Hematopoietic cell transplantation for malignant disorders

1 How do the goals of autologous transplantation and allogeneic transplantation differ?

Hematopoietic cell transplantation (HCT) is the act of restoring hematopoiesis by infusing hematopoietic stem cells. The cells that are infused can be from another person (allogeneic) or previously collected cells from the recipient (autologous). The goals and expectations between allogeneic and autologous transplantation differ.

Autologous transplantation is most used for children with chemotherapy-sensitive malignancies, such as solid tumors or relapsed lymphomas. During these transplants, higher doses of chemotherapy are used and significant myelosuppression occurs as a result. An infusion of autologous hematopoietic stem cells overcomes this myelosuppression and allows for earlier bone marrow recovery, reducing potential infectious complications. For this reason, autologous transplantation can also be referred to as high-dose chemotherapy with autologous stem cell rescue. Incorporation of tandem autologous HCT to consolidation therapy improved event-free survival (EFS) for patients with high-risk neuroblastoma from 30% to 61% at 3 years. Similarly, patients with relapsed Hodgkin lymphoma show an increased EFS from 34% to 55% with the use of autologous HCT in treatment for relapsed disease.

Conversely, allogeneic transplantation seeks to restore a defective bone marrow by replacing it with that from a healthy donor. In the case of hematologic malignancies, the bone marrow has produced a clonal population of leukemic blasts that have evaded detection by the patient’s own immune system. During allogeneic transplant, high doses of chemotherapy or radiation are given to eliminate any remaining malignant cells. Then, donor hematopoietic stem cells are infused, which will then reconstitute the bone marrow and become the dominant hematopoietic and immune cells in the body. The healthy immune system can then surveil for any recurrence of malignant cells and effectively eliminate them; this is known as graft versus leukemia (GVL). In this way, allogeneic transplantation was one of the first immunotherapies that was developed.

2 What are the indications for allogeneic transplant in patients with acute lymphoblastic leukemia?

Most patients with acute lymphoblastic leukemia (ALL) do not require allogeneic transplant. Patients with high risk for relapse, however, are considered for allogeneic transplant. Patients who are unable to achieve a morphologic remission (< 5% bone marrow blasts) after induction chemotherapy or who have persistent minimal residual disease (MRD) should be referred for consideration of allogeneic transplant in first complete remission.

For patients that relapse after therapy, early relapses are at higher risk of subsequent relapses and death and should be considered for allogeneic transplant in second remission. Patients who relapse less than 18 months from initial diagnosis were noted to have an extremely poor outcome with only 21% overall survival (OS) with chemotherapy alone. It was found that allogeneic transplant showed a significant survival benefit for patients with a bone marrow relapse within 36 months from initial diagnosis. The probability of relapse was lower with use of allogeneic transplant—43% probability of relapse with HCT using a total body irradiation (TBI)–based regimen with matched sibling transplant compared with 69% probability of relapse with chemotherapy alone. This corresponded to a leukemia-free survival (LFS) of 23% with chemotherapy alone and 41% with a TBI-containing transplant. Use of unrelated donor transplant also showed improved EFS; patients who received an unrelated donor transplant had an EFS of 44% compared with no survival (0%) for patients with high-risk disease who received chemotherapy alone. Since the integration of allogeneic HCT (AlloHCT) for these patients with high-risk disease, and improvement in supportive care strategies, survival outcomes have continued to improve over time.

Lastly, patients who suffer a third relapse with ALL should be considered for allogeneic transplant if able to achieve remission.

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