No abstract

Two children presenting with sporadic unilateral retinoblastoma and exhibiting a high degree of chromosome breakage were noted to have unusual facies, microcephaly and abnormal skin pigmentation. In the first child the pattern of both spontaneous and mitomycin‐C‐induced chromosome breakage was characteristic of Fanconi's anaemia although the degree of breakage was extreme. She also exhibited a striking increase in X‐ray‐induced chromosomal damage in G0 lymphocytes as measured by dicentric formation and increase in chromatid‐type aberrations. She had a number of typical clinical features, including cafe‐au‐lait patches and abnormalities involving the kidney; however, she demonstrated neither the hypoplasia of radius and thumb nor the typical aplastic phase of this disorder. At age 22 months the child became anaemic with trilineage myelo‐dysplasia, which was rapidly followed by the development of acute myeloblastic leukaemia. The early onset (at age 4 months) of retinoblastoma may have been associated with the underlying genomic instability. The second child exhibited a pattern of chromosome breakage characteristic of Bloom's syndrome, in addition to a moderate increase in damage induced by mytomycin‐C. She had the typical stunted growth and malar hypoplasia of Bloom's syndrome although she did not demonstrate the frequently described erythematous ‘butterfly rash’. Although patients with Fanconi's anaemia and Bloom's syndrome are recognised to be at an increased risk of cancer, retinoblastoma has not previously been described in patients with either condition. We suggest that underlying recessive chromosome breakage syndromes may be underdiagnosed in paediatric cancer patients, with important implications for prognosis and genetic counselling.

A study has been in progress since June 1985 to evaluate the use of myeloablative therapy (cyclophosphamide [60 mg/kg x 2] and total body irradiation [200 cGy x 6]) followed by reinfusion of autologous bone marrow in patients in second or subsequent remission of B-cell non-Hodgkin's lymphoma. The marrow mononuclear cell fraction is being treated in vitro with three cycles of the monoclonal antibody anti-CD20 (anti-B1, Coulter Immunology) and baby rabbit complement (Pel-Freez). Thirty-eight patients with follicular lymphoma (age range 29-61 years, median 43) have been treated to date. At the time of treatment, 28 patients were in second remission, 7 were in third, and 3 were in more than third remission. Twenty-three patients were in complete remission, 15 had residual disease (7 had lymph nodes less than 2 cm diameter, 4 had less than 10% bone marrow infiltration, 1 had involvement of lymph nodes and bone marrow, and 3 had involvement at other sites). Of the 38 study patients, 32 are alive; 6 have died, 4 in remission. Two of the deaths were treatment related: 1 resulted from cerebral haemorrhage at 29 days; 1 resulted from systemic fungal infection at three months). One patient died from secondary acute myelogenous leukaemia at four years, and another from an unrelated cause. Two patients died following relapse. The median time to engraftment was 28 days (range 15-45 days) for neutrophils greater than 0.5 x 10(9)/L and 28 days (range 15-46 days) for platelets greater than 20 x 10(9)/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-one patients with refractory myeloma (10 primary resistant and 11 relapsed resistant) were treated with a combination of high dose methyl prednisolone and recombinant interferon alpha 2b (IFN-alpha 2b). This treatment included three megaunits/m2 of IFN-alpha 2b three times a week for 12 weeks, plus 5-day pulsed high dose methyl prednisolone every 3 weeks for two courses. A partial response (more than 50 per cent reduction in paraprotein) was observed in six patients; two of these had a greater than 75 per cent reduction in paraprotein, and evaluation of bone marrow showed <5 per cent plasma cells. A minimal response (more than 25 per cent reduction in paraprotein) was seen in four patients, giving an overall objective response rate of 10/21 (48 per cent). Subjective response, in terms of subsidence of pain and improvement of performance status, was seen in all patients who had adequate therapy. The protocol was generally well tolerated with minimal side-effects. There were 4/21 (19 per cent) treatment-related deaths which, though considerable, was anticipated in such a study population. The excellent subjective response seen supplements the objective response observed, and suggests a potential role for the combination of methyl prednisolone and IFN-alpha 2b in refractory myeloma.