Review Article
HISTORY OF PEDIATRIC O N C O L O G Y
JamesA. 'wolff, MD Pediatr Hematol Oncol Downloaded from informahealthcare.com by Chinese University of Hong Kong on 12/26/14 For personal use only.
0 Professor, Emeritus, College of Physicians and Surgeons, Columbia University, New York, New York, USA
0 Pediatric oncology emerged as a subspeciality in the United States of America following the observations in 1948 of Farber and his associates of the benefits of chemotherapy for acute leukemia. The establishment of national cooperative chemotherapy groups furthered its development. More recently, the subspecialily has been recognized by the American Board of Pediatrics. Even more recently, training programs for the subspecialty have been given accreditation. Parallel to development of the specialty in the United States has been a similar evolution of pediatric oncology in Europe.
KEY WORDS: hematology, oncolofl, pediatrics
In the United States of America, pediatric oncology gradually developed as a subspecialty in the years following the end of World War 11. Up to that time, children with cancer were treated by general practitioners and pediatricians, with the assistance of surgeons, pathologists, and therapeutic radiologists when indicated. With the exception of treatment of leukemia, drug therapy virtually was not used. Chemical agents, given occasionally to children with leukemia, were nonspecific and highly toxic. Transfusion therapy was used only for profound anemia. During World War I , mustard gas was used first by the German army. In addition to its vescicant action, the gas caused overwhelming infection in soldiers exposed to it. Moreover, leukopenia rather than leukocytosis was found to characterize the infections. At autopsy, lymphoid atrophy was noted. During World War 11, studies were conducted to determine the toxicity of sulfur mustard. Nitrogen mustard, given intravenously to animals, produced severe destruction of the bone marrow. Gilman' reported regression of lymphoid masses in mice. Shortly after, studies carried out in adult humans reported regression of lymphoid masses in lymphoma and leukemia.' This study was the first to document a benefit from chemotherapy in human cancer. At about the same time, Sidney Farber, a pediatric pathologist at Boston Children's Hospital, prompted by a report that folic acid stimulates the growth of leukemic cells in mice, evaluated the effect of folic acid on childhood leukemia. His studies were interpreted to show stimulation of the leukemia.
Pediatric Hematology and Oncology, 8:89-91, 1991 Copyniht @ 1991 by Hemisphere Publishing Corporation
89
Pediatr Hematol Oncol Downloaded from informahealthcare.com by Chinese University of Hong Kong on 12/26/14 For personal use only.
90
1. A. WOLFF
A number of compounds capable of antagonizing the action of folic acid were later synthesized at Lederle Laboratories. Farber administered some of these compounds to children with leukemia. In 1948 he and his co-workers reported that 4-aminopteroylglutamicacid (aminopterin) produced temporary remissions of acute childhood leukemia.’ This report, the first to demonstrate successful use of chemotherapy in children with leukemia, was followed by increasing numbers of reports of other compounds with therapeutic effect in both childhood leukemia and in children with solid tumors. By 1954 steroid hormones and purine analogues (particularly, 6mercaptopurine) had been shown to be beneficial when administered to children with acute leukemia. In the mid1950s Farber began to report at national meetings on the beneficial effects of chemotherapy given to children with solid tumors of childhood, especially actinomycin-D for advanced Wilms’ tumor, even though these trials were not published until a decade later. At the same time, investigators at M.D. Anderson Hospital in Houston, Texas, reported successful treatment of Wilms’ tumor with another chemical agent, the alkaloid, vincristine. In the 1950s and early 1960s, chemotherapy consisted of single agents in Phase I or Phase I1 clinical trials. As a result of the establishment of cooperative groups, Phase I11 studies with multiple drugs were begun. In 1955 Children’s Cancer Study Group A (CCSGA) was formed, with Dr. Joseph Burchenal of Memorial Hospital in New York City as its first chairman. Subsequent chairpersons have been Dr. Lois Murphy (1959-1965), Dr. John Hartmann (1965-1968) and Dr. Denman Hammond (1968 to the present). At first, investigations of the group, now known as Children’s Cancer Study Group (CCSG), concerned acute leukemia only. In the early 1960s chemotherapeutic trials for histiocytosis X, neuroblastoma, and Wilms’ tumor were started by CCSG. The group today conducts over 50 concurrent studies for leukemia and solid tumors. According to Robert E. Weiner, assistant to the CCSG chairman, CCSG investigators care for more than one-half of the children with cancer who are newly diagnosed in North America each year. Largely through the leadership of Dr. Giulio D’Angio, the first Intergroup Study Committee (the National Wilms’ Tumor Study Committee) was formed. D’Angio was appointed chairman and has continued in this position to the present. Two other pediatric cooperative groups were formed shortly after CCSG was estabIished. These were the Southwest Oncology Group (SWOG) and Cooperative Acute Leukemia Group B (CALGB). In 1979 CALGB (which included adult oncologists) merged with SWOG. In 1986 the pediatric members withdrew and formed the Pediatric Oncology Group (POG). Forty institutions currently are represented, according to Dr. Teresa Vetti, POG chairwoman.
