GeriQBank · Paper III · Q2
Bone Marrow Transplantation
- Chapter
- Haematology & Oncology
- Years asked
- Not recorded in the source
- Frequency
- Set 1× in Paper IV (2009–2025)
As set in the university paper
Bone marrow transplant.
Paper IV · Oncology, Haematology & Cancer Screening · asked ×1 · 7-mark note · see in paper list
Detailed answer
Pro · free in betaAttempt it firstOutline your answer as a 7-mark note before revealing it — definition, causes, evaluation, management and the geriatric angle.Reveal answer
Bone Marrow Transplantation Discuss the types, indications, procedure and complications of bone marrow transplantation, with emphasis on the older patient.
(15 marks)
Definition and Types
Definition. Bone marrow transplantation — more accurately haematopoietic stem cell transplantation (HSCT) — is the intravenous infusion of haematopoietic stem cells to re-establish marrow function in a patient whose marrow has been damaged, is defective, or has been deliberately destroyed by high-dose therapy.
Autologous transplantation. The patient's own stem cells are collected, stored, and returned after high-dose chemotherapy. Here the transplant is simply a rescue procedure that permits a chemotherapy dose which would otherwise be lethal to the marrow. There is no graft-versus-host disease and no graft-versus-tumour effect, and no donor is required.
Allogeneic transplantation. Stem cells come from another person — an HLA-matched sibling, a matched or mismatched unrelated donor, a haploidentical (half-matched) family member, or umbilical cord blood. The therapeutic benefit comes from two sources: the conditioning chemotherapy and, crucially, the graft-versus-tumour effect of donor immune cells. The price of that effect is graft-versus-host disease and the need for prolonged immunosuppression.
Sources of stem cells. Peripheral blood stem cells mobilised with G-CSF (with or without plerixafor) are now used in over 90% of adult transplants — collection is by apheresis, engraftment is faster, but chronic GVHD is commoner. Bone marrow harvested from the posterior iliac crest under anaesthesia gives slower engraftment but less chronic GVHD. Umbilical cord blood permits greater HLA mismatch but has a limited cell dose and slow engraftment.
Conditioning regimens — the key concept in geriatrics. Myeloablative conditioning (for example busulfan–cyclophosphamide, or cyclophosphamide with total body irradiation) destroys the marrow irreversibly. It is too toxic for most patients over 55–60. Reduced-intensity conditioning (RIC) — typically fludarabine with melphalan or busulfan — relies mainly on the graft-versus-tumour effect rather than on the chemotherapy. This is the single development that made transplantation possible in older adults. Non-myeloablative regimens (fludarabine with low-dose total body irradiation) are gentler still and can be given largely as an outpatient.
Indications
Autologous Allogeneic Comment for the older patient Multiple myeloma (commonest indication Acute myeloid leukaemia Autologous transplant is far better tolerated worldwide); relapsed/refractory diffuse (intermediate/adverse risk); higher-risk and, with melphalan dose reduced to 140 mg/m², large B-cell lymphoma; relapsed Hodgkin myelodysplastic syndrome; acute is routinely performed up to about age 75. lymphoma; germ-cell tumours; POEMS lymphoblastic leukaemia; myelofibrosis; Allogeneic transplant is the only curative syndrome; some autoimmune disease CML failing multiple TKIs; aplastic option in higher-risk MDS and AML and is anaemia; thalassaemia and sickle cell now offered selectively into the early seventies disease; primary immunodeficiency The Procedure — Six Steps
Step 1 — Patient evaluation. Confirm the disease and its risk category; assess cardiac function (echocardiogram), pulmonary function with DLCO, renal and hepatic function; screen for HIV, hepatitis B and C, CMV, EBV and tuberculosis; dental review; and calculate the HCT-CI (Haematopoietic Cell Transplantation Comorbidity Index). Perform a full geriatric assessment in anyone over 60.
Step 2 — Donor selection. High-resolution HLA typing at A, B, C, DRB1 and DQB1. Preference order: matched sibling → 10/10 matched unrelated donor → mismatched unrelated donor or haploidentical relative → cord blood. Match CMV serostatus where possible. The availability of haploidentical donors has effectively abolished the "no donor" barrier — highly relevant in India, where unrelated donor registries are small and most patients have an available parent, sibling or child.
Step 3 — Stem cell collection. Mobilisation with G-CSF 10 µg/kg daily for 4–5 days, then apheresis targeting a CD34+ cell dose of at least 2 × 10⁶/kg (ideally 4–5 × 10⁶/kg) of recipient body weight.
