Hematopoietic stem cell (HSC) transplantation is a rapidly evolving technique that offers a potential cure for hematologic cancers (leukemias, lymphomas, myeloma) and other hematologic disorders (eg, primary immunodeficiency, aplastic anemia, myelodysplasia). Hematopoietic stem cell transplantation is also sometimes used for solid tumors (eg, some germ cell tumors) that respond to chemotherapy.
(See also Overview of Transplantation.)
Hematopoietic stem cell transplantation contributes to a cure by
Restoring bone marrow after myeloablative cancer-eradicating treatments
Replacing abnormal bone marrow with normal bone marrow in nonmalignant hematologic disorders
Hematopoietic stem cell transplantation may be autologous (using the patient's own cells) or allogeneic (using cells from a donor). Stem cells may be harvested from
Bone marrow
Peripheral blood
Umbilical cord blood
Peripheral blood has largely replaced bone marrow as a source of stem cells, especially in autologous hematopoietic stem cell transplantation, because stem cell harvest is easier and neutrophil and platelet counts recover faster. Umbilical cord hematopoietic stem cell transplantation has been restricted mainly to children because there are too few stem cells in umbilical cord blood for an adult. A potential future source of stem cells is induced pluripotent stem cells (certain cells taken from adults and reprogrammed to act like stem cells).
There are no contraindications to autologous hematopoietic stem cell transplantation.
Contraindications to allogeneic hematopoietic stem cell transplantation are relative and include
Age > 50
Previous hematopoietic stem cell transplantation
Significant comorbidities (eg, renal failure)
Allogeneic hematopoietic stem cell transplantation is limited mainly by lack of histocompatible donors. A human leukocyte antigen (HLA)-identical sibling donor is ideal, followed by an HLA-matched sibling donor. Because only one fourth of patients have such a sibling donor, mismatched related or matched unrelated donors (identified through international registries) are often used. However, long-term disease-free survival rates may be lower than those with HLA-identical sibling donors.
The technique for umbilical cord hematopoietic stem cell transplantation is still in its infancy, but it is gaining interest. Because cord blood contains immature stem cells, HLA matching appears less crucial than for the other types of hematopoietic stem cell transplantation. One concern about the procedure is that immune cells in cord blood do not have experience with the viruses responsible for latent infections, leading to a higher percentage of naive T cells and thus increased vulnerability to reactivation of cytomegalovirus or Epstein-Barr virus infection.
Procedure
For bone marrow stem cell harvest, 700 to 1500 mL (maximum 15 mL/kg) of marrow is aspirated from the donor’s posterior iliac crests; a local or general anesthetic is used.
For peripheral blood harvest, the donor is treated with recombinant growth factors (granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor) to stimulate proliferation and mobilization of stem cells; standard apheresis is done 4 to 6 days afterward.
For umbilical cord blood harvest, the cord is clamped after delivery of the baby, and blood is drawn from the cord with a needle and collected in a sterile bag.
Fluorescence-activated cell sorting is used to identify and separate stem cells from other cells. Stem cells are then infused over 1 to 2 hours through a large-bore central venous catheter.
Conditioning regimens
Similar conditioning regimens are used before allogeneic hematopoietic stem cell transplantation, even when cancer is not the indication, to reduce incidence of rejection and relapse.
Such conditioning regimens are not used before autologous hematopoietic stem cell transplantation for cancer; cancer-specific drugs are used instead.
Posttransplantation
After hematopoietic stem cell transplantation, recipients are given colony-stimulating factors to shorten duration of posttransplantation leukopenia, prophylactic anti-infective drugs
Engraftment typically occurs 10 to 20 days after hematopoietic stem cell transplantation (earlier with peripheral blood stem cells) and is defined by an absolute neutrophil count > 500/mcL (> 0.5 × 109/L).
Complications of Hematopoietic Stem Cell Transplantation
(See also Posttransplantation Complications.)
Complications of stem cell transplantation can occur early (< 100 days after transplantation) or later. After allogeneic hematopoietic stem cell transplantation, risk of infections is increased.
Early complications
Major early complications include
Failure to engraft
Acute graft-vs-host disease (GVHD)
Failure to engraft and rejection affect < 5% of patients and manifest as persistent pancytopenia or irreversible decline in blood counts. Treatment is corticosteroids for several weeks.
Acute GVHD, in which immune cells from the donor attack tissue in the recipient, occurs in recipients of allogeneic hematopoietic stem cell transplants (in 40% of HLA-matched sibling graft recipients and 80% of unrelated donor graft recipients). It causes fever, rash, hepatitis with hyperbilirubinemia, vomiting, diarrhea, abdominal pain (which may progress to ileus), and weight loss.
Risk factors for acute GVHD include
HLA and sex mismatching
Unrelated donor
Older age of recipient, donor, or both
Donor presensitization
Inadequate GVHD prophylaxis
Later complications
Major later complications include
Chronic GVHD
Disease relapse
Chronic GVHD may occur by itself, develop from acute GVHD, or occur after resolution of acute GVHD. It typically occurs 4 to 7 months after hematopoietic stem cell transplantation (range 2 months to 2 years). Chronic GVHD occurs in recipients of allogeneic hematopoietic stem cell transplants (in about 35 to 50% of HLA-matched sibling graft recipients and 60 to 70% of unrelated donor graft recipients).
Chronic GVHD affects primarily the skin (eg, lichenoid rash, sclerotic skin changes) and mucous membranes (eg, keratoconjunctivitis sicca, periodontitis, orogenital lichenoid reactions), but it also affects the gastrointestinal tract and liver. Immunodeficiency is a primary feature; bronchiolitis obliterans similar to that after lung transplantation can also develop. Ultimately, GVHD causes death in 20 to 40% of patients who have it.
Treatment may not be necessary for GVHD that affects the skin and mucous membranes; treatment of more extensive disease is similar to that of acute GVHD. T-cell depletion of allogeneic donor grafts using monoclonal antibodies or mechanical separation reduces incidence and severity of GVHD but also eliminates the graft-vs-tumor effect that may enhance stem cell proliferation and engraftment and reduce disease relapse rates. Relapse rates with autologous hematopoietic stem cell transplantation are higher because there is no graft-vs-tumor effect and because circulating tumor cells may be inadvertently collected with stem cells and transplanted. Ex vivo tumor cell purging before autologous transplantation is under study.
In patients without chronic GVHD, all immunosuppression can be stopped 6 months after hematopoietic stem cell transplantation; late complications are rare in these patients.
Prognosis for Hematopoietic Stem Cell Transplantation
Prognosis after hematopoietic stem cell transplantation varies by the type of transplant (autologous vs allogeneic) and the recipient's disease.
Overall, disease relapse occurs in
40 to 75% of recipients of autologous hematopoietic stem cell transplants
10 to 40% of recipients of allogeneic hematopoietic stem cell transplants
Overall, success (cancer-free bone marrow) rates are
30 to 40% for patients with relapsed, chemotherapy-sensitive lymphoma
20 to 50% for patients with acute leukemia
Compared with chemotherapy alone, hematopoietic stem cell transplantation improves survival of patients with multiple myeloma. Success rates are low for patients with more advanced disease or with responsive solid cancers (eg, germ cell tumors). Relapse rates are reduced in patients with graft-vs-host disease (GVHD), but overall mortality rates are increased if GVHD is severe.
