Spontaneous Remission Of B-chronic Lymphocytic Leukaemia

Abstract

We read with interest the recent report by Thomas et al (2002) regarding the spontaneous clinical regression of chronic lymphocytic leukaemia (CLL), as we have experienced a spontaneous and continuous regression, leading to a complete remission, in a patient with B-CLL. As Thomas et al (2002) point out, true clinico-haematological remission, as defined by Cheson et al (1988) is very rare. Unfortunately, a precise estimation of the status or the degree of remission in their patients is not possible as a bone marrow (BM) aspirate was performed in only three of the ten cases during follow-up. In addition, for a proper assessment of clinico-haematological remission, only two of their cases and three additional patients from the literature (reviewed in Thomas et al, 2002) were sufficiently documented for evaluation. We report a 64-year-old man diagnosed with B-CLL stages Rai 1 and Binet A in October 1998, after a lymphocytosis (absolute lymphocyte count of 21·6 × 109/l) was observed during a routine blood analysis. Only two axillary lymph nodes (of 1·5 and 1 cm diameter approximately) were palpable by physical examination. The haemoglobin concentration (15·3 g/dl) and the platelet count (214 × 109/l) were normal. BM aspirate revealed 61·6% lymphocytes. Immunophenotypic analysis revealed a monoclonal (SmIg κ) B-cell population with an immunophenotype compatible with B-CLL, CD19+/CD20dim/CD22dim/CD23dim/CD5+/CD6+/CD38−/FMC7, which represented 85% and 78% of the leucocytes in blood and BM respectively. The patient received no treatment for B-CLL, or any other treatment except for omeprazol for a hiatus hernia and an angiotensin-converting enzyme inhibitor for a mild chronic cardiac insufficiency. Figure 1 shows an overview of the peripheral leucocyte count and percentage of B-CLL cells analysed by flow cytometry during follow-up. The disease was initially stable, but from June 2000 (20 months after diagnosis) we observed a continuous decrease of the absolute lymphocyte count until a normal count was achieved and thereafter a progressive decrease in the percentage of immunologically positive B-CLL cells to only 0·5% of the leucocytes. At the last follow-up, apart from a normal physical examination, BM examination revealed only 0·6% of leucocytes with B-CLL immunophenotype. Distribution of the leucocyte population during follow-up of the patient. Within each column the upper portion represents the lymphocyte population and the lowest part the remaining normal white cell population. Please note that whenever immunophenotypic analysis was done (at diagnosis, and at 32, 34 and 42 months follow-up interval), the lymphocyte portion is further subdivided into B-CLL cells and normal lymphocytes. At these time intervals, the percentage of malignant B cells was: 68%, 5%, 3% and 0·5% of the leucocytes respectively. Just as ‘smouldering’ B-CLL has certain distinct features (Montserrat et al, 1988), we wondered whether those cases with spontaneous regression can also be identified a priori. Cytogenetic analysis at diagnosis of our patient showed a 13q14 deletion as the only cytogenetic abnormality, which has been associated with a long treatment-free interval (Döhner et al, 2000). The absence of CD38 expression in this patient also indicates a good prognosis (Damle et al, 1999). In summary, this patient provided well-documented evidence that spontaneous regression and even clinico-haematological remission of B-CLL is possible, and can be easily monitored by immunophenotyping. Further, it confirms the principle that early stages of B-CLL should not be treated.