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Blood Feb 1999
Review
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Cardiomyopathies; Clinical Trials as Topic; Cohort Studies; Combined Modality Therapy; Dacarbazine; Doxorubicin; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Infections; Laparotomy; Lung Diseases, Interstitial; Lymphography; Mechlorethamine; Middle Aged; Neoplasm Staging; Neoplasms, Radiation-Induced; Neoplasms, Second Primary; Prednisone; Procarbazine; Prognosis; Radiation Injuries; Radiotherapy; Remission Induction; Salvage Therapy; Vinblastine; Vincristine
PubMed: 9920825
DOI: No ID Found -
Blood Sep 1998Autologous stem-cell transplantation has become a widely used therapy in Hodgkin's disease (HD). To appreciate the early and late risks associated with this procedure,...
Autologous stem-cell transplantation has become a widely used therapy in Hodgkin's disease (HD). To appreciate the early and late risks associated with this procedure, its lethal toxicity and effects on the incidence of secondary cancers were studied. Data related to 467 French patients grafted from 1982 to 1995 for primary sensitive disease (PSD, 22%), primary refractory disease (PRD, 18%), first relapse (R1, 45%), or subsequent relapses (R2, 15%) were analyzed. Grafted patients (PSD, PRD, and R1; n = 393) were matched (3 controls for 1 case) on age, gender, clinical stage, B symptoms, and time at risk with 1179 conventionally treated patients issued from international databases. The proportional hazards (Cox) model was used to assess relative risks (RR). Among grafted patients, 8% died of toxicity related to the procedure, and 18 secondary cancers occurred leading to a 5-year cumulative incidence rate of 8.9%. In this series, risk factors for second cancer were age >/=40 years (RR = 3.73, P = .007) and the use of peripheral blood stem cells as source of graft (RR = 3.10, P = .03). Among grafted and matched ungrafted patients, risk factors for the development of secondary cancer were age >/=40 years (RR = 2.90, P < .001), relapse versus no relapse (RR = 5.22, P = .006), PRD versus other patients (RR = 3.86, P = .033), and grafted versus ungrafted patients (RR = 2.04, P = . 024). Solid tumors were more frequent in grafted than in ungrafted patients (RR = 5.19, P = .001) although the incidence of myelodysplasia and acute myeloid leukemia was similar in the two groups. We conclude that high-dose chemotherapy administered as first-line treatment or after relapse is associated with an acceptable toxic death rate. The risk of secondary myelodysplasia or acute myeloid leukemia is not significantly increased after autologous stem-cell transplantation for HD, whereas an increased risk of solid tumors exists. The peripheral blood stem-cell-associated risk of secondary cancer among grafted patients needs further investigations.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Male; Mechlorethamine; Middle Aged; Neoplasms, Second Primary; Prednisone; Procarbazine; Risk Factors; Transplantation, Homologous; Vincristine
PubMed: 9731050
DOI: No ID Found -
British Journal of Cancer Mar 1998The aim of this study was to assess the prognostic role of soluble interleukin-2 receptors (sIL-2R) in Hodgkin's disease (HD) both in the achievement of complete...
The aim of this study was to assess the prognostic role of soluble interleukin-2 receptors (sIL-2R) in Hodgkin's disease (HD) both in the achievement of complete remission (CR) and in predicting disease relapse. Between August 1988 and June 1993 sIL-2R serum levels were measured in 174 untreated patients; in 137 of them evaluation was repeated at the end of treatment and in 132 also during the follow-up. Baseline sIL-2R levels (mean+/-standard error) were significantly higher in patients than in 65 healthy control subjects (1842+/-129 U ml(-1) vs 420+/-10 U ml(-10, P< 0.0001). At the end of treatment 135 out of 137 evaluated patients achieved complete response (CR) and their mean sIL-2R serum levels were significantly lower than those at diagnosis (635+/-19 U ml(-1) vs 1795+/-122 U ml(-1), P=0.0001). After a median follow-up of 5 years, sIL-2R remained low in 114 patients in continuous CR, while they increased in 9 out of 12 patients (75%) who relapsed. However, a temporary increase was also observed in six patients (5%) still in CR. Treatment outcome in terms of freedom from progression was linearly related to sIL-2R levels. Our study confirms that patients with untreated HD have increased baseline levels of sIL-2R compared with healthy subjects and that their pretreatment values may be an indication of disease outcome similar to other conventional prognostic factors, such as number of involved sites, presence of B symptoms and extranodal extent.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bleomycin; Combined Modality Therapy; Confidence Intervals; Cyclophosphamide; Dacarbazine; Disease-Free Survival; Doxorubicin; Epirubicin; Etoposide; Female; Hodgkin Disease; Humans; Lymph Nodes; Male; Mechlorethamine; Middle Aged; Neoplasm Staging; Prednisone; Procarbazine; Receptors, Interleukin-2; Recurrence; Reference Values; Retrospective Studies; Vinblastine; Vincristine
PubMed: 9528846
DOI: 10.1038/bjc.1998.163 -
British Journal of Cancer 1997Risk of second primary malignancy was assessed in follow-up to June 1991 of 1039 patients first treated for Hodgkin's disease at the Royal Marsden Hospital during...
