Recommendations of Project 9: Chronic myeloproliferative diseases (MPN)

Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference
Blood. 2009 May 14;113(20):4829-33. Epub 2009 Mar 10
Abstract: European experts were convened to develop a definition of response to treatment in polycythemia vera (PV) and essential thrombocythemia (ET). Clinicohematologic (CH), molecular, and histologic response categories were selected. In ET, CH complete response (CR) was: platelet count less than or equal to 400 x 10(9)/L, no disease-related symptoms, normal spleen size, and white blood cell count less than or equal to 10 x 10(9)/L. Platelet count less than or equal to 600 x 10(9)/L or a decrease greater than 50% was partial response (PR). In PV, CH-CR was: hematocrit less than 45% without phlebotomy, platelet count less than or equal to 400 x 10(9)/L, white blood cell count less than or equal to 10 x 10(9)/L, and no disease-related symptoms. A hematocrit less than 45% without phlebotomy or response in 3 or more of the other criteria was defined as PR. In both ET and in PV, molecular CR was a reduction of any molecular abnormality to undetectable levels. Molecular PR was defined as a reduction more than or equal to 50% in patients with less than 50% mutant allele burden, or a reduction more than or equal to 25% in patients with more than 50% mutant allele burden. Bone marrow histologic response in ET was judged on megakaryocyte hyperplasia while on cellularity and reticulin fibrosis in PV. The combined use of these response definitions should help standardize the design and reporting of clinical studies.

Myeloproliferative neoplasms: contemporary
diagnosis using histology and genetics
Nat. Rev. Clin. Oncol. 6, 627–637 (2009); published online 6 October 2009
Abstract: The 2008 WHO classification system for hematological malignancies is comprehensive and includes histology and genetic information. Myeloid neoplasms are now classified into five categories: acute myeloid leukemia, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), MDS/MPN, and myeloid and/or lymphoid malignancies associated with eosinophilia and PDGFR or FGFR1 rearrangements. MPN are subclassified into eight separate entities: chronic myelogenous leukemia, polycythemia vera, essential thrombocythemia, primary myelofibrosis, systemic mastocytosis, chronic eosinophilic leukemia not otherwise specified, chronic neutrophilic leukemia, and unclassifiable MPN. The diagnosis of chronic myelogenous leukemia requires the presence of BCR-ABL1, while its absence is required for all other MPN. Additional MPN‑associated molecular markers include mutations of JAK2, MPL, TET2 and KIT. JAK2 V617F is found in most patients with polycythemia vera, essential thrombocythemia, or primary myelofibrosis and is, therefore, useful as a clonal marker in those settings. The diagnostic utility of MPL and TET2 mutations is limited by low mutational frequency. In systemic mastocytosis, presence of KIT D816V is expected but not essential for diagnosis. Chronic eosinophilic leukemia not otherwise specified should be distinguished from both PDGFR‑rearranged or FGFR1‑rearranged neoplasms and hypereosinophilic syndrome. We discuss histologic, cytogenetic and molecular changes in MPN and illustrate their integration into practical diagnostic algorithms.

Classification and diagnosis of myeloproliferative neoplasms: The 2008 World Health Organization criteria and point-of-care diagnostic algorithms
Leukemia. 2008 Nov;22(11):2118-9.
The 2001 World Health Organization (WHO) treatise on the classification of hematopoietic tumors lists chronic myeloproliferative diseases (CMPDs) as a subdivision of myeloid neoplasms that includes the four classic myeloproliferative disorders (MPDs)—chronic myelogenous leukemia, polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF)—as well as chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia/hypereosinophilic syndrome (CEL/HES) and 'CMPD, unclassifiable'. In the upcoming 4th edition of the WHO document, due out in 2008, the term 'CMPDs' is replaced by 'myeloproliferative neoplasms (MPNs)', and the MPN category now includes mast cell disease (MCD), in addition to the other subcategories mentioned above. At the same time, however, myeloid neoplasms with molecularly characterized clonal eosinophilia, previously classified under CEL/HES, are now removed from the MPN section and assembled into a new category of their own. The WHO diagnostic criteria for both the classic BCR–ABL-negative MPDs (that is PV, ET and PMF) and CEL/HES have also been revised, in the 2008 edition, by incorporating new information on their molecular pathogenesis. The current review highlights these changes and also provides diagnostic algorithms that are tailored to routine clinical practice.

The 2008 revision of theWorld Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes
Blood. 2009;114:937-951
Recently the World Health Organization (WHO), in collaboration with the European Association for Haematopathology and the Society for Hematopathology, published a revised and updated edition of the WHO Classification of Tumors of the Hematopoietic and Lymphoid Tissues. The 4th edition of the WHO classification incorporates new information that has emerged from scientific and clinical studies in the interval since the publication of the 3rd edition in 2001, and includes new criteria for the recognition of some previously described neoplasms as well as clarification and refinement of the defining criteria for others. It also adds entities—some defined principally by genetic features—that have only recently been characterized. In this paper, the classification of myeloid neoplasms and acute leukemia is highlighted with the aim of
familiarizing hematologists, clinical scientists, and hematopathologists not only with the major changes in the classification but also with the rationale for those changes.

A unified definition of clinical resistance and intolerance to hydroxycarbamide in polycythaemia vera and primary myelofibrosis: results of a European LeukemiaNet (ELN) consensus process
Br J Haematol. 2009 Nov 23. [Epub ahead of print]