Stem cell transplantation (SCT; more precisely, hematopoietic stem cell transplantation; HSCT; blood stem cell transplantation) is a form of blood cell stem cell transfer. It is used to restore destroyed hematopoiesis (blood formation) through radiatio (radiation therapy) and/or chemotherapy. Stem cells are located in the bone marrow as well as in the peripheral blood. They have the ability to differentiate into the various blood cells.
Indications (areas of application)
- Acute leukemias/blood cancers (acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML)).
- Aplastic anemia – bone marrow failure with pancytopenia (synonym: tricytopenia), that is, of all three cell series in the blood (anemia, leukopenia and thrombocytopenia) due to acquired (common) or congenital (rare) bone marrow aplasia.
- Bronchial carcinoma (lung cancer) – in early-stage small cell lung cancer currently being tested.
- Chronic leukemias (chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML)).
- Germ cell tumors – form of therapy currently being tested.
- Mammary carcinoma (breast cancer) – in a recurrence or metastatic stage currently being tested.
- Hodgkin’s disease – malignant disease affecting the lymphatic system.
- Myelodysplastic syndrome (MDS) – acquired clonal disease of the bone marrow associated with a disorder of hematopoiesis (blood formation).
- Non-Hodgkin’s lymphoma (NHL) – this collective term includes all malignant (malignant) diseases of the lymphatic system (malignant lymphomas), which are not Hodgkin’s disease.
- Ovarian cancer (ovarian cancer) – currently in trial with minimal residual tumor.
- Plasmocytoma (multiple myeloma) – malignant (malignant) disease caused by abnormal proliferation of plasma cells (special blood cells).
- Severe combined immunodeficiencies
- Sickle cell disease (sickle cell anemia)
The procedure
In the past, bone marrow transplantation was predominantly performed. Today, stem cells are increasingly obtained from peripheral blood using blood cell separation (hematopoietic stem cell transplantation) after growth factors have mobilized them into the but (leukapheresis). After the stem cells have been extracted from the blood, myeloablative therapy (“standard conditioning”) is performed to destroy all diseased blood cells. This usually requires a combination of chemotherapy and radiation therapy.Once the hematopoietic cells are destroyed, stem cells are given, which then cause the formation of new, healthy blood cells. The following forms of stem cell transplantation can be distinguished:
- Autologous stem cell transplantation (ASZT; auto-SZT)/autologous hematopoietic stem cell transplantation (auto-HSZT) – in this procedure, the patient’s own stem cells are returned to him.
- Allogeneic stem cell transplantation//allogeneic hematopoietic stem cell transplantation (alloHSZT) – in this case, the affected person is given stem cells from another, but HLA-identical person.
In the case of allogeneic transplantation, the most important requirement is a histocompatible donor. Ideal donors are HLA-identical siblings or family members. HLA typing is performed to determine if a donor is suitable. A 10/10 match is ideal, but is found in only about half of cases.Note: HLA matching may not be necessary for stem cells from the umbilical cord. The probability of overall survival after receiving a transplant from an umbilical cord blood donor was at least as favorable as that after receiving a transplant from an HLA-mismatched unrelated donor and significantly higher than that after receiving a transplant from an HLA-mismatched unrelated donor. Furthermore, the likelihood of recurrence was lower in the cord blood donor group than in any of the other groups. Stem cell transplantation can be from the following cell types:
- Bone marrow
- Peripheral blood stem cells
- Umbilical cord blood (rare)
Stem cell transplantation is a high-risk form of therapy, the indication for which must be considered very carefully. It should be performed only in specialized centers. Pre-therapy for stem cell transplantation:
- Conditioning therapy before allogeneic hematopoietic stem cell transplantation (HSCT) in adults with malignant and nonmalignant diseases and in malignant diseases in children older than one month: treosulfan (prodrug; belongs to the bifunctional alkylants) combined with fludarabine (cytostatic drug from the group of purine analogs)
- Through a multicenter study (follow-up 24 months), it was demonstrated that the administration of an anti-lymphocyte globulin (ATG) prior to allogeneic stem cell therapy as part of myeloablative conditioning (consisting of radiation and/ or chemotherapy) was able to prevent chronic graft-versus-host disease (GvHR) to a large extent. This is of great importance as it is the prevention of a late complication. Results:
- Conditioning plus ATG: 32.2% chronic GvHD (95 percent confidence interval 22.1 to 46.7 percent).
