Back to Search
Start Over
Mobilization of human immature hematopoietic progenitors through combinatory use of bortezomib and immunomodulatory drugs.
- Source :
-
International journal of hematology [Int J Hematol] 2017 Apr; Vol. 105 (4), pp. 423-432. Date of Electronic Publication: 2016 Nov 21. - Publication Year :
- 2017
-
Abstract
- Combination use of the proteasome inhibitor bortezomib and the immunomodulatory drugs lenalidomide or thalidomide has provided superior outcomes in multiple myeloma over their single use; however, these combinations can produce significant toxicities. Unexpectedly, we found a small but significant increase in the population of immature granulocytes and erythrocytes/megakaryocytes in peripheral blood in 16 of 22 patients (73%) treated with dexamethasone in combination with bortezomib and immunomodulatory drugs (triplet), but not in any of 25 patients treated with either bortezomib or immunomodulatory drugs with dexamethasone (doublet). These immature cells gradually increased to a peak level (mean 2.6% per white blood cells) with triplet therapy, and disappeared immediately after therapy cessation. The numbers of circulating CD34 <superscript>+</superscript> cells and colony-forming cells derived from peripheral blood mononuclear cells increased after triplet therapy compared with those in patients treated by either bortezomib or immunomodulatory drugs plus dexamethasone. Furthermore, triplet regimen downregulated the expression of CXCR4, a chemokine receptor essential for bone marrow retention, on CD34 <superscript>+</superscript> cells, suggesting an unexpected effect on normal hematopoietic stem/progenitor cells through the reduced interaction with the bone marrow microenvironment. Our observations suggest that combination use should be carefully evaluated to exert synergistic anti-myeloma effects while avoiding unexpected adverse events.
- Subjects :
- Aged
Antigens, CD34 drug effects
Blood Cells drug effects
Bone Marrow Cells drug effects
Bortezomib therapeutic use
Dexamethasone adverse effects
Dexamethasone therapeutic use
Drug Therapy, Combination
Female
Humans
Immunologic Factors therapeutic use
Lenalidomide
Male
Middle Aged
Multiple Myeloma drug therapy
Receptors, CXCR4 drug effects
Thalidomide adverse effects
Thalidomide analogs & derivatives
Thalidomide therapeutic use
Bortezomib adverse effects
Hematopoietic Stem Cell Mobilization methods
Hematopoietic Stem Cells drug effects
Immunologic Factors adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1865-3774
- Volume :
- 105
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- International journal of hematology
- Publication Type :
- Academic Journal
- Accession number :
- 27873175
- Full Text :
- https://doi.org/10.1007/s12185-016-2148-2