Key points
- Full recovery after a transplant usually takes 3 to 5 years [1]. Some problems may appear years later; that is why you should always go to your follow-up visits [2].
- The most important late problem after a transplant from a donor is the chronic reaction of the transplanted cells against the body (chronic GVHD) [3]. About one in 3 patients needs medicine for it, and it usually starts in the first year [4].
- This reaction can affect the skin, mouth, eyes, lungs, liver, gut and joints. Lung involvement has no symptoms at first and is found with breathing tests [5].
- The first treatment is steroids [4]. If that is not enough, ruxolitinib tablets worked about twice as often as other treatments [6] and are now the next treatment [7].
- There are other problems too: an underactive thyroid, infertility, thinning bones, cataracts, high blood pressure and blood sugar, kidney disease, tiredness and forgetfulness. Most of them are found early with regular tests and treated [2].
- The risk of a new cancer in later years is higher than in other people; regular checks of the skin and mouth and screening tests are important [2].
- Tell your transplant doctor early about new breathlessness or cough, tightening of the skin or less movement in your joints, dry and painful eyes, mouth sores, weight loss and hip pain [2, 5].
Why do some effects of a transplant last?
Late problems after a transplant come from several things: the drugs and radiotherapy before the transplant, the strong chemotherapy or radiotherapy in the days before the transplant, the medicines you take after the transplant (such as steroids and immunosuppressive medicines), and the chronic reaction of the transplanted cells [2]. Some of these problems appear years later [2].
Recovery is slow: the body gets better sooner than your spirits and ability to work, and full recovery usually takes 3 to 5 years [1]. Finding these problems early and treating them in time is the key to a better life [2]. For the first months see the guide to after leaving the transplant unit, and for an overview the blood stem cell transplant page.
What is chronic GVHD?
After a transplant from a donor, the donor's immune cells sometimes see your body as "foreign" and attack it. This is called graft-versus-host disease (GVHD). Its chronic form usually appears in the first year, often when immunosuppressive medicines are being reduced [4].
About one in 3 patients needs medicine for it [4]. The mild form often gets better with creams, drops or mouthwashes; the more severe form or lung involvement needs medicines [4, 5]. With treatment, about half of patients recover completely within a few years and their medicines are stopped [4].
For physicians
In graft-versus-host disease (GVHD), the donor's immune cells recognise the recipient's tissues as foreign and attack them. Its chronic form may resemble autoimmune or other immune diseases such as scleroderma, Sjögren's syndrome or bronchiolitis obliterans [4].
About 30 to 40% of allogeneic transplant recipients need systemic treatment for chronic GVHD within 2 years, and this risk is higher after peripheral blood stem cell transplant than after bone marrow [4]. Symptoms usually appear in the first year and often while immunosuppressive medicines are being reduced; onset can be from 2 months to 7 years after the transplant, but onset after the first year happens in fewer than 10% of cases [4].
Mild chronic GVHD that involves only one or two organs mildly is often controlled with topical treatment, but involvement of 3 or more organs, moderate or severe involvement of any organ, or any lung involvement usually needs systemic treatment [4, 5]. With treatment, about half of patients have a complete recovery within 7 years of starting systemic treatment and stop their medicines; the median length of treatment is about 2 years after bone marrow transplant and about 3.5 years after peripheral blood cell transplant [4].
