S. N. Adil ( Department of Pathology, Aga Khan University Hospital,Karachi. )
M. Usman ( Department of Pathology, Aga Khan University Hospital,Karachi. )
Adult acute lymphoblastic leukemia (ALL) is a significantly different disease when compared to childhood acute lymphoblastic leukemia. In adults it is basically a disease of early adulthood with a higher incidence in males. Etiology as with most other cancers is unknown. However, certain factors are important that include hereditary disorders, high socioeconomic status and radiation exposure.1 Like childhood ALL, adult ALL also comprises of B and T phenotype2, however with the introduction of more intensive therapeutic protocols, there is no difference in these two subtypes as far as the long term prognosis is concerned which was previously poor for T ALL. The main biological difference is presence of Philadelphia chromosome seen only in 3-5% of childhood ALL when compared to adult ALL present in up to 25% of patients. It is probably the most important poor prognostic factor with dismal outcome.3-6 In countries like Pakistan, most of these patients are late presenters carrying bulky disease and often with very high white cell count and that is again an established predictor of poor outcome.
Age is also an important prognostic factor. Many studies reveal continuous decline in complete remission rates from more than 90% in children to 60% or less in patients older than 50 - 60 years and associated with shorter survival. Higher remission rates have been observed for women and survival was always inferior in men. Treatment options include cytotoxic therapy and bone marrow transplantation. Traditionally the treatment of adult ALL follows the same pattern as that of childhood ALL i.e., induction, intensification consolidation, CNS directed therapy and maintenance.7-9 Although initial remission rates were comparable to childhood ALL but long term survival is poor.10 This lead to incorporation of more cytotoxic drugs in the treatment protocols and one such protocol (adult UKALLXII) which is more commonly used in Pakistan is a mixture of around 14-15 drugs.11,12 This translates into high morbidity and mortality due to poor nutritional status, bulky disease and relatively high chances of infections.13 Allogenic bone marrow transplantation is an effective therapy alternative for the treatment of ALL. However, the effectiveness of allogenic transplantation is balanced by a significant mortality because of regimen related toxic effects, graft versus host disease, long term toxicities of preparatory regimens and compromised quality of life. Some of the definite indications of allogenic bone marrow transplantation include patients with Philadelphia chromosome positive disease, refractory disease, relapsed ALL or patients with mature B cell disease. Autologous transplantation in adult ALL is another option but major limitation is the possible contamination of malignant cells in the cryopreserved marrow, even when procured during remission that can contribute to relapse after bone marrow transplant. At present the role of autologous bone marrow transplant is not well established and large studies are required to establish the efficacy of this mode of treatment modality.
In summary, the achievements of treating childhood ALL with 70-80% cure rate do not translate into adult ALL probably due to different biology of the disease along with more induction deaths and high relapse rate. We need more information regarding the intensity of cytotoxic drugs according to risk stratification with role of autologous and allogenic bone marrow transplantation.
1. Cortes JE, Kantarjian HM. Acute lymphoblastic leukemia. A comprehensive review with emphasis on biology and therapy. Cancer 1995;76:2393-2417.
2. Boucheix C, David B, Sebban C, et al. Immunophenotyping of adult acute lymphoblastic leukemia, clinical parameters and outcomes: an analysis of a prospective trial including 562 tested patients (LALA87). Blood 1994;84:1603-12.
3. Hoelzer D, Thiel E, Loffler H, et al. Prognostic factors in a multicenter study for the treatment of acute lymphoblastic leukemia in adults. Blood 1988;71:123-31.
4. Charrin C, Magaud JP, Sebban C, et al. Cytogenetic abnormalities in acute lymphoblastic leukemia: Correlations with hematological findings and outcome: a collaborative study of the Groupe Francais de Cytogenetique Hematologique. Blood 1996;87:3135-42.
5. Baccarini M, Corbelli G, Amadori S, et al. Adolescent and adult acute lymphoblastic leukemia: prognostic features and outcome of therapy: a study of 293 patients. Blood 1982;60:677-83.
6. Bloomfield CD, Alimena G, Goldman AI, et al. Chromosomal abnormalities identify high risk and low risk patients with acute lymphoblastic leukemia. Blood 1986;67: 415-20.
7. Preti A, Kantarjian HM. Management of adult acute lymphoblastic leukemia: present issues and key challenges. J Clin Oncol 1994;12:1323.
8. Larson RA, Dodge RK, Burns CP, et al. A five-drug induction regime with intensive consolidation for adult acute lymphoblastic leukemia: Cancer and leukemia group B study 8811. Blood 1995;85:2025-37.
9. Durrant IJ, Prentice HG, Richards SM. Intensification of treatment for adults with acute lymphoblastic leukemia: results of U.K. Medical Research Council. Randomized trial UK ALL X. Br J Haematol 1997;99:84-92.
10. Omura GA, Raney M. Long term survival in adult acute lymphoblastic leukemia: follow up of a South Eastern Cancer Study Group trial. J Clin Oncol 1985;3:1053-59.
11. Chim CS, Kwong YL. Improved treatment outcome in adult acute lymphoblastic leukemia using the intensive German Protocol, a preliminary report. Hematol Oncol 1997;15:19-26.
12. Annino L, Vegna ML, Camera A, et al. Treatment of adult acute lymphoblastic leukemia: Long term follow up of the GIMEMA ALL0288 randomized study. Blood 2002;99:863-71.
13. Eriksson KM, Cederholm T, Palmblad JEW. Nutrition and acute leukemia in adults. Relation between nutritional status and infection complications during remission induction. Cancer 1998;82:1071-7.