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History of Leukemia: Diagnosis and Treatment from Beginning to Now

Sahar Mehranfar, Sirous Zeinali, Rana Hosseini, Mozhdeh Mohammadian, Abolfazl Akbarzadeh, Abbasali Hossein Pour Feizi

In 1845, leukemia was known as a systemic illness; and it was more than 100 years later that the first report of a significant therapy for leukemia was published in 1948. Leukemia was known as a multifactorial disease rather than a single disease till 1900. In 1965, less than 1% of children with acute leukemia were predictable to have long-term survivors; today, approximately 80% of children and adolescents with acute lymphoblastic leukemia are cured, these achievements are due to the cooperative effort of researchers and physicians in the field. Despite this success, leukemia is still the leading cause of death globally. This review aims to elucidate the history of leukemia from the beginning of the 19th century when scientists defined unusual disorders of the blood cells, till present. Additionally, we tried to discuss the history of the diagnosis and treatment of leukemia with particular emphasis on acute leukemia. [GMJ.2017;6(1):12-22]

Lymphoblastic Leukemia; Cancer; Myeloid Leukemia

Jahedi M, Shamsasenjan K, Sanaat Z, Aliparasti M, Almasi S, Mohamadian M, et al. Aberrant Phenotype in Iranian Patients with Acute Myeloid Leukemia. Adv Pharm Bull. 2014;4(1):43.

Einollahi N, Alizadeh S, Dashti N, Nabatchian F, Zare Bovani M, Abbasi S, et al. Serum lipid profile alterations in acute leukemia before and after chemotherapy. Iran Blood Cancer j. 2013;6(1):3-9.

Hooke R. 1665. Micrographia London. 1961.

Piller G. The history of leukemia: a personal perspective. Blood cells. 1992;19(3):521-9; discussion 30-5.

Kampen KR. The discovery and early understanding of leukemia. Leuk Res. 2012;36(1):6-13.

Piller GJ. Leukaemia–a brief historical review from ancient times to 1950. Br J Haematol. 2001;112(2):282-92.

Pasteur L. Louis Pasteur. Société des traités religieux de Lausanne; 1913.

Wintrobe MM. Blood, pure and eloquent. McGraw-Hill; 1980.

Hewson W, Falconar M. Experimental inquiries. J. Johnson; 1774.

Degos L, Hirst W, Buggins A, Mufti G, Mercier E, Branger B, et al. John Hughes Bennett, Rudolph Virchow... and Alfred Donne: the first description of leukemia. Hem J. 2000;2(1):1-.

Lichtman MA. Battling the hematological malignancies: the 200 years' war. Oncologist. 2008;13(2):126-38.

Seufert W, Seufert WD. The recognition of leukemia as a systemic disease. J Hist Med Allied Sci. 1982;37(1):34-50.

Ehrlich P. Beiträge zur Kenntniss der Anilinfärbungen und ihrer Verwendung in der mikroskopischen Technik. Archiv für mikroskopische Anatomie. 1877;13(1):263-77.

Duplay M. Observation d’une altération très grande du sang. Arch Gen Med, Paris, II. 1834;6:223-34.

Velpeau A. Sur la resorption du pusaet sur l’alteration du sang dans les maladies clinique de persection nenemant. Premier observation. Rév Méd. 1827;2:216.

Delasiauve LJF. J Med Mentale. 1868.

Virchow R. Zur pathologischen Physiologie des Bluts. Virchows Arch Pathol Anat Physiol Klin Med.1847;1(3):547-63.

Andral G. Essai d'hématologie pathologique.14th ed. Paris, Masson; 1843.

Holt LE. The diseases of infancy and childhood. D. Appleton & Company; 1897.

Zech NH, Shkumatov A, Koestenbauer S. The magic behind stem cells. J Assist Reprod Genet. 2007;24(6):208-14.

Rolleston H. The history of haematology. J R Soc Med. 1934;27(9):1161.

Addison W. Experimental and practical researches on inflammation, and on the origin and nature of tubercles of the lungs. Churchill; 1843.

Virchow R. Gesammelte abhandlungen zur wissenschaftlichen medicin. Meidinger; 1856.

Piller GJ. The history and presentation of leukaemia 1845-1960.UK, NY: Doctoral dissertation, Open University; 1992.

Hajdu SI. The discovery of blood cells. Ann Clin Lab Sci. 2003;33(2):237-8.