| Organ | Symptoms you may notice | Care and local treatment |
|---|---|---|
| Skin, hair and nails | Red, purple, dark or light patches, dryness and itching, tightening and thickening of the skin, hair loss and brittle nails [5, 8] | Regular moisturiser, steroid cream, sun protection with clothing and a sunscreen with UVA and UVB protection; sunlight can make skin GVHD worse [8] |
| Mouth | Lacy white lines on the lining, dry mouth, sores and pain, sensitivity to spicy, sour or rough foods [5, 8] | A strong steroid mouthwash or gel, frequent sips of water and saliva substitutes, fluoride and regular dental check-ups; a yearly check for mouth cancer [8] |
| Eyes | Dryness, a gritty feeling, burning, pain, sensitivity to light or sometimes a lot of watering [5, 8] | Preservative-free artificial tears, ciclosporin drops, plugging the tear ducts and special lenses; follow-up with an eye specialist who knows about GVHD [8] |
| Lungs (bronchiolitis obliterans) | Breathlessness on activity, cough or wheezing; but often no symptoms at first [5] | Regular lung function tests, an inhaled steroid, pulmonary rehabilitation and avoiding cigarette smoke and dust [8] |
| Liver | Rising liver tests and sometimes jaundice; often when immunosuppressive medicines are being reduced [5] | Regular liver tests; your doctor also checks for other causes such as infection or medicine effects [5] |
| Oesophagus and bowel | Difficulty or pain swallowing, poor appetite, nausea, diarrhoea and weight loss [5] | Checking for infection, widening the oesophagus by endoscopy if it has narrowed, and help from a dietitian [8] |
| Joints and the tissue under the skin | Stiffness and reduced movement of the wrists, elbows, shoulders or ankles, swelling of the limbs and, at a late stage, joint contractures [5] | Early physiotherapy and regular stretching and strengthening exercises at home to keep the range of movement [8] |
| Genitals | Women: dryness, burning, pain during sex, adhesions or narrowing of the vagina; men: burning, pain during sex and tightening of the foreskin [5] | A strong steroid ointment, oestrogen cream if levels are low, a device to keep the vagina open and regular gynaecological check-ups [2, 8] |
Before symptoms are put down to GVHD, infection, drug side effects and disease relapse must be excluded [5]; supportive care is based on the report of the NIH consensus supportive care group [8].
For physicians
Diagnosis and severity of chronic GVHD (NIH consensus 2014)
- Diagnosis: at least one "diagnostic" manifestation (such as poikiloderma, lichen planus-like lesions of the skin, mouth or genitals, deep sclerosis, morphea-like or lichen sclerosus-like features, vaginal scarring or adhesions, phimosis, oesophageal web or stricture, fasciitis), or one "distinctive" manifestation plus biopsy, a test (such as PFT or Schirmer), specialist assessment or imaging in the same or another organ; exclusion of infection, drug toxicity and relapse is mandatory. The liver has no diagnostic or distinctive manifestations [5].
- BOS: (1) FEV1/VC below 0.7 or below the 5th percentile predicted; (2) FEV1 below 75% predicted with a decline of 10% or more in less than 2 years, not corrected by bronchodilator; (3) no respiratory infection; (4) one of two supporting findings: air trapping, small airway thickening or bronchiectasis on CT, or RV above 120% predicted or raised RV/TLC. If chronic GVHD is already established in another organ, the first three criteria are enough; isolated BOS needs a lung biopsy for entry into general trials [5].
- Global severity: mild = 1 or 2 organs with a maximum score of 1 and a lung score of zero; moderate = 3 or more organs with a maximum score of 1, or at least one non-lung organ with a score of 2, or a lung score of 1; severe = at least one organ with a score of 3 or a lung score of 2 or 3. For the skin the higher subscore (BSA or skin features) and for the lung the FEV1 is used; an organ whose abnormality is fully explained by another cause is not counted, but a multifactorial cause does not lower the score [5].
- Indication for systemic treatment: involvement of 3 or more organs or a score of 2 or more in any organ; in the mouth, eyes and genitals, intensive topical treatment alone may be enough. Thrombocytopenia (below 100,000/µL) and "progressive" onset from acute GVHD are the factors most consistently associated with late mortality [5].
- Steroid refractoriness and dependence: refractory = progression on prednisone 1 mg/kg/day or more over 1 to 2 weeks, or stable disease on 0.5 mg/kg/day or more over 1 to 2 months; dependent = inability to taper prednisone below 0.25 mg/kg/day in at least two unsuccessful attempts at least 8 weeks apart [9].
- Lung monitoring: PFT around day 100, at diagnosis of chronic GVHD, at 1 year after transplant and every 6 months in the first 2 years after diagnosis of chronic GVHD [5]; 2023 international recommendation: PFT every 3 months in the first year after transplant, every 6 months in the second year and then yearly up to 5 years, and with chronic GVHD at least spirometry every 3 to 6 months until systemic treatment is stopped [2].
