G-CSF IS A MAJOR COMPONENT OF COLONY-STIMULATING ACTIVITY (CSA) IN THE PLASMA OF PATIENTS WITH MULTIPLE-MYELOMA AFTER TREATMENT WITH HIGH-DOSE MELPHALAN (HDM)

Colony-stimulating activity (CSA) was measured by the production of gr anulocyte-macrophage colony-forming units (GM-CFU,) from normal donor bone marrow in the plasma of 29 patients with multiple myeloma (MM) af ter intensive treatment with high-dose melphalan (HDM) with or without autologous bone marrow rescue (ABMR). Although patients who received ABMR had an earlier recovery of circulating neutrophils compared with those who received HDM alone, the time at which CSA reached a maximum was similar in both groups (10 to 11 days) after therapy. The decline in CSA correlated with the recovery of the neutrophil count. In plasma from patients who received recombinant human granulocyte colony-stimu lating factor (rhG-CSF), in addition to an autograft, CSA reached a ma ximum earlier (7 days). Furthermore, neutrophil recovery was earlier i n these patients. Platelet recovery was not increased by rhG-CSF. The time at which CSA was maximum in four patients who were undergoing int ensive therapy for the second time occurred 9 days after treatment wit h HDM. Although the period without neutrophils was longer in three (of four) patients who survived long term, one patient who received rhG-C SF had a shorter period of neutropenia than the two who had not had th e cytokine. G-CSF was detected in plasma from seven of seven patients but not at all times after treatment. In plasma samples that contained G-CSF, colony numbers were increased by recombinant interleukin-4 (rI L-4) in vitro. Neither IL-3 nor GM-CSF was detected in plasma; however , antibody to GM-CSF reduced CSA in all samples after intensive therap y. The data suggest that CSA is a consistent physiologic response to i ntensive therapy, even in previously treated patients, but that hemato logic recovery is dependent on the availability of viable progenitor c ells.