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Fifty years of studies of the biology and therapy of childhood leukemia.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kersey, John H. |
| Copyright Year | 1997 |
| Abstract | S using a combination of agents. While the late 1940s and 1950s were characterized by single agent chemotherapy deINCE CHEMOTHERAPY beginnings 50 years ago by Farber and his colleagues, childhood leukemia treatment has been one of the most dramatic cancer success velopment, the 1960s were characterized by the beginning stories. Currently more than 70% of children with acute of investigation into multiagent chemotherapy by several lymphoblastic leukemia are alive and disease-free at 5 years, groups. These groups included the St. Jude Children’s Reprobably making it the most successfully treated of the dissearch Hospital, led by Don Pinkel; the Children’s Cancer seminated human cancers. Certain forms of acute childhood Study Group ‘‘A’’ (the forerunner of the current Childrens leukemia have a 90% probability of cure, yet there is a group Cancer Group); other investigators in Boston; and later the that is still very therapy resistant. Concurrently, in recent Pediatric Oncology Group and investigators elsewhere. The years, our knowledge of the molecular and cellular biology relatively rapid dissemination of results demonstrated the underlying these pediatric leukemias has significantly insuccess of multiagent chemotherapy. This approach quickly creased. We are at the point where we can reasonably answer became the accepted form of treatment with dramatic imthese questions: What are the reasons for childhood leukemia provement in survival. These results are shown in Fig 1. treatment success compared with other cancers? Why are Figure 1 demonstrates the change from the slow improvecertain subgroups of patients therapy-resistant while most ment of outcomes of single agent therapy in the 1950s to a patients have very therapy-sensitive disease? I believe that second dramatic shift in the curve beginning in the mid our knowledge of the molecular genetic abnormalities will 1960s, largely a result of combination chemotherapy. As provide the key to understanding the treatment successes shown in the figure, the results are most dramatic in ALL. and failures in childhood leukemia. Induction chemotherapy with vincristine, prednisone, and Lasparginase, followed by postremission therapy with merCHEMOTHERAPY BEGINNINGS captopurine and methotrexate, quickly became the standard The post World War II era witnessed the availability of childhood ALL treatment. chemical agents with potential value for cancer treatment. In There were at least two additional therapeutic advances the late 1940s, the thinking by investigators such as Sidney responsible for the significant improvement in outcome durFarber, was that agents that antagonize important metaboing the 1970s and 1980s. One important advance was the lites, eg, folic acid, could be useful. One such agent, introduction of presymptomatic therapy for central nervous aminopterin, was found to produce temporary remission in system leukemia. A second advance was the introduction children with acute leukemia. By the early 1950s, an entirely of alternative combinations and timings of chemotherapy different group of agents, ACTH and the glucocorticoids, combining multiple agents. Multiagent chemotherapy studbecame available and showed responses in childhood acute ies, while reported by several groups throughout the world, leukemia. It was apparent, even from these early studies were particularly well organized by the Berlin-Frankfurtwith both folic acid antagonists and glucocorticoids, that Munster groups in Germany and the CCG, which demonchildhood acute leukemias were among the most responsive strated the value of delayed intensification. These of all cancers studied. Despite these responses, these early multiagent, intensive therapy trials have continued to the agents resulted in few cures. As the 1960s, 1970s, and 1980s present; their future probably will be tied to therapies specific progressed, other chemical agents, eg, methotrexate, Lfor genetically defined patient subgroups. asparginase, epipodophylotoxins, vincristine, anthracyclines, oxazaphosphorines, and more recently myeloablative therapy followed by bone marrow transplantation, have become From the University of Minnesota Cancer Center, Minneapolis, MN. important in childhood acute leukemia treatment success. Submitted June 9, 1997; accepted June 16, 1997. J.H.K. is a recipient of an Outstanding Investigator Grant Award COMBINATION CHEMOTHERAPY AS A MAJOR (CA 49721) from the National Cancer Institute. ADVANCE IN CHILDHOOD ACUTE LEUKEMIA Address reprint requests to John H. Kersey, MD, University of Minnesota, Box 806 Mayo, 420 Delaware St SE, Minneapolis, MN Acute Lymphoblastic Leukemia (ALL) 55455. Probably the single most important advance in childhood q 1997 by The American Society of Hematology. 0006-4971/97/9011-0001$3.00/0 acute leukemia treatment is the success with chemotherapy, |
| File Format | PDF HTM / HTML |
| DOI | 10.1182/blood.v92.5.1838.spll2_1838_1838 |
| PubMed reference number | 9373234 |
| Journal | Medline |
| Volume Number | 90 |
| Issue Number | 11 |
| Alternate Webpage(s) | http://www.bloodjournal.org/content/bloodjournal/92/5/1838.1.full.pdf?sso-checked=true |
| Alternate Webpage(s) | http://www.bloodjournal.org/content/bloodjournal/90/11/4243.full.pdf?sso-checked=1 |
| Alternate Webpage(s) | https://doi.org/10.1182/blood.v92.5.1838.spll2_1838_1838 |
| Journal | Blood |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
