Risk factors, mechanisms, and strategies to optimize collection in predicted poor mobilizer patients
| Risk factor . | Postulated mechanism . | Mobilization strategy . |
|---|---|---|
| Low steady-state platelet counts and PB CD34+ level | Reflects overall HSC reserve | Regimen promoting HSC proliferation, eg, SCF, cyclophosphamide |
| Low steady-state TNF-α level | May reflect niche dysfunction, including the macrophage response to G-CSF | Regimen bypassing the macrophage-dependent pathways, eg, plerixafor-containing regimen |
| Increasing age | Reduced HSC reserve because of the following:
| Regimen promoting HSC proliferation, eg, SCF, cyclophosphamide Add risk-adapted plerixafor to augment niche response to G-CSF Bisphosphonate treatment continued throughout collection PTH of interest in experimental models |
| Underlying disease | Paraneoplastic niche dysfunction Loss of niche to mass effect of tumor | Aim to clear BM of disease before collection |
| Prior extensive radiotherapy (RT) to red marrow | Direct HSC toxicity Toxicity to HSC niche | Rainy day collection before extensive RT when possible Risk-adapted plerixafor Regimen promoting HSC proliferation, eg, SCF, cyclophosphamide |
| Prior chemotherapy | ||
| Melphalan | Direct HSC toxicity | Avoid melphalan until autologous cells collected |
| Fludarabine | Direct HSC toxicity, niche damage | Collect HSCs early, after < 4 cycles of fludarabine |
| Intensive chemotherapy (eg, hyper-CVAD) | Dose-dense cycles may cause niche damage, and HSCs forced into cell cycle may not engraft as well | Use SCF or preemptive risk-adapted plerixafor for fludarabine-exposed and heavily pretreated patients |
| Prior lenalidomide | Possible effects on HSC motility Possible dysregulated HSC niche because of antiangiogenic effects | Collect HSC early, after < 4 cycles of treatment Temporarily withhold lenalidomide during collection. |
| Risk factor . | Postulated mechanism . | Mobilization strategy . |
|---|---|---|
| Low steady-state platelet counts and PB CD34+ level | Reflects overall HSC reserve | Regimen promoting HSC proliferation, eg, SCF, cyclophosphamide |
| Low steady-state TNF-α level | May reflect niche dysfunction, including the macrophage response to G-CSF | Regimen bypassing the macrophage-dependent pathways, eg, plerixafor-containing regimen |
| Increasing age | Reduced HSC reserve because of the following:
| Regimen promoting HSC proliferation, eg, SCF, cyclophosphamide Add risk-adapted plerixafor to augment niche response to G-CSF Bisphosphonate treatment continued throughout collection PTH of interest in experimental models |
| Underlying disease | Paraneoplastic niche dysfunction Loss of niche to mass effect of tumor | Aim to clear BM of disease before collection |
| Prior extensive radiotherapy (RT) to red marrow | Direct HSC toxicity Toxicity to HSC niche | Rainy day collection before extensive RT when possible Risk-adapted plerixafor Regimen promoting HSC proliferation, eg, SCF, cyclophosphamide |
| Prior chemotherapy | ||
| Melphalan | Direct HSC toxicity | Avoid melphalan until autologous cells collected |
| Fludarabine | Direct HSC toxicity, niche damage | Collect HSCs early, after < 4 cycles of fludarabine |
| Intensive chemotherapy (eg, hyper-CVAD) | Dose-dense cycles may cause niche damage, and HSCs forced into cell cycle may not engraft as well | Use SCF or preemptive risk-adapted plerixafor for fludarabine-exposed and heavily pretreated patients |
| Prior lenalidomide | Possible effects on HSC motility Possible dysregulated HSC niche because of antiangiogenic effects | Collect HSC early, after < 4 cycles of treatment Temporarily withhold lenalidomide during collection. |