Follow-up for patients after allogeneic stem cell transplantationMedical editor Lorentz Brinch MD
Oslo University Hospital
An allogeneic stem cell transplantation is an intensive and demanding treatment for the patient.
Until the patient is discharged from the hospital, the focus of the patient and the treating health personnel is on the patient to survive the treatment. When the patient returns home, they often expect they will normalize along with their environment. However, many patients experience resuming their the normal daily life as diffucult after treatment. There are many causes for this, for example complications, GVHD, or fatigue. Many transplanted patients experience less energy during the day which may affect the entire family.
Close follow-up of stem cell transplanted patients is a central part of the treatment scheme.
- Allogeneic stem cell transplantation
- The patient is able to cope with their changed life situation.
- The local health clinic has knowledge about follow-up and expected complications.
- The patient feels secure and taken care of.
An allogeneic stem cell transplantation is a treatment form which is only offered to patients with diseases having a primarily poor prognosis. That is, their expected survival time is limited with other treatment forms.
The treatment involves using chemotherapy and possibly radiation to remove immune cells from the bone marrow of the patient and replacing them with new bone marrow from the donor. The treatment is so intense that it is associated with life-threatening complications including death.
Before the transplantation, the patient will receive thorough information from a:
The patient and family may also establish contact with a:
- transplantation coordinator
- social worker
- physical therapist
- hospital priest
The patient will also be offered to talk to another patient who has previously undergone a stem cell transplantation.
If the patient has children, it is very important the school/health personnel are contacted and informed about the treatment and precautions which must be taken in connection with the treatment.
Work-up and treatment occurs at the section for blood diseases at Oslo University Hosptial and for some patient groups in collaboration with the Norwegian Radium Hospital.
The stay has 3 phases:
- Examinations before the transplantation takes 2–3 days and usually occur 1-2 months before the transplantation.
- Bed rest associated with the transplantation is generally 4-8 weeks with myeloablative conditioning, sometimes much shorter for non-myeloablative.
- When isolation is no longer necessary, the patient is moved to another room at the department. The patient is then discharged but must stay at the patient hotel or other place in the Oslo region, or at home if the patient lives in the vicinity of the hospital. For the first period after the patient is discharged, the patient will have follow-up visits 2–3 times per week at the outpatient clinic.
- Later follow-up occurs in close dialog with the patient's regional health clinic or local hospital.
During the first weeks after the patient is discharged, the patient will have an outpatient consultation with both a doctor and nurse.
At the consultation, the following are focused upon:
- nutritional status
- blood tests
- need for transfusions
- physical, psychological, and social rehabilitation
- infection status
- acute GVHD
An important part of the blood testing in the first 6-12 months is to follow the level of ciclosporin and CMV-PCR. Most patients can stop taking ciclosporin 1 year after the transplant.
If the patient has newly diagnosed or a recurrence of GVHD, it may be necessary to increase the dose of ciclosporin, possibly in combination with steroids or other immunosuppressant.
After returning home, follow-up visits are divided between the regional and local hospitals.
The vein catheter is removed when there is no longer a need for transfusions and the patient is able to take sufficient amounts of per oral fluid and solid food, which is usually after 3 months.
The patient will complete comprehensive testing of blood and body function after 3, 6, 9, and 12 months. At these visits, the patient will also be offered to speak to a nurse. The nurse will convey information to relevant cooperation partners, for instance a social worker, psychologist, the school, and the Cancer Registry.
Women receive regular follow-up by a gynecologist with emphasis on hormone treatment and development of chronic GVHD. Eye and lung examinations are also performed at some visits.
Thereafter, the patient is seen annually for 5 years.
Bone marrow function and the immune system during the first 3 months
The immune system of a transplanted patient needs at least 12 months before it functions normally, provided the patient does not have chronic GVHD. The patient will therefore be more susceptible to infections than normal and runs a certain risk for bleeding if the thrombocyte count is considerably reduced. The problem decreases gradually, but it is very important that signs of infection or bleeding are taken seriously.
Patients receiving steroid treatment for GVHD will have a reduced immune system long after the transplantation. It is therefore especially important that this patient group is taken seriously when contacting a doctor with suspicion of infection. If adequate treatment is not started immediately, there is a risk of sepsis with serious infections.
