-
Blood Jul 1995Patients with Hodgkin's disease (HD) who fail to enter a complete remission after an initial course of combination chemotherapy are usually considered to have an... (Clinical Trial)
Clinical Trial
High-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV +/- P) and autologous transplantation for patients with Hodgkin's disease who fail to enter a complete remission after combination chemotherapy.
Patients with Hodgkin's disease (HD) who fail to enter a complete remission after an initial course of combination chemotherapy are usually considered to have an induction failure (IF); this subset of patients has an extremely poor outcome with further conventional therapy. Since 1985, we have entered 30 IF patients into protocols using conditioning with high-dose cyclophosphamide, carmustine (BCNU), and etoposide (VP16-213) with or without cisplatin (CBV +/- P) followed by autologous stem cell transplantation (ASCT) with bone marrow (19 patients), peripheral blood stem cells (PBSCs; 8 patients), or both (3 patients). All except 2 patients had previously received chemotherapy regimens for HD that contained at least 7 drugs, and 9 had received prior radiotherapy (RT). After documentation of IF, the majority of patients received some cytoreductive therapy as specified by protocol (local RT in 9, two cycles of conventional chemotherapy in 2, both modalities in 2, or high-dose cyclophosphamide to enhance PBSC collection in 11) before CBV +/- P. Five treatment-related deaths occurred, all before day 150 posttransplant. Eleven patients have had progressive HD at a median of 6 months (range, 0.1 to 45 months) after ASCT. The actuarial progression-free survival (PFS) at a median follow-up of 3.6 years (range, 0.2 to 8.2 years) is 42% (95% confidence intervals, 21% to 61%). The statistical analysis identified only prior clinical bleomycin lung toxicity as an adverse risk factor for PFS, mainly because of the increased nonrelapse mortality seen in these patients. CBV +/- P and ASCT can produce durable remission in a substantial proportion of IF HD patients who otherwise have a poor survival, and we believed ASCT approaches represent the best therapy currently available for these patients. Additional measures are needed to reduce the primary problem of disease progression despite high-dose chemotherapy and stem cell transplantation.
Topics: Actuarial Analysis; Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Bone Marrow Diseases; Bone Marrow Transplantation; Carmustine; Cisplatin; Cyclophosphamide; Dacarbazine; Disease-Free Survival; Doxorubicin; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Leucovorin; Male; Mechlorethamine; Methotrexate; Prednisolone; Prednisone; Procarbazine; Remission Induction; Salvage Therapy; Survival Analysis; Treatment Outcome; Vinblastine; Vincristine
PubMed: 7541661
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 -
Blood May 1982The prognostic value of age, sex, symptoms, histopathology, lymphocyte count, skin tests, immunocompetence (lymphocyte response profile to a spectrum of PHA...
The prognostic value of age, sex, symptoms, histopathology, lymphocyte count, skin tests, immunocompetence (lymphocyte response profile to a spectrum of PHA concentrations), and stage was evaluated in 35 previously untreated patients with Hodgkin's disease by multiple linear regression and logistic analysis. Immunocompetence exhibited the highest correlation (R = 0.537) with survival status and was required as a common denominator for deriving best sets of two or more variables. In addition, immunocompetence contributed to all other variables combined (p = 0.023), whereas stage did not (p = 0.116). Immunocompetence, age, symptoms, and histopathology generated a highly discriminant (R = 0.784) model not improved by stage or by other variables (p greater than or equal to 0.159). The utility and generalizability of this model are shown by a correct classification of 91.2% of cases according to expected versus actual survival status and by a predicted correlation (R) of 0.71, respectively, neither improved by sex, lymphocyte count, skin tests, or stage. In comparison, the conventional triad of stage, symptoms, and histopathology correctly classified only 70.6% of cases and showed actual and predicted correlations with survival status of R = 0.550 and R = 0.51. We conclude that immunocompetence is a powerful discriminant risk factor in Hodgkin's disease that exerts a pivotal role on survival and serves as a basis for models of greater discriminant power and generalizability than the conventional stage-based evaluation triad. Immunocompetence-based models are expected to provide a more discriminating basis for clinical evaluation, prediction of prognosis, and treatment selection for patients with Hodgkin's disease.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Therapy, Combination; Female; Hodgkin Disease; Humans; Immunocompetence; Lymphocyte Activation; Male; Mechlorethamine; Middle Aged; Prednisone; Procarbazine; Radiotherapy Dosage; Risk; Vincristine
PubMed: 6896162
DOI: No ID Found -
Blood Apr 1985Six men undergoing potentially curative chemotherapy for advanced lymphomas received daily injections (50 micrograms) of an analogue of luteinizing hormone releasing...
