Key points
- Most problems during the hospital stay come from the strong chemotherapy before the transplant and the fall in blood counts: nausea, mouth sores, diarrhoea, hair loss, tiredness and the need for blood transfusions are common, and most are temporary [1, 2].
- A temperature of 38 °C or higher during these days is an emergency; antibiotics must be started within an hour [3, 4].
- Mouth sores are very common; rinsing the mouth regularly and, with some drugs, holding ice in the mouth during the infusion help [5, 6].
- Report rapid weight gain, a swollen tummy, pain under the right ribs or yellowing of the skin in the first weeks straight away; it may be a problem with the liver's blood vessels that has a specific medicine [7, 8].
- After a transplant from a donor, a skin rash, diarrhoea or yellowing of the skin may be a sign of the transplanted cells reacting against the body (GVHD); the first treatment is steroids, and if they do not work there are other medicines [9, 10, 11].
- After CAR-T cell therapy, report fever, low blood pressure, confusion or trouble speaking straight away; stay near the treatment centre for at least 2 weeks and do not drive [12, 13].
Why do complications happen during the transplant?
The strong chemotherapy or radiotherapy before the transplant temporarily shuts down the bone marrow as well as the cancer cells, and damages the lining of the mouth and gut. That is why nausea, mouth sores, diarrhoea, hair loss, tiredness, poor appetite and a sharp fall in blood cells and platelets are common [1, 2].
Until the new cells settle in (engraftment), the risk of infection is high [14]. After a transplant from a donor, the donor's immune cells may attack the patient's body (GVHD) [1]. Some medicines can also put strain on the liver and kidneys [7, 16].
| Timing | More common complications |
|---|---|
| The days of chemotherapy before the transplant and a few days after | Nausea and vomiting, diarrhoea and mouth sores [2, 17] |
| Until the new cells settle in (about 2 to 6 weeks) | Fever and infection, and the need for platelet and blood transfusions [14, 18] |
| The first three weeks (sometimes later) | A problem with the small blood vessels of the liver (VOD) [7] |
| When the blood counts rise | Fever without infection, rash and swelling (engraftment syndrome) [19] |
| Up to about 3 months after a transplant from a donor | The acute reaction of the transplanted cells (acute GVHD) and reactivation of the CMV virus [1, 14] |
| The first few days after CAR-T | Fever and low blood pressure, and later sometimes confusion [13] |
The timings are approximate and depend on the type of transplant, the conditioning regimen and the source of the cells.
Nausea, mouth sores, diarrhoea and hair loss
Nausea and vomiting: several anti-sickness medicines are given together before chemotherapy; if you still feel sick, say so, because there are other medicines [17] (nausea and vomiting).
Mouth sores: most patients get mouth sores [5]. Rinsing the mouth regularly and, with some drugs, holding ice in the mouth during the infusion help [5, 6]. Strong painkillers are given for severe pain, and if you cannot eat there is extra nutritional support [5, 20] (mouth sores).
Diarrhoea: very common [2]. Because it may also come from infection or GVHD, tell your nurse how often you go and how much [9, 14].
Hair loss: temporary; hair usually grows back 2 to 3 months after treatment ends [1, 21] (hair loss).
For physicians
Nausea and vomiting: high-dose chemotherapy is likely to cause significant delayed nausea and vomiting. The 2023 MASCC/ESMO guideline recommends a combination of three anti-sickness drugs before high-dose chemotherapy and considers adding olanzapine possible; for nausea that continues despite medicines, olanzapine is a treatment option [17]. See the nausea and vomiting guide.
Mouth sores (mucositis): about 80% of patients having high-dose chemotherapy before a transplant get oral mucositis [5]. Regular mouth care, oral cryotherapy (holding ice chips in the mouth during the infusion) with high-dose melphalan regimens and low-level laser (photobiomodulation) are recommended for prevention [5, 6]. For severe pain, a strong painkiller such as morphine is used, including with a pump the patient controls [5]. If you cannot eat enough because of mouth sores, nutritional support is considered [20]. See the mouth sores guide.
Diarrhoea: common with conditioning regimens; for example, 93% of patients had diarrhoea with high-dose melphalan [2]. Because diarrhoea in transplant patients may be caused by a gut infection (such as Clostridioides difficile) or, after an allogeneic transplant, by GVHD, the care team looks for the cause and records the stool volume [9, 14]. If loperamide does not work, octreotide injections are the next option [5].
Hair loss: a common short-term side effect of a transplant [1]. Hair usually grows back 2 to 3 months after chemotherapy ends and may at first be finer, curlier or a different colour [21]. See the hair loss guide.
Things that help
Mouth care
Rinse your mouth 4 to 6 times a day with sterile water, saline or a baking soda solution, and clean your teeth 2 to 3 times a day with a soft toothbrush [14].
Ice in the mouth
If your regimen includes high-dose melphalan, ask your nurse whether you should hold ice chips in your mouth during the infusion [6].
