Skip to main content
NCBI home page
Canadian Medical Association Journal logoLink to Canadian Medical Association Journal
. 1981 Jan 15;124(2):129–142.

Childhood acute lymphocytic leukemia: progress and problems in treatment.

W P Bowman
PMCID: PMC1705168  PMID: 7006781

Abstract

Acute lymphocytic leukemia is the most common cancer of childhood. A series of total therapy studies begun in 1962 at St. Jude Children's Research Hospital in Memphis, Tennessee has had a dramatic impact on the survival of children with this disease. These studies have systematically examined various drug combinations and radiation therapy in an effort to cure acute lymphocytic leukemia. As a result, a once uniformly fatal condition is now curable in nearly one half of cases. In addition to improved control of the primary disease, refinements in drug treatment and in supportive care have diminished the frequency of severe infections, which may complicate aggressive therapy. Although the quality of life for the survivors so far appears generally good, treatment-induced toxic effects may impose subtle, though significant, handicaps in some cases. A combination of clinical and laboratory investigations begun in the mid-1970s is beginning to demonstrate a previously unknown heterogeneity among patients with acute lymphocytic leukemia. It is now possible to recognize a substantial minority of patients on the basis of these studies as being at "high risk" for treatment failure. For them, drastic modifications of present programs are being investigated in an attempt to improve their prognosis. For patients lacking high-risk features improvements are still needed, but changes in their treatment must be kept within the framework of what is presently successful and must address the hazard of long-term toxicity.