Effect of a luteinizing hormone releasing hormone agonist given during combination chemotherapy on posttherapy fertility in male patients with lymphoma: preliminary observations.
Six men undergoing potentially curative chemotherapy for advanced lymphomas received daily injections (50 micrograms) of an analogue of luteinizing hormone releasing hormone (LH-RHa) in an attempt to protect posttreatment gonadal function. The median duration of combined LH-RHa-chemotherapy administration was 25 weeks (range, 14 to 31 weeks). During the simultaneous administration of LH-RHa and chemotherapy, plasma testosterone levels decreased to subnormal levels, while both follicle-stimulating hormone (FSH) and luteinizing hormone levels declined to the lower limit of normal. All subjects became oligospermic or azoospermic within eight weeks of starting treatment. Following discontinuation of chemotherapy and LH-RHa, both plasma testosterone and LH promptly increased and stabilized within the normal range. FSH progressively increased to a level well above the normal range. Only one patient has recovered evidence of active spermatogenesis at 84 weeks postcessation of chemotherapy. No untoward side effects due to LH-RHa were experienced. Although LH-RHa can be administered safely during combination chemotherapy, no improvement in posttreatment fertility has yet been demonstrated.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Therapy, Combination; Fertility; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Lymphoma; Male; Mechlorethamine; Prednisone; Procarbazine; Sperm Count; Testosterone; Triptorelin Pamoate; Vincristine
PubMed: 3884062
DOI: No ID Found -
British Journal of Cancer Oct 1999Hodgkin's disease is curable in the majority of patients, although a proportion of patients are resistant to or relapse after initial therapy. High-dose therapy with...
High-dose BEAM chemotherapy with autologous haemopoietic stem cell transplantation for Hodgkin's disease is unlikely to be associated with a major increased risk of secondary MDS/AML.
Hodgkin's disease is curable in the majority of patients, although a proportion of patients are resistant to or relapse after initial therapy. High-dose therapy with autologous stem cell support has become the standard salvage therapy for patients failing chemotherapy, but there have been reports of a high incidence of myelodysplasia/acute myeloid leukaemia (MDS/AML) following such treatment. Patients who receive such therapy form a selected group, however, who have already been subjected to other leukaemogenic factors, such as treatment with alkylating agents. In order to ascertain the true risk of MDS/AML, comparison must be made with other patients subjected to the same risks but not undergoing transplantation. We report a retrospective comparative study of 4576 patients with Hodgkin's disease from the BNLI and UCLH Hodgkin's databases, which includes 595 patients who have received a transplant. Statistical analysis including Cox's proportional hazards multivariate regression model with time-dependent covariates was employed. This analysis reveals that the risk of developing MDS/AML was dominated by three factors, namely quantity of prior therapy (relative risk [RR] 2.01, 95% confidence intervals [CI] 1.49-2.71, for each treatment block, P < 0.0001) and whether the patient had been exposed to MOPP (RR 3.61, 95% CI 1.64-7.95, P = 0.0009) or lomustine chemotherapy (RR 4.53, 95% CI 1.96-10.44, P = 0.001). Following adjustment for these factors in the multivariate model the relative risk associated with transplantation was 1.83 (95% CI 0.66-5.11, P = 0.25). This study provides no evidence of a significantly increased risk of MDS/AML associated with BEAM therapy and autologous transplantation in Hodgkin's disease. Concern over MDS/AML should not mitigate against the timely use of this treatment modality.
Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Child; Child, Preschool; Chlorambucil; Cohort Studies; Combined Modality Therapy; Cytarabine; Doxorubicin; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Incidence; Infant; Leukemia, Myeloid; Life Tables; Lomustine; Male; Mechlorethamine; Melphalan; Middle Aged; Myelodysplastic Syndromes; Neoplasms, Second Primary; Podophyllotoxin; Prednisolone; Prednisone; Procarbazine; Retrospective Studies; Risk; Salvage Therapy; Vinblastine; Vincristine
PubMed: 10507773
DOI: 10.1038/sj.bjc.6690718 -
Annals of the Rheumatic Diseases Aug 1992Temporary remission of scleroderma during the successful treatment of an associated malignant lymphoma by chemotherapy is reported in a patient with systemic sclerosis...