Recording diarrhoea
For physicians
Guideline summary for physicians: nausea, mucositis and diarrhoea
- Antiemetics (MASCC/ESMO 2023): for high-dose chemotherapy before transplant, a 5-HT3 antagonist, dexamethasone and an NK1 antagonist are recommended before chemotherapy (I, A); olanzapine can be added at night and continued for 2 to 3 days after chemotherapy. In a double-blind randomised trial of 98 patients, adding olanzapine 10 mg to fosaprepitant, ondansetron and dexamethasone increased the overall complete response from 26% to 55%. For breakthrough nausea, olanzapine (some evidence: 10 mg daily for 3 days) is recommended (II, B) [17].
- Oral mucositis (MASCC/ISOO 2020): oral cryotherapy in autologous transplant with high-dose melphalan (level II); intraoral photobiomodulation with low-level laser for prevention in adults having high-dose chemotherapy with or without TBI, using one of the selected protocols (level I); IV palifermin in autologous transplant for haematological malignancies with regimens including high-dose chemotherapy and TBI (level I); IV glutamine is not recommended (higher mortality in transplant patients) and topical GM-CSF should not be used [6]. Palifermin dose in the 2014 guideline: 60 µg/kg a day for 3 days before the conditioning regimen and 3 days after transplant; morphine PCA is recommended for mucositis pain in transplant [5].
- Diarrhoea: octreotide ≥100 µg subcutaneously twice a day for diarrhoea from standard- or high-dose chemotherapy in transplant when loperamide fails [5]. Consider Clostridioides difficile infection and gut GVHD [9, 14].
Fever and infection
Until the new cells have settled in, white blood cells are very low and an infection can become dangerous very quickly. Report a temperature of 38 °C or higher or shivering straight away, and do not take fever medicine without your doctor's advice [3]. Antibiotics must be started within an hour [4].
For prevention, antibacterial, antifungal and antiviral medicines are usually given; washing hands and keeping away from visitors who are ill also matter [14, 24]. After a transplant from a donor, the CMV virus may become active again; weekly blood tests or a preventive medicine keep it under control [14, 25]. Report redness, pain or swelling where the catheter goes in [3] (low blood counts and infection).
For physicians
Until engraftment, the neutrophil count is very low and infection can quickly become dangerous. Report a temperature of 38 °C or higher and shivering straight away, and do not take fever medicine without your doctor's advice [3]. All patients with fever and neutropenia must be treated promptly with broad-spectrum antibiotics, and the first dose must be given within an hour [4, 23].
To reduce the risk of infection, transplant patients usually receive preventive medicines: an antibiotic (such as levofloxacin) for prolonged neutropenia, an antifungal (such as fluconazole) and, for people with a dormant herpes virus, aciclovir [14, 24]. HEPA-filtered rooms, hand hygiene and keeping away from ill visitors are also part of prevention [14].
CMV in allogeneic transplant: this virus may become active again after the transplant; that is why the patient's blood status for it is checked before the transplant [14]. The guidelines accept two approaches: a weekly blood test from about day 10 to at least day 100 and starting an antiviral (such as ganciclovir) as soon as the test is positive, or preventive medicine [14]. Letermovir is approved for prevention in CMV-positive allogeneic recipients, and in a phase 3 trial it reduced clinically significant CMV infection by week 24 from 60.6% to 37.5% [25, 26].
A central venous catheter can also be a source of infection; report redness, pain or swelling at the catheter site [3, 14]. For more information see the guide to low blood counts and preventing infection.
Preventing and treating infection (for physicians)
- Febrile neutropenia (IDSA): fever = a single oral temperature ≥38.3 °C or ≥38.0 °C sustained over an hour; neutropenia = ANC below 500/µL or an ANC expected to fall below 500 within 48 hours; prompt empirical treatment with broad gram-positive and gram-negative cover [23]. First antibiotic dose within an hour of triage [4].
- Antibacterial and antifungal prophylaxis: recommended for deep and prolonged neutropenia (fewer than 100 neutrophils/µL for more than 7 days) [24]. In adult transplant, a fluoroquinolone (levofloxacin) for expected neutropenia of 7 days or more, usually from cell infusion until neutropenia recovers or empirical antibiotics start (BI) [14].
- Antifungal: fluconazole is the drug of choice for preventing candidiasis before engraftment in allogeneic transplant (AI) and is started at the start or end of the conditioning regimen; doses below 200 mg are not recommended, and continuing to day 75 was associated with longer protection. In patients with GVHD, posaconazole has prevented mould infections (BI). Watch for interactions between azoles and calcineurin inhibitors [14].
- Antiviral: aciclovir for all HSV-positive allogeneic recipients, from the start of conditioning until engraftment or resolution of mucositis (whichever is later), about 30 days after transplant (AI) [14]; ASCO/IDSA also recommend nucleoside analogue prophylaxis for HSV-positive patients in allogeneic transplant [24].