Risk of second primary malignancy was assessed in follow-up to June 1991 of 1039 patients first treated for Hodgkin's disease at the Royal Marsden Hospital during 1963-91. A total of 77 second malignancies occurred. There were significantly raised risks of stomach [standardized incidence ratio (SIR)=4.0], lung (SIR=3.8), bone (SIR=26.5), soft tissue (SIR=16.9) and non-melanoma skin (SIR=3.9) cancers, non-Hodgkin's lymphoma (SIR=4.6), and acute and non-lymphocytic leukaemia (SIR=31.3), with a relative risk of 3.3 for all second cancers other than non-melanoma skin cancer. Solid cancer risk was raised to a similar extent in patients treated only with radiotherapy (SIR=2.6, P<0.001), only with chemotherapy (SIR=2.1, P=0.08) and with both (SIR=3.1, P<0.001). Leukaemia risk was raised only in those receiving chemotherapy, whether alone or with radiotherapy. The relative risk for solid cancers was much greater in patients who were younger at first treatment (trend P<0.001), whereas leukaemia risk was greatest for those first treated at ages 25-44. For solid cancers (P<0.001) but not leukaemia (P=0.05) there was a strong gradient of greater relative risks at younger attained ages. The relative risk of second cancers overall was 27.5 at ages under 25 and 2.0 at ages 55 and above. Leukaemia and solid cancer risks in patients treated with chlorambucil, vinblastine, procarbazine and prednisone (ChlVPP) were not significantly greater than those in patients treated with mustine, vincristine, procarbazine and prednisone (MOPP). Number of cycles of chemotherapy was significantly related to risk of leukaemia (P<0.001), and there was a trend in the same direction for solid cancers (P=0.07). The study adds to evidence that alkylating chemotherapy may increase the risk of solid cancers, and that ChlVPP does not provide a less carcinogenic alternative to MOPP chemotherapy. The very large relative risks found for solid cancers at young attained ages and in patients treated when young may have important implications as, in the long term, the majority of second malignancies after Hodgkin's disease are solid cancers. The risks of solid malignancies need clarification by larger collaborative epidemiological studies.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Chlorambucil; Female; Hodgkin Disease; Humans; Male; Mechlorethamine; Middle Aged; Neoplasms, Second Primary; Prednisone; Procarbazine; Risk; Risk Factors; Vinblastine; Vincristine
PubMed: 9000608
DOI: 10.1038/bjc.1997.19 -
Haematologica 1996To test the adequacy of the CVPP four-drug regimen as ancillary chemotherapy associated with extended-field radiotherapy in the treatment of early, unfavorable,... (Clinical Trial)
Clinical Trial
CCNU, vinblastine, procarbazine and prednisone (CVPP) with extended-field radiotherapy in the treatment of early unfavorable Hodgkin's disease. A prospective study on behalf of the Gruppo Italiano per lo Studio dei Linfomi (GISL).
PURPOSE
To test the adequacy of the CVPP four-drug regimen as ancillary chemotherapy associated with extended-field radiotherapy in the treatment of early, unfavorable, clinically staged Hodgkin's disease.
PATIENTS AND METHODS
The population of this prospective, multicenter study consisted of 49 patients with stage I-II disease, associated with bulky involvement or unfavorable histology (lymphocyte-depleted nodular sclerosis or lymphocyte depletion), systemic symptoms or extranodal involvement, or presenting with stage III A favorable-histology disease, with or without extranodal involvement.
RESULTS
Complete remission was achieved in 39 patients, partial remission in 2, while 8 patients did not respond. Four patients have relapsed so far (median follow-up: 43 months), all of whom were subsequently rescued with different salvage treatments. Dose intensity (mean +/- SD: 0.83 +/- 0.12) and hematological toxicity (including 2 deaths from infection) were higher when RT followed CT than when it was interposed in the middle of the 6 cycles. No growth factors were used. Nonhematological toxicity was very low and fully tolerable.
