Response of Polycythemia to Treatment with a New Agent: Hydroxyurea.

West, Wilk O.

doi:10.7326/0003-4819-72-5-795_3

Cited by 6 publications

(3 citation statements)

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“…Historically, treatment in MPN was documented more in PV and included skeletal radiation therapy (1917) [86], acetylphenylhydrazine (1918) [87], potassium arsenite (1933) [88], P-32 (1940) [89], lead acetate (1942) [90], nitrogen mustard (1950) [91], triethylene melamine (1952) [92], pyrimethamine (1954) [93], busulfan (1958) [94], 6-mercaptopurine (1962) [95], pipobroman (1962) [96], uracil mustard (1964) [97], chlorambucil (1965) [98], and dapsone (1966) [99]. Hydroxyurea and melphalan were added to the list in 1970 [100,101].…”

Section: Background Information On Treatment In Myeloproliferative Nementioning

confidence: 99%

Myeloproliferative neoplasms: A decade of discoveries and treatment advances

2015

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Myeloproliferative neoplasms (MPN) are clonal stem cell diseases, first conceptualized in 1951 by William Dameshek, and historically included chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). In 1960, Nowell and Hungerford discovered an invariable association between the Philadelphia chromosome (subsequently shown to harbor the causal BCR‐ABL1 mutation) and CML; accordingly, the term MPN is primarily reserved for PV, ET, and PMF, although it includes other related clinicopathologic entities, according to the World Health Organization (WHO) classification system. In 2005, William Vainchenker and others described a Janus kinase 2 mutation (JAK2V617F) in MPN and this was followed by a series of additional descriptions of mutations that directly or indirectly activate JAK‐STAT: JAK2 exon 12, myeloproliferative leukemia virus oncogene (MPL) and calreticulin (CALR) mutations. The discovery of these, mostly mutually exclusive, “driver” mutations has contributed to revisions of the WHO diagnostic criteria and risk stratification in MPN. Mutations other than JAK2, CALR and MPL have also been described in MPN and shown to provide additional prognostic information. From the standpoint of treatment, over the last 50 years, Louis Wasserman from the Unites States and Tiziano Barbui from Italy had skillfully organized and led a number of important clinical trials, whose results form the basis for current treatment strategies in MPN. More recently, allogeneic stem cell transplant, as a potentially curative treatment modality, and JAK inhibitors, as palliative drugs, have been added to the overall therapeutic armamentarium in myelofibrosis. In the current review, I will summarize the important advances made in the last 10 years regarding the science and practice of MPN. Am. J. Hematol. 91:50–58, 2016. © 2015 Wiley Periodicals, Inc.

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Section: Background Information On Treatment In Myeloproliferative Nementioning

confidence: 99%

Myeloproliferative neoplasms: A decade of discoveries and treatment advances

2015

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“…127 Hydroxyurea and melphalan were added to the list in 1970. 128,129 However, immediately before the initiation of the PVSG clinical trials, the two most frequently used therapeutic modalities were phlebotomy and intravenous P-32. Phlebotomy has been the cornerstone of treatment in PV for over a century.…”