- CMV: pre-emptive strategy: screening about once a week from day 10 to at least day 100 (AIII); pre-emptive treatment for at least 2 weeks, with ganciclovir as first-line drug (valganciclovir has also been used); monitor ANC at least twice a week during ganciclovir; foscarnet if intolerant; after pre-emptive treatment stops, continue weekly screening until at least day 100 after transplant [14]. Letermovir prophylaxis: 480 mg once a day (oral or IV), or 240 mg with concomitant ciclosporin, starting between day 0 and 28 and continuing to day 100 after transplant; to day 200 at risk of late CMV [25]. In the phase 3 trial (565 CMV-positive patients), all-cause mortality by week 48 was 20.9% with letermovir versus 25.5% with placebo; vomiting, oedema and atrial fibrillation or flutter were slightly more common [26].
- Pneumocystis and hepatitis B: pneumocystis prophylaxis with regimens carrying a risk above 3.5% (such as ≥20 mg prednisone equivalent daily for ≥1 month); entecavir or tenofovir at high risk of HBV reactivation [24].
Low platelets, bleeding and blood transfusion
During these days platelets and red blood cells are also low, and several transfusions of blood or platelets may be needed [18]. Report easy bruising, tiny red spots on the skin, bleeding gums or nose, red urine or black stools. Brush with a very soft toothbrush and do not take aspirin or ibuprofen without your doctor's advice [27].
For physicians
Until engraftment, platelets and red blood cells are also low. Report easy bruising, tiny red or purple spots on the skin, bleeding gums or nose, red urine or black stools; clean your teeth with a very soft toothbrush and do not take aspirin or ibuprofen without your doctor's advice [27].
The AABB guideline recommends prophylactic platelet transfusion in admitted adults with low platelets from treatment when the platelet count is 10,000/µL or less [18]. In the TOPPS trial, omitting prophylactic platelet transfusion increased bleeding (50% vs 43%), although in the autologous transplant subgroup bleeding rates were similar with the two approaches [28]. The ASCO guideline also says that in adults having autologous transplant in experienced centres, platelets can be given at the first sign of bleeding, but in allogeneic transplant and paediatric autologous transplant, prophylactic transfusion based on a count threshold is still recommended [29].
Blood products for transplant patients are prepared in special ways; for example, in CMV-negative allogeneic recipients, products from CMV-negative donors or leukocyte-reduced (filtered) products are used so that the virus is not passed on [14].
A problem with the small blood vessels of the liver (VOD)
Sometimes the strong medicines before a transplant damage the very small blood vessels of the liver and blood gets held up in the liver [7]. Signs: rapid weight gain, a swollen tummy, pain under the right ribs and yellowing of the skin, usually in the first 3 weeks [7].
Most cases get better within a few weeks, but the severe form is dangerous; that is why you are weighed every day and early diagnosis matters [7, 8]. Ursodiol tablets are usually given for prevention, and there is a specific medicine called defibrotide for treatment [8, 32].
For physicians
In this complication, toxic products of the conditioning regimen damage the lining of the very small blood vessels of the liver (sinusoids); these vessels narrow and blood flow in the liver is disrupted [7]. The result is weight gain and fluid retention, fluid in the abdomen (ascites), an enlarged and painful liver and jaundice, and in severe cases the lungs, kidneys and brain are also involved [7].
VOD/SOS usually happens in the first 3 weeks after the transplant, but 15 to 20% of cases start later [7]. Its rate is about 10 to 15% after a myeloablative allogeneic transplant and below 5% after an autologous transplant or a reduced-intensity allogeneic transplant [7]. Previous liver disease, regimens with high-dose busulfan or high-dose total body irradiation, a second transplant and previous use of drugs such as gemtuzumab or inotuzumab ozogamicin increase the risk [8].
Most cases improve gradually within a few weeks, but severe forms with multi-organ failure have a mortality above 80%; that is why early diagnosis matters [7]. Diagnosis is based on weight gain, a painful enlarged liver, ascites, blood bilirubin and sometimes ultrasound [8].
Prevention and treatment: in adults, ursodeoxycholic acid (ursodiol) is recommended from the start of conditioning until day 90 after the transplant [8]; in a randomised trial this drug reduced liver problems and severe acute GVHD and improved 1-year survival, although the rate of VOD itself did not differ [30]. Treatment includes careful fluid management and the drug defibrotide, which is the only treatment for severe VOD/SOS [8, 31, 32]. In a phase 3 trial in patients with severe VOD and multi-organ failure, day-100 survival with defibrotide was 38.2% versus 25% in a historical control group [33]. The commonest side effects of defibrotide are low blood pressure, diarrhoea, vomiting, nausea and nosebleeds, and it increases the risk of bleeding [32].
| Category | Criterion |
|---|---|
| Possible | At least two of: bilirubin ≥2 mg/dL, painful hepatomegaly, weight gain above 5%, ascites, ultrasound and/or elastography findings suggesting VOD/SOS [8] |
| Clinical | Bilirubin ≥2 mg/dL plus two of: painful hepatomegaly, weight gain above 5%, ascites [8] |
| Proven | Histological proof, or haemodynamic proof with a hepatic venous pressure gradient ≥10 mmHg [8] |
| Time of onset | Up to day 21 after transplant: classical VOD/SOS; after day 21: late VOD/SOS [8] |
Symptoms must not be due to another cause. In the 2016 criteria, diagnosing late VOD without a rise in bilirubin required haemodynamic or ultrasound evidence [7].
