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Hematopoietic Stem Cell Transplantation

By Martin Hertl, MD, PhD, Jack Fraser Smith Professor of Surgery, Director of Solid Organ Transplantation, and Chief Surgical Officer, Rush University Medical Center

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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). HSC transplantation is also sometimes used for solid tumors (eg, some germ cell tumors) that respond to chemotherapy.

HSC 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

HSC transplantation may be autologous or allogeneic. 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 HSC transplantation, because stem cell harvest is easier and neutrophil and platelet counts recover faster. Umbilical cord HSC 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 HSC transplantation.

Contraindications to allogeneic HSC transplantation are relative and include age > 50, previous HSC transplantation, and significant comorbidities.

Allogeneic HSC transplantation is limited mainly by lack of histocompatible donors. An 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 HSC transplantation is still being defined, but HLA-matching is probably unimportant.


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. Fluorescence-activated cell sorting is used to identify and separate stem cells from other cells.

Stem cells are then infused over 1 to 2 h through a large-bore central venous catheter.

Conditioning regimens

Before allogeneic HSC transplantation for cancer, the recipient first is given a conditioning regimen (eg, a myeloablative regimen such as cyclophosphamide 60 mg/kg IV once/day for 2 days with full-dose total body irradiation or busulfan 1 mg/kg po qid for 4 days plus cyclophosphamide without total body irradiation) to induce remission and suppress the immune system so that the graft can be accepted.

Similar conditioning regimens are used before allogeneic HSC transplantation, even when cancer is not the indication, to reduce incidence of rejection and relapse.

Such conditioning regimens are not used before autologous HSC transplantation for cancer; cancer-specific drugs are used instead.

Nonmyeloablative conditioning regimens (eg, with cyclophosphamide, thymic irradiation, antithymocyte globulin [ATG], and/or cyclosporine) may reduce morbidity and mortality risks and may be useful for elderly patients, patients with comorbidities, and patients susceptible to a graft-vs-tumor effect (eg, those with multiple myeloma).


After transplantation, recipients are given colony-stimulating factors to shorten duration of posttransplantation leukopenia, prophylactic anti-infective drugs, and, after allogeneic HSC transplantation, up to 6 mo of prophylactic immunosuppressants (typically methotrexate and cyclosporine) to prevent donor T cells from reacting against recipient HLA molecules (graft-vs-host disease). Broad-spectrum antibiotics are usually withheld unless fever develops.

Engraftment typically occurs 10 to 20 days after HSC transplantation (earlier with peripheral blood stem cells) and is defined by an absolute neutrophil count > 500 ×106/L.


Complications of stem cell transplantation can occur early (< 100 days after transplantation) or later. After allogeneic HSC 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 occurs in recipients of allogeneic HSC 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

Diagnosis of acute GVHD is obvious based on history, physical examination, and liver function test results. Treatment is methylprednisolone 2 mg/kg IV once/day, increased to 10 mg/kg if there is no response within 5 days.

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 mo after HSC transplantation (range 2 mo to 2 yr). Chronic GVHD occurs in recipients of allogeneic HSC 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, scleroderma) and mucous membranes (eg, keratoconjunctivitis sicca, periodontitis, orogenital lichenoid reactions), but it also affects the GI 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 membrane; 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 HSC transplantation are higher because there is no graft-vs-tumor effect and because circulating tumor cells may be transplanted. Ex vivo tumor cell purging before autologous transplantation is under study.

In patients without chronic GVHD, all immunosuppression can be stopped 6 mo after HSC transplantation; thus, late complications are rare in these patients.


Prognosis after HSC transplantation varies by indication and procedure.

Overall, disease relapse occurs in

  • 40 to 75% of recipients of autologous HSC transplants

  • 10 to 40% of recipients of allogeneic HSC transplants

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 in remission

Compared with chemotherapy alone, HSC 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.

Intensive conditioning regimens, effective GVHD prophylaxis, cyclosporine-based regimens, and improved supportive care (eg, antibiotics as needed, herpesvirus and cytomegalovirus prophylaxis) have increased long-term disease-free survival after HSC transplantation.

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