Transplantation Consultation Center
Disease information
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Post-
transplant
Infectious
Complications -
Cytomegalovirus
infection -
Hemorrhagic
cystitis -
Post-
transplant
vaccinations
Post-transplant Infectious Complications
Patients receiving stem cells from a donor, a procedure known as allogeneic hematopoietic stem cell transplantation, face a higher risk of infections. This is because their immune systems are weak after the transplant. While they are healing, they might get sick more easily, especially if they are taking medicines to keep their body from rejecting the new cells, or if they have graft-versus-host disease, which is when the new cells attack their body. The kind of stem cell transplant they had also plays a role in how likely they are to get infections.
| Types of Infections | Pre-engraftment Period (First 2-4 weeks) |
Early Post-engraftment Period (Up to 2-3 Months) |
Late Post-engraftment Period (After 2-3 Months) |
|---|---|---|---|
| Risk factor |
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| Bacteria |
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| Fungi |
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| Virus |
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| Others |
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When doctors suspect an infection, they often begin treatment with antibiotics without waiting for test results. If the specific cause of the infection is found, they can change the medicine to target the exact germ, based on recommendations from infectious disease experts. While the patient is being treated, doctors might run tests to find the infection, like blood cultures, imaging tests, or procedures to get samples from where the infection might be.
Two primary preventive treatments, known to be effective, are prophylactic antimicrobial agents and vaccinations. The availability and suitability of these treatments can vary, depending on each patient's specific health situation. Some may not have access to certain medications, or vaccinations may not be safe for them. Because of this, it's important to consult with an infectious diseases specialist to tailor the right preventive approach.
Preventive measures using medication
-
1.
Bacteria
- In the early phase of a transplant, known as the pre-engraftment period, to prevent bacterial infection complications, doctors look at how likely it is for patients to get an infection and give them antibiotics to help prevent it. If a patient is likely to have a very low number of neutrophils, which are cells that help fight infection, for more than 10 days, they're seen as having a high risk for infection. They might need to take antibiotics to prevent infections for as long as they're at risk, which is usually until their neutrophil levels get back to normal.
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2.
Fungi
- To prevent fungal infections, doctors consider how long a patient has low neutrophils, which are important cells for fighting infections. Other risk factors include being older than 65, having other health conditions, a past severe fungal infection, graft-versus-host disease (when transplanted cells attack the patient's body), and viruses that become active again. Depending on these risks, doctors may give antifungal medications like voriconazole (Vfend), isavuconazole (Cresemba), or posaconazole (Noxafil) to help prevent an infection.
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3.
Pneumocystis
- To prevent Pneumocystis pneumonia, a serious lung infection, in people who have had an allogeneic transplant, doctors usually recommend taking the antibiotic trimethoprim/sulfamethoxazole for at least six months or until they no longer need to take drugs that suppress their immune system. If these patients have stopped taking the antibiotic after six months but then need to start taking immunosuppressants again because their graft-versus-host disease gets worse or changes, they may need to begin the antibiotic again to prevent the infection.
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4.
Herpes Simplex, Varicella-Zoster Virus
- During the first year after a transplant, there's a higher chance that the herpes simplex virus and the varicella-zoster virus will wake up again in the body. After an allogeneic transplant, the chance of getting shingles is about 22% in the first year, 31% by the second year, and 39% by the third year. Taking antiviral medicines can really help lower this risk.
- For people who've had a transplant, getting the live vaccines for chickenpox or shingles is not safe. In Korea, most adults have been exposed to these viruses, so it's a good idea for transplant patients to talk to a specialist. The specialist can give them antiviral drugs and a special shingles vaccine that doesn't use a live virus.
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5.
Cytomegalovirus (CMV)
- Before a transplant from another person, doctors test both the patient and the donor for antibodies to cytomegalovirus (CMV). This is a common virus that can cause problems for people with weak immune systems. High-risk patients might get medicine to prevent the virus from causing trouble. After the transplant, the doctors keep an eye out for CMV, and if they find it in the blood, they start treating it right away.
- This treatment starts even if the patient doesn't have any symptoms because it's based on how much virus is in the blood and other risks, like how bad the graft-versus-host disease is, what kind of medicine to weaken the immune system they're taking, and the type of transplant. They can use antiviral medicines or given by injection for this early treatment
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6.
Tuberculosis
- After a transplant, things that can increase the risk of getting tuberculosis (TB) include having graft-versus-host disease for a long time, a past TB infection, getting full-body radiation before the transplant, and having T-cells removed from the transplant. In Korea, data shows that TB usually shows up about 300 days after a stem cell transplant. Also, 42% of these TB cases don't just affect the lungs but other parts of the body too, which is more than the usual 15-20% seen in the general population.
