The chronic myeloid disorders are a diverse group of malignant bone marrow conditions that are presumed to originate in a mutated multipotential hematopoietic progenitor cell or pluripotential stem cell.¹ This heterogeneous group of disorders shares an initially indolent biological behavior, but has a dangerous propensity to evolve into overt acute leukemia—a troublesome transformational tendency that may be encouraged by the well-intentioned use of genotoxic therapeutic agents. Even in the absence of leukemia, cellular excesses or deficiencies and their consequences can be extremely problematic for patients. The major entities in this broad syndromic group include (1) the myelodysplastic syndromes (MDS, discussed in Chapter 125); (2) chronic myeloid leukemia (CML, discussed in Chapter 127); (3) a poorly delineated cluster of atypical myeloid disorders that includes the myeloproliferative/myelodysplastic overlap syndromes, the disorders of mast cell proliferation (discussed in Chapter 131), the hypereosinophilic syndromes, chronic neutrophilic leukemia, and the all-too-common defiantly unclassifiable cases; and (4) the chronic myeloproliferative disorders (CMPD, Figure 137-1).

The last group, the topic of this chapter, includes three distinct clinicopathologic entities: essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis with myeloid metaplasia (MMM).² The first clear descriptions of ET, PV, and MMM were relatively recent; credit for priority is customarily given to Epstein and Goedel (Vienna, 1934), Vaquez (Paris, 1892), and Heuck (Heidelberg, 1879), respectively.^3–5 Descriptions of plethoric patients extend back to the Hippocratic corpus, however, and it is quite likely that some cases described in this way actually represented PV and were one of the few situations where the Galenic practice of blood letting actually helped.⁶ William Dameshek (Boston, 1951) observed that ET, PV, MMM, and CML share considerable overlapping clinicopathological features, and he classified them together under the diagnostic rubric “CMPD.”⁷

CML is defined by the presence of the Philadelphia chromosome, t(9;22)(q34q11), or its molecular equivalent, the aberrant bcr-abl translocation, and is the most well-defined and clearly characterized of the original CMPD group.⁸ Because of its distinct pathogenesis and treatment, CML is considered separately from the other CMPD, which are diseases for which a unifying pathogenetic lesion has yet to be discovered.⁹ Because the Philadelphia-chromosome-negative CMPD lack diagnostic markers that are as clear and convincing as that which exists for CML, for the time being these non-CML CMPD must remain syndromes of exclusion. Each “aPhiladelphic” entity can be diagnosed only after eliminating the presence of a series of look-alike disorders, and even then some uncertainty may remain, especially for cases with atypical features.

The CMPD can be found lurking under many synonyms in the medical literature. Among other names, ET is also known as essential thrombocytosis, idiopathic thrombocytosis/thrombocythemia, primary thrombocytosis/thrombocythemia, Mortenson syndrome, and Epstein-Goedel syndrome. MMM is also called agnogenic myeloid metaplasia, osteomyelofibrosis, osteomyelosclerosis, idiopathic myelofibrosis, and primary myelofibrosis. PV has been termed polycythemia rubra vera, primary erythrocytosis, Osler-Vaquez disease, myelopathic polycythemia, cryptogenic polycythemia, and true polycythemia. A thorough library archive archeological excavation will uncover even more synonyms, most with extremely limited usage. The terms used in this chapter (ET, MMM, PV) are chosen because they are simple and widely recognized.

Clonality has been assumed to be a hallmark of CMPD since monoclonal hematopoiesis was first demonstrated in the late 1970s via X-linked glucose-6-phosphate dehydrogenase (G6PD) techniques.^10,11 However, this blanket assumption and its implications are now being called into question, especially for ET.^12–14 That such a central pillar of our collective understanding can be shaken at this late date illustrates how much has yet to be learned about this intriguing and perplexing cluster of conditions.