Step 4 — Conditioning. Given over roughly days −7 to −1. Choice of intensity is the single most important determinant of non-relapse mortality in an older patient.
Step 5 — Infusion (day 0) and the aplastic phase. Cells are infused through a central line. Expect neutrophil engraftment (ANC >500/µL) at about day +12 to +21 and platelet engraftment at about day +20 to +30. During this period the patient is profoundly pancytopenic and needs protective isolation, irradiated leucodepleted blood products, and antimicrobial prophylaxis.
Step 6 — GVHD prophylaxis and long-term follow-up. Traditional prophylaxis is calcineurin inhibitor (tacrolimus or ciclosporin) plus methotrexate. The modern standard is post-transplant cyclophosphamide with tacrolimus and mycophenolate mofetil. Long-term care covers immune reconstitution, revaccination from 6–12 months, endocrine and bone surveillance, and screening for second malignancies.
Complications
Timing Complication Notes
Early (0–30 days) Mucositis, nausea and vomiting, febrile neutropenia, Mucositis is the commonest and most distressing bacterial and fungal sepsis, haemorrhagic cystitis complication, and in older patients precipitates (cyclophosphamide, BK virus), sinusoidal obstruction dehydration, delirium and malnutrition. Sinusoidal syndrome (formerly veno-occlusive disease), obstruction syndrome — weight gain, tender engraftment syndrome, graft failure hepatomegaly, jaundice — is treated with defibrotide Intermediate (30–100 Acute GVHD; CMV reactivation; Pneumocystis Acute GVHD affects skin, gut and liver — days) jirovecii; invasive aspergillosis; idiopathic pneumonia maculopapular rash, secretory diarrhoea, cholestatic syndrome jaundice; graded I–IV; first-line treatment is methylprednisolone 2 mg/kg/day. Ruxolitinib is the standard for steroid-refractory disease Late (>100 days) Chronic GVHD; late infection with encapsulated Chronic GVHD is the leading cause of late non-organisms; bronchiolitis obliterans; cataract, relapse mortality and resembles an autoimmune hypothyroidism, hypogonadism, infertility; disease — sicca syndrome, scleroderma-like skin osteoporosis and avascular necrosis; iron overload; change, lichenoid oral lesions, and lung involvement. It secondary malignancy; relapse of the original disease is a major cause of poor quality of life The Older Transplant Recipient
Why age was historically a barrier. Reduced marrow and organ reserve, more comorbidity, higher infection risk, slower immune reconstitution and greater treatment-related mortality. Traditional upper limits of 55 years for allogeneic and 65 for autologous transplant excluded the very patients in whom AML and MDS are commonest.
What changed. Reduced-intensity conditioning, better supportive care and antimicrobial prophylaxis, haploidentical donors, and modern GVHD prophylaxis have together shifted the question from "how old is the patient?" to "what is the patient's comorbidity and functional reserve?"
Selecting the older candidate — four tools. HCT-CI (Sorror index) — the transplant-specific comorbidity score; higher scores predict non-relapse mortality. Comprehensive geriatric assessment — ADL/IADL, gait speed, cognition (Mini-Cog), nutrition (MNA), polypharmacy, social support and depression all independently predict outcome. Performance status — Karnofsky ≥70% is the usual threshold. Disease risk index — the likelihood of relapse must justify the risk of the procedure.
Two practical points that dominate the geriatric transplant ward. First, caregiver availability is a hard requirement — the patient needs a competent 24-hour caregiver for at least 100 days, and lack of one is a common reason older patients are declined. Second, delirium is markedly commoner in older transplant recipients and independently predicts mortality; it should be actively prevented and screened for.
Prognosis. Historical one-year non-relapse mortality in patients aged 70 and above was around 25%. With current conditioning and prophylaxis this has fallen substantially, and outcomes in fit older patients now approach those of patients in their sixties. The dominant predictors are comorbidity, performance status and disease risk — not chronological age.
Latest Updates (2023–present)
BMT CTN 1703 has changed GVHD prophylaxis
This phase 3 trial randomised 431 adults undergoing allogeneic transplantation with a matched related or matched/7-of-8 mismatched unrelated donor after reduced-intensity conditioning to either post-transplant cyclophosphamide with tacrolimus and mycophenolate mofetil or tacrolimus with methotrexate. The primary endpoint was GVHD-free, relapse-free survival at one year, with events defined as grade III–IV acute GVHD, chronic GVHD requiring systemic treatment, relapse or death.
