Hematopoietic Stem Cell Transplantation
Summary of Key Points
• Hematopoietic cell transplantation (HCT) is a potentially curative treatment for a variety of hematopoietic, immune, metabolic, and malignant diseases.
• Hematopoietic stem cells for transplantation can be collected from bone marrow, peripheral blood, or umbilical cord blood.
• With the advent of unrelated donor, haploidentical, and cord blood transplantation, virtually every patient can now have a suitable donor.
• Reduced-intensity conditioning regimens are associated with lower treatment-related mortality and allow for transplantation in elderly and patients with comorbidities who are not candidates for myeloablative HCT.
• Allogeneic HCT is most frequently performed for patients with acute and chronic leukemias, myelodysplastic syndromes, immune deficiencies, metabolic disorders, and bone marrow failure states.
• Autologous HCT is usually performed as part of the initial treatment for multiple myeloma, relapsed Hodgkin and non-Hodgkin lymphoma, and select solid tumors.
• Common complications of HCT include regimen-related organ toxicity, graft rejection, graft-versus-host disease, infections, and secondary malignancies.
1. All of these conditions increase the risk of graft-versus-host disease (GVHD) except:
A Increasing human leukocyte antigen (HLA) disparity
B Use of a matching unrelated donor versus a matching sibling donor
C Peripheral blood progenitor cells versus bone marrow–derived progenitor cells
2. A 48-year-old white man is diagnosed with stage IIIB diffuse large B-cell lymphoma (DLBCL). He receives treatment with six cycles of the rituxan, cyclophosphamide, doxorubicin, vincristine, and prednisone regimen. Restaging evaluation after the completion of three cycles showed complete remission. Eighteen months after the original diagnosis, the patient noticed a lump in the right side of his neck. An excisional biopsy confirmed the diagnosis of relapsed DLBCL. Whole-body computed tomography scans reveal lymphadenopathy in the mediastinum and abdomen. The patient is otherwise healthy, with a good performance status, and is motivated to do everything he can to beat this cancer. What is an appropriate treatment plan for this patient?
A Three cycles of chemotherapy with rituximab, ifosfamide, carboplatin, and etoposide (RICE) followed by careful clinical monitoring once complete remission is obtained
B Three cycles of chemotherapy with etoposide, methylprednisone, cytarabine, and cisplatin (ESHAP) followed by autologous hematopoietic stem cell transplantation regardless of the response
C Palliative treatment only because the disease is unlikely to respond to any salvage therapy
D Treatment with RICE followed by autologous hematopoietic stem cell transplantation (HCT) once a complete or partial response is achieved
3. All of the following statements are correct except that umbilical cord blood transplantation is associated with:
1. Answer: D. The risk of GVHD increases with increasing HLA disparity and with unrelated donor transplants compared with sibling donors. The use of peripheral blood progenitor cells is associated with increased risk of chronic GVHD compared with bone marrow–derived progenitor cells. GVHD is primarily a T-cell–mediated disease, and depletion of T cells from the grafts has been shown to reduce the incidence and severity of acute and chronic GVHD, although it may increase the risk of disease relapse.
2. Answer: D. Both RICE and ESHAP are reasonable treatment choices for the patients with relapsed DLBCL. Most patients achieve some degree of response; however, it is usually short lived. Long-term disease-free survival can be achieved with autologous HCT in patients with chemotherapy-sensitive relapse. The outcome of patients who do not respond to salvage therapy is poor even with autologous HCT. The patient described is relatively young and is in good shape. Once a response to the salvage therapy is documented, he should be evaluated for autologous HCT. In the presence of effective salvage therapies, palliative care is not the correct choice in this motivated patient.
3. Answer: D. Umbilical cord blood transplantation allows for increased representation of ethnic minorities in the cord blood banks. In addition, the donor pool is expanded because of less-stringent requirements for HLA matching. Time to procure a cord blood unit is usually much shorter than for unrelated donors. The immune reconstitution is delayed after cord blood transplantation compared with matched unrelated or matched sibling donors. One of the limitations of cord blood units is the limited number of hematopoietic progenitor cells, which may not be sufficient for transplantation in adult patients. Several strategies such as double cord blood transplantation and expansion of the stem cell pool in cord blood units are currently under investigation to overcome this problem.
