In a prelminary communication, we described the establishment of a continuous human myeloid cell line (HL-60). Here we report the detailed properties of this cell line and document its derivation from the peripheral blood leukocytes of a patient with acute promyelocytic leukemia. As characterized by light and electron microscopy, the predominant cell type in both the fresh and cultured sources is a neutrophilic promyelocyte with prominent nuclear/cytoplasmic asynchrony. Up to 10% of the cultured cells spontaneously differentiate beyond the promyelocyte stage, and the proportion of terminally differentiated cells is markedly enhanced by compounds known to stimulate differentiation of mouse (Friend) erythroleukemia cells. The HL-60 cells lack specific markers for lymphoid cells, but express surface receptors for Fc fragment and complement (C3), which have been associated with differentiated granulocytes. They exhibit phagocytic activity and responsiveness to a chemotactic stimulus commensurate with the proportion of mature cells. As characteristic of transformed cells, the HL-60 cells form colonies in semisolid medium and produce subcutaneous myeloid tumors (chloromas) in nude mice. A source of colony-stimulating activity stimulated the cloning efficiency in soft agar 5--30-fold. Despite adaptations to culture, the morphological phenotype and responsiveness to chemical induction of differentiation is essentially unchanged through at least 85 passages. Cytogenetic studies reveal aneuploidy. Metaphases with 44 chromosomes predominated in vivo and in early culture passages; however, clones with 45 or 46 chromosomes became predominant with continued passaging. The most consistent karyotypic abnormalities were the deletion of chromosomes 5, 8, and X and the addition of a marker resembling a D-group acrocentric and of a submetacentric marker, most likely an abnormal E-group chromosome. No DNA herpesvirus or RNA retrovirus was isolated in the fresh or cultured cells. The HL-60 cultured cell line provides a continuous source of human cells for studying the molecular events of myeloid differentiation and the effects of physiologic, pharmacologic, and virologic elements on this process.

We treated 17 patients who had Philadelphia-chromosome-positive chronic myelogenous leukemia (4 of whom had not received therapy and 13 of whom had been treated with hydroxyurea or busulfan for less than six months) with recombinant human interferon alpha A (Roferon-A). The interferon was given as 5 X 10(6) units per square meter of body-surface area per day intramuscularly during induction therapy. Fourteen patients responded to the treatment, of whom 13 had a hematologic remission and 1 had a partial hematologic remission. The median number of white cells in those patients declined from 60.9 X 10(3) to 3.4 X 10(3) per microliter, and the median number of platelets decreased from 476 X 10(3) to 231 X 10(3) per microliter. Among the five responding patients who had splenomegaly before treatment, the spleen size returned to normal in four and decreased by 75 percent in one, although it remained enlarged. Bone marrow cellularity declined from a median of 92.5 percent to a median of 57.5 percent. In six of the patients with hematologic remission, complete suppression of Philadelphia cells was observed on at least one examination. Of the 14 patients who responded, 11 have received the interferon therapy for 9 to 15 months. One patient relapsed during the treatment, and the treatment has been temporarily interrupted in two patients because of toxicity. These data are preliminary and will need further confirmation, but they suggest that recombinant human interferon alpha A is effective in inducing hematologic remission in most patients with benign-phase chronic myelogenous leukemia and in suppressing the Philadelphia chromosome in some of these patients.

Thirty-three patients with chronic lymphocytic leukemia (CLL) with advanced Rai stage (III-IV) or progressive Rai stage (0-II) disease were treated with fludarabine as a single agent. Eleven patients (33%) obtained a complete remission (CR), 13 (39%) a clinical CR with residual nodules as the only evidence of disease (nodular partial remission [PR]), and two patients (6%) achieved a PR for a total response rate of 79%. Response was rapid, usually occurring after three to six courses of treatment. The major morbidity was infection. Febrile episodes occurred in 13% of the courses (pneumonia 6%, minor infection 4%, and transient fever of undocumented cause 3%). Fludarabine appears to be the most cytoreductive single agent so far studied in CLL.

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