[Randomized multi-center trial of the administration of erythropoietin in anemia of prematurity]. / Estudio multicéntrico aleatorizado de administración de eritropoyetina en la anemia de la prematuridad.

OBJECTIVES: The purpose of this study was to test the therapeutic effect of human recombinant erythropoietin (rH-EPO) on anemia of prematurity. MATERIAL AND METHODS: Fifty-eight preterm infants less than 34 weeks of gestational age from three different hospitals were studied. Transfusional policies were similar in all three centers. Infants with ABO or Rh incompatibility were excluded. At 28 days after birth, 28 infants (48.3%) had hemoglobin levels under 10.5 g/dL and were randomized to receive rH-EPO or standard care. Those infants ascribed to the treatment group received 200 U/kg of body weight of rH-EPO subcutaneously once a day, three days a week for 4 weeks together with oral supplements of ferrous sulfate at a dosage of 4 mg/kg/day. Both groups received daily doses of 50 micrograms of folic acid and 5U of vitamin E per os. Erythropoietin and ferritin were determined at randomization and at 60 days of age. Hemoglobin, reticulocytes, leucocytes, granulocytes and platelets were measured once a week, from the beginning of the treatment until 60 days of age. RESULTS: At randomization into treatments, there were no significant differences between the groups with respect to weight, gestational age, hemoglobin (9.42 +/- 0.73 vs 9.26 +/- 0.68 g/dL), reticulocytes (61.7 +/- 32.2 vs 68.0 +/- 61.0 x 10(9)/L), ferritin, EPO1 leucocytes or platelets. At 60 days of age, the treatment group showed higher hemoglobin values (10.5 +/- 1.73 vs 9.1 +/- 1.0 g/dL, p < 0.05). There were no significant differences between reticulocyte counts (176.4 +/- 91.1 vs 112.6 +/- 85.0 x 10(9)/L), granulocytes (2,351 +/- 868 vs 2,075 +/- 856 x 10(9)/L), platelets (400 +/- 138 vs 316 +/- 164 x 10(9)/L) or ferritin (209 +/- 177 vs 393 +/- 328 micrograms/mL). Of the infants in the nontreated group, 13.3% received blood transfusions between 30 and 60 days of age, while only 6.7% of the treatment group did (p = 0.31). DISCUSSION: We have been able to find 11 controlled studies in the medical literature which deal with the clinical usage of rH-EPO in newborns. Six use the hormone in an early phase and 5 in a posterior one. Our study should be included in the later and, as happens in most of them, demonstrates the efficacy of rH-EPO in the treatment of late anemia of the preterm newborn as shown by an increment in the hemoglobin levels and a trend towards the diminution in the use of blood transfusions. We have not observed substantial adverse effects.

[Evolution of the treatment of acute nonlymphoblastic leukemias in children (1968-1990)]. / Evolución del tratamiento de las leucemias agudas no linfoblásticas en el niño (1968-1990).

Changes in treatment of ANLL in children over 23 years (1968-90) and advances made in the last ten years in a pediatric hematological unit are reported herein. Of 124 patients under 15 years of age, 18 of whom were infants, 118 were evaluable. Of these, 58 were treated before 1980 and, although complete remission (CR) was attained in 75%, the median duration was lower than 12 months and no patient survived in CR more than 6 years. From 1981 to 1987, 40 patients received one or two induction treatments followed by three consolidations and then blocks of sequential intensive chemotherapy for 12-15 months. CR was attained in 87.5% and event-free survival (EFS) was 22.5% at 8 years: 14% for those treated from 1981 to 1983 and 33% for those included in the ANLL-84 protocol. In 1988, a post-remission protocol with intensification therapy (two high-dose ARA-C treatments combined with mitoxantrone in the first and amsacrine in the second) followed by allogeneic or autologous bone marrow transplant (BMT) was initiated. Of 20 patients included, 17 reached CR (85%) and 16 underwent BMT. EFS of the 20 patients was 65% at 2 years and post-BMT relapse-free survival was 75%. These results are compared with those obtained separately with present intensive chemotherapy protocols and with BMT and it is concluded that intensification treatment followed by BMT (allogeneic or autologous) might constitute an advance in the treatment of children with ANLL.

[Intensification chemotherapy followed by allogenieic and autologous bone marrow transplantation in acute non-lymphoblastic leukemia in children]. / Quimioterapia de intensificación seguida de trasplante de médula ósea alogénico o autólogo en leucemias agudas no linfoblásticas en niños.

