G. Sokal

Detection of skeletal involvement in Hodgkin's disease: a comparison of radiography, bone scanning and bone marrow biopsy in 38 patients.

As part of the staging of 38 patients with Hodgkins disease seen over an 18‐month period, we have used radioisotopic scanning of bone, as well as radiography and bone marrow biopsy, in an attempt to assess osseous and bone marrow involvement. Of the 38 patients, 14 were found to have skeletal involvement. In 11 this was histologically proved. In 8 patients, the radioisotopic scan first raised the suspicion of localized bone involvement, which was subsequently proved by bone marrow biopsy or by radiography. We believe that bone marrow involvement may at times be localized when patients with Hodgkins disease are first staged and may precede local osseous involvement. If this is so, a reasonable approach to the search for bone marrow or osseous involvement would be to start with a bone scan and to follow this with a bone marrow biospy from the suspicious area or a careful radiography of the same site; the latter is important if the site of increased uptake of the radionuclide is inaccessible to the biopsy needle.

Daunorubicin-DNA: Further clinical trials in acute non-lymphoblastic leukemia

Abstract Treatment with daunorubicin-DNA (DNR-DNA), given as a slow infusion, in combination with small doses of vincristine (VCR) or arabinosine cytoside (ARA-C) has been evaluated in 19 patients with acute non-lymphoblastic leukemia. A complete remission was obtained in 11 patients ( 58% ) with an overall median survival time estimated at 31 weeks. The toxicity of DNR-DNA seems to be very low since only one patient (age 75 years) died during the induction period. No cardiac toxicity was observed in the four patients who received total doses of DNR-DNA of 600 mg/m 2 or more (up to 1021 mg/m 2 ). The main advantage of this therapeutic scheme using DNR-DNA is to induce an excellent remission rate at a low cost of toxicity. It is estimated that the use of lysosomotropic drugs like daunorubicin-DNA is promising and deserves further clinical trials.

Bone marrow transplantation in sickle cell anaemia.

Sickle cell anaemia is still responsible for severe crippling and death in young patients living in developing countries. Apart from prophylaxis and treatment of infections, no active treatment can be safely proposed in such areas of the world. Therefore a bone marrow transplantation was performed in 12 patients staying in Belgium and planning to return to Africa. Twelve patients, aged between 11 months and 23 years (median 4 years), underwent a HLA identical bone marrow transplantation. The conditioning regimen included oral busulphan for four consecutive days (4 mg/kg) followed by four days of intravenous cyclophosphamide (50 mg/kg). In 10 patients the engraftment was rapid and sustained. A further patient suffered transient red cell hypoplasia and another underwent a second bone marrow transplantation from the same donor at day 62 because of graft rejection. All patients are alive and well with a follow up ranging from 9-51 months (median 27 months). In all cases a complete cessation of vaso-occlusive episodes and haemolysis was observed as was a change in the haemoglobin pattern in accordance with the donors electrophoretic pattern.

Autoimmune Haemolytic Anaemia and Ovarian Tumour

A 32‐yr‐old female suffered from haemolytic anaemia with autoanti‐bodies of Rh specificity. The haemolytic process was completely arrested by the removal of an ovarian dermoid cyst which contained these antibodies at a concentration 10 times that found in the serum. The information obtained in this study suggests, therefore, that autoantibody may be produced by an ovarian cyst.

HLA haplotypes and long survival in childhood acute lymphoblastic leukaemia treated with transfer factor.

Association between HLA haplotypes and a long survival was investigated in 116 children with acute lymphoblastic leukaemia. It was found that patients with A2 B12 and/or A2 B40 haplotypes survived longer than patients without these two haplotypes. Since all children were treated with transfer factor obtained from their relatives, it is suggested that children possessing A2 B12 or A2 B40 haplotypes may respond better to this type of immunotherapy.

Clinical trials with daunorubicin-DNA and adriamycin-DNA in acute lymphoblastic leukemia of childhood, acute nonlymphoblastic leukemia, and bronchogenic carcinoma.