Full text

PDF
129

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aur R. J., Hustu H. O., Verzosa M. S., Wood A., Simone J. V. Comparison of two methods of preventing central nervous system leukemia. Blood. 1973 Sep;42(3):349–357. [PubMed] [Google Scholar]
  2. Aur R. J., Simone J. V., Hustu H. O., Verzosa M. S. A comparative study of central nervous system irradiation and intensive chemotherapy early in remission of childhood acute lymphocytic leukemia. Cancer. 1972 Feb;29(2):381–391. doi: 10.1002/1097-0142(197202)29:2<381::aid-cncr2820290219>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
  3. Aur R. J., Simone J. V., Verzosa M. S., Hustu H. O., Barker L. F., Pinkel D. P., Rivera G., Dahl G. V., Wood A., Stagner S. Childhood acute lymphocytic leukemia: study VIII. Cancer. 1978 Nov;42(5):2123–2134. doi: 10.1002/1097-0142(197811)42:5<2123::aid-cncr2820420507>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  4. Aur R. J., Simone J., Hustu H. O., Walters T., Borella L., Pratt C., Pinkel D. Central nervous system therapy and combination chemotherapy of childhood lymphocytic leukemia. Blood. 1971 Mar;37(3):272–281. [PubMed] [Google Scholar]
  5. Baum E., Sather H., Nachman J., Seinfeld J., Krivit W., Leikin S., Miller D., Joo P., Hammond D. Relapse rates following cessation of chemotherapy during complete remission of acute lymphocytic leukemia. Med Pediatr Oncol. 1979;7(1):25–34. doi: 10.1002/mpo.2950070106. [DOI] [PubMed] [Google Scholar]
  6. Baumer J. H., Mott M. G. Sex and prognosis in childhood acute lymphoblastic leukaemia. Lancet. 1978 Jul 15;2(8081):128–129. doi: 10.1016/s0140-6736(78)91509-x. [DOI] [PubMed] [Google Scholar]
  7. Bennett J. M., Catovsky D., Daniel M. T., Flandrin G., Galton D. A., Gralnick H. R., Sultan C. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol. 1976 Aug;33(4):451–458. doi: 10.1111/j.1365-2141.1976.tb03563.x. [DOI] [PubMed] [Google Scholar]
  8. Billing R., Rafizadeh B., Drew I., Hartman G., Gale R., Terasaki P. Human B-lymphocyte antigens expressed by lymphocytic and myelocytic leukemia cells. I. Detection by rabbit antisera. J Exp Med. 1976 Jul 1;144(1):167–178. doi: 10.1084/jem.144.1.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bollum F. J. Terminal deoxynucleotidyl transferase as a hematopoietic cell marker. Blood. 1979 Dec;54(6):1203–1215. [PubMed] [Google Scholar]
  10. Borella L., Sen L. T- and B-lymphocytes and lymphoblasts in untreated acute lymphocytic leukemia. Cancer. 1974 Sep;34(3):646–651. doi: 10.1002/1097-0142(197409)34:3<646::aid-cncr2820340322>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  11. Bowman W. P., Melvin S., Mauer A. M. Cell markers in lymphomas and leukemias. Adv Intern Med. 1980;25:391–425. [PubMed] [Google Scholar]
  12. Catovsky D., Cherchi M., Greaves M. F., Janossy G., Pain C., Kay H. E. Acid-phosphatase reaction in acute lymphoblastic leukaemia. Lancet. 1978 Apr 8;1(8067):749–751. doi: 10.1016/s0140-6736(78)90861-9. [DOI] [PubMed] [Google Scholar]
  13. Chessells J. M., Hardisty R. M., Rapson N. T., Greaves M. F. Acute lymphoblastic leukaemia in children: Classification and prognosis. Lancet. 1977 Dec 24;2(8052-8053):1307–1309. doi: 10.1016/s0140-6736(77)90361-0. [DOI] [PubMed] [Google Scholar]
  14. Coleman M. S., Greenwood M. F., Hutton J. J., Holland P., Lampkin B., Krill C., Kastelic J. E. Adenosine deaminase, terminal deoxynucleotidyl transferase (TdT), and cell surface markers in childhood acute leukemia. Blood. 1978 Dec;52(6):1125–1131. [PubMed] [Google Scholar]
  15. Dow L. W., Borella L., Sen L., Aur R. J., George S. L., Mauer A. M., Simone J. V. Initial prognostic factors and lymphoblast-erythrocyte rosette formation in 109 children with acute lymphoblastic leukemia. Blood. 1977 Oct;50(4):671–682. [PubMed] [Google Scholar]
  16. Eiser C. Intellectual abilities among survivors of childhood leukaemia as a function of CNS irradiation. Arch Dis Child. 1978 May;53(5):391–395. doi: 10.1136/adc.53.5.391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Feldman S., Hughes W. T., Daniel C. B. Varicella in children with cancer: Seventy-seven cases. Pediatrics. 1975 Sep;56(3):388–397. [PubMed] [Google Scholar]
  18. Flandrin G., Brouet J. C., Daniel M. T., Preud'homme J. L. Acute leukemia with Burkitt's tumor cells: A study of six cases with special reference to lymphocyte surface markers. Blood. 1975 Feb;45(2):183–188. [PubMed] [Google Scholar]
  19. Freeman A. I., Wang J. J., Sinks L. F. High-dose methotrexate in acute lymphocytic leukemia. Cancer Treat Rep. 1977 Jul;61(4):727–731. [PubMed] [Google Scholar]
