We have examined basophil production (BP) in suspension cultures of separated peripheral blood cells from patients with chronic myeloid leukemia (CML). Seventy cultures were performed in 47 patients, 33 in chronic and 14 in the accelerated/acute phase of CML. None of 13 normal controls, 0/21 treated chronic phase, 3/33 untreated chronic phase, and 14/18 (p < 0.0001) accelerated/acute phase CML cultures showed at least twofold increases in basophils and histamine in vitro at 14-21 days. A gradient effect of disease phase on BP was observed: maximal histamine content (ng/106 cells) was 16 ± 4 for chronic, 56 ± 19 for accelerated, and 183 ± 73 for acute phase CML cultures (mean ± SE, p < 0.002), while basophils (per 103 cells) numbered 23 ± 7, 59 ± 20, and 267 ± 81, (mean ± SE, p < 0.0003), respectively. Multivariate analysis of maximal differences in basophils or histamine in vitro and simple linear regression slopes of basophils or histamine on time revealed that disease phase, and not therapy, accounted for the changes in BP in vitro. Serial studies over periods of 6-29 mo in 4 patients followed from chronic through acute phases of disease revealed a reversal of BP in vitro from negative to positive in 4/4, with death supervening within 3 mo of study in 3 cases and refractory leukemia developing in the other. Whole blood histamine values were highest in untreated chronic phase CML (1559 ± 306 ng/ml, mean ± SE), while accelerated /acute phase values were comparable to treated chronic phase (513 ±131 and 521 ± 101 ng/ml, respectively). Whole blood histamine and BP in CML relate closely to impending acute blastic transformation. The potential role of basophils and histamine in myelopoiesis and acute leukemic transformation of CML is discussed.
