The Value of Bone Marrow Biopsy in the Mobilization of Hematopoietic Stem Cells into the Peripheral Blood in Hematologic Malignancies.

Background: The mobilization the Peripheral Blood Stem Cells (PBSC) from bone marrow (BM) to peripheral blood (PB) is a complex process yet. This process is related to mobilization growth factor and/or chemotherapy protocol and disease status. CXCR4, receptor of SDF-1 and VLA-4 searched in primitive CD34+ and CD34+Thy+ cells have shown some functions in migration of CD34+ cells. Marrow disease infiltration and grade of fibrosis seem to be important features related to CD34+ cells trafficking from BM to PB. The objective of this study was to compare the cellularities, degrees of disease infiltration, and grades of fibrosis of hematopoietic stem cells (HSCs) in BM biopsies before and after mobilization and to correlate the results with the success of the mobilization in patients with hematologic malignancies and in donors.

Patients and Methods: Fifty-nine patients and 21 PB stem cell (PBSC) donors participated in this prospective study between January/2003 and May/2006. The patients included 21 with non-Hodgkin lymphoma (NHL), 21 with multiple myeloma (MM), 10 with Hodgkin lymphoma (HL), and 7 with leukemia (5 AML, 1 ALL, and 1 CLL). The mobilization regimen consisted of 5 g/m² of cyclophosphamide in 29 patients (21 MM, 4 NHL, 3 HL, and 1 CLL), DHAP in 8 (7 NHL and 1 NHL), ICE in 14 (9 NHL and 5 HL), high-dose Ara-C in 5 (all with AML), and G-CSF in 24 (21 donors, 1 NHL, 1 HL, and 1 ALL). The mean numbesr for previous chemotherapy cycles were 11, 10, 6, and 5 for NHL, HL, MM, and leukemia, respectively. We collected PBSC using a Spectra-Cobe device (Cobe, Lakewood, CO, USA). Large-volume leukoapheresis (LVL) was used in all cases. Mobilization success was defined as > 8 × 10⁶ CD34⁺ cells/L in PB before collection, and adequate LVL yield was defined as 2 × 10⁶ CD34⁺ cells/kg in LVL products. Overall BM and WBC precursor cellularities were visually assessed as normal (20–50%), decreased (<20%), and increased (> 50%). Fibrosis was graded as absent, slight (grades 1/2), or severe (grades 3/4). The clonal patterns of infiltration were confirmed by immunohistochemicaly analyses using monoclonal antibodies.

Results: Eighty proposals (59 patients and 21 donors) were presented for mobilization. There were 49 men and 31 women; the median age and mean duration of disease at time of mobilization were 40.3 years (range 25–68 years) and 15.9 months (range 10.3–20.1 months). Eighteen patients were complete responders, 37 were partial responders, and 4 had refractory disease. The median duration of G-CSF usage was 5 days. Mobilization failed in 17 patients (2 MM, 8 NHL, 3 HL, and 4 leukemia) and 1 donor. The mean numbers of CD+34 cells/μL in the PB at time of LVL were 110 in MM (1.1–647), 64.5 in NHL (0–211), 29.3 in HL (2–80), and 16.2 in leukemia (1.3–65). The mean yield of PBSC × 10⁶/Kg in LVL were 15.3 in MM (1.1–85.5), 9.4 in NHL (2.4–26.6), 6.3 in HL (1.3–14.1), 6.1 in donors (1.9–11.9), and 5.0 in leukemia (2.9–7.3). There were correlations between successful mobilization and high overall cellularity pre- and post-mobilization (p=0.015 and p=0.002, respectfully) and successful mobilization and high WBC precursors post-mobilization (p=0.009).

Conclusion: BM biopsy is a method important to re-statement at pre transplant, should be continue searched by overall and WBS precursor’s celularities, fibrosis and clonal infiltration before mobilization.