Pediatr Hematol Oncol Downloaded from informahealthcare.com by Chinese University of Hong Kong on 12/26/14 For personal use only.
HISTORY OF PEDIATRIC ONCOLOGY
91
Efforts were begun in 1972 to form a subspeciality board in hematology and oncology under the American Board of Pediatrics. These efforts culminated in 1974 in the first examination for this subboard. The examination for certification was given every 2 years until 1984,when the cycle was changed to every 3 years. At present, 963 individuals have been certified. Accredited programs for the training of pediatric hematologistsoncologists were required first in 1987.There are now 55 accredited programs in the United States. Unlike the separation of subspecialty boards by the American Board of Internal Medicine, which offers certification in hematology and oncology separately, the American Board of Pediatrics offers only a combined examination for hematology and oncology. In 1981 the American Society of Pediatric HematologylOncology (ASPHO) was established. During its first year of existence there were 50 members. The membership since then has expanded to 820 reports Dr. Carl Pochedly, ASPHO secretary. The official journal of the society is the American Journal of Hmtology/Oncology. Development of pediatric oncology in Europe paralleled that in the United States of America. A small group of pediatricians, surgeons, pathologists, and others met at the Pediatric Department of the Institut Gustav-Roussy in Villejuif/Paris in 1967 to form the Pediatric Oncology Club. Two years later in Madrid the club was transformed to the Societi Internationale d’oncologie Pediatrique (SIOP). Initially the society was mainly clinically oriented, promoting active involvement in clinical studies and trials, such as medulloblastoma, nephroblastoma, and rhabdomyosarcoma. In recent years, more basic scientific aspects of pediatric oncology have been featured at the annual meeting.‘
REFERENCES 1 . Gilman A, and Philips FS. The biologic actions and therapeutic applications of the &chlorethyl amines and sulfates. Scimc. 1946; 103:409. 2. Goodman LS, Wintrobe MM, Dameskek W, Goodman MJ, Gilman A, and McLennan MT. Nitrogen mustard therapy.JAMA. 1946;132:126-132. 3. Farber S, Diamond LK, Mercer RD, Sylvester RF, Wolff JA. Temporary remissions in acute leukemia in children prolonged by folic acid antagonist, 4-aminopteroyl glutamic acid (aminopterin). N Engl J MGd. i94a;23a:78. 4. An Introduction to SIOP. Published by SIOP with sponsorship from the Norwegian Cancer Society, 1990.
Rccciucd October 22, 1990 Acccpted Ociober 21, 1990 Addrcrs correspondmc to James A . U61& 518 Isle o j CaF; Fort La&&,
Flmido 33301 USA.
HISTORY OF PEDIATRIC O N C O L O G Y
JamesA. 'wolff, MD Pediatr Hematol Oncol Downloaded from informahealthcare.com by Chinese University of Hong Kong on 12/26/14 For personal use only.
0 Professor, Emeritus, College of Physicians and Surgeons, Columbia University, New York, New York, USA
0 Pediatric oncology emerged as a subspeciality in the United States of America following the observations in 1948 of Farber and his associates of the benefits of chemotherapy for acute leukemia. The establishment of national cooperative chemotherapy groups furthered its development. More recently, the subspecialily has been recognized by the American Board of Pediatrics. Even more recently, training programs for the subspecialty have been given accreditation. Parallel to development of the specialty in the United States has been a similar evolution of pediatric oncology in Europe.
KEY WORDS: hematology, oncolofl, pediatrics
In the United States of America, pediatric oncology gradually developed as a subspecialty in the years following the end of World War 11. Up to that time, children with cancer were treated by general practitioners and pediatricians, with the assistance of surgeons, pathologists, and therapeutic radiologists when indicated. With the exception of treatment of leukemia, drug therapy virtually was not used. Chemical agents, given occasionally to children with leukemia, were nonspecific and highly toxic. Transfusion therapy was used only for profound anemia. During World War I , mustard gas was used first by the German army. In addition to its vescicant action, the gas caused overwhelming infection in soldiers exposed to it. Moreover, leukopenia rather than leukocytosis was found to characterize the infections. At autopsy, lymphoid atrophy was noted. During World War 11, studies were conducted to determine the toxicity of sulfur mustard. Nitrogen mustard, given intravenously to animals, produced severe destruction of the bone marrow. Gilman' reported regression of lymphoid masses in mice. Shortly after, studies carried out in adult humans reported regression of lymphoid masses in lymphoma and leukemia.' This study was the first to document a benefit from chemotherapy in human cancer. At about the same time, Sidney Farber, a pediatric pathologist at Boston Children's Hospital, prompted by a report that folic acid stimulates the growth of leukemic cells in mice, evaluated the effect of folic acid on childhood leukemia. His studies were interpreted to show stimulation of the leukemia.
Pediatric Hematology and Oncology, 8:89-91, 1991 Copyniht @ 1991 by Hemisphere Publishing Corporation
89
Pediatr Hematol Oncol Downloaded from informahealthcare.com by Chinese University of Hong Kong on 12/26/14 For personal use only.