- Before the transplant, doctors check for hidden TB, and if they find it, patients might need to take medicine to stop it from coming back. The usual treatment for hidden TB is to take a medicine called isoniazid for 9 months, or isoniazid with another medicine called rifampin for 3 months. But for people who've had a stem cell transplant, taking rifampin can be tricky because it can interact with medicines that suppress the immune system, so they usually just take isoniazid for 9 months. While taking the medicine, doctors will watch things like liver enzymes to make sure there aren't any side effects. It's best to decide whether to take this medicine after talking it over with a specialist and looking at the whole health picture.
Cytomegalovirus infection
After a hematopoietic stem cell transplant, there's a risk of cytomegalovirus (CMV) becoming active again or a new infection occurring. This can lead to a range of symptoms, from showing no symptoms at all to more severe issues like fever, inflammation of the esophagus, stomach, intestines, eyes, liver, lung infection, and brain inflammation.
To prevent CMV reactivation or infection, the antiviral drug letermovir (Prevymis) is used to CMV seropositive recipeints until 100 days post-transplantation when virus is not detected.
When the virus is found, even if there are no symptoms, the usual way to handle it is to start treatment right away to stop the virus from causing disease. The antiviral medicines used for this include ganciclovir, valganciclovir, foscarnet, cidofovir, and maribavir. If finding the virus is delayed, these drugs might not work as well. So, it's really important to diagnose it quickly and have a specialist who knows how to treat it effectively.
Hemorrhagic cystitis
Typical symptoms consist of blood in the urine (hematuria), the need to urinate often, a feeling of incomplete bladder emptying, and a sudden, compelling urge to urinate (urgency). It's common for these symptoms to fluctuate, with periods of increased severity followed by times when they lessen.
The primary approach to treatment typically includes reducing immunosuppressants as quickly as possible. Alongside this, supportive care such as ensuring proper fluid intake, bladder irrigation, and other established treatments are used. When dealing with severe hemorrhagic cystitis of grade 3 or above, particularly when it's caused by viruses like BK virus, adenovirus, or cytomegalovirus, the antiviral medication cidofovir may be beneficial if there's no improvement with the conservative methods.
Post-transplant vaccinations
During the process of a hematopoietic stem cell transplant, patients lose their immune memory cells because of the strong conditioning treatments and immunosuppressants they receive. So, vaccines they've had before, like the one for pneumonia, don't work anymore. Getting vaccinated again is a key way to protect against a range of infections and to cut down on using antibiotics when they're not needed, which helps make life better for patients. That's why getting re-vaccinated is really encouraged for these patients.
Usually, patients can start getting vaccines after a transplant once their immune system begins to recover, often after the first three months. Even if they're taking immunosuppressants to manage graft-versus-host disease, it might be better to stick to the vaccination schedule instead of putting it off. This decision depends on how the patient is doing and how much immunosuppressant they're taking.
Vaccines after a transplant get scheduled out step by step, kind of like how they do for babies. It doesn't typically matter what kind of transplant was done or if the stem cells were the patient's own (autologous) or from someone else (allogeneic)—the vaccine plan follows a certain timetable. But, the patient's immune status and how long it's been since the transplant might make some vaccines a no-go (like the live attenuated zoster vaccine or measles-mumps-rubella). So, it's a good move to chat with a specialist before deciding on vaccines.
The family members of the organ donor or the patient who got the stem cell transplant should think about getting certain vaccines as well. Like, they should get the flu shot at the same time the patient does every year. For any other vaccines, they should also talk things over with a specialist.
| Vaccinations | Post-Transplant Vaccination Initiation Time | Number of Vaccinations | |
|---|---|---|---|
| Inactivated vaccines | Pneumococcus | 3 - 6 Months | 3-4a |
| Inactivated influenza | 4 - 6 Months | 1, Annually | |
| Tetanus - Diphtheria- acelluar Pertussisb | 6 - 12 Months | 3c | |
| Inactivated poliovirus | 6 - 12 Months | 3 | |
| Hemophilus influenza type b | 6 - 12 Months | 3 | |
| Meningococcus | 6 - 12 Months | 1 - 2 | |
| Hepatitis A | 6 - 12 Months | 2 | |
| Hepatitis B | 6 - 12 Months | 3 | |
| Recombinant zoster | Consider Depending on Condition | 2 | |
| Human papillomavirus | After 6-12 Months (Up to 26 Years Old, Up to 45 Years Old) |
3 | |
| Live vaccined | Measles - Mumps - Rubella | 24 Months | 1 - 2 |
| Chickenpox | 24 Months | 1 | |
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a.
Administering the 23-valent polysaccharide pneumococcal vaccine after 3 doses of the 13-valent conjugate vaccine can help to cover a broader range.
In patients with chronic graft-versus-host disease after transplantation, where it is expected that immune response to the polysaccharide vaccine may be low, a fourth dose of the conjugate vaccine is considered after at least 6 months have passed. -
b.