Bennett JH. On the employment of the microscope in medical studies. 1841.

Bennett JH. Case of Hypertrophy of the Spleen and Liver: In which Death Took Place from Suppuration of the Blood. Stark and Comp; 1845.

Neumann E. Ein neuer fall von Leukamie mit erkrankung des knochenmarks. Arch Heilkunde. 1872;13:502-8.

Neumann E. Ueber myelogene leukämie. 1878.

Friedreich N. Ein neuer fall von leukämie. Virchows Arch. 1857;12(1):37-58.

Virchow R. Normal and pathological new-formation. Cell Pathol trans. 1858.

Wintrobe MM. Clinical hematology. Acad Med. 1962;37(1):78.

Osler W. An account of certain organisms occurring in the liquor sanguinis. R Soc Lond. 1873;22(148-155):391-8.

Bizzozero J. Ueber einen neuen Formbestandtheil des Blutes und dessen Rolle bei der Thrombose und der Blutgerinnung. Archiv für pathologische Anatomie und Physiologie und für klinische Medicin. 1882;90(2):261-332.

Dewees WP. A treatise on the physical and medical treatment of children. Blanchard and Lea; 1858.

Lippman HS. A morphologic and quantitative study of the blood corpuscles in the new-born period. Am J Dis Child. 1924;27(5):473-526.

Hersh EM, Bodey GP, Nies BA, Freireich EJ. Causes of death in acute leukemia: A ten-year study of 414 patients from 1954-1963. Jama. 1965;193(2):105-9.

Burchenal JH, Murphy M, Ellison R, Sykes M, Tan T, Leone L, et al. Clinical evaluation of a new antimetabolite, 6-mercaptopurine, in the treatment of leukemia and allied diseases. Blood. 1953;8(11):965-99.

Pearson HA. History of pediatric hematology oncology. Pediatr Res. 2002;52(6):979-92.

Burchenal JH. Long‐term survivors in acute leukemia and Burkitt's tumor. Cancer. 1968;21(4):595-9.

Kastner P, Dupuis A, Gaub M-P, Herbrecht R, Lutz P, Chan S. Function of Ikaros as a tumor suppressor in B cell acute lymphoblastic leukemia. Am J Blood Res. 2013;3(1):1-13.

Bairey O, Vanichkin A, Shpilberg O. Arsenic‐trioxide‐induced apoptosis of chronic lymphocytic leukemia cells. Int J Lab Hematol. 2010;32(1p1):e77-e85.

Böttger H. Handelsrecht, Strafrecht und das gerichtliche Verfahren. Die Apotheken—Gesetzgebung des deutschen Reiches und der Einzelstaaten auf der Grundlage der allgemeinen politischen, Handels-und Gewerbegesetzgebung dargestellt. Springer; 1880. p. 128-92.

Gilman A, Philips FS. The biological actions and therapeutic applications of the B-chloroethyl amines and sulfides. Science. 1946;103(2675):409-36.

Rhoads CP. Nitrogen mustards in the treatment of neoplastic disease: Official statement. J Am Med Assoc. 1946;131(8):656-8.

Iacobucci I, Storlazzi CT, Cilloni D, Lonetti A, Ottaviani E, Soverini S, et al. Identification and molecular characterization of recurrent genomic deletions on 7p12 in the IKZF1 gene in a large cohort of BCR-ABL1–positive acute lymphoblastic leukemia patients: on behalf of Gruppo Italiano Malattie Ematologiche dell'Adulto Acute Leukemia Working Party. Blood. 2009;114(10):2159-67.

Wilkinson J, Fletcher F. Effectof β-Chlorethylamine Hydrochlorides in leukemia, Hodgkin's Diseases, and Polycythemia Vera: report on eighteen cases. Lancet. 1947;250(6476):540-5.

Freireich EJ, Wiernik PH, Steensma DP. The leukemias: a half-century of discovery. J Clin Oncol. 2014;32(31):3463-9.

Blundell J. The after management of floodings and on transfusion. Lancet. 1828;13:673.

Senn N. Case of Splenomedullary Leukaemia Successfully Treated by the Use of the Roentgen Ray. 1903.

Frei 3rd E, Karon M, Levin RH, Freireich EJ, Taylor RJ, Hananian J, et al. The effectiveness of combinations of antileukemic agents in inducing and maintaining remission in children with acute leukemia. Blood. 1965;26(5):642.

