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CORRESPONDENCE We have read with great interest the papers by Ibrahim et
al1 and Hamblin et al2 regarding conversion
of CD38 expression and prognosis of B-CLL. The former described how one
of their B-CLL patients showed a change of CD38 expression level from
low (< 30%) to high ( Here, we describe 3 B-CLL patients who showed a conversion of CD38
expression (case #1, Table 1), CD13
expression (case #2, Table 1), or CD38 and CD15 expression (case #3,
Table 1) from low level to high level during follow-up. The expression
of these markers was evaluated by multicolor flow cytometry using fresh bone marrow samples. The low level or high level of expression of each
marker was defined using 30% as the cutoff value as reported by
previous studies.1-4 This conversion occurred at about 15, 8, and 12 years after diagnosis, respectively, and appeared to be
associated with a change in clinical course from indolent to aggressive. These patients died with disease 21 months (case #1), 7 months (case #2), and 3 years (case #3) following this conversion. Of the 3 patients, 2 (cases #2 and #3) also required
chemotherapy after conversion. Additionally, there was no evidence of
morphologic transformation in the neoplastic cells during this
conversion. Thus, the change of surface marker expression status was
the only detectable sign for the conversion of clinical course.
Previous studies by others and us have suggested that expression of
myeloid-associated markers such as CD13, CD14, CD11c, or CD11b on
neoplastic lymphocytes in B-CLL correlate with an unfavorable
prognosis.5-10 The change of expression of
myeloid-associated markers from low to high level and the possible
relationship with clinical progression has not been described
previously, to our knowledge.
Whether the levels of CD38 expression change over the course of B-CLL remains controversial. In contrast to the studies cited above, Damle et al have reported that levels of CD38 expression do not show significant change during follow-up among the B-CLL patients they studied.4 Stable CD38 expression again was noted in another recent study by Durig et al.3 The cause of this discrepancy among different studies is unclear but may be due to the differences in the length of follow-up of the patients studied, since the conversion may occur very late in the clinical course (15 years in case #1.) In summary, the findings in our cases suggest that levels of CD38 and myeloid-associated marker expression can change over the course of disease in B-CLL patients and support the observations by Ibrahim et al1 and Hamblin et al.2 Furthermore, the conversion from low- to high-level expression of these markers may be associated with a change from an indolent to an aggressive clinical course as observed by Ibrahim et al.1 Periodic monitoring of CD38 and, possibly, myeloid-associated markers may be necessary to fully assess the clinical/prognostic status of B-CLL patients. Also, as noted by others, additional studies are necessary to determine the most appropriate prognostic markers and methods for monitoring these patients.
Chung-Che Chang and Ronald P. Cleveland
References
1.
Ibrahim S, Keating M, Do KA, et al.
CD38 expression as an important prognostic factor in B-cell chronic lymphocytic leukemia.
Blood.
2001;98:181-186
2.
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 3. 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].
4.
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 5. Liu YC, Cleveland RP, Madelaire C, Hines JD. Discordant immunophenotype of chronic B-cell lymphoproliferative disorders in simultaneous specimens from bone marrow and peripheral sites. Arch Pathol Lab Med. 1995;119:53-58[Medline] [Order article via Infotrieve].
6.
Pinto A, Del Vecchio L, Carbone A, et al.
Expression of myelomonocytic antigens is associated with unfavourable clinicoprognostic factors in B-cell chronic lymphocytic leukaemia.
Ann Oncol.
1991;2(suppl 2):107-113 7. Molica S. Myelomonocytic associated antigens in early B-chronic lymphocytic leukemia correlate with disease activity. Am J Hematol. 1992;40:319-320[Medline] [Order article via Infotrieve]. 8. Pinto A, Del Vecchio L. Expression of myelomonocytic antigens on chronic lymphocytic leukemia B cells. Blood. 1988;72:1438[Medline] [Order article via Infotrieve]. 9. Tassies D, Montserrat E, Reverter JC, Villamor N, Rovira M, Rozman C. Myelomonocytic antigens in B-cell chronic lymphocytic leukemia. Leuk Res. 1995;19:841-848[CrossRef][Medline] [Order article via Infotrieve]. 10. Callea V, Morabito F, Oliva BM, et al. Surface CD14 positivity in B-cell chronic lymphocytic leukaemia is related to clinical outcome. Br J Haematol. 1999;107:347-352[CrossRef][Medline] [Order article via Infotrieve].   CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
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30%), with significant worsening in the
patient's clinical condition. The latter investigators also reported
changes in CD38 expression over time in 10 of 41 CLL patients.
Of these 10 patients, 2 showed a conversion from low to high
levels of CD38 expression. However, the authors concluded that this
conversion was not definitely associated with changes in clinical course.
