Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
Current status of HTLV-I-associated adult T-cell leukemia-lymphoma (ATL) (Meeting abstract).
Lymphoma: the next questions. April 2-4, 1992, Orlando, FL, 1992.. Unique Identifier : AIDSLINE ICDB/93690627 Shimoyama M; Natl. Cancer Center Hosp., Tokyo, Japan
Abstract:
Most ATL are closely associated with HTLV-I, but about 7% were HTLV-I-negative. The diagnostic criteria of HTLV-I+ ATL can be defined as (1) histologically and/or cytologically proven T-cell malignancy (mostly CD4+) and (2) positive antibody to HTLV-I at diagnosis. A multivariate analysis of 854 ATL patients (pts) revealed that 5 factors--advanced PS, high LDH, age 40, increased lesions, and hypercalcemia--were negatively associated with survival. Diagnostic criteria defined 4 clinical subtypes of ATL: (1) smoldering type (ST), (2) chronic type (CT), (3) lymphoma type (LT), and (4) acute type (AT). A total of 818 ATL pts were analyzed by these criteria. MST was 6.2 mo for AT, 10.2 mo for LT, 24.3 mo for CT, and not yet reached for ST. Projected 2- and 4-yr survival rates were, respectively, 16.7 and 5.0% for AT, 21.3 and 5.7% for LT, 52.4 and 26.9% for CT, 77.7 and 62.8% for ST. ATL is difficult to treat successfully with chemotherapy. Complete remission was achieved in 45% of the pts treated with a 2nd generation combination chemotherapy, but 2-yr survival rate was still low (20%). A Phase II study of deoxycoformycin, 5 mg/m2 iv weekly, revealed efficacy with a response rate of 33.3%. Three routes of HTLV-I infection are known: breast milk feeding, blood transfusions, and sexual contact. Incidence of ATL from healthy carriers was calculated to be about 0.1% per year after 40 yr of age. There is a long latent period from infection by HTLV-I. Concurrent occurrence of HTLV-I-associated myelopathy and ATL is rare, indicating that the mechanism of both diseases may be different. HTLV-I has tax/rex gene, known to transactivate cellular genes for lymphokines and their receptors (eg, IL-2 and IL-2 receptor), which were actively expressed in HTLV-I-infected T-lymphocytes, resulting in polyclonal growth of HTLV-I-infected T-lymphocytes by an autocrine mechanism through IL-2 and IL-2 receptor. HTLV-I has not been known to have mutagenic/oncogenic activity. The idea that other mechanisms than HTLV-I may exist in leukemogenesis of ATL is supported by indirect but reliable evidence such as the presence of HTLV-I-negative ATL, and the multistage leukemogenesis hypothesis of ATL, evidenced by clear fitness of Weibull distribution of ATL onset ages. The number of independent leukemogenic events in ATL is calculated to be five; these events may be somatic mutations. Clonal chromosomal abnormalities were found in 96% of 107 cases of ATL, but there were no specific abnormalities, such as trisomy 3 (21%), monosomy X (38%) in female, 14q32 (28%), and del 6q (23%), indicating that these changes may be associated with the multistage leukemogenesis and progression of ATL.
Keywords: Adult Clinical Trials, Phase II Genes, pX Human HTLV-I/GENETICS HTLV-I Infections/TRANSMISSION Leukemia-Lymphoma, T-Cell, Acute, HTLV-I-Associated/DIAGNOSIS/ DRUG THERAPY/GENETICS/*PATHOLOGY Mutation Pentostatin/THERAPEUTIC USE Remission Induction ABSTRACT 930830
M9380839
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