| Measure | Mild | Moderate | Severe | Very severe |
|---|---|---|---|---|
| Time since first symptoms | More than 7 days | 5 to 7 days | 4 days or less | Any time |
| Bilirubin (mg/dL) | ≥2 and below 3 | ≥3 and below 5 | ≥5 and below 8 | ≥8 |
| Rate of bilirubin rise | — | — | Doubling in 48 hours | — |
| Transaminases | ≤2 times normal | More than 2 and ≤5 times | More than 5 and ≤8 times | More than 8 times |
| Weight gain | — | — | ≥5% | ≥10% |
| Creatinine | At baseline at transplant | Below 1.5 times baseline | ≥1.5 and below 2 times baseline | ≥2 times baseline or multi-organ failure |
The patient is placed in the category in which they meet two or more criteria; if two or more criteria fall in two different categories, the more severe category applies. With two or more risk factors, the patient is placed one grade higher. Multi-organ failure (≥2 organs with a SOFA score ≥2) is always "very severe". EBMT recommends early defibrotide in severe and very severe VOD and also in moderate VOD, and considers supportive care with close monitoring enough in mild VOD [8].
Engraftment syndrome
In the days when the blood counts rise, there is sometimes fever without infection, a red rash, swelling and weight gain, and sometimes breathlessness [15, 19]. Because the fever may be from infection, antibiotics are given first. Many cases get better on their own, and if not, steroids usually work well [15, 19].
For physicians
In the days when the neutrophil count rises, a group of symptoms sometimes appears: fever without infection, a red skin rash, weight gain and fluid retention, and sometimes fluid in the lungs with low oxygen; diarrhoea and temporary liver or kidney problems may also be seen [15, 19]. This complication has mostly been described after autologous transplant; in patients with myeloma after autologous transplant, its rate has been reported at about 10 to 29% in different studies [19], and it has been more common in patients aged 65 and over [2].
Because the fever may be caused by infection, antibiotics are given first and other causes are investigated. Many cases get better on their own, and when treatment is needed, corticosteroids often work strikingly well, especially on the lung symptoms [15, 19].
Diagnostic criteria and treatment (for physicians)
Spitzer criteria: major: fever (≥101 °F, about 38.3 °C) without an infectious cause, an erythrodermatous rash over more than 25% of the body surface not attributable to a drug, and non-cardiogenic pulmonary oedema; minor: liver dysfunction (bilirubin ≥2 mg/dL or a doubling of transaminases from baseline), kidney dysfunction (a doubling of creatinine from baseline), weight gain of 2.5% and transient encephalopathy with no other cause. Diagnosis: all three major criteria, or two major criteria and at least one minor criterion, within 96 hours of neutrophil engraftment. Maiolino criteria: non-infectious fever with diarrhoea, rash or pulmonary infiltrates within 24 hours of engraftment [19].
Suggested treatment approach: after excluding infection and drug causes, if symptoms do not improve within 48 to 72 hours and treatment is needed: methylprednisolone 1 to 1.5 mg/kg a day until symptoms start to improve (usually 2 to 3 days), then oral prednisone 40 to 50 mg a day for 2 to 3 days and a reduction of 10 mg every 2 to 3 days; if there is no improvement 72 hours after starting steroids, further assessment and biopsy of the affected organ [19].
The acute reaction of transplanted cells against the body (acute GVHD)
This problem happens only after a transplant from a donor: the donor's immune cells see your body as "foreign" and attack it. The acute form usually appears in the first 3 months [1, 9]:
- Skin: a red rash that may spread [9].
- Bowel: diarrhoea; severe tummy pain or blood in the stool is a sign of severity [9].
- Stomach: nausea, vomiting or a lasting loss of appetite [9].
- Liver: yellowing of the skin [9].
For prevention, immunosuppressive medicines are given from the days of the transplant and their blood levels are measured regularly [14, 34]. The first treatment is steroids; if that is not enough, ruxolitinib tablets helped more patients [10, 11]. Read about the chronic form in long-term effects after a transplant.
For physicians
GVHD happens only after an allogeneic transplant: the donor's white blood cells regard the patient's tissues as foreign and attack them. Its acute form usually appears in the first 3 months after the transplant and affects the skin, gut and liver [1, 9]:
- Skin: a red (maculopapular) rash that may start on a small part of the body and spread; in its most severe form, blisters and peeling [9].
- Bowel: diarrhoea; its severity is measured by daily volume or frequency, and severe tummy pain or visible blood in the stool is a sign of severe disease [9].
- Upper gut: nausea, vomiting or a persistent loss of appetite [9].
- Liver: a rise in bilirubin and jaundice [9].
