Imatinib mesylate for lymphocytic variant of hypereosinophilic syndrome: A response
Authors: Anna Christoforidou
Journal: American Journal of Hematology (2011)

We thank Dr Helbing for his very interesting comments on our L-HES case, which gives us the opportunity to discuss some points on this rare entity. The flow cytometric assessment was indeed performed in bone marrow the first time, whereas the second measurement was made both in marrow and blood showing identical findings in both compartments. The patient did not have increased IgE. In the Simon HU et al. series, only half of the patients had elevated IgE [1]. Also, we did not use a direct measurement of eosinophilopoietic cytokines in serum because these are more relevant when production by PBMC is shown in vitro [1], but the latter could not be performed in our laboratory at the time. Although this can provide additional evidence for L-HES diagnosis or for research purposes, it can doubtfully be proposed as a sine qua non for the diagnosis due to technical difficulties. We agree with Dr Helbig that if the T-cell clone was a single finding by the very sensitive PCR technique we could not argue for a certain association, according to his results showing a high incidence in HES patients [2]. However, our patient had a clonal TCR rearrangement in a significant fraction of the CD4 cell compartment (65%), which were phenotypically normal. The theory of a secondary effect of eosinophils or chronic inflammation on clonal T-cell expansion does not easily apply to our patient because this clone was not diminished despite hematological remission and symptom relief. An incidental finding cannot be excluded but we believe that the specificity of the immunophenotype technique and the quantitative information provided may differentiate such cases from similar observations in the elderly or in autoimmune diseases that represent mainly CD4(+)CD8(+) or oligoclonal CD8+ T-cell expansions [3, 4]. Nevertheless, clonality in CD3(−)CD4(+) cases should be demonstrated by TCR gene rearrangement studies due to the absence of surface T-cell receptor. We did not suggest that the patient had a complete remission in terms of complete resolution of any disease signs. By contrast, we gave insight into the imatinib course: it was effective in lowering the eosinophils and abbreviating or even eliminating the symptoms with no side effects, but indeed it did not affect the T-cell clone or the colonic eosinophilic infiltrate. Can this be considered a success? It should be compared with other therapies for which there is limited data. Corticosteroids are quite effective but very few patients can continue them in the long term. Besides, as mentioned in our presentation and by Dr Helbig, they do not commonly affect the abnormal clone [5]. Alemtuzumab would seem more targeted but conferring to significant morbidity at least at the usual dosing and its withdrawal was associated with frequent relapses at least in the HES/CEL setting [6]. Interferon alpha along with corticosteroids can also control the disease but it remains to be shown at what extend. The increased probability of lymphoma transformation requires a close monitoring in L-HES patients, but it is not known which patients are more prone and pre-emptive therapy is not justified. Thus, though imatinib has little, if any, role as first line treatment of L-HES, it can be of use in the resistant or intolerant patient. Anna Christoforidou*, * Department of Hematology, University Hospital of Alexandroupolis, Alexandroupolis, Greece.