Five years follow-up after 2-chloro deoxyadenosine treatment in thirty patients with hairy cell leukemia: Evaluation of minimal residual disease and CD4+lymphocytopenia after treatment

Between March 1992 and August 1993, thirty patients with hairy cell leukemi a (HCL) were treated in a single institution with 2-chlorodeoxyadenosine (2 -CdA) for one course (N=27) or two courses at six month intervall (N=3). Si xteen patients were previously untreated, 14 had been treated with alpha in terferon (alpha IFN) (N=5), alpha IFN and splenectomy (N=8) and splenectomy , alpha IFN and Deoxycoformycin (N=1). Overall results in 29 evaluable pati ents were: 25 CR (86%), 3 PR (10%), one failure. The three PR patients rela psed after 18, 24 months and five years. Two were retreated successfully. T wo CR patients relapsed after five years. Careful clinical survey, sequenti al bone marrow biopsies (BMB) with DBA44 immunostaining for assessment of r esponse and detection of residual disease and serially evaluation of lympho cyte subsets counts were performed. Results of bone marrow biopsies study s how 1) a progressive reduction in hairy cell infiltration during the first six months after therapy and not after that indicating that the best moment for the evaluation of response may be the sixth month, 2) the persistence of a very small number of DBA44 + cells (80% of BMB). There was a correlati on between the presence of > 5% DBA44 positive cells on 6th month BMB and r elapse. 60% had an absolute CD4+ lymphocyte count less than 0.2 10(9)/l at least on one examination after treatment. CD4+ lymphocyte level persisted less than baseline level in 8/18 patients tested after four and/or five years. Lymph openia was less marked in splenectomized patients: 7/7 splenectomized patie nts tested have recovered a CD4+ lymphocyte count equal to pre-therapy leve l compared to 3/11 non splenectomized patients (p: 0.004). Three opportunis tic infections were observed early (first 6 months) after 2CdA therapy: pne umocystis pneumonia, retinitis due to toxoplasma in the patient who failed and legionella pneumonia in a patient retreated after relapse. Two patients developed a second carcinoma 6 and 12 months after therapy. Five patients died, three from a cause unrelated to HCL, one from HCL and one from infect ion while in second CR. At five pears, overall survival is 83% and progress ion free survival is 66%. Our study shows 1) long-lasting response in the m ajority of patients after 2-CdA, 2) a correlation between persistent minima l residual disease detected with DBA44 immunostaining and occurence of rela pse and 3) a profound and persistent CD4+ lymphopenia mon marked in non spl enectomized patients.