Stromal damage as consequence of high-dose chemo/radiotherapy in bone marrow transplant recipients

Bone marrow transplant (BMT) relies on the engraftment of donor hemopoietic precursors in the host marrow space. Colony forming units-fibroblasts (CFU -f), the precursor compartment for the osteogenic lineage, are essential to hemopoietic stem cell survival, proliferation and differentiation. We have studied CFU-f in donors (aged 5 months to 62 years) and in patients who ha d received allogeneic BMT (aged 2 months to 63 years). In donor marrows we found an inverse correlation between CFU-f frequency and age. In BMT recipi ents CFU-f frequencies were reduced by 60%-90% (p < 0.05) and the numbers d id not recover up to 12 years after transplant. Stromal reconstitution to n ormal levels was found only in patients < 5 Sears old, In all patients stud ied CFU-f post-BMT were of host origin. Patients with low CFU-f levels disp layed also a decreased bone mineral density (p < 0.05) and significantly re duced levels of long-term culture-initiating cells (LTC-IC) (p < 0.05). Our study demonstrates that the marrow stromal microenvironment is seriously a nd irreversibly damaged after BMT. Donor cells do not contribute to reconst itute the marrow microenvironment, whose residual CFU-fs remain of host ori gin. (C) 1999 International Society for Experimental Hematology, Published by Elsevier Science Inc.