CONCLUSIONS
Results confirmed the mild neurological and gastroenteric side effects of CVPP that make it an interesting MOPP-variant regimen. This combination seems most indicated when a regimen devoid of cardiac and pulmonary toxicity is required for association with full-dosage mediastinal radiotherapy, as is often the case in early, unfavorable Hodgkin's disease. The optimal sequence consists of radiotherapy administered after completion of the chemotherapy program. The use of growth factors for correction (or prevention) of marked leukopenia seems appropriate.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Hodgkin Disease; Humans; Lomustine; Male; Mechlorethamine; Middle Aged; Prednisone; Procarbazine; Prognosis; Prospective Studies; Remission Induction; Vinblastine; Vincristine
PubMed: 9009437
DOI: No ID Found -
American Journal of Hematology Nov 1996We report the successful and maintained response of lymphomatoid granulomatosis using a new approach to therapy, cyclosporin-A, after failure of aggressive multiagent...
We report the successful and maintained response of lymphomatoid granulomatosis using a new approach to therapy, cyclosporin-A, after failure of aggressive multiagent chemotherapy.
Topics: Antineoplastic Combined Chemotherapy Protocols; CD4-Positive T-Lymphocytes; Combined Modality Therapy; Cyclophosphamide; Cyclosporine; Doxorubicin; Etoposide; Humans; Immunosuppressive Agents; Lung Diseases; Lymphomatoid Granulomatosis; Male; Mechlorethamine; Methotrexate; Middle Aged; Prednisone; Procarbazine; Recurrence; Remission Induction; Salvage Therapy; Vincristine
PubMed: 8895691
DOI: 10.1002/(SICI)1096-8652(199611)53:3<192::AID-AJH8>3.0.CO;2-U -
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 -
Oncology (Williston Park, N.Y.) Apr 1996
Clinical Trial Randomized Controlled Trial
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Combined Modality Therapy; Dacarbazine; Disease-Free Survival; Doxorubicin; Hodgkin Disease; Humans; Mechlorethamine; Prednisone; Procarbazine; Recurrence; Remission Induction; Salvage Therapy; Treatment Outcome; Vinblastine; Vincristine
PubMed: 8723294
DOI: No ID Found -
Oncology (Williston Park, N.Y.) Feb 1996In most patients with newly diagnosed Hodgkin's disease, initial therapy is curative. However, a small portion of patients treated with radiotherapy alone for limited... (Review)
Review
In most patients with newly diagnosed Hodgkin's disease, initial therapy is curative. However, a small portion of patients treated with radiotherapy alone for limited favorable disease, and a larger percentage of patients treated with combination chemotherapy, with or without radiotherapy, for advanced-stage or unfavorable disease relapse after initial remission. Patients relapsing after radiotherapy alone should do as well with salvage combination chemotherapy as patients with advanced disease who have never received radiation. In patients who relapse after combination chemotherapy, retreatment with the same regimen or employment of a non-cross-resistant regimen offers high response rates among those with favorable characteristics. However, long-term disease-free survival is achieved in a minority of these patients, and in even fewer of those with early relapse or other unfavorable characteristics. High-dose therapy with autografting shows the greatest promise in the treatment of patients at relapse.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Transplantation; Combined Modality Therapy; Dacarbazine; Doxorubicin; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Mechlorethamine; Prednisone; Procarbazine; Prognosis; Recurrence; Salvage Therapy; Time Factors; Transplantation, Autologous; Vinblastine; Vincristine
PubMed: 8838268
DOI: No ID Found -
Oncology (Williston Park, N.Y.) Dec 1995While it would seem obvious that dose intensity is an important determinant of treatment outcome in aggressive lymphomas, actually there are very few prospective data to... (Review)
Review
While it would seem obvious that dose intensity is an important determinant of treatment outcome in aggressive lymphomas, actually there are very few prospective data to support this hypothesis. Circumstantial evidence derived from retrospective analyses suggests that dose intensity is of clinical significance. However, based on available phase II and III data and the one prospective randomized trial to date that has specifically addressed this issue, it remains unclear what impact dose intensity has on treatment outcome.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Clinical Trials, Phase II as Topic; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Etoposide; Humans; Leucovorin; Lymphoma, Non-Hodgkin; Mechlorethamine; Methotrexate; Prednisone; Procarbazine; Randomized Controlled Trials as Topic; Vincristine
PubMed: 8771102
DOI: No ID Found