An analysis of prognostic factors in early stage Hodgkin's disease.

An analysis of prognostic factors has been carried out in 398 patients presenting with clinical Stage I and II Hodgkin's disease treated between 1963 and 1979. By life table analysis older age, lymphocyte depletion histology, systemic symptoms, mediastinal node bulk, and erythrocyte sedimentation rate (ESR) greater than 40 mm/h were associated with a significantly worse survival probability. On multiple factor regression analysis only age and stage were independent prognostic variables for survival, with systemic symptoms having borderline significance. Using this information, together with other analyses of prognosis in early Hodgkin's disease three groups of patients are defined. The first with a predicted 5-year survival of 78% would include patients possessing at least one of the following features; age greater than 60, lymphocyte depletion, greater than 3 sites involved, systemic symptoms, mediastinal/thoracic ratio of greater than 1/3. The second groups present with at least two of the following factors; ESR greater than 40 mm/h, male sex, 3 involved sites, or mixed cellularity histology, and the 5 year survival probability is 84%. The remaining Stage I and II patients would constitute a good prognosis group with a predicted 5-year survival of 92%.

T-cell involvement in benign phase chronic myelogenous leukemia.

T cells from the peripheral blood of patients with chronic myeloid leukemia (CML) were cultured with phytohemagglutinin and T-cell growth factor (TCGF) in agar culture. These T-cell colonies were pooled and expanded further in liquid culture with TCGF and then simultaneously analysed for the E-rosette receptor with the monoclonal antibody OKT11 and for the presence of the Philadelphia (Ph1) chromosome. OKT11 analysis showed these populations to be composed 99.5% or more of T cells. In four of the seven patients the T-cell suspension showed 7/50 (14%), 3/36 (8%), 2/34 (6%), and 4/44 (9%) Ph1 metaphases. Furthermore, Ph1 metaphases were demonstrated in T-cell cultures in two patients when bone marrow metaphases simultaneously showed 90 and 100% Ph1 negative metaphases secondary to human leukocyte interferon therapy or combination chemotherapy. A minority of T cells in benign phase CML have the Ph1 abnormality despite reduced number of Ph1 metaphases in bone marrow from therapy.

E rosette-positive agar colonies containing the Philadelphia chromosome in chronic myeloid leukaemia.

In an attempt to document possible T-cell involvement in chronic myeloid leukaemia, E rosette-positive colonies (ERPC) were grown in agar culture using a T-cell-conditioned medium. Colonies were grown from whole mononuclear cells (WMN), nonadherent E rosette-positive (NAT+) and nonadherent E rosette-negative (NAT-) cells. Cells collected from the colonies after 10 d in culture were 99-100% E rosette-positive. 8 metaphases were obtained from both NAT+ and NAT- ERPCs. In NAT- ERPCs, 5 out of 8 metaphases were positive for the Philadelphia (Ph1) chromosome as compared to 1 Ph1 positive out of 8 metaphases in the NAT+ ERPCs. These results suggest that, at least in this particular patient we studied, a subpopulation of E rosette-positive cells derived from the NAT- cell fraction express the Ph1 chromosome.

Chemotherapy and irradiation in childhood Hodgkin's disease.

Eighty children aged less than 16 years with newly diagnosed Hodgkin's disease were treated between 1974 and 1982. Complete remission occurred in 95%, with actuarial five year overall survival of 94%, and relapse free survival of 82%: median follow up was 4.8 years. Sixty one children were staged clinically while 19 had staging laparotomies before treatment. Most received combined modality treatment with Ch1VPP chemotherapy (chlorambucil, vinblastine, procarbazine, and prednisolone) followed by irradiation of initial bulk disease. Nodular sclerosis predominated in both sexes, accounting for 60% of the total. Girls with stage IV disease, nodal sclerosis histology, and bulky mediastinal masses had a relatively poor prognosis. Ten children have relapsed, and three prolonged (6 to 7 years) second remissions have been observed. Four died of disease, and one from infection. Clinical staging, avoiding splenectomy, reduced the risk of serious infections. Our current policy is to treat stage IA disease with local irradiation and all other stages with chemotherapy, adding irradiation for bulky mediastinal disease.

The interpretation of marker protein assays: a critical appraisal in clinical studies and a xenograft model.

Although useful in the management of malignant testicular tumours, alphafoetoprotein and human chromonic gonadotrophin are not perfect parameters of tumour bulk. In a series of 65 patients with marker-positive advanced disease, 23 showed the phenomenon of discordance of markers or dissociation from tumour response. Transplantable human malignant teratoma xenografts were established in immune-suppressed mice as models of the human disease. In the model system, it was demonstrated that tumour AFP concentration was reflected by AFP titres in the blood, but that tumour AFP (or blood AFP) did not correlate well with tumour size. One xenograft line illustrated the evolution of marker-negative tumour cells from a patient who was initially AFP-positive.