| Organ | Score 1 | Score 2 | Score 3 |
|---|---|---|---|
| Skin | 1 to 18% of body surface | 19 to 50% of body surface or superficial sclerosis (can be pinched) | More than 50% of body surface, or deep sclerosis (cannot be pinched), impaired movement or ulceration |
| Mouth | Mild symptoms with signs of disease, without significant limitation of eating | Moderate symptoms with partial limitation of eating | Severe symptoms with major limitation of eating |
| Eyes | Mild dryness not affecting daily activities; lubricant drops at most 3 times a day | Moderate dryness partly affecting activities; drops more than 3 times a day or punctal plugs, without loss of vision from KCS | Severe dryness significantly affecting activities, inability to work or loss of vision from KCS |
| Gastrointestinal tract | Symptoms without significant weight loss (below 5%) | Weight loss of 5 to 15% or moderate diarrhoea without significant interference with daily life | Weight loss above 15%, needing supplements for most calories, oesophageal dilatation or severe diarrhoea |
| Liver | Normal bilirubin with ALT three to five times or ALP three times the upper limit or more | Bilirubin raised up to 3 mg/dL or ALT more than five times the upper limit | Bilirubin above 3 mg/dL |
| Lung (FEV1) | FEV1 60 to 79% | FEV1 40 to 59% | FEV1 39% or less |
| Joints and fascia | Mild tightness of the arms or legs with normal or slightly reduced range of movement, not affecting daily activities | Tightness or contractures, erythema from fasciitis, moderate reduction in range of movement and mild to moderate limitation of activities | Contractures with severe reduction in range of movement and severe limitation of daily activities |
| Genitals | Mild findings | Moderate findings; may come with symptoms or discomfort on examination | Severe findings with or without symptoms |
A score of zero means no involvement; for the lung, if symptoms and FEV1 do not agree, FEV1 is used, and the genitals and eyes are best assessed by a specialist [5].
Treating chronic GVHD
Treatment regimens and doses: index6 regimens
The aim of treatment is to reduce symptoms and prevent lasting damage. Because stronger medicines also raise the risk of infection, your doctor gives the smallest amount of medicine that calms the disease [5]. The care in the table above, physiotherapy, good food and preventing infection are also part of treatment [4].
Medicine treatment usually lasts at least a year, and about half of patients need a second medicine within 2 years [4].
The main medicines
- Steroids (such as prednisolone): the first treatment. Because long-term use has side effects such as weight gain, thinning bones, high blood sugar and cataracts, your doctor lowers the dose little by little; do not stop them yourself [4].
- If steroids are not enough: ruxolitinib tablets; in a large study they worked about twice as often as other treatments [6] and are now the next standard treatment [7].
- If that still does not work: newer medicines such as ibrutinib, belumosudil and axatilimab, which worked in most of the patients tested [11, 3, 14].
- There are other options too, which your transplant doctor chooses based on your situation [4].
For physicians
Medicine treatment options
Steroids (prednisolone) with or without ciclosporin or tacrolimus
The standard first treatment for moderate to severe chronic GVHD: usually prednisolone or prednisone 0.5 to 1 mg per kg of body weight a day, then a gradual reduction to alternate-day dosing. Long-term steroid use can cause weight gain, thinning bones, muscle weakness, diabetes, high blood pressure, mood swings, cataracts and infection; so the aim is the lowest effective dose [4].
Ruxolitinib
An oral inhibitor of the JAK1 and JAK2 enzymes. In the phase 3 REACH3 trial in 329 patients with steroid-refractory or steroid-dependent chronic GVHD, the overall response at week 24 was 49.7% with ruxolitinib versus 25.6% with best available therapy, and failure-free survival was longer (median more than 18.6 vs 5.7 months); the commonest serious side effects were low platelets and anaemia [6]. At 3-year follow-up, the median of this survival was 38.4 versus 5.7 months [10]. The 2024 EBMT guideline regards it as the standard treatment for steroid-refractory chronic GVHD [7].
Ibrutinib
An oral inhibitor of BTK (and of the ITK enzyme in T cells). In a phase 1b/2 study in 42 patients in whom 1 to 3 previous treatments had failed, the best overall response was 67%, and 71% of responders had a sustained response for at least 20 weeks; common side effects were tiredness, diarrhoea, muscle cramps, nausea and bruising [11]. It is approved for chronic GVHD after failure of one or more lines of systemic treatment [12].