Section: Treatment Of Polycythemia Vera Prior To the Pvsg Studiesmentioning

confidence: 99%

The history of myeloproliferative disorders: before and after Dameshek

Tefferi

2007

Leukemia

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In 1951, William Dameshek described the concept of 'myeloproliferative disorders (MPDs)' by grouping together chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and erythroleukemia; he reasoned that a self-perpetuating trilineage myeloproliferation underlined their pathogenesis. Pre-Dameshek luminaries who laid the foundation for this unifying concept include Bennett, Virchow, Heuck, Vaquez, Osler, Di Guglielmo and Epstein. In 1960, Nowell and Hungerford discovered the Philadelphia (Ph) chromosome in CML. In 1967, Fialkow and colleagues used X-linked polymorphisms to establish CML as a clonal stem cell disease. Also in 1967, the PV Study Group was summoned by Louis Wasserman to study the natural history of PV and conduct large-scale clinical trials. In 1972, Janet Rowley deciphered the Ph chromosome as a reciprocal translocation between chromosomes 9 and 22, thus paving the way for its subsequent characterization as an oncogenic BCR-ABL mutation. In 1996, Brian Druker discovered imatinib-a small molecule ABL inhibitor with exceptional therapeutic activity in CML. In 2005, a gain-of-function JAK2 mutation (JAK2V617F) was described in BCR-ABL-negative MPDs, raising the prospect of a CML-like treatment strategy in PV, ET and PMF. The current review considers these and other landmark events in the history of MPDs.

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“…The pre-PVSG era included mostly ineffective and potentially detrimental treatment modalities, save for therapeutic phlebotomy [15,16], including skeletal radiation therapy (1917) [17], acetylphenylhydrazine (1918) [18], potassium arsenite (1933) [19], radiophosphorus (P32) (1940) [20], lead acetate (1942) [21], nitrogen mustard (1950) [22], triethylene melamine (1952) [23], pyrimethamine (1954) [24], busulfan (1958) [25], 6-mercaptopurine (1962) [26], pipobroman (1962) [27], uracil mustard (1964) [28], chlorambucil (1965) [29], and dapsone (1966) [30]. Hydroxyurea (HU) and melphalan were added to the list in 1970 [31,32]. Early retrospective studies in PV had suggested a superior median survival with myelosuppressive therapy as opposed to either no treatment (median survival ∼18 months) or treatment with phlebotomy alone (median survival close to 4 years) [33], while at the same time raised concerns regarding myelosuppressive drug leukemogenecity [34,35].…”

Section: Historical Preludementioning

confidence: 99%

Polycythemia vera: historical oversights, diagnostic details, and therapeutic views

2021

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Polycythemia vera (PV) is a relatively indolent myeloid neoplasm with median survival that exceeds 35 years in young patients, but its natural history might be interrupted by thrombotic, fibrotic, or leukemic events, with respective 20-year rates of 26%, 16%, and 4%. Current treatment strategies in PV have not been shown to prolong survival or lessen the risk of leukemic or fibrotic progression and instead are directed at preventing thrombotic complications. In the latter regard, two risk categories are considered: high (age >60 years or thrombosis history) and low (absence of both risk factors). All patients require phlebotomy to keep hematocrit below 45% and once-daily low-dose aspirin, in the absence of contraindications. Cytoreductive therapy is recommended for high-risk or symptomatic low-risk disease; our first-line drug of choice in this regard is hydroxyurea but we consider pegylated interferon as an alternative in certain situations, including in young women of reproductive age, in patients manifesting intolerance or resistance to hydroxyurea therapy, and in situations where treatment is indicated for curbing phlebotomy requirement rather than preventing thrombosis. Additional treatment options include busulfan and ruxolitinib; the former is preferred in older patients and the latter in the presence of symptoms reminiscent of post-PV myelofibrosis or protracted pruritus. Our drug choices reflect our appreciation for long-term track record of safety, evidence for reduction of thrombosis risk, and broader suppression of myeloproliferation. Controlled studies are needed to clarify the added value of twice- vs once-daily aspirin dosing and direct oral anticoagulants. In this invited review, we discuss our current approach to diagnosis, prognostication, and treatment of PV in general, as well as during specific situations, including pregnancy and splanchnic vein thrombosis.

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Response of Polycythemia to Treatment with a New Agent: Hydroxyurea.

Cited by 6 publications

References 0 publications

Myeloproliferative neoplasms: A decade of discoveries and treatment advances

Myeloproliferative neoplasms: A decade of discoveries and treatment advances

The history of myeloproliferative disorders: before and after Dameshek

Polycythemia vera: historical oversights, diagnostic details, and therapeutic views

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