G-CSF-stimulated BM progenitor cells supplement suboptimal peripheral blood hematopoietic progenitor cell collections for auto transplantation.

Peripheral blood hematopoietic progenitor cells (PBHC) are the standard source of support for high-dose chemotherapy because of faster recovery of marrow function. Unfortunately, a proportion of patients are unable to mobilize adequate progenitors to proceed to autologous hematopoietic cell transplant (AHCT). Granulocyte-CSF-stimulated BM-derived hematopoietic progenitor cells (BMHC) may circumvent this problem. From 1999 to 2006, 52 patients (cases) with AML, Hodgkin (HL) or non-Hodgkin's lymphoma (NHL) in whom PBHC mobilization failed underwent a G-CSF-stimulated bone marrow harvest and proceeded to AHCT. Their outcome was compared with 422 patients (controls) with AML, HL and NHL undergoing AHCT using only PBHC. Twenty-three patients received BMHC alone and 29 patients received a combination of PBHC and BMHC. Median engraftment time for neutrophils (>0.5 x 10(9)/l) and platelets (>20 x 10(9)/l) were 14 and 27 days, but significantly longer when compared with controls (11 days, 11 days, P<0.0001). Patients receiving both PBHC and BMHC had faster engraftment, when compared with those receiving BMHC alone (P<0.001). In conclusion, performing an AHCT using G-CSF-stimulated BMHC in patients failing PBHC collection is feasible with faster engraftment seen in patients receiving both BMHC and PBHC over BMHC alone.

Cyclophosphamide, etoposide and G-CSF to mobilize peripheral blood stem cells for autologous stem cell transplantation in patients with lymphoma.

We aimed to assess the effectiveness of cyclophosphamide, etoposide and G-CSF (C+E) to mobilize peripheral blood stem cells for autologous stem cell transplantation in patients with lymphoma. A matched cohort study was performed comparing patients mobilized with C+E to patients mobilized with cyclophosphamide and G-CSF (C alone). Patients were matched for disease, prior radiotherapy and a chemotherapy score reflecting the amount and type of prior chemotherapy. Thirty-eight consecutive patients mobilized with C+E were compared with 38 matched controls. C+E was equivalent to C alone in terms of numbers of patients achieving a minimum threshold of > or =2 x 10(6)/kg CD34(+)cells (82% vs 79%, P = 0.74). C+E was superior, however, in terms of total CD34(+) yield (6.35 vs 3.3 x 10(6)/kg, P < 0.01), achieving a target graft of > or =5 x 10(6)/kg (55% vs 34%, P = 0.04) and obtaining both a minimum (61% vs 32%, P < 0.01) and target (45% vs 13%, P < 0.01) graft in one apheresis. This superiority was largely confined to patients with lower chemotherapy scores. There was no difference in neutrophil and platelet recovery or transfusion requirements for those who subsequently received high-dose therapy and stem cell transplantation. Thus, C+E improves the efficiency of peripheral blood stem cell collection, but does not increase the number of patients who can proceed to transplantation. Most of the benefit of the regimen was confined to patients who had not received extensive prior therapy. Novel strategies are required to increase the collection efficiency of 'hard to mobilize' patients.

Microbial contamination of harvested bone marrow and peripheral blood.

The incidence and clinical consequences of microbiological contamination of autologous bone marrow and peripheral blood progenitor cells are not well documented. We therefore retrospectively analysed our experience with bacterial or fungal contamination of harvested bone marrow and/or peripheral blood. From January 1987 to the end of January 1994, 499 patients were harvested or which 301 were transplanted. A total of 3910 specimens obtained during three stages in the processing were assessed for microbial contamination: (1) in the operating room immediately after harvesting (1662 bags) with 2.1% culture positivity, (2) after processing for cryopreservation (1039 bags) with a further 1.1% cultures positive, and (3) after thawing at the time of reinfusion (1209 bags) of which 2.2% were culture positive. There were no culture positive specimens obtained from any peripheral blood progenitor cell products. The vast majority of the 85 culture positive specimens obtained from marrow were skin flora (89%) and 35% of all positive harvest specimens remained positive following processing and freezing. At least 36% of culture positive specimens were thought to have arisen as a result of exogenous contamination of blood culture bottles. Potentially pathogenic enteric organisms were present in nine (0.2%) specimens and infusion of these organisms occurred in four cases. A further seven patients were reinfused with marrow culture positive for skin organisms. No adverse clinical sequelae were noted following infusion of any contaminated products. However, clinical decision making continues to be influenced by culture results and multistage microbial culture continues to be of value in the management of our marrow recipients.

Interleukin-3 followed by GM-CSF for delayed engraftment after autologous bone marrow transplantation.

Recombinant human interleukin-3 (IL-3) is well-tolerated according to phase I studies, and produces trilineage hematologic responses in patients with normal bone marrow. In addition, promising results have been obtained in a variety of bone marrow failure states. We studied IL-3 in 7 patients with markedly delayed engraftment after autologous bone marrow transplantation (ABMT) for hematologic malignancies (acute myeloid leukemia 4, chronic myeloid leukemia 1, myeloma 1, non-Hodgkin's lymphoma 1). All patients were red blood cell- and platelet transfusion-dependent, had an absolute neutrophil count (ANC) < 0.7 x 10(9)/L and failed to achieve a sustained ANC > 1.0 x 10(9)/L after receiving granulocyte-macrophage colony stimulating factor (GM-CSF) for 28 days. IL-3 was given daily for 21 days at 2 micrograms/kg/d (2 patients) and 5 micrograms/kg/d (5 patients). Toxicity was mild and consisted mostly of low-grade fever and malaise. No changes in platelet, hemoglobin or reticulocyte levels were observed. Four patients had at least a 2-fold increase in ANC at the end of IL-3 treatment. Five patients received GM-CSF 10 micrograms/kg/d subcutaneously for 7 to 10 days immediately after IL-3 and 4 had a further increase in ANC (median 1.7-fold, range 1.6- to 5.8-fold), but no change in platelet transfusion requirements. Hematopoietic colony assays of bone marrow cells obtained before and after treatment showed that granulocyte-macrophage colony-forming cell (CFU-GM) and erythroid blast-forming cell (BFU-E) levels were severely reduced and multilineage progenitors (CFU-GEMM) absent in all patients, and remained low after IL-3 treatment for 21 days. Sequential IL-3 and GM-CSF produced a significant but transient increase in the neutrophil counts of some patients. IL-3 appears to be of limited benefit in patients who are severely aplastic after ABMT and have very low levels of bone marrow progenitors.