Belumosudil
An oral inhibitor of the ROCK2 enzyme. In the ROCKstar trial in patients who had received 2 to 5 previous treatments, the best overall response was 74% with 200 mg daily and 77% with 200 mg twice a day, and the median duration of response reached 54 weeks [3]. It is approved for chronic GVHD after failure of at least two lines of systemic treatment [13], and EBMT has added it to the options for steroid-refractory chronic GVHD [7].
Axatilimab
An antibody blocking the CSF1R receptor that targets the monocytes and macrophages involved in chronic GVHD, given by IV infusion every 2 weeks. In the phase 2 AGAVE-201 trial in 241 patients with recurrent or refractory chronic GVHD, the overall response at a dose of 0.3 mg/kg was 74% [14]. It is approved for chronic GVHD after failure of at least two lines of systemic treatment in patients of at least 40 kg [15].
Other options
Extracorporeal photopheresis (ECP), rituximab, imatinib, mycophenolate, mTOR inhibitors such as sirolimus and several other drugs have also been used; their evidence comes mostly from non-randomised studies, and the choice depends on the doctor's experience, the type of involvement, the need for monitoring and side effects [4].
- Preventing infection during systemic treatment: PJP prophylaxis (co-trimoxazole first choice) and prevention of encapsulated bacteria in all patients on systemic treatment; anti-mould prophylaxis (posaconazole or voriconazole) in high-risk patients such as those taking prednisone above 0.5 to 1 mg/kg a day; CMV monitoring in seropositive patients; IVIG is not routinely recommended and can be considered with IgG below 400 mg/dL and recurrent sinopulmonary infections [8]. Continue PJP and encapsulated bacteria prophylaxis until 6 months after all systemic treatment stops [4].
- Azoles: ruxolitinib with fluconazole 200 mg or less: start at 5 mg twice a day; do not combine with fluconazole above 200 mg a day; with other strong CYP3A4 inhibitors, monitor blood counts frequently [16]. Ibrutinib (age 12 and over): with voriconazole 200 mg twice a day, 280 mg; with posaconazole tablets 300 mg or IV, 140 mg daily; other strong CYP3A inhibitors are contraindicated (for use of 7 days or less, hold temporarily) [12].
- Belumosudil: with a proton pump inhibitor or a strong CYP3A inducer, increase the dose to 200 mg twice a day [13].
- Pregnancy: belumosudil and axatilimab may harm an unborn baby; continue effective contraception until 1 week after the last dose of belumosudil and 30 days after axatilimab [13, 15].
- Azithromycin: not indicated for preventing BOS; in the ALLOZITHRO trial, 250 mg three times a week from conditioning was associated with lower airflow-decline-free survival and overall survival and more haematological relapse [17, 18].
For physicians
Regimens and doses in chronic GVHD and BOS
Prednisone or prednisolone ± calcineurin inhibitor (first line)
Moderate to severe chronic GVHD (3 or more organs, a score of 2 or more in any organ or any lung involvement) or milder cases with high-risk features such as thrombocytopenia, hyperbilirubinaemia or onset while on steroidsCycle length: Continuous
Moderate to severe chronic GVHD (3 or more organs, a score of 2 or more in any organ or any lung involvement) or milder cases with high-risk features such as thrombocytopenia, hyperbilirubinaemia or onset while on steroids
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Start | |||
| Prednisone (or prednisolone) | 0.5 to 1 mg/kg a day | Oral | Daily |
| Tapering | |||
| Prednisone (or prednisolone) | Reduce by about 20 to 30% every 2 weeks down to an alternate-day regimen | Oral | Alternate days thereafter |
| Add-on (optional) | |||
| Ciclosporin or tacrolimus | According to blood level | Oral | Daily |
Taper after a complete or very good response, with examination before each reduction; on flare, go up 2 levels and give daily for 2 to 4 weeks, then at least 3 months of treatment before trying again. Once at 0.1 mg/kg (adrenal replacement equivalent) on alternate days for at least 4 weeks, stopping may be possible. Randomised trials showed no benefit from adding azathioprine, thalidomide, mycophenolate or hydroxychloroquine to first-line treatment; adding ciclosporin did not change survival but avascular necrosis was less common. Indications for second line: worsening or new organ involvement, no improvement after 1 month, inability to reduce prednisone below 1 mg/kg within 2 months or significant toxicity. Calcium 1500 mg and vitamin D 1000 units a day during steroid treatment [4]. Definitions of steroid refractoriness and dependence: [9].