90
1. A. WOLFF
A number of compounds capable of antagonizing the action of folic acid were later synthesized at Lederle Laboratories. Farber administered some of these compounds to children with leukemia. In 1948 he and his co-workers reported that 4-aminopteroylglutamicacid (aminopterin) produced temporary remissions of acute childhood leukemia.’ This report, the first to demonstrate successful use of chemotherapy in children with leukemia, was followed by increasing numbers of reports of other compounds with therapeutic effect in both childhood leukemia and in children with solid tumors. By 1954 steroid hormones and purine analogues (particularly, 6mercaptopurine) had been shown to be beneficial when administered to children with acute leukemia. In the mid1950s Farber began to report at national meetings on the beneficial effects of chemotherapy given to children with solid tumors of childhood, especially actinomycin-D for advanced Wilms’ tumor, even though these trials were not published until a decade later. At the same time, investigators at M.D. Anderson Hospital in Houston, Texas, reported successful treatment of Wilms’ tumor with another chemical agent, the alkaloid, vincristine. In the 1950s and early 1960s, chemotherapy consisted of single agents in Phase I or Phase I1 clinical trials. As a result of the establishment of cooperative groups, Phase I11 studies with multiple drugs were begun. In 1955 Children’s Cancer Study Group A (CCSGA) was formed, with Dr. Joseph Burchenal of Memorial Hospital in New York City as its first chairman. Subsequent chairpersons have been Dr. Lois Murphy (1959-1965), Dr. John Hartmann (1965-1968) and Dr. Denman Hammond (1968 to the present). At first, investigations of the group, now known as Children’s Cancer Study Group (CCSG), concerned acute leukemia only. In the early 1960s chemotherapeutic trials for histiocytosis X, neuroblastoma, and Wilms’ tumor were started by CCSG. The group today conducts over 50 concurrent studies for leukemia and solid tumors. According to Robert E. Weiner, assistant to the CCSG chairman, CCSG investigators care for more than one-half of the children with cancer who are newly diagnosed in North America each year. Largely through the leadership of Dr. Giulio D’Angio, the first Intergroup Study Committee (the National Wilms’ Tumor Study Committee) was formed. D’Angio was appointed chairman and has continued in this position to the present. Two other pediatric cooperative groups were formed shortly after CCSG was estabIished. These were the Southwest Oncology Group (SWOG) and Cooperative Acute Leukemia Group B (CALGB). In 1979 CALGB (which included adult oncologists) merged with SWOG. In 1986 the pediatric members withdrew and formed the Pediatric Oncology Group (POG). Forty institutions currently are represented, according to Dr. Teresa Vetti, POG chairwoman.
Pediatr Hematol Oncol Downloaded from informahealthcare.com by Chinese University of Hong Kong on 12/26/14 For personal use only.
HISTORY OF PEDIATRIC ONCOLOGY
91
Efforts were begun in 1972 to form a subspeciality board in hematology and oncology under the American Board of Pediatrics. These efforts culminated in 1974 in the first examination for this subboard. The examination for certification was given every 2 years until 1984,when the cycle was changed to every 3 years. At present, 963 individuals have been certified. Accredited programs for the training of pediatric hematologistsoncologists were required first in 1987.There are now 55 accredited programs in the United States. Unlike the separation of subspecialty boards by the American Board of Internal Medicine, which offers certification in hematology and oncology separately, the American Board of Pediatrics offers only a combined examination for hematology and oncology. In 1981 the American Society of Pediatric HematologylOncology (ASPHO) was established. During its first year of existence there were 50 members. The membership since then has expanded to 820 reports Dr. Carl Pochedly, ASPHO secretary. The official journal of the society is the American Journal of Hmtology/Oncology. Development of pediatric oncology in Europe paralleled that in the United States of America. A small group of pediatricians, surgeons, pathologists, and others met at the Pediatric Department of the Institut Gustav-Roussy in Villejuif/Paris in 1967 to form the Pediatric Oncology Club. Two years later in Madrid the club was transformed to the Societi Internationale d’oncologie Pediatrique (SIOP). Initially the society was mainly clinically oriented, promoting active involvement in clinical studies and trials, such as medulloblastoma, nephroblastoma, and rhabdomyosarcoma. In recent years, more basic scientific aspects of pediatric oncology have been featured at the annual meeting.‘
REFERENCES 1 . Gilman A, and Philips FS. The biologic actions and therapeutic applications of the &chlorethyl amines and sulfates. Scimc. 1946; 103:409. 2. Goodman LS, Wintrobe MM, Dameskek W, Goodman MJ, Gilman A, and McLennan MT. Nitrogen mustard therapy.JAMA. 1946;132:126-132. 3. Farber S, Diamond LK, Mercer RD, Sylvester RF, Wolff JA. Temporary remissions in acute leukemia in children prolonged by folic acid antagonist, 4-aminopteroyl glutamic acid (aminopterin). N Engl J MGd. i94a;23a:78. 4. An Introduction to SIOP. Published by SIOP with sponsorship from the Norwegian Cancer Society, 1990.
Rccciucd October 22, 1990 Acccpted Ociober 21, 1990 Addrcrs correspondmc to James A . U61& 518 Isle o j CaF; Fort La&&,
Flmido 33301 USA.