DTaP is recommended over Tdap. If only Tdap is available, it can be substituted for DTaP.
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c.
A booster of Td or Tdap is needed every 10 years.
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d.
Vaccination is considered in patients who have passed more than 24 months after transplantation and have no graft-versus-host disease or have stopped immunosuppressive treatment.
| Hematopoietic Stem Cell Transplantation Date: Year/Month/Day (Autologous, Allogeneic) | ||||||
|---|---|---|---|---|---|---|
| Type | Post-Transplant Period | Remarks | ||||
| Pneumococcal | 3-6 Months | (+) 1 Months | (+) 2 Months | (+) 8-10 Months | Consider starting at 3-6 months post-transplant, up to 4 doses recommended. Consider the type of administration depending on the presence or absence of chronic graft-versus-host disease. |
|
| Hemophilus influenzae type B | 6-12 Months | (+) 1 Months | (+) 2 Months | 3 Doses | ||
| DTap-Polio | 6-12 Months | (+) 1 Months | (+) 2 Months | 3 Doses. Revaccination every 10 years after completion. | ||
| Meningococcal | 6-12 Months | (+) 2 Months | 2 Doses | |||
| Measles, Mumps, Rubella | Consider 24 months after transplantation when not taking immunosuppressants (2 Doses) | |||||
| Influenza | Vaccination annually starting 4-6 months after transplantation | |||||
| Hepatitis | Hepatitis B | 6-12 Months | (+) 1 Months | (+) 6 Months | Start vaccination after antibody test. 3 doses, antibody test 1-2 months later. If there is no response to the vaccine, revaccinate 3 times. |
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| Hepatitis A | 6-12 Months | (+) 6 Months | Start vaccination after antibody test. 2 Doses |
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| Recombinant zoster | 9-12 Months | (+) 2 Months | Discuss vaccination timing depending on condition. Second dose is possible within 2-6 months. |
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| Human papilloma virus | 9-12 Months | (+) 2 Months | (+) 6 Months | Men and Women Under 26 Years Old (Consider Up to 45 Years Old) | ||
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*
After discussing the best timing for the flu vaccine with your attending physician, please visit the infectious disease department to receive your vaccination. Additionally, it's important for your family members living with you to also get their flu shots, which can be done at a nearby hospital or health center.
| Before the Age of 7 | ||
|---|---|---|
| Post-Transplant Period | Type | Vaccination Initiation interval and dose |
| 6 Months (Annually there after) Mid-October to November |
Influenza (Split Vaccine) |
6-35 Months : 0.25mlx2 (interval>4 weeks) 3-8 years : 0.5mlx2 (interval>4 weeks) 2 times in the first year, once IM if the A type does not change the following year. |
| 12 Months | Pneumococcal | 0.5 ml IM |
| 13 Months | Hib | 0.5 ml IM |
| Hepatitis B | 0.5 ml IM | |
| 14 Months | DPT | 0.5 ml IM |
| IPV | 0.5 ml IM | |
| 15 Months | Hib | 0.5 ml IM |
| Hepatitis B | 0.5 ml IM | |
| 16 Months | DPT | 0.5 ml IM |
| IPV | 0.5 ml IM | |
| 25 Months | Hib | 0.5 ml IM |
| Hepatitis B | 0.5 ml IM | |
| 26 Months | DPT | 0.5 ml IM |
| IPV | 0.5 ml IM | |
| 27 Months | Pneumococcal | 0.5 ml IM |
| 36 Months | MMR | 0.5 ml SC |
| 4 - 6 years | DPT | 0.5 ml IM |
| After the Age of 7 | ||
|---|---|---|
| Post-Transplant Period | Type | Vaccination Initiation interval and dose |
| 6 Months (Annually thereafter) Mid-October to November |
Influenza | 3-8 years : 0.5mlx2(interval>4 weeks) 2 times in the first year,
once if the A type does not change the following year. 9-12 years : 0.5mlx1 >12 years : 0.5mlx1 ,IM |
| 12 Months | Pneumococcal | 0.5 ml IM |
| 13 Months | Hib | 0.5 ml IM |
| Hepatitis B | >10 years : 1.0ml IM ≤9 years : 0.5 ml IM |
|
| 14 Months | Td | 0.5 ml IM |
| IPV | 0.5 ml IM | |
| 15 Months | Hib | 0.5 ml IM |
| Hepatitis B | 0.5 ml IM | |
| 16 Months | Td | 0.5 ml IM |
| IPV | 0.5 ml IM | |
| 25 Months | Hib | 0.5 ml IM |
| Hepatitis B | >10세 : 1.0ml IM ≤9 years : 0.5 ml IM |
|
| 26 Months | Td | 0.5 ml IM |
| IPV | 0.5 ml IM | |
| 27 Months | Pneumococcal | 0.5 ml IM 0.5 ml IM |
| 36 Months | MMR | 0.5 ml SC |