Post-transplant cyclophosphamide was significantly superior, and this regimen is now the standard prophylaxis after reduced-intensity conditioning.
The subgroup analysis in patients aged 70 and above is the geriatric headline. Of the 431 patients enrolled, 96 were aged 70 or over. Despite the concern that older adults would experience more treatment-related toxicity and GVHD, post-transplant cyclophosphamide produced markedly better results in this group as well, published in Blood Advances in 2025.
The authors note that allogeneic transplantation remains underutilised in adults aged 70 and above, and that morbidity driven by GVHD is considered the major barrier to its use — a barrier this trial directly addresses.
Age itself is not the driver of GVHD
A 2025 systematic review and meta-analysis of outcomes in patients aged 70 and above reported that graft source and prophylaxis regimen, rather than advancing age, determine GVHD incidence. Peripheral blood stem cell grafts and tacrolimus-based prophylaxis increased GVHD, with similar incidence across the 60–64, 65– 69 and 70-and-above age groups.
The same review identifies post-transplant cyclophosphamide as the principal strategy for reducing non-relapse mortality in older patients.
Real-world feasibility in the elderly
A ten-year single-centre series of allogeneic transplantation for AML at a median age of 68 found it feasible and safe: 65% received grafts from a 10/10 or 9/10 matched unrelated donor, 14% from a matched sibling and 20% from a haploidentical donor; all received reduced-intensity conditioning and 98% received peripheral blood stem cells. Acute GVHD occurred in 44% (grade III–IV in 5 patients) and CMV reactivation in 39% by day +100.
Registry work continues to show that older transplant candidates are a frailer population overall, reinforcing the case for formal geriatric assessment rather than age cut-offs.
Other developments worth naming
Ruxolitinib is now standard for steroid-refractory acute and chronic GVHD, with belumosudil and axatilimab as further options in chronic disease.
Letermovir prophylaxis has substantially reduced clinically significant CMV reactivation. A dedicated trial (NCT06799195) is now enrolling adults aged 60 and older with Karnofsky performance status ≥70% receiving reduced-intensity conditioning to optimise GVHD prophylaxis specifically in this population — the first study designed around the older recipient rather than including them incidentally.
Current Practice Update
Area Traditional position Current practice (2023–2026)
Upper age limit Allogeneic 55 years; autologous 65 years No fixed limit — allogeneic transplant into the early seventies, autologous to about 75, decided by comorbidity and function Conditioning Myeloablative Reduced-intensity conditioning is standard in older adults GVHD prophylaxis Calcineurin inhibitor + methotrexate Post-transplant cyclophosphamide + tacrolimus + MMF (BMT CTN 1703), including in patients ≥70 Donor availability Matched sibling or unrelated donor only Haploidentical transplantation has removed the donor barrier Patient selection Chronological age and performance status HCT-CI plus comprehensive geriatric assessment Steroid-refractory GVHD Second-line immunosuppression, poor outcome Ruxolitinib; belumosudil and axatilimab in chronic GVHD CMV Pre-emptive monitoring and treatment Letermovir prophylaxis Stem cell source Bone marrow harvest Peripheral blood stem cells in over 90% of adult transplants Exam one-liners Autologous = rescue from high-dose chemotherapy. Allogeneic = replacement plus a graft-versus-tumour effect. Myeloma is the commonest indication for autologous, AML and higher-risk MDS for allogeneic transplant. Reduced-intensity conditioning is what made transplantation possible in the elderly — it borrows its efficacy from the donor immune system, not from the chemotherapy.
Aim for a CD34+ dose of at least 2 × 10⁶/kg. Neutrophils engraft around day +14, platelets around day +21. Acute GVHD = skin, gut, liver, within 100 days. Chronic GVHD = an autoimmune-like multisystem illness and the leading cause of late non-relapse mortality.
Post-transplant cyclophosphamide is now standard prophylaxis — and BMT CTN 1703 showed it works in patients aged 70 and above too.
Age is not the risk factor; comorbidity is. Use the HCT-CI plus a geriatric assessment, not the birth certificate. No caregiver, no transplant — 24-hour support for 100 days is a hard requirement. Haploidentical donors mean almost every Indian patient now has a donor.
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References
- PAPERS-2-3-4_COMBINED.pdf — page 879
- GeriQBank source PDF — p. 879
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