Pfiffner J, Binkley S, Bloom E, Brown R, Bird O, Emmett A, et al. Isolation of the antianemia factor (vitamin Bc) in crystalline form from liver. Science. 1943;97(2522):404-5.

Stokstad E. Some properties of a growth factor for Lactobacillus casei. J Biol Chem. 1943;149(2):573-4.

Leuchtenberger C, Lewisohn R, Laszlo D, Leuchtenberger R. “Folic Acid” a Tumor Growth Inhibitor. Exp Biol Med. 1944;55(3):204-5.

SubbaRow Y. Folic acid. Academy; 1946.

Farber S, Diamond LK, Mercer RD, Sylvester Jr RF, Wolff JA. Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid (aminopterin). N Engl J Med. 1948;238(23):787-93.

Farber S, Schwachman H, Toch R, Downing V, Kennedy BH, Hyde J, editors. The effect of ACTH in acute leukemia in childhood. First Clinical ACTH Conference New York: Blakiston; 1950.

Pearson O, Eliel L, Rawson RW, Dobriner K, Rhoads C. Acth‐and cortisone‐induced regression of lymphoid tumors in man. A preliminary report. Cancer. 1949;2(6):943-5.

Elion GB, Burgi E, Hitchings GH. Studies on condensed pyrimidine systems. IX. The synthesis of some 6-substituted purines. J Am Chem Soc. 1952;74(2):411-4.

Elion GB, Hitchings GH, Vanderwerff H. Antagonists of nucleic acid derivatives VI. Purines. J Biol Chem. 1951;192(2):505-18.

Freireich EJ. The history of leukemia therapy—a personal journey. Clin Lymphoma Myeloma Leuk. 2012;12(6):386-92.

Frei E, 3rd, Holland JF, Schneiderman MA, Pinkel D, Selkirk G, Freireich EJ, et al. A comparative study of two regimens of combination chemotherapy in acute leukemia. Blood. 1958;13(12):1126-48.

Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, et al. Chimeric antigen receptor–modified T cells for acute lymphoid leukemia. N Engl J Med . 2013;368(16):1509-18.

Möricke A, Zimmermann M, Reiter A, Henze G, Schrauder A, Gadner H, et al. Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000. Leukemia. 2010;24(2):265-84.

Thomas DA, O'Brien S, Faderl S, Garcia-Manero G, Ferrajoli A, Wierda W, et al. Chemoimmunotherapy With a Modified Hyper-CVADand Rituximab Regimen Improves Outcome in De Novo Philadelphia Chromosome–Negative Precursor B-Lineage Acute Lymphoblastic Leukemia. J Clin Oncol. 2010:JCO. 2009.26. 9456.

Druker BJ, Lydon NB. Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukemia. J Clin Invest. 2000;105(1):3.

Dobbelstein M, Moll U. Targeting tumour-supportive cellular machineries in anticancer drug development. Nat Rev Drug Discov. 2014;13(3):179-96.

Druker B, Talpaz M, Resta D, Peng B, Buchdunger E, Ford J, et al., editors. Clinical efficacy and safety of an ABL specific tyrosine kinase inhibitor as targeted therapy for chronic myelogenous leukemia. Blood; 1999: AMER SOC HEMATOLOGY 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA.

Greaves M, Maley CC. Clonal evolution in cancer. Nature. 2012;481(7381):306-13.

Schultz KR, Bowman WP, Aledo A, Slayton WB, Sather H, Devidas M, et al. Improved early event-free survival with imatinib in Philadelphia chromosome–positive acute lymphoblastic leukemia: A children's oncology group study. J Clin Oncol. 2009;27(31):5175-81.

Leung W, Campana D, Yang J, Pei D, Coustan-Smith E, Gan K, et al. High success rate of hematopoietic cell transplantation regardless of donor source in children with very high-risk leukemia. Blood. 2011;118(2):223-30.

Sievers EL, Larson RA, Stadtmauer EA, Estey E, Löwenberg B, Dombret H, et al. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol. 2001;19(13):3244-54.

Mohammadian M, Shamsasenjan K, Lotfi Nezhad P, Talebi M, Jahedi M, Nickkhah H. Mesenchymal stem cells: new aspect in cell-based regenerative therapy. Adv Pharm Bull. 2013;3(2):433-7.

Dick D. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3:730-7.


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