Ruxolitinib (REACH3)
Steroid-refractory or steroid-dependent chronic GVHD after failure of 1 or 2 lines of systemic treatment; adults and children aged 12 and overCycle length: Continuous
Steroid-refractory or steroid-dependent chronic GVHD after failure of 1 or 2 lines of systemic treatment; adults and children aged 12 and over
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Ruxolitinib | 10 mg twice a day | Oral | Daily |
Tapering: one dose level about every 8 weeks (10 mg twice → 5 mg twice → 5 mg once a day). Side effects: platelets below 20,000/µL or neutrophils below 750 (drug-related): one level lower; neutrophils below 500: hold for up to 14 days and resume one level lower; bilirubin 3 to 5 times the upper limit: one level lower until improved; more than 5 to 10 times: hold for up to 14 days; more than 10 times: hold for up to 14 days and stop if no improvement. CrCl 15 to 59: 5 mg twice a day; dialysis: 10 mg after each session; do not use with CrCl below 15 not on dialysis. CBC and bilirubin before starting and every 2 to 4 weeks until the dose is stable, blood lipids 8 to 12 weeks after starting; before starting, check for a history of tuberculosis, herpes and hepatitis B; periodic skin examination (non-melanoma skin cancer) and avoid abrupt stopping [16]. Results: overall response at week 24 49.7% versus 25.6% (OR 2.99), failure-free survival with a median of more than 18.6 versus 5.7 months (HR 0.37) [6] and at 3-year follow-up 38.4 versus 5.7 months (HR 0.36) [10].
Ibrutinib
Chronic GVHD after failure of 1 or more lines of systemic treatment; adults and children aged 1 and overCycle length: Continuous
Chronic GVHD after failure of 1 or more lines of systemic treatment; adults and children aged 1 and over
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Age 12 and over | |||
| Ibrutinib | 420 mg once a day | Oral | Daily |
| Age 1 to under 12 | |||
| Ibrutinib | 240 mg/m² once a day (maximum 420 mg) | Oral | Daily |
Adjustment with azoles (age 12 and over): voriconazole 200 mg twice a day or posaconazole suspension up to 200 mg twice a day: 280 mg; posaconazole suspension 200 mg three times a day or 400 mg twice a day, delayed-release tablet 300 mg or IV 300 mg: 140 mg; moderate CYP3A inhibitor: no change. Grade 3 or 4 non-haematological toxicity, grade 3 or 4 neutropenia with fever or infection, or grade 4 haematological toxicity: hold and after recovery resume at 280 mg and, the second time, 140 mg; grade 2 heart failure or grade 3 arrhythmia: after recovery at a lower dose; grade 3 or 4 heart failure or grade 4 arrhythmia: stop [12]. In the phase 1b/2 study (42 patients), the best overall response was 67%, and the median steroid dose of responders fell from 0.29 to 0.12 mg/kg a day by week 49 [11].
Belumosudil (ROCKstar)
Chronic GVHD after failure of at least 2 lines of systemic treatment; adults and children aged 12 and overCycle length: Continuous
Chronic GVHD after failure of at least 2 lines of systemic treatment; adults and children aged 12 and over
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Usual | |||
| Belumosudil | 200 mg once a day with food | Oral | Daily |
| With a proton pump inhibitor or a strong CYP3A inducer | |||
| Belumosudil | 200 mg twice a day | Oral | Daily |
Swallow the tablet whole, at about the same time each day and with food. Bilirubin, AST and ALT at least monthly; grade 3 AST or ALT (5 to 20 times) or grade 2 bilirubin (1.5 to 3 times): hold until grade 0 to 1 and resume at the recommended dose; grade 4 AST or ALT or grade 3 or higher bilirubin: stop permanently; other grade 3 toxicities: hold temporarily; grade 4: stop permanently. Avoid in moderate or severe hepatic impairment without liver GVHD. Effective contraception until 1 week after the last dose [13]. ROCKstar results: best overall response 74% (95% CI 62 to 84) and 77% (95% CI 65 to 87), median duration of response 54 weeks, and discontinuation for possibly related adverse events 12% [3].
