Although the presence or absence of somatic mutations in the immunoglobulin variable region (IgV H ) genes in chronic lymphocytic leukemia (B-CLL) identifies subtypes with very different prognoses, the assay is technically complex and unavailable to most laboratories. CD38 expression has been suggested as a surrogate marker for the 2 subtypes. IgV H mutations and CD38 expression in 145 patients with B-CLL with a long follow-up were compared. The 2 assays gave discordant results in 41 patients (28.3% Damle et al 2 suggested that the expression of surface CD38 on the tumor cells gave the same information and might be a surrogate assay. Initial analysis of 50 of our patients, however, failed to show a significant correlation between IgV H gene mutation status and CD38 expression. 5 CD38 is a type 2 trans-membrane glycoprotein that acts as a complex ecto-enzyme with adenosine diphosphate-ribosyl cyclase and cyclic adenosine diphosphate-ribose hydrolase activities. 6 In the B-cell compartment CD38 is not a lineage marker, but it is expressed at times during B-cell development when cell-to-cell interactions are crucial to development. 7 Examples include an early bone marrow precursor cell, cells in the germinal center, and plasma cells. 8 All the factors that signal its up-regulation are as yet unknown, but they include ␣-and ␥-interferon. 9 Standard management for stage A B-CLL is to delay therapy until there is evidence of progression. 10 Meta-analysis of 6 trials involving 2048 patients showed no benefit of immediate treatment over delayed treatment with alkylating agents. 11 Nevertheless, approximately half the patients allocated to the watch-and-wait option eventually require treatment, and one fourth die of a cause related to B-CLL. 12 If those whose disease is destined to progress are identifiable at diagnosis, either by knowledge of the degree of CD38 expression or the status of IgV H mutations, it might be feasible to treat the disease more effectively with newer agents while the tumor burden is low.We have detailed clinical information on more than 600 patients with B-CLL who have been treated and followed up by this department for the past 28 years. This long follow-up has enabled us to appreciate fully the natural history of B-CLL and has allowed us to take death, rather than simply time to progression, as the end-point for our studies. For the past 10 years we have been cryopreserving sequential blood samples from many of these patients. This has given us a rare opportunity to examine IgV H mutations and CD38 expression as prognostic indicators for B-CLL. Moreover, we have the opportunity to establish whether CD38 expression is a reproducible and stable marker in the disease. Patients, materials, and methodsOne hundred forty-five patients were chosen from more than 600 patients with B-CLL who have attended the hematology clinics of the Royal For personal use only. on May 11, 2018. by guest www.bloodjournal.org From Bournemouth Hospital in the past 28 years. An attempt was made to include a representative ...

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