UNLABELLED: Both intensification therapies with high-doses ARA-C and bone marrow transplant, allogeneic (BMT) or autologous (ABMT), have proved effective in relapse prevention in ANLL. The present study combines both treatments. METHODS. Remission induction treatment was DAE combination. The first intensification consisted of HD ARA-C and mitoxantrone and the second HD ARA-C and AMSA. CNS prophylaxis consisted of 6 doses of i.t. ARA-C and MTX. Later, patients in remission with HLA-compatible donor received BMT and those without it, ABMT with "ex vivo" treatment of the bone marrow with ASTA-Z. Pre-BMT treatment was the same in both cases: fractionated total body irradiation (TBI) and cyclophosphamide in patients over 3 years of age; in patients under 3 busulfan was given instead of TBI. PATIENTS. Between April 88 and March 90, 18 patients (age 3 months to 14 years) were included. FAB subtypes were M1 + M2: 4; M3: 2; M4: 4; M5: 5; M6: 1; M7: 2. Two patients died of cranial haemorrhage before the 10th day, 15 achieved complete remission (CR) after one or two induction treatments and 1 only attained CR after the first intensification. RESULTS: 1 patient with M7 relapsed after the 2nd intensification. Of the remaining 15, five received BMT and ten ABMT. Average interval between CR and transplant was 4 months (3 to 8). Of the 5 with BMT, one died from progressive obliterating bronchiolitis at 9 months and the other four continued in CR for 6 to 28 months. Of the 10 with ABMT none died from complications, 2 suffered early relapse and 8 continued in CR for 6 to 28 months.(ABSTRACT TRUNCATED AT 250 WORDS)

[Intensification of the initial treatment in acute lymphoblastic leukemias of middle and high risk in children]. / Intensificación del tratamiento inicial en las leucemias agudas linfoblásticas de medio y alto riesgo en el niño.

The aim of study LAL 17/84 was to reduce the number of relapses by intensifying initial treatment. Patients were classified as high (HR) and standard-risk (SR) groups following the established risk index. Early response, after 2 weeks of treatment was also considered. SR protocol includes a ten-week induction and CNS prophylaxis phase: in the first 5 weeks, prednisolone (PRED), vincristine (VCR), daunorubicin (DAUNO) and asparaginase (ASPAR) are given; in the last 5 weeks two intravenous infusions of Ara-C and three of intermediate dose (ID) methotrexate (MTX) are administered simultaneously with 5 it injections of both drugs. CNS prophylaxis is completed with 5 further it injections: one at the beginning and 4 at monthly intervals from the 3rd to the 6th months. In the HR protocol, the initial phase lasts 16 weeks: in the first 5 the same drugs as in SR are used but doses of PRED and ASPAR are higher. CNS prophylaxis includes holocranial radiotherapy (18 Gy), 2 iv infusions of Ara-C and a further 2 of MTX ID and 6 it doses of MTX and Ara-C. Finally, a consolidation phase of PRED, VCR (3 doses), tenoposide (3 doses) and cyclophosphamide is given. Complementary chemotherapy in both protocols consists of daily mercaptopurine and weekly MTX for 2 years; moreover, the randomized half of the patients received monthly reinforcements with PRED, VCR (and DAUNO in HR group) for 4 months. Between Oct. 83 and Nov. 87,87 patients with ages between 3 months and 15 years were enrolled; 86 are evaluable. All achieved remission.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cytomegalovirus disease in immunosuppressed patients]. / Enfermedad por virus citomegálico en pacientes inmunodeprimidos.

Cytomegalovirus (CMV) infection is relatively frequent and severe in immunosuppressed patients giving rise to diagnostic and therapeutic problems. We describe a series of 7 patients, six with acute lymphoblastic leukemia and one with aplastic anemia. All patients had CMV infection at the moment of maximum immunodepression. Two patients had undergone recent bone-marrow transplant. Six had been transfused in the two months prior to the onset of infection. Diagnosis was established through isolation of CMV from blood or serological methods. Symptoms ranged from prolonged fever to multi-organic involvement. Two cases had pulmonary involvement as well as fever, hepatitis and petechial rash. Two other cases presented with fever and hepatosplenomegaly and in the remaining, 3, fever was the only sign. Clinical course was favourable in all cases including the two with pneumonitis; of these two the first received acyclovir and anti-CMV Ig and the other received no specific therapy. One of the remaining cases was also given acyclovir and specific anti CMV Ig was administered to the 3 patients with isolated fever. In conclusion, CMV infection should be suspected in immunosuppressed patients with prolonged fever.