Axatilimab (AGAVE-201)
Chronic GVHD after failure of at least 2 lines of systemic treatment; adults and children of at least 40 kgCycle length: Every 14 days
Chronic GVHD after failure of at least 2 lines of systemic treatment; adults and children of at least 40 kg
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Axatilimab | 0.3 mg/kg (maximum 35 mg) | 30-minute IV infusion with a 0.2 micron filter | Every 2 weeks |
Monitor AST, ALT, ALP, CPK, amylase and lipase before starting, every 2 weeks in the first month and then every 1 to 2 months until abnormalities resolve. Grade 1 to 2 infusion reaction: pause or slow the rate by 50% and premedicate (antihistamine and antipyretic) for later doses; grade 3 to 4: stop permanently. Grade 3 AST or ALT with bilirubin at most grade 1 on the infusion day: delay until grade 2 and continue at 0.2 mg/kg (maximum 23 mg). Grade 3 or higher rise in CPK, amylase or lipase without organ damage: continue without dose reduction. Contraception until 30 days after the last dose [15]. Results: overall response 74% (0.3 mg/kg every 2 weeks), 67% (1 mg/kg every 2 weeks) and 50% (3 mg/kg every 4 weeks); discontinuation for adverse events 6% at the 0.3 dose [14].
FAM with a short steroid pulse (newly diagnosed BOS)
Newly diagnosed (less than 6 months) bronchiolitis obliterans syndrome after transplant, after excluding airway infectionCycle length: Continuous
Newly diagnosed (less than 6 months) bronchiolitis obliterans syndrome after transplant, after excluding airway infection
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| FAM | |||
| Fluticasone propionate | 440 µg twice a day | Inhaled | Daily |
| Azithromycin | 250 mg | Oral | 3 days a week |
| Montelukast | 10 mg | Oral | Every night |
| Steroid pulse | |||
| Prednisone | 1 mg/kg a day for 2 weeks, then reduce by 0.25 mg/kg a week down to 0.25 mg/kg a day | Oral | Over about 5 weeks |
In a single-arm phase 2 study (36 patients), treatment failure (FEV1 decline of 10% or more) at 3 months was 6% versus 40% in a historical control group, the steroid dose was reduced by at least 50% in 48%, and failure at 6 months was 36%. Children's doses in the study: fluticasone 220 µg twice a day (age 6 to 11), azithromycin 5 mg/kg (maximum 250) three days a week, montelukast 5 mg (age 6 to 13) [19]. FAM is for treating established BOS; long-term azithromycin is not indicated for preventing BOS, and in ALLOZITHRO 2-year survival was 56.6% versus 70.1% and 2-year haematological relapse 33.5% versus 22.3% [17, 18].
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Other second-line options and supportive care
- Range of overall responses reported in mostly non-randomised studies: ECP 65 to 70%, rituximab 66 to 86%, imatinib 22 to 79%, pentostatin 53 to 56%, mesenchymal stem cells 50 to 74%, mycophenolate 26 to 64%, mTOR inhibitors 76% and interleukin-2 52%; there is no consensus on the best choice among them [4].
- The 2024 EBMT guideline regards ruxolitinib as the standard second-line treatment and belumosudil as an added option for steroid-refractory chronic GVHD [7].
- Bone: with steroid treatment for more than 3 months, DEXA and antiresorptive treatment (a bisphosphonate, or hormone replacement in deficiency), especially at high fracture risk; baseline and yearly calcium and vitamin D [8].
- Eyes: pulsed topical steroids only under an ophthalmologist (risk of raised eye pressure, cataract and silent infectious keratitis) [8].
- Lungs: pulmonary rehabilitation and a 6-minute walk test to identify the need for oxygen (SpO2 below 87% on room air); lung transplant can be discussed in severe BOS with the underlying disease in remission [8].
Other late effects of a transplant
Late effects and ways to prevent them
Thyroid and glands
An underactive thyroid is the commonest gland problem after a transplant and usually appears a few years later; a thyroid test is needed one year after the transplant and then every year [2]. Long-term steroids (even creams or inhalers) can reduce the work of the adrenal glands; change your steroid dose only on your doctor's advice [2].
Fertility and hormones
Most patients have fertility problems after a transplant, but in some, fertility comes back to a greater or lesser degree [2]. Hormones are checked one year after the transplant; if a woman has gone through an early menopause, hormone therapy is an option, and if you want children talk to a fertility specialist [2].