Prevention: immunosuppressive medicines are given from a few days before or after the cell infusion; the classic regimen is a calcineurin inhibitor (tacrolimus or ciclosporin) with methotrexate [34]. The phase 3 BMT CTN 1703 trial showed that post-transplant cyclophosphamide with tacrolimus and mycophenolate mofetil increased 1-year GVHD-free, relapse-free survival from 34.9% to 52.7% [34]. The EBMT guideline regards antithymocyte globulin (ATG) or post-transplant cyclophosphamide as standard prophylaxis in peripheral blood transplants from an unrelated donor [35]. Tacrolimus or ciclosporin blood levels are monitored carefully, especially when interacting drugs such as azole antifungals or letermovir are started or stopped [14, 25].
Treatment: a systemic corticosteroid (methylprednisolone or prednisone) is the standard first-line treatment for acute GVHD [10]. If the disease does not improve or gets worse (steroid-refractory GVHD), ruxolitinib is the next standard treatment: in the REACH2 trial, the day-28 overall response was 62% with ruxolitinib versus 39% with other usual treatments [11, 35].
The chronic form of GVHD usually occurs from 3 months after the transplant onwards [1] and is explained in the guide to long-term and chronic effects after a transplant.
| Stage | Skin (active erythema only) | Liver (bilirubin, mg/dL) | Upper gut | Lower gut (daily stool) |
|---|---|---|---|---|
| 0 | No active GVHD rash | Below 2 | No nausea, vomiting or anorexia, or intermittent | Below 500 mL or fewer than 3 episodes |
| 1 | Maculopapular rash below 25% of body surface | 2 to 3 | Persistent nausea, vomiting or anorexia | 500 to 999 mL or 3 to 4 episodes |
| 2 | Maculopapular rash 25 to 50% of body surface | 3.1 to 6 | — | 1000 to 1500 mL or 5 to 7 episodes |
| 3 | Maculopapular rash above 50% of body surface | 6.1 to 15 | — | Above 1500 mL or more than 7 episodes |
| 4 | Generalised erythroderma (above 50% of body surface) with blistering and desquamation over more than 5% of body surface | Above 15 | — | Severe abdominal pain with or without ileus, or grossly bloody stool (regardless of volume) |
In children, the lower gut criteria are in mL per kg [9].
| Grade | Definition |
|---|---|
| 0 | No stage 1 to 4 in any organ |
| I | Skin stage 1 to 2, with no liver, upper gut or lower gut involvement |
| II | Skin stage 3 and/or liver stage 1 and/or upper gut stage 1 and/or lower gut stage 1 |
| III | Liver stage 2 to 3 and/or lower gut stage 2 to 3, with skin stage 0 to 3 and/or upper gut stage 0 to 1 |
| IV | Skin, liver or lower gut stage 4, with upper gut stage 0 to 1 |
The overall grade is set by the most severe organ involvement [9]. The right time for second-line treatment: progression after 3 days, or no improvement after 1 week in grade III or 2 weeks in grade II [10].
Kidneys and bladder
In the first 3 months, the kidneys may be damaged; some essential transplant medicines play a part in this. That is why kidney tests and medicine levels are checked regularly [16, 36].
If passing urine burns or there is blood in it, say so; sometimes a virus damages the bladder [37]. Drink as much as your care team has told you [37].
For physicians
Acute kidney injury is common in the first 100 days after transplant and has been reported in 12 to 73% of patients in different studies; the highest rate is with myeloablative allogeneic transplant [36]. Calcineurin inhibitors (ciclosporin and tacrolimus), amphotericin B, vancomycin, VOD/SOS, total body irradiation, high blood pressure, allogeneic transplant and cord blood transplant are among its risk factors; that is why the care team watches kidney function and the use of these medicines carefully [16].
Blood in the urine: haemorrhagic cystitis caused by the BK virus occurs in 7 to 54% of adults after allogeneic transplant and comes with symptoms of cystitis (such as burning and pain on passing urine) and visible blood in the urine [37]. Drink fluids as your care team advises, although high-volume hydration alone has shown limited preventive effect [37]. High-dose post-transplant cyclophosphamide is given with hydration and a bladder-protecting medicine (mesna) [34].
Food on the transplant unit
Many patients lose weight on the transplant unit, because nausea, mouth sores and diarrhoea make eating hard [20]. Your nutrition is checked every week, and if you do not eat enough, supplement drinks or tube feeding help [20].
You do not need to cut out fruit and vegetables completely; studies did not show that doing so reduces infection [38, 20]. But follow your own transplant centre's rules: meat, fish and eggs thoroughly cooked, and fruit and vegetables well washed or peeled [3] (nutrition during treatment).
For physicians
Many patients, especially after allogeneic transplant, are malnourished on admission, and nausea, mouth sores, diarrhoea and infections make eating harder; weight loss is especially common in the first 40 days after admission [20]. The ESPEN guideline recommends assessing nutritional status on admission and then monitoring it every week, and starting counselling, oral supplements, enteral (tube) feeding or parenteral nutrition early if intake is short [20]. If oral intake is not enough, enteral feeding is preferred to parenteral nutrition, except with severe mouth sores, refractory vomiting, bowel obstruction, severe malabsorption, prolonged diarrhoea or symptomatic gut GVHD [20]. Glutamine is not recommended in transplant [20].
