Hematopoietic Stem Cell Transplantation Quiz

Study Notes

Hematopoietic Stem Cell Transplantation: Types, Donor Sources, and Conditioning Regimens

Hematopoietic stem cell transplantation (HSCT) involves infusing hematopoietic progenitor stem cells (HPCs) from a donor to a recipient after a preparative regimen of chemotherapy and/or radiation to re-establish normal hematopoietic and immune function.
HSCT is used to treat and cure various malignant and non-malignant disorders.
Hematopoietic stem cells (HSCs) are pluripotent stem cells that differentiate into hematopoiesis stem cells primarily in the bone marrow of specific bones in the body.
Autologous transplantation involves removing bone marrow or peripheral blood stem cells from the patient and administering them after harvesting or replacing the patient’s stem cells with peripheral blood stem cells after the patient receives high-dose chemotherapy or radiation.
In-vitro purging may be used to remove cancerous cells from contaminated cancer cells after stem cell collection.
Allogeneic transplantation involves a patient receiving bone marrow from a healthy matched donor who is not an identical twin.
Finding a suitable matched donor is important to reduce the risk of post-transplant complications and can take time if the patient does not have a matched sibling.
Myeloablative conditioning is designed to ablate the patient’s bone marrow, eradicate cancer cells, suppress the immune system, and open spaces in bone marrow for engraftment of donor stem cells.
Reduced intensity conditioning (RIC) regimen uses a much-reduced conditioning regimen and is preferred in the elderly since it causes less toxicity, mixed chimerism upon engraftment, and less graft vs. host disease (GVHD).
Non-myeloablative HSCT conditioning regimens use low-dose chemotherapy and/or low-dose total body irradiation, with tumor eradication depending on the graft versus tumor (GVT) effect, which occurs due to donor T-cells.
Stem cell mobilization involves increasing the number of circulating stem cells to the peripheral blood for harvesting, with various methods of mobilization such as single-agent granulocyte colony-stimulating factor (G-CSF) or plerixafor.
Umbilical cord blood (UCB) stem cells are an alternative source of stem cells, with advantages such as ease of collection, no risk for mother or child, and less costly than bone marrow collection, but the small number of stem cells obtained from UCB may require adults to need more than two units.Stem Cell Transplantation: Preparative Regimen, Engraftment, Immunosuppression, and Side Effects
Preparative regimen includes Busulfan IV, TBI, VP-16, and medication to prevent GVHD.
Stem cell rescue infusion is the intravenous reinfusion of hematopoietic cell graft into the patient following myeloablative or non-myeloablative therapy.
Complications of stem cell rescue include facial flushing, tickling sensation in throat, and rare side effects such as bradycardia, abdominal pain, seizure, renal failure, and encephalopathy.
Engraftment usually occurs within 2 to 4 weeks following transplantation, and complete recovery of immune function takes much longer, up to several months for autologous transplant recipients and 1 to 2 years for patients receiving allogeneic transplants.
Engraftment criteria include sustained ANC >500/mm3 for 3 consecutive days and sustained platelet count 20,000/mm3 for 7 consecutive days.
Engraftment failure can be primary or secondary, and the risk factors include aplastic disease, occurrence of GVHD, and use of non-myeloblative therapies.
Immunosuppression is used to prevent graft rejection, eradicate host immune system, and suppress donor immune system to minimize recognition of host cells as foreign.
Commonly used immunosuppressants include calcineurin inhibitors, mycophenolate mofetil, methotrexate, corticosteroids, and mTOR inhibitor.
Recovery after stem cell transplantation can be complicated by mucositis/stomatitis, venoocclusive occlusion, and interstitial pneumonitis.
B-cell counts usually return to normal within 3-12 months post-transplant, and recovery may not occur until at least 2 years in patients with chronic GVHD.
Short-term side effects of stem cell transplantation include nausea, vomiting, diarrhea, stomatitis, hair loss, loss of appetite, fatigue, and electrolyte wasting.
Long-term side effects of stem cell transplantation include secondary malignancies, reproductive and sexual issues, body image changes, skin changes, and memory loss.