CD56 antigenic expression in acute myeloid leukemia identifies patients with poor clinical prognosis.

CD56 antigen, a 200-220 kDa cell surface glycoprotein, identified as an isoform of the neural adhesion molecules (NCAM), has been found frequently expressed in several lympho-hematopoietic neoplasms including acute myeloid leukemias (AML). In fact, in these latter diseases it has been reported that the presence of CD56 antigen on the blasts of AML patients with t(8;21) (q22;q22), and in those with M3 subtype, identifies a subgroup of patients with a more unfavorable prognosis. On the basis of these findings, we evaluated in 152 newly diagnosed AML patients CD56 surface expression, and results were correlated with morphology, immunophenotype, cytogenetic pattern and clinical outcome. CD56 antigen was recorded in 37 out of 152 cases (24%) and particularly in those with M2 and M5 cytotypes. Moreover, CD56 expression was significantly associated with P-glycoprotein (PGP) hyperexpression (P = 0.007), unfavorable cytogenetic abnormalities (P = 0.008) and with a reduced probability of achieving complete remission (CR) (36% vs 68%) (P = 0.035) as well as with a shorter survival (6 vs 12 months) (P = 0.032). In conclusion, CD56 antigenic expression on AML cells represents an important adverse prognostic factor and therefore its presence should be regularly investigated for a better prognostic assessment of AML patients at diagnosis.

Long-lasting complete remission in patients with hairy cell leukemia treated with 2-CdA: a 5-year survey.

Between January 1991 and January 1994, 40 patients with hairy-cell leukemia (HCL), 30 males and 10 females, with a median age of 54 years, were treated with a single course of 2-chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg/kg/day continuous infusion for 7 days. Thirteen patients were untreated and 27 had previously received alpha-interferon. Thirty out of 40 patients (75%) achieved complete remission (CR) and 10 (25%) partial remission (PR). The median follow-up duration for patients in CR has been 48 months (range 30-66). Five of the complete responders (17%) relapsed at 12, 24, 26, 30 and 36 months after treatment as documented by the increase of hairy cells (Hc) in the bone marrow and two of them, who were retreated with 2-CdA after showing an initial impairment of peripheral blood values, obtained a second CR. The remaining three relapsed patients were never retreated and still show normal peripheral counts after 30, 38 and 40 months. Twelve of the continuous complete responder patients are still in CR after more than 5 years. In contrast, 8 out of 10 partial responders progressed after 8-36 months and all of them were retreated with 2-CdA at a dose of 0.15 mg/kg/day for 5 days i.v. Four of them (50%) achieved a CR, three a better PR and one patient died 6 months after the second 2-CdA course because of infectious complications. Two additional patients, both in CR, died after 28 and 37 months because of a second neoplasm. Toxic side-effects consisted of febrile episodes recorded in 16 patients: in seven of them, fever lasted only 24-48 h after the end of treatment and was apparently not infection-related. In the remaining nine patients, showing in addition severe neutropenia (neutrophils less than 1.0 x 10(9)/l), fever was related to bacterial infection requiring systemic antibiotics in all of them and G-CSF in three cases. In conclusion, 2-CdA induces a very high proportion of complete and long-lasting remissions in patients with HCL. In a number of cases relapse at bone marrow level may not affect peripheral blood values for prolonged time. However, in those patients with initial pancytopenia a retreatment with 2-CdA is still effective in inducing a durable second CR.

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

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.

2-Chlorodeoxyadenosine in the treatment of relapsed/refractory chronic lymphoproliferative disorders.

2-Chlorodeoxyadenosine (2-CdA) is a purine analog with cytotoxic activity on both resting and cycling lymphocytes which has been used as salvage therapy in advanced/resistant chronic lymphoproliferative disorders. In our study 39 patients (19 B-CLL, 5 B-PLL, 9 low-grade B-NHL, 5 CTCL and 1 high-grade T-NHL) who relapsed or became resistant after 1-4 chemotherapy regimens were treated with 2-CdA 6 mg/m2 per day by 2 h infusion for 5 d every 28 d. The overall clinical response rate, including complete remission (CR) and partial remission (PR), was 66%. Two of 19 (10%) B-CLL patients achieved a CR lasting 9 months, while 11/19 B-CLL (58%) and 4/5 B-PLL (3 B-PLL/B-CLL and 1 B-PLL) (80%) achieved a PR. Interestingly, 5 of 6 patients who had been previously treated with fludarabine obtained a clinical response (2 CR and 3 PR). One of 9 (11%) low-grade B-NHL patients achieved a CR and relapsed after 26 months, and 5/9 (55%) achieved a PR. One of 5 (20%) CTCL achieved a CR lasting 32 months, while 2/5 (40%) achieved a PR. The overall mean duration of PR was 7.4 months and no differences were observed among different groups of patients. Toxicity was acceptable, as only a transient severe hematological impairment was observed in 20% of the patients while nonhematological toxicity was not documented. Two patients died because of bacterial pneumonia, 1 of meningitis due to Listeria and 9 from progression of the disease. In conclusion, treatment with 2-CdA in heavily pretreated patients with chronic lymphoproliferative disorders is well tolerated and obtains high response rates, even in patients relapsed after treatment with fludarabine.