HEMATOPOIETIC STEM CELL TRANSPLANTATION
Hematopoietic stem-cell transplantation (HSCT) is a potentially curative treatment option for hematologic and lymphoid cancers, selected solid tumors, and nonneoplastic diseases, including autoimmune disorders, amyloidosis, and aplastic anemia.1 Since the first HSCT was performed in 1956, there has been a steady increase in the number performed worldwide, with more than 35,000 autologous and 30,000 allogeneic HSCTs now performed annually.2 In the United States in 2018, a total of 9028 allogeneic and 14,006 autologous HSCTs were performed.3 As peritransplant management strategies have improved, HSCTs are being performed increasingly often for a wider range of conditions, and in patients who are older and with more comorbidities.
During HSCT, patients undergo high-dose conditioning chemotherapy and/or radiation therapy with a view to eradicate their immune system along with any residual malignant cells. Stem cells are collected beforehand and are administered after conditioning is complete to reconstitute the immune system. HSCT may be autologous (where the donor stem cells are the patient’s own) or allogeneic (where the donor stem cells are from an appropriately matched donor). The main indications for autologous transplant include multiple myeloma and lymphomas. The main indications for allogeneic transplants include acute and chronic leukemia, lymphoma, and myelodysplastic syndrome. Stem cells are typically harvested from peripheral blood after mobilization with agents such as G-CSF, cyclophosphamide, and plerixafor, but they can also be harvested directly from bone marrow or from cord blood.3
Autologous HSCT is always myeloablative: the conditioning regimen needs to eradicate any malignant cells that remain after induction chemotherapy, so no residual marrow remains. Allogeneic HSCT has intrinsic graft-versus-tumor effect, where the donor bone marrow attacks residual tumor cells. This allows for the option of nonmyeloablative and reduced-intensity conditioning regimens. These regimens are lower intensity so may leave residual tumor cells behind, but they are also easier to tolerate for older patients and those with more comorbidities.
Following HSCT, the immune system recovers along predictable patterns depending on the underlying disorder, type of transplant, stem cell source, and posttransplant complications.4 Recovery occurs faster in autologous transplant recipients, in those who receive peripheral blood stem cell grafts, and in those allogeneic transplant recipients who receive nonmyeloablative conditioning. The posttransplant period is classically divided into three phases: peri-engraftment, early posttransplant, and late posttransplant.5 The peri-engraftment phase (0 to 30 days) is characterized by neutropenia and breaks in the mucocutaneous barriers with a high burden of sepsis, pneumonia, aspiration, and critical illness. The early post-engraftment phase (30–100 days) is characterized by impaired cell-mediated immunity. The impact of this cell-mediated defect is greater in allogeneic transplant recipients who are prone to the development of GVHD, often resulting in the initiation of immunosuppressant medications further increasing their risk of opportunistic infection. The late posttransplant phase (>100 days) is characterized by defects in cell-mediated and humoral immunity, as well as dysfunction of the reticuloendothelial system in allogeneic transplant recipients.