Long-term outcome with pentostatin treatment in hairy cell leukemia patients. A French retrospective study of 238 patients.

With the introduction of new drugs such as alpha-interferon (IFN) and purine analogs, the management of hairy cell leukemia (HCL) patients has changed. However, deoxycoformycin (DCF) produced higher complete remission rates than IFN. The current study was undertaken to provide long-term data on duration of overall survival (OS) and disease-free survival (DFS) and incidence of subsequent malignancies. We retrospectively analyzed the data of patients treated with DCF (4 mg/m2/day, every 2 weeks) from 39 French centers. In 84 of 238 included patients, DCF was the first-line therapy. Pretreatment variables influencing the achievement of complete remission, DFS, and OS were identified by multivariate analysis. Two hundred and thirty-eight patients received a median of nine cycles (range, 1-19 cycles). A complete remission was obtained in 182 of 230 evaluable patients (79%) and a partial response was obtained in 38 patients, for an overall response rate of 95.6%. In the multivariate analysis hemoglobin level less than 100 g/l and leukocytes less than 2 x 10(9)/l were parameters adversely influencing complete remission achievement. With a median follow-up of 63.5 months (range, 0.39-138.4 months), disease recurrence was observed in 34 of 220 responding patients (15%). The estimated 5-years and 10-years DFS was 88.1% and 68.8%, respectively. Hemoglobin level less than 100 g/l and leukocytes less than 2 x 10(9)/l were the pre-treatment variables associated with a shorter DFS. The estimated 5-year and 10-year OS were 89.4% and 88.7%, respectively. Hemoglobin level less than 100 g/l, leukocytes less than 2 x 10(9)/l, and adenopathy were significant factors of reduced survival. Hematologic toxicity was the main side-effect, followed by infection and emesis. During the period of follow-up, 18 patients developed second cancer, but the standardized incidence ratio was 0.95. Pentostatin is a highly effective regimen for hairy cell leukemia that produces durable complete responses. Toxicity of DCF is acceptable. Subsequent malignancies do not appear to be increased with pentostatin treatment.

[Value of pulsed Doppler tissue imaging for early detection of myocardial dysfunction with anthracyclines]. / Intérêt du Doppler tissulaire pulsé pour le dépistage précoce de l'altération de la fonction myocardique aux anthracyclines.

The cumulative and definitive nature of chronic cardiotoxicity of anthracyclines requires a preventive strategy of early diagnosis. The authors undertook a prospective study of the association of echocardiography, mitral Doppler and pulsed Doppler tissue imaging of the left ventricular lateral and posterior walls in the context of this problem in 20 patients without cardiac disease undergoing cancer chemotherapy including anthracyclines. Doppler echocardiography was performed before the first session of chemotherapy and at the end of treatment, 6 +/- 4 months later. After a total cumulative dose of 227 +/- 91 mg/m2 of doxorubicine, there were no changes in left ventricular ejection fraction but a significant decrease in mitral E wave velocity (p = 0.04) and in E/A ratio (p = 0.01), suggesting early changes in left ventricular relaxation. The Doppler tissue examination confirmed the presence of radial and longitudinal abnormalities in myocardial relaxation (decreases in myocardial E wave velocities of the posterior and lateral walls of the left ventricle, p = 0.02 and p = 0.01, respectively). The peak velocity of the myocardial systolic wave (Sm) was significantly decreased in the lateral wall (p = 0.02) and approached statistical significance in the posterior wall (p = 0.07). These results suggest concomitant changes in myocardial systolic and diastolic function with moderate doses of anthracyclines. Therefore, pulsed Doppler tissue examination enables earlier detection of left ventricular cardiotoxicity with anthracyclines than classical echocardiographic parameters.

Effect of chlorambucil on bone mineral density in the course of chronic lymphoid leukemia.

