone; Procarbazine; Survival Rate; Treatment Outcome; Vinblastine; Vincristine; Vindesine
PubMed: 16428496
DOI: 10.1158/1078-0432.CCR-05-1707