  20. George S. L., Aur R. J., Mauer A. M., Simone J. V. A reappraisal of the results of stopping therapy in childhood leukemia. N Engl J Med. 1979 Feb 8;300(6):269–273. doi: 10.1056/NEJM197902083000601. [DOI] [PubMed] [Google Scholar]
  21. Goldstone A. H., McVerry B. A., Janossy G., Walker H. Clonal identification in acute lymphoblastic leukemia. Blood. 1979 May;53(5):892–898. [PubMed] [Google Scholar]
  22. Greaves M., Paxton A., Janossy G., Pain C., Johnson S., Lister T. A. Acute lymphoblastic leukaemia associated antigen. III ALterations in expression during treatment and in relapse. Leuk Res. 1980;4(1):1–14. doi: 10.1016/0145-2126(80)90043-0. [DOI] [PubMed] [Google Scholar]
  23. Green D. M., Freeman A. I., Sather H. N., Sallan S. E., Nesbit M. E., Jr, Cassady J. R., Sinks L. F., Hammond D., Frei E., 3rd Comparison of three methods of central-nervous-system prophylaxis in childhood acute lymphoblastic leukaemia. Lancet. 1980 Jun 28;1(8183):1398–1402. doi: 10.1016/s0140-6736(80)92664-1. [DOI] [PubMed] [Google Scholar]
  24. Haghbin M., Murphy M. L., Tan C. C., Clarkson B. D., Thaler H. T., Passe S., Burchenal J. A long-term clinical follow-up of children with acute lymphoblastic leukemia treated with intensive chemotherapy regimens. Cancer. 1980 Jul 15;46(2):241–252. doi: 10.1002/1097-0142(19800715)46:2<241::aid-cncr2820460203>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  25. Hansen J. A., Clift R. A., Thomas E. D., Buckner C. D., Storb R., Giblett E. R. Transplantation of marrow from an unrelated donor to a patient with acute leukemia. N Engl J Med. 1980 Sep 4;303(10):565–567. doi: 10.1056/NEJM198009043031007. [DOI] [PubMed] [Google Scholar]
  26. Janossy G., Bollum F. J., Bradstock K. F., McMichael A., Rapson N., Greaves M. F. Terminal transferase-positive human bone marrow cells exhibit the antigenic phenotype of common acute lymphoblastic leukemia. J Immunol. 1979 Oct;123(4):1525–1529. [PubMed] [Google Scholar]
  27. Janossy G., Hoffbrand A. V., Greaves M. F., Ganeshaguru K., Pain C., Bradstock K. F., Prentice H. G., Kay H. E., Lister T. A. Terminal transferase enzyme assay and immunological membrane markers in the diagnosis of leukaemia: a multiparameter analysis of 300 cases. Br J Haematol. 1980 Feb;44(2):221–234. doi: 10.1111/j.1365-2141.1980.tb01204.x. [DOI] [PubMed] [Google Scholar]
  28. Judelsohn R. G., Meyers J. D., Ellis R. J., Thomas E. K. Efficacy of zoster immune globulin. Pediatrics. 1974 Apr;53(4):476–480. [PubMed] [Google Scholar]
  29. Kaplan J., Ravindranath Y., Peterson W. D., Jr T and B lymphocyte antigen-positive null cell leukemias. Blood. 1977 Mar;49(3):371–378. [PubMed] [Google Scholar]
  30. Miller D. R. Acute lymphoblastic leukemia. Pediatr Clin North Am. 1980 May;27(2):269–291. doi: 10.1016/s0031-3955(16)33851-2. [DOI] [PubMed] [Google Scholar]
  31. Miller D. R. Prognostic factors in childhood leukemia. J Pediatr. 1975 Oct;87(4):672–676. doi: 10.1016/s0022-3476(75)80889-4. [DOI] [PubMed] [Google Scholar]
  32. Ochs J. J., Berger P., Brecher M. L., Sinks L. F., Kinkel W., Freeman A. I. Computed tomography brain scans in children with acute lymphocytic leukemia receiving methotrexate alone as central nervous system prophylaxis. Cancer. 1980 May 1;45(9):2274–2278. doi: 10.1002/1097-0142(19800501)45:9<2274::aid-cncr2820450909>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  33. Ortega J. A., Nesbit M. E., Jr, Donaldson M. H., Hittle R. E., Weiner J., Karon M., Hammond D. L-Asparaginase, vincristine, and prednisone for induction of first remission in acute lymphocytic leukemia. Cancer Res. 1977 Feb;37(2):535–540. [PubMed] [Google Scholar]
  34. Peylan-Ramu N., Poplack D. G., Pizzo P. A., Adornato B. T., Di Chiro G. Abnormal CT scans of the brain in asymptomatic children with acute lymphocytic leukemia after prophylactic treatment of the central nervous system with radiation and intrathecal chemotherapy. N Engl J Med. 1978 Apr 13;298(15):815–818. doi: 10.1056/NEJM197804132981504. [DOI] [PubMed] [Google Scholar]
  35. Pinkel D., Hernandez K., Borella L., Holton C., Aur R., Samoy G., Pratt C. Drug dosage and remission duration in childhood lymphocytic leukemia. Cancer. 1971 Feb;27(2):247–256. doi: 10.1002/1097-0142(197102)27:2<247::aid-cncr2820270202>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  36. Price R. A., Jamieson P. A. The central nervous system in childhood leukemia. II. Subacute leukoencephalopathy. Cancer. 1975 Feb;35(2):306–318. doi: 10.1002/1097-0142(197502)35:2<306::aid-cncr2820350203>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  37. Reinherz E. L., Nadler L. M., Sallan S. E., Schlossman S. F. Subset derivation of T-cell acute lymphoblastic leukemia in man. J Clin Invest. 1979 Aug;64(2):392–397. doi: 10.1172/JCI109474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Reinherz E. L., Schlossman S. F. Current concepts in immunology: Regulation of the immune response--inducer and suppressor T-lymphocyte subsets in human beings. N Engl J Med. 1980 Aug 14;303(7):370–373. doi: 10.1056/NEJM198008143030704. [DOI] [PubMed] [Google Scholar]