Bones
Thinning bones are common after a transplant [2]. Sometimes part of a bone, most often in the hip joint, is damaged because its blood supply falls; this happens most often with steroids. Take new hip pain seriously [2]. A bone density scan one year after the transplant, calcium and vitamin D and regular exercise are recommended [2].
Eyes
Early cataracts are more common after total body irradiation, some chemotherapy drugs and steroids, and steroid eye drops can raise the pressure in the eye. Tell your doctor about dry eyes or changes in vision so an eye specialist can examine you [2].
Heart, blood pressure and blood sugar
Tummy fat, high blood pressure, high blood sugar and high blood fats are common after a transplant, and the risk of heart disease rises over the years [2]. Blood pressure and weight are checked at every visit and blood sugar and blood fats regularly; healthy food, exercise and not smoking are the best prevention [2].
Kidneys
A new cancer
Tiredness
Tiredness after a transplant is very common [2]. Regular exercise, counselling and mindfulness exercises help most [20]. See the guide to fatigue from cancer and its treatment.
Memory and concentration
Some patients have forgetfulness or slow thinking after a transplant. Your doctor should ask about this every year and check for treatable causes such as depression, poor sleep or medicine effects [2].
Mood and life
Mouth and teeth
Dry mouth, tooth decay and gum disease are more common after a transplant. A dental check-up at 6 months, one year and then every year, careful brushing and flossing, avoiding smoking and sugary drinks, and the HPV vaccine after the transplant are recommended [2].
Lungs and infection
Lung problems may appear years later [2]. Infection is an important cause of late death, and vaccine-preventable diseases are much more common in transplant survivors; complete your vaccinations [2]. The vaccine schedule is in the guide to after leaving the transplant unit.
The long-term screening and follow-up plan
The table below summarises the 2023 international recommendations for people who have had a transplant. Your transplant doctor adjusts the plan to your situation [2].
Which tests, and when?
- Follow-up visits: day 100, 6 months and one year after the transplant, and then every year [2].
- Blood, liver and kidney tests, blood pressure and weight: at most visits [2].
- Blood sugar and blood fats: from a few months after the transplant and then every year [2].
- Breathing tests (lung function): every 3 months in the first year, every 6 months in the second year and then every year up to 5 years [2].
- Thyroid and bone density: one year after the transplant, and the thyroid every year after that [2].
- Eyes, mouth and teeth, and skin: regular checks; dental check-ups at 6 months, one year and then every year [2].
- Cancer screening (breast, bowel, cervix and others): based on age and history of radiotherapy, earlier than for other people [2].
- Memory, mood and life worries: ask and talk about them at your visits [2].
For physicians
| Area | Check | Timing and frequency |
|---|---|---|
| Follow-up visit | Symptoms, medicines and adherence, physical activity and psychological distress | At least at day 100, 180 and 365 and then yearly [2] |
| Blood and liver | Full blood count; bilirubin, ALP and ALT | Blood count at most visits for at least 10 years; liver tests every 1 to 2 months in the first year and then at least yearly [2] |
| Kidneys and blood pressure | Urinalysis, urine protein-to-creatinine ratio, BUN and creatinine; blood pressure | 6 months, 1 year and then at least yearly; blood pressure at every visit [2] |
| Heart and metabolism | Weight and body mass index, blood lipids, HbA1c | Weight at every visit; blood lipids from 6 months and then yearly (every 3 to 6 months on steroids, a calcineurin inhibitor or sirolimus); HbA1c from 3 to 6 months and then yearly (every 6 months at high risk) [2] |
| Lungs | Lung function test (spirometry and DLCO) | Every 3 months in the first year, every 6 months in the second year and then yearly up to 5 years; with chronic GVHD at least spirometry every 3 to 6 months until systemic treatment stops [2] |
| Eyes | Questions about eye symptoms; eye examination; eye pressure on steroids | Questions at every visit; examination at onset of chronic GVHD, dry eyes or change in vision [2] |
| Mouth and teeth | Dental and mouth examination for GVHD and mouth cancer | 6 months, 1 year and then yearly; every 6 months at high risk of mouth cancer [2] |
| Skin | Regular self-examination and full skin examination | At least every 6 to 12 months [2] |
| Glands and sexual health | TSH and free T4; gonadal assessment; conversation about sexual health | Thyroid at 1 year and then yearly; gonads at least at 1 year; sexual health from 3 to 6 months and then yearly [2] |
| Bones | Bone density scan (DEXA); calcium and vitamin D | At 1 year after the transplant (at 3 months at high risk or on high-dose steroids); repeat every 1 to 2 years if abnormal [2] |
| Nerves, memory and mental health | Neurological examination; questions about memory and concentration; screening for anxiety and depression; carer situation and financial problems | Neurological examination at 6 to 12 months and then at least yearly; memory yearly; mental health at follow-up visits [2] |
| Second cancers | Mammography and breast MRI in women with a history of TBI or chest radiotherapy; colonoscopy with a history of abdominal and pelvic radiotherapy or TBI; yearly thyroid examination; cervical screening by age | Breast from age 25 or 8 years after radiation (whichever is later) and at the latest by age 40; colonoscopy from 5 years after radiation and at the latest by age 45, by shared decision; the rest according to general guidelines [2] |
Based on the 2023 international recommendations for transplant and cellular therapy survivors [2]. The revaccination schedule is set separately.
