Monocyte differentiation and HIV replication after prolonged culture of peripheral blood mononuclear cells from HIV-infected individuals.

Primary cultures of peripheral blood mononuclear cells (PBMC) from 51 HIV+ hemophiliac patients (HIV+ PBMC) were set up, allowing undisturbed cellular interaction in the absence of any exogenous stimuli. The optimum time for p24 detection was between 12 and 25 days. Infective virus was recovered from the culture supernatants (HIV+ SN) and the amount of p24 released ranged from 25 to 5300 pg/ml. Cells of the monocyte/macrophage (M/M) lineage were the main source of HIV in the HIV+ SN, as judged by intracellular staining of permeabilized cells with anti-p24 (KC57 monoclonal antibody) and flow cytometry analysis. M/M activation, differentiation, and proliferation occurred along the culture before the peak of in vitro HIV replication. Release of HIV p24 was highest in patients with >200 CD4+ T lymphocytes/mm3 who did not receive highly active antiretroviral therapy (HAART), but it was still detectable in 60-90% of patients who had responded to 1-2 years of HAART, reducing their plasma viral load to undetectable levels. It is proposed that this simple experimental system can be used to assess ongoing HIV infection of M/M with the patient's own viral variants.

[The future of oncohematology]. / El futuro de la oncohematología.

The last 40 years have witnessed important changes in the understanding and treatment of oncohematological affections. Palliative therapy was gradually replaced by chemotherapy (CT) which rapidly proved unexpectedly effective. In 1948, the first antifolic drugs, aminopterin and methotrexate, were discovered, followed in 1950 by the corticoids and in 1953 by antipurine agents. By 1967, a combination of these drugs yielded a survival index of 50% in acute lymphoblastic leukemia (ALL) with a progressive increase in all important cancer centers today, including in GATLA (Argentine Group for Acute Leukemia). As for acute myeloblastic leukemia (AML) the CT results were not as spectacular although now there is a 25% survival index which reaches 40-50% in young adults. As for allogeneic transplant in acute leukemia, its use must be evaluated for each patient and for each circumstance. Leukemias are genetic diseases for which gene therapy undoubtedly has potential value. However, the problems raised by the election of the right gene or gene marker and specially of the adequate vector have not yet been solved. In Hodgkin's disease, the results obtained with CT since the decade of the 60s have been spectacular and today different combinations of drugs have yielded a survival rate above 80%. Immunotherapy with or without CT has opened up a completely new and promising field. The route from basic research to clinical application has been long and arduous but the results obtained in leukemia and lymphomas have undoubtedly been life-saving and hopefully will open up even better possibilities in the near future.

[Concurrence of cytochemical and immune patterns of different cell lines in cases of acute leukemia]. / Concurrencia de marcación citoquímica e inmune de diferentes linajes celulares en casos de leucemias agudas.

Mixed, bilineal, biclonal and hybrid leukemias are synonymous, differing from biphenotypical ones. Mixed acute leukemia is defined by the coincidence of 1) two cytochemical markers of different lineage, or 2) one of them with more than one opposite immunological marker, or 3) more than one immunological marker opposite to another immunological lineage. Seven cases of mixed acute leukemia are presented, two of which showed posttreatment switching. It is concluded that mixed acute leukemias are associated with a poor prognosis, and therapeutic criteria are defined.

An update of two randomized trials in previously untreated multiple myeloma comparing melphalan and prednisone versus three- and five-drug combinations: an Argentine Group for the Treatment of Acute Leukemia Study.

An update of two consecutive randomized studies in previously untreated multiple myeloma was performed. The first study (10-M-73) began in 1973; 150 patients were treated with melphalan and prednisone (MP) or semustine, cyclophosphamide, and prednisone (MeCP). In a second randomized study (3-M-77), begun in 1977, 260 patients were treated with MP or melphalan, prednisone, cyclophosphamide, semustine, and vincristine (MPCCV). A total of 27 of the 67 patients (40%) treated with MP and 33 of the 83 patients (40%) treated with MeCP showed a good response in protocol 10-M-73; 48 of 145 patients (33%) treated with MP and 51 of the 115 patients (44%) treated with MPCCV in protocol 3-M-77 obtained a good response (P is not significant). Median survival in protocol 10-M-73 was 30 months for MeCP and 38 months for MP. At 84 months, 19% and 9% remain alive, respectively. Median survival for protocol 3-M-77 was 44 months for those treated with MPCCV and 42 months for MP. At 60 months, 9% and 11% remain alive; this difference was not significant. Also, there was no survival difference for favorable or unfavorable prognostic groups among the four treatment arms of both protocols. It can be concluded, with a long-term follow-up of both protocols, that the combination of MP is as effective as the three- and five-drugs combinations, and in view of its simplicity and cost-saving advantages, it should be favored for initial therapy of multiple myeloma patients.