Abstract
Patients with chronic idiopathic neutropenia (CIN) usually show chronic inflammation in their bone marrow stromal cells, but the etiologies of this disorder are still unknown. We suspected viral infection of the bone marrow stromal cells and used polymerase chain reaction (PCR) analysis to test for cytomegalovirus (CMV) infection in 4 patients with CIN and in 6 healthy volunteers. Peripheral blood mononuclear cells did not yield signals in any of the patients or healthy volunteers, but PCR analysis for CMV DNA in bone marrow stromal cells showed positive signals in 2 of the patients with CIN. CMV DNA was not detected in the other 2 patients or in the healthy volunteers. The 2 patients who were positive for stromal CMV received 500 mg/day ganciclovir for 14 days. After this treatment, the PCR band showing the presence of stromal CMV disappeared, and the neutrophil numbers of the 2 patients who received this viral eradication therapy normalized 6 months after treatment. In conclusion, the etiology in some cases of CIN is speculated to be infection by CMV in bone marrow stromal cells, and treatment with ganciclovir may be effective in treating such patients.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Kyle RA, Linman JW. Chronic idiopathic neutropenia: a newly recognized entity?N Engl J Med. 1968;279:1015–1019.
Jakubowski AA, Souza L, Kelly F, et al. Effects of human granulocyte colony-stimulating factor in a patient with idiopathic neutropenia.N EnglJ Med. 1989;320:38–42.
Kohgo Y, Hirayama Y, Matsunaga T, Kato J, Sakamaki S, Niitsu Y. Chronic idiopathic neutropenia associated with abnormal expression of granulocyte colony-stimulating factor mRNA of bone marrow stromal cells.Int J Hematol. 1994;59:177–180.
Papadaki HA, Giouremou K, Eliopoulous GD. Low frequency of myeloid progenitor cells in chronic idiopathic neutropenia of adults may be related to increased production of TGF-βl by bone marrow stromal cells.Eur J Haematol. 1999;63:154–162.
Papadaki HA, Coulocheri S, Eliopoulos GD. Patients with chronic idiopathic neutropenia of adults have increased serum concentration of inflammatory cytokines and chemokines.Am J Hematol. 2000;65:271–277.
Simmons P, Kaushansky K, Torok-Storb B. Mechanisms of cytomegalovirus-mediated myelosuppression: perturbation of stromal cell function versus direct infection of myeloid cells.Proc Natl Acad Sci USA. 1990;87:1386–1390.
Suwansirikul S, Rao N, Dowking JN, Ho M. Primary and secondary cytomegalovirus infection: clinical manifestation after renal transplantation.Arch Intern Med. 1977;137:1026–1029.
Hirayama Y, Sakamaki S, Matsunaga T, et al. Concentrations of thrombopoietin in bone marrow in normal subjects and in patients with idiopathic thrombocytopenic purpura, aplastic anemia, and essential thrombocythemia correlate with its mRNA expression of bone marrow stromal cells.Blood. 1998;92:46–52.
Sakamaki S, Hirayama Y, Matsunaga T, et al. Transforming growth factor β1 (TGF-β1) induces thrombopoietin from bone marrow stromal cells, which stimulates the expression of TGF-β receptor on megakaryocytes and, in turn, renders them susceptible to suppression by TGF-β itself with high specificity.Blood. 1999;94: 1961–1979.
Jiwa NM, van Gemert GW, Raap AK, et al. Rapid detection of human cytomegalovirus DNA in peripheral blood leukocytes of viremic transplant recipients by the polymerase chain reaction.Transplantation. 1989;48:72–76.
Kyle RA. Natural history of chronic idiopathic neutropenia.N Engl J Med. 1980;302:908–909.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Hirayama, Y., Sakamaki, S., Tsuji, Y. et al. Recovery of Neutrophil Count by Ganciclovir in Patients with Chronic Idiopathic Neutropenia Associated with Cytomegalovirus Infection in Bone Marrow Stromal Cells. Int J Hematol 79, 337–339 (2004). https://doi.org/10.1532/IJH97.03155
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1532/IJH97.03155