SummaryTreatment with daunorubicin-DNA (DNR-DNA) or adriamycin-DNA (ADM-DNA) has been evaluated in acute lymphoblastic leukemia of childhood (ALL), acute nonlymphoblastic leukemia (ANLL) and bronchogenic carcinoma (BC). The Five-year survival rate in 69 children with ALL was 73.7% when ADM-DNA was introduced in the treatment and 38% with DNR-DNA (P=0.03).A randomization between free DNR and DNR-DNA for remission induction in 26 patients with ANLL has shown that the drugs were of equivalent effectiveness. The one-year survival rate was 66% for the DNR group and 64% for the DNR-DNA group.In 59 patients with BC, a randomized trial between ADM-DNA and cyclophosphamide-vinblastine (CTX-VLB) did not show an advantage infavor of one of these treatments. In anaplastic BC (51 patients), there was no difference in survival rate or remission rate between patients treated with ADM or ADM-DNA.No cardiotoxicity was noted among the patients treated with the complexed drugs. ADM-DNA and DNR-DNA are as effective as the free drugs. Cardiotoxicity appears to be reduced.

Plasma levels and biotransformation of infused daunorubicin and daunorubicin-DNA complex in rabbits: A preliminary report

Abstract Plasma levels and biotransformation of daunorubicin and daunorubicin-DNA complex were studied in rabbits after an i.v. bolus injection and during and after a 4 hr infusion period. The administered dose was 5 mg/kg expressed as the free drug. The levels of daunorubicin (DNR) and its active metabolite, daunorubicinol (DNR-ol), were determined on plasma extracts by high-pressure liquid chromatography. The results demonstrated a slower disposition of the complex. In addition, a five-fold higher DNR-ol plasma level was achieved at the end of the infusion of the complex as compared with the free DNR infusion. Incubations of DNR and DNR-DNA complex with whole rabbit blood indicated also a slower disposition of the complex. Cell DNR-reductase activity in the rabbit was intense. Indeed, DNR-ol appeared rapidly during infusion of free drug and complex and during in vitro incubation with whole rabbit blood.

Adriamycin and adriamycin—DNA in inoperable bronchogenic carcinoma. A randomized study with cyclophosphamide vinblastine

Abstract In a randomized study on 59 patients with inoperable bronchogenic carcinoma, the chemotherapeutic efficacy and toxicity of ADM-DNA was compared with that of free ADM and that of the association cyclophosphamide-vinblastine. No significant differences in initial chemotherapeutic response could be observed between the groups of patients treated respectively with cyclophosphamide-vinblastine, free adriamycin or adriamycin—DNA. The cardiotoxicity of ADM seems however reduced by its combination with DNA, since no signs of cardiotoxicity were observed, even in the 15 patients who received a total dosage of adriamycin—DNA exceeding 500 mg/m 2 .

Le Syndrome Hypereosinophilique (She) A Propos De Deux Cas Et Revue De La Litterature.

SummaryIdiopathic hypereosinophilic syndrome is characterized by prolonged eosinophiliaof undetected cause and multiple organ system involvement (lung, kidney, nervous system, skin, …). Nevertheless, the prognosis has been correlated with heart involvement, which usually results in a restrictive cardiomyopathy with apical obliteration by fibrosis, mural thrombi and mitral and tricuspid regurgitation.This disease has a wide range of severity: some patients suffer from a real myeloproliferative syndrome and may develop blastic transformation while others present only skin involvement or are asymptomatic.Corticosteroids and hydroxyurea are both effective treatments. Interferon a seems to be active for the myeloproliferative form of the disease.Cytotoxic activity of activated eosinophil granular proteins may play an important role in tissue damage. The cause of eosinophilic proliferation (primitive malignant proliferation or resulting from a T lymphocyte stimulus) and activation remains uncertain.

Chimiotherapie des stades avances de la maladie de Hodgkin stades III b et IV

SummaryIn a series of 38 patients treated for advanced Hodgkin’s disease with the MOPP combination chemotherapy of DeVita, Serpick and Carbone, the complete remission rate was 84%. In this series 1/4 of the patients had been previously treated with other methods. Most of them, with a relapse of their disease, had a larger extension of their disease in comparison with the initial stage.In the evaluation of complete remission, the persistence of a splenomegaly (3 patients) is not necessarily a sign of incomplete remission; the histological study of the three spleens demonstrated no involvement of Hodgkin’s disease.The treatment is generally well tolerated. For the whole group, no more than an average decrease of 10 to 15% of the theoretical dose, mainly of the alkylating agents, was applied. The decrease was more important in patients who didn’t respond to the treatment; this allows us to suppose that haematological intolerance is a factor in bad prognosis.With a view to determining the best therapy for mai...