Therapy-related acute myeloid leukaemia after successful therapy for acute promyelocytic leukaemia with t(15;17): a report of two cases and a review of the literature.

We describe two patients with positive t(15;17) acute promyelocytic leukaemia (APL) that developed into a therapy-related myelodysplasia 2-2.5 years after complete remission (CR) and then evolved into therapy-related acute myeloid leukaemia (t-AML). Both patients received anthracyclines as potential leukaemogenic drugs. In both cases, cytogenetic changes usually occurring after use of alkylating agents were noticed: monosomy 7 associated with monosomy 5 or 5q- chromosome. A review of the literature on t-AML occurring after successful therapy for APL showed only one report similar to these two cases. These observations suggest that anthracyclines can cause t-AML similar to that induced by alkylating agents.

Evaluation of carboplatin as a single agent in highly refractory acute myeloid leukemia.

Thirteen patients (pts) with highly refractory acute myeloid leukemia (AML) 10 pts with de novo AML and 3 with blast crisis of chronic myeloid leukemia were treated with carboplatin (CP) 150 mg/m2/day through continuous IV infusion for 7 consecutive days. Seven of them received CP at least as third or more line therapy after a median duration of the disease of 26 weeks. None achieved a complete remission but a good hematologic response, with disappearance of circulating blast cells along with correction of bone marrow failure, persisting for 3 months was obtained in one patient and correction of hyperbasophilemia was observed in another with blast crisis of chronic myelogenous. Myelosuppression was the most consistent toxic effect. Two deaths occurred, one from renal acute failure and the other from sepsis. Median survival after CP was 8 weeks (range 4 days-11 months) and the majority of patients were able to return home. When used as a single agent and with the dose-schedule used in this study, CP does not appear effective in refractory AML. Other studies are necessary to assess its role at an higher dose or in combination with other agents in earlier phases of the disease.

Novel combination of epirubicin, bleomycin, vinblastine and prednisone (EBVP II) before radical radiotherapy in localized stages (I-IIIA) of Hodgkin's disease. Early results in 100 consecutive patients. Pierre-et-Marie-Curie Group.

A novel combination of epirubicin, bleomycin, vinblastine and prednisone (EBVP II) was scheduled to reduce the toxicity of chemotherapy and to improve its application in treatment of Hodgkin's disease. This combination followed a previous regimen given every 15 days (EBVP I) by the same cooperative group. EPVP II is given every 21 days with increased dosage and increased intensity of epirubicin. This regimen was given to 100 consecutive patients with favourable or unfavourable limited-stage disease (clinical stages I-IIIA) excluding very favourable stages I and II and stages IIIB and IV. Such patients first received three injections of EBVP II and were then radically irradiated; those with unfavourable prognosis factors received three subsequent injections of EBVP II. The present analysis reports the early results of such treatment and considers particularly toxicity and the obtention of complete remission, which is pre-eminent for a cure. EBVP II was given in full dosage in 99% of the primary set of three injections. The main toxicity was alopecia and to a lesser degree nausea and vomiting and veinitis. Complete remission was obtained in 76 patients before radiotherapy and in 20 others after radiotherapy. With a median follow-up of 30 months 1 patient died from Hodgkin's disease, 9 are alive after relapse and 90 with no evidence of disease. This treatment appears to be as efficient as previous chemotherapy, well tolerated and particularly easy to give. It deserves further comparison with other proved regimens taking into consideration the survival and quality of life of patients.

Combination of ABVD and radiotherapy in early stages of Hodgkin's disease: analysis of a series of 94 patients. Pierre and Marie Curie Group (GPMC).

In order to reduce, if not completely suppress, late complications of combined chemotherapy and radiotherapy in Hodgkin's disease (HD), MOPP regimen (mechlorethamine, vincristine, procarbazine and prednisone) was replaced by ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine). Ninety-four patients with HD clinical stages I to IIIA with no staging laparotomy were treated by three courses of ABVD followed by radiotherapy. Irradiation was performed on extended fields in 41 cases and on involved fields in 53 others. Consolidation chemotherapy was planned in 67 cases with at least one unfavorable prognostic factor, but achieved only in 33 cases. Seventeen patients relapsed within 1 to 46 months after the beginning of treatment. Ten patients died, 7 of HD and 3 of intercurrent diseases or accident. Disease-free survival rate with a median follow-up of 60 months is 80%. This study showed, on the one hand, many digestive and general side-effects after ABVD and, on the other, a satisfactory hematological tolerance. Furthermore, mediastinitis or cardiovascular complications were not more frequent than with MOPP. These results point out the development and use of better tolerated regimens for initial chemotherapy in HD, without jeopardizing the good results of the treatment.

