Five years follow-up after 2-chloro deoxyadenosine treatment in thirty patients with hairy cell leukemia: evaluation of minimal residual disease and CD4+ lymphocytopenia after treatment.

Between March 1992 and August 1993, thirty patients with hairy cell leukemia (HCL) were treated in a single institution with 2-chlorodeoxyadenosine (2-CdA) for one course (N=27) or two courses at six month interval (N=3). Sixteen patients were previously untreated, 14 had been treated with alpha interferon (alpha IFN) (N=5), alpha IFN and splenectomy (N=8) and splenectomy, alpha IFN and Deoxycoformycin (N=1). Overall results in 29 evaluable patients were: 25 CR (86%), 3 PR (10%), one failure. The three PR patients relapsed after 18, 24 months and five years. Two were retreated successfully. Two CR patients relapsed after five years. Careful clinical survey, sequential bone marrow biopsies (BMB) with DBA44 immunostaining for assessment of response and detection of residual disease and serially evaluation of lymphocyte subsets counts were performed. Results of bone marrow biopsies study show 1) a progressive reduction in hairy cell infiltration during the first six months after therapy and not after that indicating that the best moment for the evaluation of response may be the sixth month, 2) the persistence of a very small number of DBA44+ cells (80% of BMB). There was a correlation between the presence of > 5% DBA44 positive cells on 6th month BMB and relapse. 60% had an absolute CD4+ lymphocyte count less than 0.2 10(9)/l at least on one examination after treatment. CD4+ lymphocyte level persisted less than baseline level in 8/18 patients tested after four and/or five years. Lymphopenia was less marked in splenectomized patients: 7/7 splenectomized patients tested have recovered a CD4+ lymphocyte count equal to pretherapy level compared to 3/11 non splenectomized patients (p: 0.004). Three opportunistic infections were observed early (first 6 months) after 2CdA therapy: pneumocystis pneumonia, retinitis due to toxoplasma in the patient who failed and legionella pneumonia in a patient retreated after relapse. Two patients developed a second carcinoma 6 and 12 months after therapy. Five patients died, three from a cause unrelated to HCL, one from HCL and one from infection while in second CR. At five years, overall survival is 83% and progression free survival is 66%. Our study shows 1) long-lasting response in the majority of patients after 2-CdA, 2) a correlation between persistent minimal residual disease detected with DBA44 immunostaining and occurrence of relapse and 3) a profound and persistent CD4+ lymphopenia more marked in non splenectomized patients.

[Treatment of anemia in hemodialyzed children using recombinant human erythropoietin (Eprex). Results of a French multicenter clinical trial]. / Traitement de l'anémie des enfants hémodialysés par l'érythropoïétine humaine recombinante (Eprex). Résultats de l'essai clinique multicentrique français.

Intravenous recombinant human erythropoietin (Eprex Cilag) was used in 28 hemodialyzed children, treated in 3 French paediatric centers, from November 1989 to November 1990. Transfusion dependency disappeared in all cases: the number of transfusions decreased from 7.3 unit/patient/year to 0.6 unit/pt/year. The mean haemoglobin concentration for the whole group increased from 6.6 +/- 0.8 g/dl, to 9.2 +/- 1.2 at 6 months and 9.7 +/- 0.7 g/dl at 1 year. Twenty-two out of 28 children reached the target haemoglobin value of 9.6 g/dl (6 mmol/dL) within a mean time of 16.5 weeks. Poor responses were due to either a premature withdrawal of treatment because of renal transplantation, or too low a dosage for the age. The study showed indeed that the dose requirement was significantly dependent on physical development: the mean dosage required to maintain haemoglobin concentration at the target value was 300 U/kg/week in children weighing less than 20 kg, 222 U/kg/week in 20-30 kg children, and 135 U/kg/week in those weighing more than 30 kg (p = 0.02). The only complication was an increase in blood pressure, observed in 43% of cases. The increase of anti-hypertensive medication was always successful in controlling blood pressure, and hospitalization was required in only one case. The improvement in general condition was obvious, and in several cases, the cognitive abilities seemed to improve. The growth deficit remained unchanged.

[Effectiveness of and tolerance to human recombinant erythropoietin in the treatment of kidney failure anemia in children undergoing continuous peritoneal dialysis. Multicenter study]. / Efficacité et tolérance de l'érythropoïétine recombinante humaine dans le traitement de l'anémie de l'insuffisance rénale des enfants en dialyse péritonéale continue. Etude multicentrique.

Eight young children with renal failure, undergoing continuous peritoneal dialysis (CDP) and presenting an anemia (hemoglobin level [Hb] 57 to 89 g/l) were treated by subcutaneous recombinant human erythropoietin (rHu EPO) twice weekly. The initial dose of 75 U/kg was adjusted to induce progressive increase of Hb with a target level of 100-120 g/l. Treatment duration was 24 weeks in five of these children and 10 to 13 weeks in the three others. In seven cases out of eight, anemia was corrected. The target Hb level was reached in 3 to 21 weeks with rHu EPO doses of 150 to 300 U/kg/w (mean: 200 U/kg/w) for four children without recent transfusion; then the median maintenance dose was 135 U/kg/w (range: 50-300 U/kg/w). In only one patient, Hb never reached a level higher than 77 g/l despite weekly dose of 350 U/kg, a reticulocytosis of 5.6%, rHu EPO treatment lasting up to 24 weeks and the absence of iron deficiency. In any case, no transfusion was necessary after the first day of rHu EPO treatment. In three patients, the increase of a preexisting hypertension required the adaptation of antihypertensive treatments. One patient presented a marked thrombocytosis. In conclusion, twice-a-week subcutaneous injections of 75 to 150 U/kg of rHu EPO appear to be well tolerated and effective in the treatment of anemia of CPD children.