Precautions the patient should follow for the first 3 months:
- avoid contact with people who are obviously infected with a cold or have a known contagious illness
- avoid contact with children with pediatric illnesses or people who have been in contact with pediatric illnesses
- visitors should wash their hands
- avoid contact with household animals
- follow food restrictions to avoid growth of microorganisms
Normal household cleaning is sufficient.
It is recommended that the patient uses a face mask for the first 3 months after the transplant if staying at the hospital or when in close contact with many people. When outside in fresh air, it is not necessary to use a face mask. The patient should avoid public transportation, the cinema, theater, and places with large amounts of people, in the first three months after the transplant.
Children should be taken out of day care/preschool about 14 days before the patient returns home. Children should not be allowed to attend day care/preschool in the first period after the patient returns home due to the risk of infection.
Being seriously ill over a long period of time is a great psychological burden. Treatment and consequences of treatment may be very straining in periods for both the patient and family. Often, the patient will feel depressed after returning home and it may take a significant amount of time before resuming normal activity. The patient and family must adjust their expectations for life.
It is important that the patient and their family allow time to process their experiences from the transplant and illness period. Some will benefit from psychological care or other therapy.
Long-term illness and treatment is challenging for relationships. The interaction between partners may have changed and it may be difficult to return to the state before the illness. Physical changes in both men and women may also influence sexual relations.
Even if the possibility of pregnancy is small after treatment, prevention is recommended for the first year. After the first year, there are no special precautions.
Back to work/school/studies
The time at which to resume work/school/studies depends on how quickly the patient recuperates after the transplantation. In most cases, it is recommended that the patient does not start working until 6 months after the stem cell transplantation. It is also important that the patient does not return to work before he/she feels ready. We recommend that the patient discusses this with their closest contacts, health personnel and/or other professionals. The patient should also plan with their employer before resuming work.
The patient should contact their doctor if they have the following symptoms:
- sudden and lasting cough
- shortness of breath
- unexpected bleeding
- sudden diarrhea, significant constipation, abdominal pain, nausea
- mouth soreness, significant sore throat, or problems swallowing
- pain associated with urination or bowel movements
- acute headache
- pain limited to an area in the face/body
- contact with possible infectious illness
Delayed reactions after stem cell transplantation (after 1 year)
About 30% develop GVHD, 1/3 are new cases, 1/3 are recurrence of acute GVHD, 1/3 are lasting acute GVHD. GVHD occurs more frequently with unrelated donors.
The patient should be revaccinated according to the standard vaccination program after 1 year. The patient should not be inoculated with live vaccine.
Infections in the form of Herpes zoster, CMV and encapsulated bacteria are rare, but occur if the patient has chronic GVHD.
For confirmed hypogammaglobulinemia and recurrence of serious infections, gammaglobulin substitution may be necessary.
Moderate to serious restrictive loss of function in about 20%, especially in patients with chronic GVHD.
Lung complications with obstructive failure, obliterating bronchiolitis in < 5 %, is observed especially in patients with chronic GVHD. The most important treatment is early infection therapy. Effect of increased immunosuppression is uncertain and this type of treatment requires increased attention with regard to infections.
Hemosiderosis is caused by numerous erythrocyte transfusions and may cause long-term organ damage. Blood-letting is therefore performed with ferritin > 500, from about 6 months after the transplantation, if the patient will tolerate it. Blood is drawn until ferritin is at a stable level within the normal reference area.
About 15% will become hypothyroid (preferable monitored after TBI).
Gonadal function, growth and development
All stem cell transplanted women will have a follow-up program at the women's clinic.
Almost all women remain in amenorrhea and half will develop menopausal symptoms.
Almost all stem cell transplanted men develop gonad failure with azospermia. Restitution of gonad function after multiple years has been observed in some cases.
The risk for fetal injury at birth and the first years after birth do not appear to have increased. Long-term observations indicate that the risk of fetal injury is not great.
Cataracts occur in most long-term survivors after total body irradiation. The frequency after busulfan and cyclophosphamide is still uncertain, but is not uncommon.
Very rare after 2-3 years, but can occur even after > 6 years.
- Cumulative risk after 15 years, 6% with out total body irradiation, 20% with total body irradiation.
- Lymphoid neoplasms in donor cells occur in rare cases and are often associated with EBV. This usually occurs within a year after a transplantation and especially in patients who have received T-cell filtered marrow with HLA-incompatibility and who are treated for steroid-refractory acute GVHD.
- Basal cell and squamous cell carcinoma
- Leukemia in donor cells < 1%