Pentostatin (2'deoxycoformycin) for the treatment of lymphoid neoplasms.

Knowledge of the vital role of adenosine deaminase in lymphatic tissues has led to the development of enzyme inhibitors for treatment of lymphoid neoplasms. Deoxycoformycin is a potent ADA inhibitor and has been shown to be active in acute lymphoblastic leukemia at high doses but associated with unpredictable toxicity. In indolent lymphocytic leukemia or lymphoma with low ADA concentrations, this drug is effective at low doses with mild toxicity. The on-going EORTC trial shows that pentostatin is highly effective in hairy cell leukemia and can achieve durable complete remissions even if interferon alpha has failed. It will probably play an important role in the treatment of prolymphocytic leukemia, T- and B-cell chronic lymphocytic leukemia and Sézary syndrome.

[New combination of epirubicine, bleomycin, vinblastine and prednisone (EBVP II) before radiotherapy in localized stages of Hodgkin's disease. Phase II trial in 50 patients]. / Nouvelle association d'épirubicine, bléomycine, vinblastine et prednisone (EBVP II) avant radiotherapie dans les stades localisés de maladie de Hodgkin. Essai de phase II chez 50 malades.

A new regimen of chemotherapy was used to reduce toxicity of EBVP I: the number of injections and the doses of bleomycin and vinblastine were reduced by half, the duration of treatment by third. Fifty patients with Hodgkin's disease stage I to IIIA, previously untreated, received three courses of this regimen before radiotherapy. Gastro-intestinal toxicity was similar and alopecia was more marked than with EBVP I. Immediate efficacy is similar, with 90% of complete remission and only one failure. This regimen is shorter and more intensive than EBVP I. It deserves larger comparison with previously used chemotherapy in a more extensive controlled trial.

Aspergillosis of ethmoid sinus and optic nerve, with arteritis and rupture of the internal carotid artery.

A 54-year-old woman had been treated 26 years previously for Hodgkin's disease. Eight months before presentation, the disease had recurred and the patient had received cytotoxic drugs and steroids. She presented with loss of vision of the right eye and died 5 months later from extensive subarachnoid hemorrhage. Postmortem examination revealed an aspergillus abscess of the ethmoid sinus, extending to the right frontal lobe and optic nerve, and to the wall of the right internal carotid artery (ICA). Death was due to rupture of the ICA. Such a presentation of aspergillosis is unusual. Three cases of aspergillus arteritis causing rupture of the ICA have been reported previously.

[The combination of epirubicin, bleomycin, vinblastine and prednisone (EBVP) before radiotherapy in localized stages of Hodgkin's disease. Phase II trials]. / Association d'épirubicine, bléomycine, vinblastine et prednisone (EBVP) avant radiotherapie dans les stades localisés de la maladie de Hodgkin. Essai de phase II.

A new regimen of chemotherapy was used to reduce toxicity of ABVD: adriamycin is replaced by epirubicin and dacarbazine by prednisone. Thirty eight patients with Hodgkin's disease, stage I to IIIA, previously untreated, received three courses of this regimen before radical radiotherapy. Gastro-intestinal toxicity and alopecia appeared less marked than with ABVD. Immediate efficacy is similar with 80% of complete remission (one third observed at day 28) and only 2 failures. This regimen appears thus as a clear improvement in the treatment of patients with Hodgkin's disease and deserves larger comparison with previously used chemotherapy in a more extensive controlled trial.

A phase II study of alternating combination chemotherapy in 55 myeloma patients. A comparison with non-alternating combination chemotherapy and treatment with a single cytostatic.

Fifty-five consecutive patients with stage II and III myeloma were treated at 7 centers with alternating combinations of 7 cytostatics and prednisolone. 30/48 evaluable patients responded to the combination chemotherapy, 10/55 patients died within 15 months, and the median survival was 40 months. No advantage could be shown over a previous non-alternating combination of two cytostatics. However, stage III patients had a significantly better survival statistically (p less than 0.05) than earlier patients from the same center given only one cytostatic.