The "neutropenic" diet (cooked food only): in a randomised trial of 153 patients with acute myeloid leukaemia in isolation rooms, cutting out fresh fruit and vegetables did not prevent serious infection or death (serious infection 29% vs 35%) [38], and ESPEN sees insufficient evidence to recommend a low-microbial diet beyond 30 days after allogeneic transplant [20]. Even so, follow your transplant centre's food safety rules: meat, fish and eggs should be thoroughly cooked and fruit and vegetables well washed or peeled [3]. See the guide to nutrition during treatment.
CAR-T cell therapy: fever and confusion after the infusion
In CAR-T, the patient's own immune cells, trained in the laboratory, go back into the body and attack the cancer [12]. It has two specific complications:
- High fever and low blood pressure, usually in the first few days; sometimes oxygen is needed [12, 13].
- Confusion, a lot of sleepiness, trouble speaking, shaking or sometimes seizures [12, 13]. Nurses check you with simple questions (the year, the month, naming a few objects, writing a sentence) [39].
Both have effective treatments [12]. After the infusion, at least a week of daily monitoring is needed; stay near the treatment centre for at least 2 weeks and do not drive [13].
For physicians
In CAR-T cell therapy, the patient's own modified T lymphocytes multiply in the body after infusion and attack the cancer cells [12]. Its two specific complications are:
- Cytokine release syndrome (CRS): the T cells release large amounts of chemical messengers (cytokines) that cause high fever and a sharp fall in blood pressure, and sometimes oxygen is needed [12, 39]. With axicabtagene ciloleucel, the median onset of CRS in the registration studies was 2 to 3 days after infusion [13].
- Neurological complications (ICANS): confusion, a lot of sleepiness, trouble speaking, shaking and sometimes seizures [12, 13]. Nurses check mental status with simple questions, such as asking the year, month and city, naming a few objects and writing a sentence [39].
CRS is usually treated with tocilizumab and, if needed, a corticosteroid, and ICANS is often treated with a corticosteroid [12]. According to the current axicabtagene ciloleucel label, the patient must be monitored daily for CRS and neurological complications for at least 7 days after infusion, stay near the treatment centre for at least 2 weeks and not drive during these 2 weeks [13].
| Grade | Fever | Hypotension | Hypoxia |
|---|---|---|---|
| 1 | ≥38 °C | None | None |
| 2 | ≥38 °C | Not requiring vasopressors | Requiring low-flow nasal cannula (≤6 L/min) or blow-by oxygen |
| 3 | ≥38 °C | Requiring one vasopressor, with or without vasopressin | Requiring high-flow cannula (above 6 L/min), face mask, non-rebreather mask or Venturi mask |
| 4 | ≥38 °C | Requiring multiple vasopressors (excluding vasopressin) | Requiring positive pressure (CPAP, BiPAP, intubation and mechanical ventilation) |
The grade is set by the more severe of hypotension or hypoxia; after antipyretics, tocilizumab or steroids, fever is not required for grading. ICANS is graded with the ICE score (10 points: orientation 4, naming 3 objects 3, following a command 1, writing a sentence 1 and counting backwards from 100 in tens 1) together with level of consciousness, seizures, motor findings and raised intracranial pressure; ICE score 7 to 9 = grade 1, 3 to 6 = grade 2, 0 to 2 = grade 3 and 0 because of being unarousable = grade 4 [39].
Step-by-step management of CRS and ICANS (tocilizumab, corticosteroids and treatments for refractory cases) is covered in the specialist lesson Immunotherapy toxicity: checkpoint inhibitors, CAR-T and bispecific antibodies.
What does the transplant team monitor?
On the transplant unit these are checked every day: blood tests (until the counts rise), weight and fluids, temperature, skin and diarrhoea, and after a transplant from a donor the CMV virus and the level of immunosuppressive medicines in the blood [2, 8, 9, 14]. After CAR-T, you are checked every day for fever and confusion for at least a week [13].
For physicians
Monitoring on the transplant unit
Monitoring and care continue after discharge too; see the guide to after leaving the transplant unit.
Important medicines during the transplant
Treatment regimens and doses: index7 regimens
On the transplant unit you usually receive these medicines: anti-sickness medicines [17], medicines to prevent infection (antibacterial, antifungal and antiviral) [14], and after a transplant from a donor, medicines to prevent GVHD [34]. If a specific problem arises, its own medicine is given; for example steroids for GVHD [10] or defibrotide for the liver blood vessel problem [8]. Ask your nurse the names and times of your medicines.
For physicians
Medicines you may receive on the transplant unit
Anti-sickness medicines
Ondansetron or similar medicines, dexamethasone, aprepitant and sometimes olanzapine, before and after high-dose chemotherapy [17].
