The smoldering myeloid leukemic states: clinical and biologic features.

T H E CHRONIC myeloproliferative disorders provide a clinical setting for evaluating the evolution of relatively benign to frankly malignant neoplasia. Controversy exists regarding the categorization of patients with clonal myeloid diseases whose marrow myelodysplastic features and clinical courses are intermediate between those of the relatively clearly defined entities of acute and chronic myeloid leukemia (AML, CML). Although patients with these intermediately paced disorders have a propensity to progress to an acute blastic transformation phase resembling AML, the incidence of such transformation is highly variable. Morphological descriptions of marrow hemopoietic cells have been used to attempt to distinguish these somewhat disparate groups of patients. However, definitive differences in their natural histories have not been demonstrated clearly. A wide variety of terms has been used to describe these patients including preleukemia (or hemopoietic dysplasia), refractory anemia with excess of myeloblasts (RAEM), subacute myeloid leukemia, oligoleukemia, odo-leukemia, and myelodysplastic and dysmyelopoietic syndromes. #{176} Recently, increased numbers of these patients are being recognized following cytotoxic chemotherapy alone and in combination with radiotherapy for a variety of malignant diseases. ’3 Part ofthe difficulty surrounding the nature of these disorders relates to inexact and differing definitions of certain basic terms such as “leukemia” and “blasts.” In this review, the term smoldering myeloid leukemic states (SMLS) has been used as an inclusive nonmorphological description of these patients encompassed by the terms preleukemia, RAEM, and subacute myeloid leukemia, since it emphasizes the relatively indolent pace characterizing most of these individuals. A thesis of this article is that biologic rather than morphological characteristics of the marrow cells appear to more precisely describe the natural history of these patients. The clinical and biologic nature of these disorders will be examined with particular emphasis on determining whether the morphological features that have been used for diagnostic distinctions depict real differences regarding clinical outcome. Clinical characteristics distinguishing these patients from AML, CML, and benign cytopenias will be discussed. Biologic features of the SMLS, such as in vitro marrow cell myeloid growth and differentiation patterns and cytogenetics will be evaluated as adjunctive methods for assessing diagnosis, prognosis, evolution, and pathogenetic mechanisms underlying this spectrum of disorders. An issue of major controversy is whether the term preleukemia should only be used retrospectively (i.e., after the patients evolve into acute leukemia) or whether these patients are, in fact, already leukemic during their “preleukemic” phase. The critically reviewed data suggest that the patients considered to have SMLS already have a malignant clone established.