Long-lasting decrease of CD4+/CD45RA+ T cells in HCL patients after 2-chlorodeoxyadenosine (2-CdA) treatment

• Published in: Leukemia Vol. 13; no. 8; pp. 1254 - 1257
• Main Authors: RASPADORI, D, RONDELLI, D, BIRTOLO, S, LENOCI, M, NARDI, G, SCALIA, G, SESTIGIANI, C, TOZZI, M, MAROTTA, G, LAURIA, F
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.08.1999; Nature Publishing Group
• Subjects: Abnormalities; Adult; Aged; Antigens; Antineoplastic Agents - administration & dosage; Biological and medical sciences; CD4 antigen; CD4 Lymphocyte Count - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD45RA antigen; CD45RO antigen; Cladribine - administration & dosage; Drug toxicity and drugs side effects treatment; Female; Flow cytometry; Hairy cell leukemia; Humans; Isoforms; Leukemia; Leukemia, Hairy Cell - drug therapy; Leukemia, Hairy Cell - immunology; Leukemia, Hairy Cell - pathology; Leukocyte Common Antigens - immunology; Leukocytes; Lymphocytes; Lymphocytes T; Male; Medical sciences; Memory cells; Middle Aged; Patients; Pharmacology. Drug treatments; Pregnancy; Reduction; Time Factors; Toxicity: blood; Antineoplastic agent; Human; Toxicity; Helper cell; Malignant hemopathy; Cell subpopulation; Chemotherapy; Chronic; Immunosuppression; Hairy cell leukemia; Phenotype; Treatment; Lymphoproliferative syndrome; Cladribine; T-Lymphocyte; Purine
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2401476

The CD45RA and CD45RO isoforms of the leukocyte common antigen identify functionally distinct CD4+ T cell subsets: CD4+/CD45RA+ cells which represent a more 'naive' stage of T cell compartment and CD4+/CD45RO+ 'memory' cells. Phenotypic and functional abnormalities in T cell compartment have been frequently reported in patients with hairy cell leukemia (HCL) and, in more recent studies, a significant reduction in the absolute number of CD4+ lymphocytes bearing the CD45RO antigen has also been recorded. In our study we evaluated the CD45RA and CD45RO expression on CD4+ T cells by three-color staining in flow cytometry in 38 HCL patients, 19 untreated and 19 previously treated with 2-chlorodeoxyadenosine (2-CdA), administered at a daily dose of 0.1 mg/kg c.i. for 7 days. In HCL untreated patients, the proportion and the absolute number of CD4+/CD45RA+ and of CD4+/CD45RO+ T cell subsets were similar to normal controls. In contrast, HCL patients at 3-5 years by the end of treatment with 2-CdA, together with a reduction in the absolute number of CD4+ T cells, showed a persistent and significant decrease in the proportion and absolute number of CD4+/CD45RA+ cells as compared with both untreated HCL patients and normal controls (41 +/- 16% vs 57 +/- 14% and vs 65 +/- 7%) (P = 0.01 and 0.0001) and (0.201 +/- 0.137 x 10(9)/l vs 0.549 +/- 0.238 x 10(9)/l and vs 0.696 +/- 0.078 x 10(9)/l) (P = 0.00009 and P = 0.00001). In addition, together with the reduction of CD4+/CD45RA+ cells, we recorded a concomitant increase in the proportion of the CD4+/CD45RO+ cells as compared to untreated HCL patients and normal controls (62 +/- 16% vs 47 +/- 15% and vs 42 +/- 12%) (P = 0.08 and 0.02). These findings may suggest that CD4+/CD45RA+ cells are more sensitive than CD4+/CD45RO+ to the toxic effect of 2-CdA.