Hematopoietic Cell Transplantation for Malignant Conditions

Qaiser Bashir, Mehdi Hamadani

• Publisher: Elsevier
• Year: 2019
• ISBN:
  9780323568036
• Topic: Médecine
• Subtopic: Hématologie

Get a quick, expert overview of hematologic and non-hematologic malignancies for which hematopoietic cell transplantation is a treatment option. Drs. Qaiser Bashir and Mehdi Hamadani provide easy-to-find information on basic science of hematopoietic cell transplantation, pharmacology, workflows and procedures, possible complications and side effects, in addition to the role of HCT in conjunction with clinical cellular therapy.

• Discusses high-dose chemotherapeutic regimens and radiation therapy, patient and donor selection and workup, as well as other key aspects of hematopoietic cell transplantation.
• Includes practical information on complications, infectious disease, and special populations such as patients with HIV infection.
• Consolidates today's available information in this fast-changing area into one convenient resource.

IV

Hematopoietic Cell Transplantation for Hematologic Malignancies

Outline

Chapter 9. Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia

Chapter 10. Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia

Chapter 11. Hematopoietic Cell Transplantation for Myeloproliferative Neoplasms

Chapter 12. Hematopoietic Cell Transplantation for Chronic Lymphocytic Leukemia

Chapter 13. Allogeneic Hematopoietic Cell Transplantation in Patients With Myelodysplastic Syndrome

Chapter 14. Autologous Hematopoietic Stem Cell Transplantation for Non-Hodgkin Lymphoma

Chapter 15. Allogenic Transplant for Non-Hodgkin Lymphoma

Chapter 16. Hematopoietic Stem Cell Transplantation for Hodgkin Lymphoma

Chapter 17. Hematopoietic Cell Transplantation in Patients With Multiple Myeloma

Chapter 18. Hematopoietic Cell Transplantation for Light-Chain Amyloidosis

Chapter 19. Hematopoietic Stem Cell Transplantation for Rare Hematological Malignancies

Chapter 9

Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia

Benjamin Tomlinson, MD, and Marcos de Lima, MD

Abstract

Allogeneic hematopoietic stem cell transplant (alloHSCT) is potentially curative for acute myeloid leukemia (AML) otherwise incurable with chemotherapy. Outcomes are influenced by disease status and a variety of AML-specific prognostic variables. The mechanism of alloHSCT is a graft-versus-leukemia effect that combines synergistically with potent cytotoxic conditioning regimens. Risk stratification for AML continues to be refined to better select alloHSCT candidates and is starting to include dynamic risk prognostication with measurable residual disease testing. Myeloablative conditioning regimens are standard in younger patients, while reduced intensity conditioning is frequently offered for patients in their 60s, and 70s. Alternative donor approaches for AML with umbilical cord blood and related haploidentical alloHSCT have proven efficacy in AML and have expanded transplant to those without matched donors. Challenges to a successful transplant include graft-versus-host disease, AML recurrence and preparative regimen-related toxicity, and several lines of research are ongoing trying to address these limitations.

Keywords

acute myeloid leukemia; allogeneic hematopoietic stem cell transplant; graft versus leukemia; induction failure; maintenance chemotherapy

Introduction

Allogeneic hematopoietic stem cell transplant (allo-HSCT) plays a critical role in the management of acute myeloid leukemia (AML), offering curative potential for patients who have incurable disease with standard forms of chemotherapy. Allo-HSCT incorporates a conditioning regimen of chemotherapy with or without radiation to eradicate residual leukemia and provide recipient immunosuppression. Potent alkylating agents such as busulfan, melphalan, as well as high doses of total-body irradiation (TBI) are highly effective agents against AML, but without marrow rescue with hematopoietic progenitor cells, it can result in prolonged or fatal myelosuppression. Historically, autologous HSCT was studied as a form of consolidation, but improvements over standard consolidation have not been demonstrated.¹ Allogenic transplant requires recipients to be immunosuppressed to limit graft rejection and have additional risks for treatment-related mortality from graft-versus-host disease (GVHD), infection, and primary and secondary graft failure. Nevertheless, allo-HSCT capitalizes on an allogeneic immune effect of graft-versus-leukemia (GVL) that adds synergistically to the cytotoxic effects of the conditioning regimen. Here, we review AML risk stratification, selection of appropriate candidates for allo-HSCT, conditioning regimens, and outcomes of transplantation using matched related or unrelated donors, and alternative donor allo-HSCTs.

Mechanisms of Allo-HSCT in AML

The curative potential of allo-HSCT was recognized by early studies showing cures even in a small proportion of refractory patients.² A significant portion of the responses can be attributed to the GVL effect. The earliest implications of this were seen in murine models in which transplanted marrow eliminated leukemia even before cytotoxic irradiation was applied.³ Early studies of sibling donor transplants noted that non–T cell–depleted grafts had improved rates of leukemia relapse.⁴ By the early 1990s retrospective analyses of international transplant registries clearly demonstrated that the presence of acute or chronic GVHD was linked to a reduced risk of relapse.^5,6 Furthermore, the activity of donor lymphocyte infusion (DLI) in treating posttransplant recurrence has further cemented this observation. The concept of “adoptive immunotherapy” was developed by Mathé as he treated a leukemia patient with increasing doses of donor leukocytes.⁷ A syndrome, later recognized to be GVHD, developed, but the patient never relapsed. Susceptibility to the GVL effect may be higher in CML, but still significant in AML.⁸

Allogeneic T cells are critical to GVL. Their importance was clearly demonstrated when T cell depletion was introduced as a possible means to manage and prevent GVHD.⁹ Relapse rates for multiple hematologic malignancies, including AML, were notably higher in T cell–depleted grafts.⁵ The primary mechanism for GVL is felt to be initiated by antigen presentation by host dendritic cells. These antigen-presenting cells are responsible for the activation and maintenance of donor CD4+ T cells and cytotoxic CD8+ T cells that result in long-term disease control.^10–12 As a result, some degree of donor engraftment is expected, and DLI can result in increased activation and antileukemic efficacy.

Acute Myeloid Leukemia—Disease and Classification

AML results from clonal proliferation and differentiation blockade of hematopoietic progenitor cells. The resulting cells infiltrate the bone marrow and other tissues and lead to the clinical mani...