Treatment of Polycythemia Vera With Daraprim

Isaacs, Raphael

doi:10.1001/jama.1954.02950160021006

Cited by 22 publications

(10 citation statements)

References 6 publications

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“…Side-effects have been consistently absent at the correct therapeutic dosage; in this respect our experience resembles that of Isaacs (1954) and of Frost and Jones (1954), and differs greatly from that of Wasserman (1955). It is indeed difficult to understand how such gross toxic effects could be produced at therapeutic dosage.…”

Section: Discussionsupporting

confidence: 72%

“…A detailed study of the pharmacology of pyrimethamine was reported by Schmidt et al (1953), who found that the compound was extremely toxic in high doses, but their data indicated that erythropoietic depression might be obtained at doses low enough to avoid serious effects on other systems. Isaacs (1954) was the first to report the use of pyrimethamine in the treatment of polycythaemia rubra vera. He produced depression of the red-cell count without leucopenia or thrombocytopenia in six patients receiving 12.5-25 mg. daily.…”

mentioning

confidence: 99%

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Pyrimethamine in the Treatment of Polycythaemia Rubra Vera

Pegg¹,

Ford²

1961

BMJ

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Section: Discussionsupporting

confidence: 72%

mentioning

confidence: 99%

Pyrimethamine in the Treatment of Polycythaemia Rubra Vera

Pegg¹,

Ford²

1961

BMJ

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“…1938), an Italian physician scientist, through the Italian group for hematological diseases in adults (GIMEMA) [83][84][85]. 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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“…Pyrimethamine (Daraprim) is an amyl analogue of 2,4-diaminopyrimidine which binds dihydrofolate reductase and acts as a folate antagonist, thus preventing nuclear division (Hamilton et al, 1952). It has been used for the treatment of malaria (Covell, 1953), toxoplasmosis (Grisham, 1962), and polycythaemia vera (Isaacs, 1954). Its efficacy when administered in a once-weekly dose of 25 mg for adults and its tastelessness and relative freedom from toxic allergic reactions, have commended it for wide use as a malarial prophylaxis drug in Nigeria.…”

Section: Discussionmentioning

confidence: 99%

“…The speed of onset of the neurological symptoms suggest that the drug has a direct toxic action on the central nervous system rather than a metabolic one due to folate antagonism. It also suggests that the drug is rapidly and well absorbed from the gastrointestinal tract, though variable absorption of the drug after oral administration has been reported (Covell, 1953;Kaufmann and Caldwell, 1959). Routine measures are effective in treating the acute intoxication-that is, maintenance of a clear airway, suppression of convulsions, and forced diuresis.…”

Section: Commentmentioning

confidence: 99%