- Conditioning without ATG: prevalence of chronic GvHD 68.7% (58.4-80.7%).
- Recurrence-free survival in the first two years: 59.4 versus 64.6% [not significant].
- All-cause mortality (mortality): 74.1 versus 77.9% [not significant].
Possible complications
- Graft-versus-host disease* (GvHR; donor-versus-host reaction/rejection reaction) (approximately 25% of cases).
- Infections
* A phase III clinical trial demonstrated that therapy with the drug ruxolitinib can often prevent this immune response: control of the immune response was nearly twice as high with ruxolitinib, at nearly 40 percent of cases, compared with 22 percent with standard therapy
Late effects after allogeneic stem cell transplantation (alloHSZT)
- Recurrence of primary disease and secondary hematologic neoplasms.
- Solid tumors
- Non-malignant late sequelae after alloHSZT.
- Immunodeficiency and late infections.
- Immunological late effects and autoimmune phenomena.
- Late effects of subsequent systems: Respiratory system, skin and skin appendages, circulatory system, gastrointestinal tract (gastrointestinal tract), liver and kidneys, lungs, oral and genital mucosa, musculoskeletal system, neurological system.
- Note: Long-term treatment with azithromycin after HSCT may carry risks that exceed the expected benefits. Azithromycin is not approved for prophylactic treatment of bronchiolitis obliterans syndrome (BOS) in patients after HSCT.
- After hematopoietic stem cell transplantation, adult recipients aged significantly faster than their siblings less than 10 years after treatment. This was evident by the time they were in their early 30s. They showed increased frailty, often decreased muscle strength and endurance, and their movements were slowed.
- Severe disturbance of intestinal flora after autologous stool transplantation because of pretreatment (“conditioning”) and antibiotic therapy:Autologous stool transplantation may promote bacterial diversity in the intestine and probably decrease the number of Clostridium difficile infections.
- Hormonal dysfunction and infertility.
- Fatigue (severe tiredness)
Vaccinations
The following are vaccination recommendations after allogeneic hematopoietic stem cell transplantation (alloHSZT):
| Vaccination | Vaccination startMonth after HSCT | Number of vaccination doses |
| Pneumococcus (conjugate) | 3-6 | 3 + 1e |
| Diphtheria | 6 | 3 + 1 |
| Hemophilus (conjugate) | 6 | 3 + 1 |
| Meningococcus (conjugate) | 6 | 3 |
| Pertussis | 6 | 3 + 1 |
| Polio (inactivated) | 6 | 3 + 1 |
| Tetanus | 6 | 3 + 1 |
| Influenza (inactivated)a | 3-6 | 1-2 |
| TBEb | 6-12 | 3 |
| Hepatitis A/B (recombinant) | 6-12 | 3 |
| Human papilloma virusc | 6-12 | 3 |
| Varicella | 6-12 | 3 |
| Burl | 24 | 2 |
| Mumpsd | 24 | 2 |
| Reddish | 24 | 2 |
Legend
- AAnnual vaccination
- BRisk/endemic areas
- cIn adolescents and young adults who have not undergone infection but have been vaccinated.
- DOnly in patients with proven immunocompetence.
- E3 ×13-valent vaccine, final 23-valent vaccine (immunocompetent patients should be vaccinated sequentially with the 13-valent conjugate vaccine PCV13 and six to 12 months later with the 23-valent polysaccharide pneumococcal vaccine PPSV23).