Bone marrow transplantation in older patients

Types. Autologous transplantation uses the patient's own stem cells after high-dose chemotherapy (myeloma, relapsed lymphoma) — no graft-versus-host disease and lower transplant-related mortality. Allogeneic transplantation uses donor cells (AML, MDS, myelofibrosis) and provides a graft-versus-tumour effect at the cost of GVHD.

Age is no longer a barrier. Allogeneic transplantation is now routinely performed up to 70–75 years using reduced-intensity conditioning (RIC) or non-myeloablative regimens (fludarabine-melphalan, fludarabine-busulfan), which rely on the immunological graft-versus-tumour effect rather than dose intensity.

Selection is by physiological, not chronological, age. The HCT-CI (Hematopoietic Cell Transplantation Comorbidity Index) together with performance status, comprehensive geriatric assessment, frailty, nutrition, cognition and caregiver support predicts non-relapse mortality far better than age alone.

Indications in older adults. AML in first remission with intermediate or adverse risk, MDS with excess blasts, myelofibrosis with DIPSS intermediate-2 or high risk, and autologous transplantation for multiple myeloma (feasible to around 75 years in fit patients).

Early complications. Mucositis, prolonged pancytopenia, neutropenic sepsis, invasive fungal infection, CMV reactivation, haemorrhagic cystitis, sinusoidal obstruction syndrome (veno-occlusive disease), engraftment syndrome, and acute GVHD affecting skin, gut and liver within 100 days.

Late complications. Chronic GVHD, prolonged immunodeficiency with encapsulated organism and zoster infection (requiring revaccination from 6–12 months plus PCP and antiviral prophylaxis), secondary malignancy, endocrine failure, cataract, osteoporosis, and cognitive and functional decline — older survivors need structured survivorship care.

BMT CTN 1703 trial (NEJM 2023) — post-transplant cyclophosphamide with tacrolimus and mycophenolate mofetil is now standard GVHD prophylaxis for reduced-intensity allogeneic transplantation, significantly improving GVHD-free, relapse-free survival. It has also widened donor availability to haploidentical and mismatched unrelated donors, making transplantation accessible to substantially more older patients.