[Combination of AMSA-high dose cytosine arabinoside in acute leukemia]. / Association AMSA-fortes doses de cytosine-arabinoside dans la leucémie aiguë.

Forty patients with refractory and/or relapsing acute leukaemia were treated with AMSA (90-120 mg/sq m/day) for 5 days combined with high dose cytosine-arabinoside (HDARAC) (3 g/sq m/12 hours) during the first 2 days. Complete remission was obtained in 46% of the 26 cases of acute myelogenous leukaemia, and the complete remission rate was fair (44%) in the 20 patients refractory to conventional induction treatments. The results were less satisfactory in the few patients with other cytological types: there were 2 complete remissions in 10 patients with acute lymphoblastic leukaemia and none in 4 patients with blast crisis of chronic myelocytic leukaemia. Haematological toxicity was severe, and 6 patients died during the aplastic phase. No cardiac toxicity associated with AMSA was observed, nor did the ocular, cutaneous or cerebellar side-effects described after longer courses of HDARAC develop. Complete remissions were relatively short, and 11 of 14 remitters relapsed after 2 to 11 months (median 4 months). However, 3 remitters underwent allogenic bone marrow transplantation with 2 surviving. Another patient has a prolonged fourth complete remission with AMSA + HDARAC maintenance treatment. It is concluded that the AMSA-HDARAC combination seems to be one of the best salvage induction regimens in acute myelogenous leukaemia.

[Hodgkin's disease: the value of prognostic criteria and of the combination of radiotherapy and chemotherapy in localised lymphoid stages (I and II). 94 patients undergoing laparotomy (author's transl)]. / Maladie de Hodgkin: valeur des critères dits de pronostic et de l'association radio-chimiothérapique dans les stabes lymphoïdes localisés (I et II). 94 malades laparotomisés.

Criteria reputed to be of grave prognostic significance were studied in 94 patients suffering from Hodgkin's disease at stages I and II, after laparotomy and splenectomy. The parameters studied (age, general signs, histological type, mediastinal involvement) are less prognostic factors than indications of unrecognised extension of the disease: almost 1/3 of unrecognised lesions in the presence of one of the criteria; almost 2/3 with two or more. Exploratory laparotomy revealed lesions unsuspected on the basis of clinical evaluation only in 10% of patients with no criteria of poor prognosis. The long term prognosis of the disease depends, in fact, not upon the existence of these criteria but upon the method used in initial treatment. Five year survival and cure rates are significantly better in patients treated with combined polychemotherapy (MOPP) and radiotherapy than in those treated with radiotherapy alone. These results would indicate that routine laparotomy should be abandoned in patients with a localised clinical staging if it is decided to begin treatment with a combination of radiotherapy and chemotherapy. So-called prognostic factors could then be used simply to vary the intensity of the treatment prescribed.

[Increased hematological toxicity of antineoplastic drugs with simultaneous androgenotherapy (author's transl)]. / Aggravation de la toxicité hématologique d'agents anti-néoplasiques par l'androgénothérapie simultanée.

Thirty two patients with malignant lymphoma - mainly Hodgkin's disease - were randomized for simultaneous treatment by high doses of metenolone during MOPP chemotherapy, to reduce its hematological toxicity. The results have shown surprisingly an increased hemato-toxicity in patients receiving androgens, with significantly more marked anemia and thrombocytopenia, reducing the total doses of anti-cancer drugs. This side effect could be explained by a cycling of the hematopoietic stem-cells and call to some caution when androgens are used during cancer chemotherapy.

[Contribution of cytochemistry and delayed hypersensitivity skin tests in the diagnosis and prognosis of chronic lymphoproliferative syndromes]. / L'apport de la cytochimie et des tests cutanés d'hypersensibilité retardée dans le diagnostic et le pronostic des syndromes lymphoprolifératifs chroniques

Cytochemistry is disappointing in lymphoproliferative syndromes for it does not permit one to classify the various diseases with certainty. In the early stages, if the three indices are lowered, the prognosis seems poorer. A study of glucuronidase permits, in hyperlymphocytosis, one to differentiate benign from malignant lymphocytes, but does not permit one to differentiate from one another, the other chronic lymphoproliferative syndromes. The acid phosphatase is interesting in the study of hairy cell leukemia. Finally, it was not possible to distinguish chronic lymphoid leukemia from leukemia with lymphosarcomatous cells, nor from the cytochemical point of view nor using tests for delayed hypersensitivity.