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CORRESPONDENCE Since the first description by Damle et al,1
several investigators demonstrated the independent prognostic
significance of CD38 expression in predicting survival of patients
suffering from B-cell chronic lymphocytic leukemia
(B-CLL).2-9 But despite confirming its prognostic value,
Hamblin et al recently reported that CD38 expression may vary
during the course of the disease, enriching the scientific
debate about the biological significance of the expression of this
molecule on neoplastic B lymphocytes.8 In addition,
Chevallier et al have shown that CD38 expression may change during the
evolution of the disease, suggesting that such an expression may
be a secondary event in B-CLL.9 In particular, they
recorded an increased expression during the disease progression in some
cases. Other investigators, however, reported that CD38 expression is a
constant overtime in some of their patients serially tested.1,7 In light of this, we reviewed 162 B-CLL patients
diagnosed and followed up at our institutions in the last 3 years. We
analyzed 29 patients in which CD38 expression on peripheral B
cells was evaluated more than one time, to verify whether a
change in the immunophenotypic profile occurred. To detect the percentage of neoplastic B cells displaying the CD38
molecule on their surface, we used a 3-color fluorescence staining:
peridinin chlorophyll A protein (PerCP) for CD45s, fluorescein isothiocyanate (FITC) for CD19s, and phycoerythrin (PE) for
CD38s. All monoclonal antibodies were purchased from Becton
Dickinson Immunocytometry System (BDIS, San Jose, CA). CellQuest
software and FACSCalibur flow cytometer (BDIS) were used. All cases
were immunologically typical (CD5+CD23+) B-CLL.
Positivity was defined as expression of CD38 on CD19+ cells
of at least 30%. Globally, CD38 expression was recorded on 34% of
B-CLL patients. In the patient group in which the determination of CD38
expression was done more than one time, the mean number of
determinations was 2.4 (range, 2-5), and the mean time between the first and the last determinations was 17 months (range, 2-41 months). As shown in Table 1, we did not find a variation in CD38
expression of more than 10% between the first determination and the second determination. Interestingly, variations were not recorded in patients with progressive disease (stage shift
and/or increase in peripheral blood lymphocytes or in node size) and in
patients with stable disease as well. Moreover, no differences were
found among circulating and bone marrow B cells in terms of CD38
expression in those cases in which the determination was performed on
both samples (data not shown). In addition, other conditions, such as
spontaneous spleen rupture, viral infection (ie, Herpes
zoster), broncopneumonia, or hemodialysis for acute renal
failure were not able to induce an expression of CD38 in 4 cases with
CD38 In our opinion, methodological reasons could explain the discordant data reported so far, including the use of cryopreserved samples,10 different cytometers and operators during the time of the study, and different clones of CD38 monoclonal antibodies and gating strategies to detect it. In conclusion, though our results need to be further corroborated on a greater number of patients followed up for longer time, our feeling is that CD38 expression does not change during the disease course of B-CLL.
Giovanni D'Arena, Giuseppe Nunziata, Giuseppe Coppola, Maria Luigia Vigliotti, Alfredo Tartarone, Nicola Carpinelli, Rosella Matera, Rosario Colella Bisogno, Giuseppe Pistolese, and Nicola Di Renzo
References
1.
Damle RN, Wasil T, Fais F, et al.
Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia.
Blood.
1999;94:1840-1847
2.
Ibrahim S, Keating M, Do K-A, et al.
CD38 expression as an important prognostic factor in B-cell chronic lymphocytic leukemia.
Blood.
2001;98:181-186 3. D'Arena G, Musto P, Cascavilla N, et al. CD38 expression correlates with adverse biological features and predicts poor clinical outcome in B-cell chronic lymphocytic leukemia. Leuk Lymphoma. 2001;42:109-114[Medline] [Order article via Infotrieve]. 4. Morabito F, Mangiola M, Oliva B, et al. Peripheral blood CD38 expression predicts survival in B-cell chronic lymphocytic leukemia. Leukemia Res. 2001;25:927-932[CrossRef][Medline] [Order article via Infotrieve].
5.
Del Poeta G, Maurillo L, Venditti A, et al.
Clinical significance of CD38 expression in chronic lymphocytic leucemia.
Blood.
2001;98:2633-2639 6. Heintel D, Schwarzinger I, Chizzali-Bonfardin C, et al. Association of CD38 antigen expression with other prognostic parameters in early stages of chronic lymphocytic leukemia. Leuk Lymphoma. 2001;42:1315-1321[CrossRef][Medline] [Order article via Infotrieve]. 7. Durig J, Naschar M, Schmucker U, et al. CD38 expression is an important prognostic marker in chronic lymphocytic leukaemia. Leukemia. 2002;16:30-35[CrossRef][Medline] [Order article via Infotrieve].
8.
Hamblin TJ, Orchard JA, Ibbotson RE, et al.
CD38 expression and immunoglobulin variable region mutations are independent prognostic variables in chronic lymphocytic leukemia, but CD38 expression may vary during the course of the disease.
Blood.
2002;99:1023-1029 9. Chevallier P, Penther D, Avet-Loiseau H, et al. CD38 expression and secondary 17p deletion are important prognostic factors in chronic lymphocytic leukaemia. Br J Haematol. 2002;116:142-150[CrossRef][Medline] [Order article via Infotrieve]. 10. Deneys V, Thiry V, Hougardy N, Mazzon AM, Leveugle P, De Bruyere M. Impact of cryopreservation on B cell chronic lymphocytic leukaemia phenotype. J Immunol Methods. 1999;228:13-21[Medline] [Order article via Infotrieve].   CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
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B-CLL tested before these events occurred.
