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 Blood, 16 July 2009, Vol. 114, No. 3, pp. 638-646.
Prepublished online as a Blood First Edition Paper on April 22, 2009; DOI 10.1182/blood-2008-12-196568.

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Submitted December 29, 2008
Accepted April 7, 2009

Spontaneous regression of chronic lymphocytic leukemia: clinical and biologic features of 9 cases

Ilaria Del Giudice, Sabina Chiaretti, Simona Tavolaro, Maria Stefania De Propris, Roberta Maggio, Francesca Mancini, Nadia Peragine, Simona Santangelo, Marilisa Marinelli, Francesca Romana Mauro, Anna Guarini, and Robin Foa*

Division of Hematology, Department of Cellular Biotechnologies and Hematology, "Sapienza" University, Rome, Italy

* Corresponding author; email: rfoa{at}bce.uniroma1.it.

In chronic lymphocytic leukemia (CLL), spontaneous regressions are an exceptional phenomenon, whose biologic features are unknown. We describe 9 CLL patients who underwent a spontaneous clinical regression over an 11-year follow-up, in spite of a residual neoplastic clone detected by flow cytometry. CD38 and ZAP-70 were negative in all cases. Immunoglobulin heavy chain variable region (IgVH) genes, mutated in all 7 evaluable patients, were restricted to the VH3 family in 6, with the usage of VH3-30 gene in 2. The light chain variable region genes were mutated in 6/8 cases, with the usage of V{kappa}4-1 gene in 3. Microarray analysis of CLL cells revealed a distinctive genomic profile with an overrepresentation of BCR-related and ribosomal genes, regulators of signal transduction and transcription. The number of activated T lymphocytes expressing IFN-{gamma}, TNF-{alpha} and IL-4 was similar between CLL in spontaneous regression and healthy individuals. In conclusion, spontaneous clinical regressions can occur in CLL despite the persistence of the neoplastic clone and the biologic features include negative CD38 and ZAP-70, mutated VH3-30 and V{kappa}4-1 genes. The peculiar gene profile suggests that BCR signaling may play an important role in this scenario as the most significant feature of the leukemic clone in regression.


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