The purpose of this work was to study the effects of chronic lymphoid leukemia (CLL) and its treatments on bone mineral density (BMD). Lumbar and femoral BMD was measured by X-ray absorptiometry in 50 (32 M, 18 F, median age 65, range age: 47-87 yr) CLL patients. In order to gauge the respective effects of CLL and corticoids on bone mass, 31 CLL patients under treatment were compared with 31 controls on cortisone. Nineteen untreated patients with CLL were compared with controls devoid of osteopenia risk factor. There was no significant difference regarding lumbar and femoral BMD between the untreated patients with CLL and the healthy controls. An increase in lumbar and femoral BMD was noted in the treated CLL group compared with the controls on cortisone (lum BMD: 1.018 vs. 0.861 g/cm2, p=6.10(-4); fem BMD: 0.773 vs. 0.699 g/cm2, p=0.037). This increase was observed only in patients who had received chlorambucil (lum BMD: 1.066 vs. 0.861 g/cm2, p=0.10(-4); fem BMD: 0.806 vs. 0.699 g/cm2, p=4.10(-3)), whereas there was no difference between the CLL patients treated without chlorambucil and the controls on cortisone. Multiple linear regression analysis confirmed the marked effect of chlorambucil (r=0.3715, p<10(-3)) on BMD increase in the course of CLL.

[Acute malignant myelofibrosis. Report of 3 cases]. / Myélofibrose aiguë maligne. Rapport de trois cas.

This report describes three cases of acute malignant myelofibrosis characterized by pancytopenia, absence of splenomegaly, bone marrow fibrosis with an immature cell proliferation and rapidly fatal outcome. The authors investigated the origin of blast cells with the use of immunohistochemical markers on paraffin embedded material with anti-factor VIII, BNH9 and anti-lysozyme. They studied the expression of megakaryoblastic, erythroblastic and myeloblastic differentiation in these cells. They demonstrated the heterogeneity of blast cells which are capable of differentiating along the three hematologic cell lines. The morphometric study showed the mutilating or systematized character of myelofibrosis. The increase in reticulin fiber density compared with normal bone marrow was not significantly different from two other types of myelofibrosis. It would be interesting to correlate a quantitative parameter with the course of this disease in order to evaluate the prognosis and the treatment.

Chromosomal subclonal evolution in paroxysmal nocturnal hemoglobinuria evolving into acute megakaryoblastic leukemia.

Four cytogenetic studies were performed in the course of a paroxysmal nocturnal hemoglobinuria evolving into acute megakaryoblastic leukemia. The clonal evolution was characterized by a unique structural change (9p) at the time of diagnosis, heralding an accelerated and complex karyotypic alteration including 5q-, 12p-, +21, -5, -7. At the terminal phase, the initial population was replaced within 1 week by a new overgrowing clone with -5, +8, +17. This suggests that the paroxysmal nocturnal hemoglobinuria-associated preleukemia and leukemic states share with acute nonlymphocytic leukemia the same nonrandom chromosomal changes.

[Acute myeloblastic leukemias and myelodysplasias: treatment with low doses of aracytine]. / Leucémies aiguës myéloblastiques et myélodysplasies: traitement par aracytine à faible dose.

The anti-leukaemic effect of low-dose cytosine arabinoside was assessed in 36 patients; 15 patients presented with an acute myeloblastic leukaemia and were treated in first induction because of age or preexisting disease and clinical and biological stabilization was obtained in 7 cases, with a mean duration of 8.7 months. In 4 relapsed patients 2 complete remissions were obtained, 1 of which after several courses of cytosine arabinoside. In all cases an important haematopoietic and extra-haematopoietic toxicity was noticed. In 15 patients treated for a myelodysplastic syndrome terminating in acute myeloblastic leukaemia stabilization was obtained in 8 cases, but final conclusions were difficult. The cytotoxic effect of cytosine arabinoside even at low dosage remains important. The optimal modalities in the administration, and the actual advantages of this treatment compared with conventional chemotherapy have still to be defined.