When should I call my doctor?
Tell your transplant team about any of these symptoms without delay:
- Breathlessness on activity, a dry cough or new wheezing; bronchiolitis obliterans can start quietly, and early diagnosis and treatment improve the outcome [2, 5].
- Tightening or thickening of the skin, swelling of the hands and feet or less movement in the wrists, elbows and shoulders [5].
- Dryness, burning, pain or severe sensitivity of the eyes to light, or a change in vision [2, 5].
- A sore or white patch in the mouth that does not heal, mouth pain that stops you eating, or trouble swallowing [2, 5].
- Unexplained weight loss, ongoing diarrhoea or yellowing of the skin and eyes [5].
- Pain in the hip, knee or shoulder, especially if you take or have taken steroids [2].
- A sore or skin lesion that does not heal, or any new skin change [2].
- A temperature of 38 °C or higher or any sign of infection while you are taking immunosuppressive medicines [22].
Frequently asked questions
Does chronic GVHD mean the transplant has failed?
Why do I need tests years after the transplant when I feel well?
Because some complications such as lung disease, thinning bones, an underactive thyroid and second cancers have no symptoms at first and may appear years or even decades later; finding them early and treating them in time improves long-term results [2].
Can I have children after a transplant?
Many survivors have reduced fertility, but in some people fertility comes back fully or partly; so both seeing a fertility specialist and using contraception (if your fertility is uncertain) are recommended. Pregnancy after a transplant should be supervised by a high-risk pregnancy specialist [2]. See the guide to fertility and sex during cancer treatment.
Which chronic GVHD medicine is best for me?
The choice depends on how severe the disease is, the organs involved, previous treatments, side effects and other illnesses. Steroids are the first treatment [4]. Ruxolitinib did better than other treatments in a large study [6], and newer medicines such as belumosudil and axatilimab are approved for patients in whom at least two previous treatments have failed [13, 15].
Can thinning bones and cataracts be prevented?
Not every case can be prevented, but the lowest effective steroid dose, enough calcium and vitamin D and regular weight-bearing exercise help keep bones healthy [4]; in high-risk people, hormone replacement or bisphosphonate medicines are also an option; for cataracts, regular questions about eye symptoms and an eye examination if symptoms appear are recommended [2].
Scientific evidence
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Related guidelines
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References
22 referencesShow all references, 2 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
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- 2International Recommendations for Screening and Preventative Practices for Long-Term Survivors of Transplantation and Cellular Therapy: A 2023 Update
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- 19Fluticasone, Azithromycin, and Montelukast Treatment for New-Onset Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation
- 20Management of Fatigue in Adult Survivors of Cancer: ASCO-Society for Integrative Oncology Guideline Update
- 21Management of Anxiety and Depression in Adult Survivors of Cancer: ASCO Guideline Update
- 22Infection and Neutropenia during Cancer Treatment
This page is based on reputable scientific sources and was last updated on 28 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.
Printed from the website; the full and up-to-date version: https://drdabiri.com/en/guides/transplant-long-term-effects/