Antibiotics, antifungals and antivirals
Medicines to prevent GVHD
Tacrolimus or ciclosporin, methotrexate, mycophenolate mofetil or post-transplant cyclophosphamide, and ATG in some transplants [34, 35].
Corticosteroids and ruxolitinib
Ursodiol and defibrotide
Tocilizumab (after CAR-T)
To treat severe cytokine release syndrome, alone or with a corticosteroid [41].
- Defibrotide: contraindicated with concomitant systemic anticoagulants or fibrinolytics (except maintenance or catheter-clearing doses); before each dose there should be no significant bleeding and haemodynamics should be stable on at most one vasopressor; stop at least 2 hours before an invasive procedure [32].
- Ruxolitinib: full blood count and bilirubin before starting and every 2 to 4 weeks until the dose is stable [40]; in REACH2, thrombocytopenia (33% vs 18%) and CMV infection (26% vs 21%) were more common with ruxolitinib [11].
- Corticosteroids: after second-line treatment starts, continue the steroid and reduce it as symptoms improve [10]; with ≥20 mg prednisone equivalent daily for ≥1 month, pneumocystis prophylaxis is needed [24].
- Post-transplant cyclophosphamide: with mesna and hydration [34].
- Letermovir: with ciclosporin reduce the dose to 240 mg; monitor ciclosporin, tacrolimus and sirolimus levels frequently during use and after stopping it [25].
For physicians
Prevention and treatment of acute GVHD: doses and schedules
Tacrolimus + methotrexate
GVHD prevention in allogeneic transplant (standard arm of the BMT CTN 1703 trial with a matched related or unrelated donor and reduced-intensity conditioning)Cycle length: Non-cyclical
GVHD prevention in allogeneic transplant (standard arm of the BMT CTN 1703 trial with a matched related or unrelated donor and reduced-intensity conditioning)
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Tacrolimus | Oral 0.05 to 0.06 mg/kg a day or IV 0.02 to 0.03 mg/kg a day (according to centre practice) | Oral or IV | From day −3; taper from day 90 aiming to stop by day 180 |
| Methotrexate | 15 mg/m² on day 1; 10 mg/m² on days 3, 6 and 11 | IV bolus | Days 1, 3, 6 and 11 after transplant |
Post-transplant cyclophosphamide + tacrolimus + mycophenolate mofetil
GVHD prevention in the BMT CTN 1703 trial (reduced-intensity conditioning and peripheral blood cells from a matched related, matched unrelated or 7/8 matched unrelated donor)Cycle length: Non-cyclical
GVHD prevention in the BMT CTN 1703 trial (reduced-intensity conditioning and peripheral blood cells from a matched related, matched unrelated or 7/8 matched unrelated donor)
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cyclophosphamide | 50 mg/kg a day | IV, with mesna and hydration | Days 3 and 4 after transplant |
| Tacrolimus | Oral 0.05 to 0.06 mg/kg a day or IV 0.02 to 0.03 mg/kg a day | Oral or IV | From day 5; taper from day 90 aiming to stop by day 180 |
| Mycophenolate mofetil | 15 mg/kg per dose (maximum 1 g three times a day) | Oral or IV | Three times a day, from day 5 to day 35 |
1-year GVHD-free, relapse-free survival 52.7% versus 34.9% (HR=0.64); overall survival, relapse, transplant-related death and engraftment did not differ markedly; platelet recovery was slower and grade 2 infection more common [34]. In peripheral blood transplant from an unrelated donor, EBMT regards ATG or post-transplant cyclophosphamide as standard [35].
Methylprednisolone (first-line treatment)
Acute GVHD needing systemic treatmentCycle length: Daily
Acute GVHD needing systemic treatment
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Methylprednisolone (or prednisone) | Methylprednisolone 2 mg/kg a day or prednisone 2 to 2.5 mg/kg a day | IV (prednisone: oral) | Daily until marked improvement, then gradual tapering |
In upper gut GVHD, starting at 1 mg/kg a day is reasonable; in grade II, a starting dose of 1 mg/kg did not give worse results in a retrospective study; doses above the equivalent of 2.5 mg/kg prednisone gave no benefit. Start tapering once there is marked improvement; for example, reduce prednisone by 0.2 mg/kg a day every 3 to 5 days and more slowly once below 20 to 30 mg a day. Second-line treatment: progression after 3 days, or no improvement after 1 week (grade III) or 2 weeks (grade II) [10].
Ruxolitinib
Steroid-refractory acute GVHD in adults and children aged 12 and overCycle length: Daily and continuous
Steroid-refractory acute GVHD in adults and children aged 12 and over
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Ruxolitinib | 5 mg twice a day; after at least 3 days, if ANC and platelets have not fallen by 50% or more from day 1, increase to 10 mg twice a day | Oral | Daily and continuous |
Full blood count and bilirubin before starting and every 2 to 4 weeks until the dose is stable. Dose reduction levels: 10 mg twice a day → 5 mg twice a day → 5 mg once a day. Drug-related ANC below 1000/µL: hold for up to 14 days and resume one level lower. Rising bilirubin without liver GVHD: 3 to 5 times the upper limit, continue one level lower; more than 5 to 10 times, hold for up to 14 days until ≤1.5 times and resume at the same dose [40]. In REACH2 (309 patients, dose 10 mg twice a day), day-28 overall response: 62% versus 39%; durable response at day 56: 40% versus 22%; median failure-free survival 5 months versus 1 month [11].