Temporary remission of scleroderma during the successful treatment of an associated malignant lymphoma by chemotherapy is reported in a patient with systemic sclerosis and mixed connective tissue disease. There is a well established relation between malignant disease and polymyositis/dermatomyositis but no overall association with systemic sclerosis or mixed connective tissue disease. Reports of the coexistence of malignancy and systemic sclerosis, however, emphasise a close temporal relation in their occurrence. A review of published work has identified several postulated mechanisms for this relation which may explain the response to chemotherapy.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Female; Hodgkin Disease; Humans; Mechlorethamine; Prednisone; Procarbazine; Recurrence; Scleroderma, Systemic; Vincristine
PubMed: 1417129
DOI: 10.1136/ard.51.8.998 -
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 -
Postgraduate Medical Journal Feb 1985
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Hodgkin Disease; Humans; Laparotomy; Mechlorethamine; Prednisone; Procarbazine; Vincristine
PubMed: 3838586
DOI: 10.1136/pgmj.61.712.103 -
Postgraduate Medical Journal May 1988We report a case of focal sclerosing glomerulonephritis which developed 11 years after successful treatment of nodular sclerosing Hodgkin's disease. Hodgkin's disease...
We report a case of focal sclerosing glomerulonephritis which developed 11 years after successful treatment of nodular sclerosing Hodgkin's disease. Hodgkin's disease relapsed 7 months later and responded completely to combination chemotherapy with simultaneous improvement in renal function. This case shows that relapse of Hodgkin's disease may occur after a 10 year interval and furthermore it may preceded by nephrotic syndrome. Renal disease in such cases may not recover until the underlying Hodgkin's disease is treated.
Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Hodgkin Disease; Humans; Mechlorethamine; Middle Aged; Prednisone; Procarbazine; Time Factors; Vincristine
PubMed: 3200784
DOI: 10.1136/pgmj.64.751.395 -
Annals of Oncology : Official Journal... Feb 1991Sixty-three cases of Hodgkin's disease in intravenous drug users (IVDUs) have been collected by the Italian Cooperative Group on AIDS-Related Tumors (GICAT). In most...
Sixty-three cases of Hodgkin's disease in intravenous drug users (IVDUs) have been collected by the Italian Cooperative Group on AIDS-Related Tumors (GICAT). In most patients (74%) the histological pattern was that of mixed cellularity and lymphocyte depletion. In 39% of patients the initial symptom was a persistent lymph node enlargement due to persistent generalized lymphadenopathy (PGL). Unusual presentations included Waldeyer's ring, skin, meninges, colon, and pleura. After MOPP alternated or followed by ABVD, MOPP alone, or ABVD alone, 15 of 32 patients (47%) had a complete remission (CR) and 15 of 32 (47%) had a partial remission (PR). The median duration of CR was 14 months, while the median survival of patients with CR has not been reached; the median survival of patients treated with chemotherapy who had CD4 levels at presentation greater than or equal to 400/mm3 was significantly superior to that of those who had CD4 less than 400/mm3. The overall median survival was only 14 months. Forty-four percent of patients receiving chemotherapy, with or without radiotherapy, developed opportunistic as well as nonopportunistic infections. Lethal hepatic toxicity was observed in one patient. Among IVDUs, unusual presentations of Hodgkin's disease occurred at a lower rate than was previously reported for homosexuals. Complete remissions could be achieved in almost half the patients, but non opportunistic infections, in addition to parenchymal function impairment due to drug abuse, may limit treatment administration in IVDUs.
Topics: Acquired Immunodeficiency Syndrome; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Dacarbazine; Doxorubicin; Epirubicin; Female; Follow-Up Studies; Hodgkin Disease; Humans; Male; Mechlorethamine; Opportunistic Infections; Prednisone; Procarbazine; Remission Induction; Substance Abuse, Intravenous; Survival Rate; Vinblastine; Vincristine
PubMed: 1710920
DOI: 10.1093/annonc/2.suppl_2.201