Circadian and seasonal variations of hematopoiesis in cord blood.

Cord blood hematopoietic progenitors undergo circadian and seasonal variations. The lowest values are obtained between 4:00 and 12:00, as well as between May and August. This represents the first observation of such rhythms before birth.

Intensive chemotherapy for poor prognosis myelodysplasia (MDS) and secondary acute myeloid leukemia (sAML) following MDS of more than 6 months duration. A pilot study by the Leukemia Cooperative Group of the European Organisation for Research and Treatment in Cancer (EORTC-LCG).

We conducted a prospective, multicenter pilot study of remission induction therapy in patients with poor prognosis MDS and AML evolving from a preceding phase of MDS. Fifty evaluable patients from 15 institutions were treated with one or two remission-induction courses consisting of i.v. idarubicin 12 mg/m2/day on days 1, 2, and 3 combined with a continuous i.v. infusion of cytarabine of 200 mg/m2/day on days 1 to 7. Of the 27 complete remitters (54%), 23 received a consolidation course which was identical to the remission-induction course except for the idarubicin 12 mg/m2 which was given on day 1 only. Fifteen patients received maintenance therapy consisting of six courses of cytarabine 10 mg/m2, s.c. twice daily, for 14 days. Two complete remitters were allografted and five patients received an ABMT. The median survival of all 50 treated patients was 14 months. The median duration of disease-free survival was 11 months with two patients in CR more than 2 years after entering CR. Twenty-four of the 27 remitters have relapsed. Four patients died during remission-induction therapy, but no patient died as a result of persisting hypoplasia. No fatal complications occurred during the consolidation and maintenance courses. Age and stage of disease had no significant impact on CR rate nor on remission duration. The CR rate was significantly (P = 0.03) higher in patients with only normal metaphases compared to patients with cytogenetic abnormalities. The DFS at 2 years was 33 vs 8%, respectively, for patients without or with cytogenetic abnormalities (P = 0.02). This study shows that patients below the age of 60 years with poor risk features are candidates for treatment with combination chemotherapy. A complete remission rate of more than 50% may be expected. Maintaining remission after remission-induction chemotherapy is a difficult issue. Patients not eligible for allogeneic BMT may be treated with intensive post-remission chemotherapy or autologous BMT.

Role of allogenic bone marrow transplantation in adolescent or adult patients with acute lymphoblastic leukaemia or lymphoblastic lymphoma in first remission.

Sixty-nine adolescents and adults 15-51 years of age with untreated acute lymphoblastic leukaemia (ALL, 54 patients) or lymphoblastic lymphoma (LL, 15 patients) were referred for intensive antileukaemic therapy. Patients were treated according to one of two protocols. Both included induction and consolidation with vincristine, prednisone, daunorubicin, cyclophosphamide, Ara C and asparaginase. Fifty-eight patients achieved complete remission within 8 weeks of chemotherapy. One additional patient entered remission after allogeneic BMT. Altogether 86% of the patients achieved CR. Thirty-three patients are alive, corresponding to an actuarial survival of 48 +/- 6% at 5 years after start of therapy. Survival from time of achievement of CR is 53 +/- 7% at 5 years and disease-free survival (DFS) is 52 +/- 7%. Consolidation treatment was given to all patients except one. An HLA-identical sibling was identified for 30 patients (45%). Twenty-two patients were scheduled to be transplanted with marrow from an HLA-identical sibling. The survival and DFS in these 22 patients was 58 +/- 11% at 5 years. DFS was not significantly different compared with the DFS of the eight patients who received an auto-BMT and the 26 patients treated with maintenance chemotherapy. DFS at 5 years was 63 +/- 17% and 40 +/- 10%, respectively. We also evaluated the influence of the presence of an HLA-identical sibling on the treatment outcome of all patients alive 12 weeks after initiation of remission-induction therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of a retrovirus-related glycoprotein in immune complexes from patients with hematopoietic disorders.

Human sera from normal and leukemic individuals were found to contain various amounts of an antigen with determinants related to p15E and reverse transcriptase of retroviruses. Using a specific monoclonal antibody and the immuno-affinity purified antigen, we surveyed a series of sera and plasmas from normal individuals and hematological patients by competition radioimmunoassays and binding assays directed against this specific protein. It was detected in all the samples at various levels. The level of this 74-kd glycoprotein appeared to be related to a stimulation of the hematopoietic system. No free antibodies were found that could recognized the labelled purified antigen. Only immune complexes prepared from the blood of some hematological patients contained the specific antigen, but complexes prepared from the blood of normal individuals did not.

Study of the expression of a glycoprotein of retroviral origin in the plasma of patients with hematologic disorders and in the plasma of normal individuals.

A 74,000 molecular weight glycoprotein was purified from the plasma of a patient with chronic myelogenous leukemia in blast crisis. Monoclonal antibodies were produced in the mouse and used to characterize this protein. It was shown to contain p15E antigenic determinants and portions of a reverse transcriptase. The level of this protein was found to be elevated in leukemic patients with high white blood cell counts and also in some patients with other hematopoietic disorders as compared to the level measured in normal individuals. The level of the protein was strongly reduced in acute leukemia patients after intense chemotherapy treatment. We tentatively conclude that this protein is of endogenous retroviral origin and perhaps regulates hematopoietic tissues.