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.
VOD/SOS and cytokine release syndrome: doses and schedules
Ursodeoxycholic acid (prevention)
Prevention of liver complications in adult allogeneic transplantCycle length: Daily
Prevention of liver complications in adult allogeneic transplant
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Ursodeoxycholic acid | 12 mg/kg a day | Oral | From the day before conditioning starts until day 90 after transplant |
Dose and schedule as in a randomised trial of 242 patients: bilirubin above 50 µmol/L and grade III to IV acute GVHD were less common, 1-year survival was 71% versus 55% and non-relapse mortality 19% versus 34%; the incidence of VOD did not differ [30]. EBMT recommends it from the start of conditioning until day 90 in adults [8], and BCSH/BSBMT suggest it for prevention (2C) [31].
Defibrotide (treatment)
Hepatic VOD/SOS with kidney or lung dysfunction after transplant (FDA label); EBMT: start as early as possible in moderate, severe and very severe VODCycle length: Every 6 hours
Hepatic VOD/SOS with kidney or lung dysfunction after transplant (FDA label); EBMT: start as early as possible in moderate, severe and very severe VOD
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Defibrotide | 6.25 mg/kg (25 mg/kg a day) based on weight before conditioning | 2-hour IV infusion with a 0.2 micron in-line filter | Every 6 hours |
Contraindications: concomitant systemic anticoagulants or fibrinolytics, and hypersensitivity to the drug. Persistent, severe or life-threatening bleeding: hold and resume at the same dose once bleeding stops and haemodynamics are stable; recurrent significant bleeding: stop permanently. Stop at least 2 hours before an invasive procedure. Common side effects: hypotension, diarrhoea, vomiting, nausea and nosebleeds; bleeding of any severity in 59% of trial patients [32]. BCSH/BSBMT had recommended prophylaxis with defibrotide 6.25 mg/kg four times a day in high-risk children (1A) and suggested it in high-risk adults (2B) [31]; but in a later phase 3 trial of 372 high-risk patients, defibrotide prophylaxis did not improve VOD-free survival at day 30 [8].
Tocilizumab
Severe or life-threatening CAR-T-induced cytokine release syndrome in adults and children aged 2 and over
Severe or life-threatening CAR-T-induced cytokine release syndrome in adults and children aged 2 and over
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Tocilizumab | Weight ≥30 kg: 8 mg/kg; weight below 30 kg: 12 mg/kg; maximum 800 mg per infusion | IV infusion over 60 minutes | If no improvement, up to 3 more doses at least 8 hours apart |
Before prescribing, check each dose against the drug label, laboratory tests and the patient’s condition.
When should I call my doctor?
If you are an inpatient on the transplant unit, tell the nurse or doctor on the unit about any of these symptoms straight away; if you are at home (before admission, in an outpatient transplant or after CAR-T), call the transplant centre straight away or go to the emergency department:
- A temperature of 38 °C or higher, shivering, or redness and swelling at the catheter site [3].
- Breathlessness or a new need for oxygen [19, 39].
- A new skin rash, a lot of diarrhoea or bloody diarrhoea, or severe tummy pain [9].
- Yellowing of the skin or eyes, rapid weight gain, a swollen tummy or pain under the right ribs [7].
- Bleeding from the gums or nose that does not stop, red urine, black stools or a severe headache [27].
- Burning and pain on passing urine with blood in the urine [37].
- Mouth sores or pain that stop you eating, drinking or swallowing your medicines [5, 20].
- After CAR-T: confusion, a lot of sleepiness, trouble speaking, shaking or seizures [12, 13].
Frequently asked questions
Will my hair grow back?
Hair usually grows back 2 to 3 months after chemotherapy ends; it may at first be finer, curlier, straighter or a different colour and gradually return to how it was. After very high-dose radiotherapy, hair in the treated area may become thinner or not grow back [21].
Why are my weight and fluids measured so often?
Is GVHD always bad?
GVHD can be serious and must be treated early. On the other hand, the donor's immune cells can also destroy remaining cancer cells (the "graft-versus-leukaemia" effect) [1]. The transplant team's aim is to prevent and control GVHD; newer preventive medicines have reduced severe GVHD without the cancer coming back more often [34].
If I get a fever when my white cells are low, do I definitely have an infection?
Can I eat fresh fruit and vegetables on the transplant unit?
Are the complications of CAR-T the same as a transplant's?
Related cancer types
References
41 referencesShow all references, 7 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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- 22Aerobic physical exercise for adult patients with haematological malignancies
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- 28A No-Prophylaxis Platelet-Transfusion Strategy for Hematologic Cancers
- 29Platelet Transfusion for Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update
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- 33Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure
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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-complications-during/