  39. Rivera G., Aur R. J., Dahl G. V., Pratt C. B., Hustu H. O., George S. L., Mauer A. M. Second cessation of therapy in childhood lymphocytic leukemia. Blood. 1979 Jun;53(6):1114–1120. [PubMed] [Google Scholar]
  40. Rivera G., Dahl G. V., Bowman W. P., Avery T. L., Wood A., Aur R. J. VM-26 and cytosine arabinoside combination chemotherapy for initial induction failures in childhood lymphocytic leukemia. Cancer. 1980 Oct 15;46(8):1727–1730. doi: 10.1002/1097-0142(19801015)46:8<1727::aid-cncr2820460804>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  41. Sallan S. E., Camitta B. M., Frei E., 3rd, Furman L., Leavitt P., Bishop Y., Jaffe N. Clinical and cytokinetic aspects of remission induction of childhood acute lymphoblastic leukemia (ALL): addition of an anthracycline to vincristine and prednisone. Med Pediatr Oncol. 1977;3(3):281–287. doi: 10.1002/mpo.2950030310. [DOI] [PubMed] [Google Scholar]
  42. Sallan S. E., Cammita B. M., Cassady J. R., Nathan D. G., Frei E., 3rd Intermittent combination chemotherapy with adriamycin for childhood acute lymphoblastic leukemia: clinical results. Blood. 1978 Mar;51(3):425–433. [PubMed] [Google Scholar]
  43. Sallan S. E., Ritz J., Pesando J., Gelber R., O'Brien C., Hitchcock S., Coral F., Schlossman S. F. Cell surface antigens: prognostic implications in childhood acute lymphoblastic leukemia. Blood. 1980 Mar;55(3):395–402. [PubMed] [Google Scholar]
  44. Shaw M. T. Lack of prognostic value of the periodic acid-Schiff reaction and blast cell size in childhood acute lymphocytic leukemia. Am J Hematol. 1977;2(3):237–243. doi: 10.1002/ajh.2830020305. [DOI] [PubMed] [Google Scholar]
  45. Simone J. V., Aur R. J., Hustu H. O., Verzosa M. S., Pinkel D. Three to ten years after cessation of therapy in children with leukemia. Cancer. 1978 Aug;42(2 Suppl):839–844. doi: 10.1002/1097-0142(197808)42:2+<839::aid-cncr2820420705>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
  46. Simone J. V. Factors that influence haematological remission duration in acute lymphocytic leukaemia. Br J Haematol. 1976 Apr;32(4):465–472. doi: 10.1111/j.1365-2141.1976.tb00950.x. [DOI] [PubMed] [Google Scholar]
  47. Simone J. V., Holland E., Johnson W. Fatalities during remission of childhood leukemia. Blood. 1972 Jun;39(6):759–770. [PubMed] [Google Scholar]
  48. Simone J. V., Verzosa M. S., Rudy J. A. Initial features and prognosis in 363 children with acute lymphocytic leukemia. Cancer. 1975 Dec;36(6):2099–2108. doi: 10.1002/cncr.2820360926. [DOI] [PubMed] [Google Scholar]
  49. Simone J. Acute lymphocytic leukemia in childhood. Semin Hematol. 1974 Jan;11(1):25–39. [PubMed] [Google Scholar]
  50. Thiel E., Rodt H., Netzel D., Huhn D., Wündisch G. F., Hass R. J., Bender-Götze C., Thierfelder S. T-Zell-Antigen positive, E-Rosetten negative akute Lymphoblastenleukämie. Blut. 1978 Jun 20;36(6):363–369. doi: 10.1007/BF01000595. [DOI] [PubMed] [Google Scholar]
  51. Thomas E. D., Buckner C. D., Banaji M., Clift R. A., Fefer A., Flournoy N., Goodell B. W., Hickman R. O., Lerner K. G., Neiman P. E. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. Blood. 1977 Apr;49(4):511–533. [PubMed] [Google Scholar]
  52. Thomas E. D., Sanders J. E., Flournoy N., Johnson F. L., Buckner C. D., Clift R. A., Fefer A., Goodell B. W., Storb R., Weiden P. L. Marrow transplantation for patients with acute lymphoblastic leukemia in remission. Blood. 1979 Aug;54(2):468–476. [PubMed] [Google Scholar]
  53. Vogler L. B., Crist W. M., Bockman D. E., Pearl E. R., Lawton A. R., Cooper M. D. Pre-B-cell leukemia. A new phenotype of childhood lymphoblastic leukemia. N Engl J Med. 1978 Apr 20;298(16):872–878. doi: 10.1056/NEJM197804202981603. [DOI] [PubMed] [Google Scholar]
  54. Wagner V. M., Baehner R. L. Correlation of the FAB morphologic criteria and prognosis in acute lymphocytic leukemia of childhood. Am J Pediatr Hematol Oncol. 1979 Summer;1(2):103–106. [PubMed] [Google Scholar]
  55. Yarbro G. S., Lippman M. E., Johnson G. E., Leventhal B. G. Glucocorticoid receptors in subpopulations of childhood acute lymphocytic leukemia. Cancer Res. 1977 Aug;37(8 Pt 1):2688–2695. [PubMed] [Google Scholar]

Articles from Canadian Medical Association Journal are provided here courtesy of Canadian Medical Association

RESOURCES