Physical Address

304 North Cardinal St.
Dorchester Center, MA 02124

Infection Control, Prophylaxis, and Vaccinations in Hematopoietic Cell Transplantation Recipients

Overview Hematopoietic cell transplant (HCT) recipients are at a heightened risk of a wide range of new infections or the reactivation of latent or remote infections given the extent of immunosuppression and immune dysregulation caused by chemotherapy, immunosuppressive medications for graft-versus-host diseases (GVHDs), and environmental exposures. HCT consists of the administration of hematopoietic progenitor cells (HPCs) collected from three major sources (bone marrow, peripheral blood, and…

Natural Killer Cells: A Promising Cellular Therapy Platform to Conquer Cancer

Background: Natural Killer Cell Biology In 1973, Ivan Roitt's laboratory identified a new class of lymphocytes dubbed “null” killer cells, since they were neither T-cells nor B cells. The following year, these “null” lymphocytes were found to have spontaneous ability to kill target cells without prior immunization and without antibodies. In 1975, Rolf Keissling and colleagues described a similar natural cytotoxicity and named the effector cell…

Hematopoietic Cell Transplantation for Germ-Cell Tumors and Other Adult Solid Tumors

Introduction to Germ-Cell Tumors Germ-cell tumors (GCT) are the most common malignancy in young men ages 15 to 35 years. These tumors have great response rates to cisplatin-based chemotherapy, with cure rates for metastatic disease as high as 70% to 80%. In 2020, there were 9610 estimated new cases of GCT and 440 estimated deaths because of GCT, reflecting a 5-year survival rate of approximately 95%.…

Hematopoietic Cell Transplantation in Rare Hematologic Malignancies

Introduction There is an expanding role for hematopoietic cell transplantation (HCT) in rare hematologic malignancies. The rarity of these diseases limit well-designed prospective trials. In this chapter, we review the available data on the role of allogeneic and autologous HCT for the rare malignancies ( Table 27.1 ). Table 27.1 Rare Myeloid, Lymphoid, Histiocytic, and Dendritic Cell Malignancies Rare Myeloid Malignancies Annual Incidence in the United…

Chimeric Antigen Receptor Therapy in Lymphoma

Introduction Clinical trials of CD19 chimeric antigen receptor (CAR) T-cells have demonstrated promising survival outcomes and response rates in relapsed and/or refractory (r/r) non-Hodgkin lymphoma (NHL), providing a potentially curative treatment option for these heterogeneous, aggressive malignancies. There are currently four U.S. Food and Drug Administration (FDA)–approved commercially available CAR T-cell therapies for highly aggressive B-cell NHL, all directed toward CD19. Axicabtagene ciloleucil (axi-cel), tisagenlecleucel (tisa-cel),…

Hematopoietic Cell Transplantation for Hodgkin Lymphoma

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy composed of two distinct disease entities: the more commonly diagnosed classical HL and the rare nodular lymphocyte predominant HL. The disease has a bimodal distribution with an increased incidence in young adults as well as in patients 55 years and older. HL accounts for about 1% (7500 cases) annually of newly diagnosed cancer in the United States…

Hematopoietic Cell Transplantation for Non-Hodgkin Lymphoma

Introduction Non-Hodgkin lymphoma (NHL) is a lymphoid malignancy that represents 4.3% of all new cancer diagnosis in the United States and is estimated to be responsible for over 19,000 deaths in 2020. While newer immunotherapies have emerged that have improved treatment options and outcomes for NHL patients, hematopoietic cell transplantation (HCT) remains an important modality, providing prolonged progression-free survival (PFS) and overall survival (OS), for certain…

Hematopoietic Cell Transplantation in Light Chain Amyloidosis

Introduction Light chain (AL) amyloidosis is a plasma cell disorder characterized by the deposition of monoclonal immunoglobulin light chains in a variety of tissues leading to organ dysfunction. The treatment of this disorder focuses on eliminating the plasma cells producing these light chains and involves therapies similar to those used in multiple myeloma. The role of hematopoietic cell transplantation (HCT) in treating AL amyloidosis has evolved…

Chimeric Antigen Receptor Therapy in Multiple Myeloma

Introduction Multiple myeloma is a hematologic malignancy characterized by the clonal proliferation of malignant plasma cells within the bone marrow microenvironment causing organ dysfunction that may include anemia, lytic bone lesions, hypercalcemia, and renal dysfunction. In 2021, myeloma was expected to account for approximately 1.8% of new cancer diagnoses and 19% of new hematologic malignancy diagnoses, with an expected number of approximately 34,920 new cases and…

Hematopoietic Cell Transplantation in Multiple Myeloma

Introduction The goal of treatment for multiple myeloma, an incurable hematologic malignancy, is to achieve the deepest possible response with the longest duration of remission upfront to achieve a durable disease-free state. The pivotal multicenter trial IFM 90 established the superiority of consolidation with autologous hematopoietic cell transplant (auto-HCT) in chemosensitive disease as standard of care for upfront treatment of myeloma, with improved response rate, event-free…

Hematopoietic Cell Transplantation in Aplastic Anemia

CASE STUDY A 19-year-old Caucasian male presented with petechiae and a platelet count of 4 × 10 9 /L, neutrophils 0.3 × 10 9 /L, hemoglobin 9 g/dL with reticulocyte count of 0.019 × 10 9 Bone marrow aspirate and core biopsy showed less than 5% cellularity with stromal damage and predominantly lymphocyte infiltration. His workup for inherited/congenital bone marrow failure syndromes ( Bone Marrow…

Allogeneic Cell Transplantation for Myeloproliferative Neoplasms

Introduction Myeloproliferative neoplasms (MPN) are a heterogeneous group of myeloid stem cell disorders shared by certain clinical and biological similarities, and characterized by clonal myeloproliferation without significant dyserythropoiesis, granulocytic dysplasia, or monocytosis. Primary myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocythemia (ET) are collectively grouped together under chronic Philadelphia chromosome-negative MPNs compared to the distinguished Philadelphia chromosome-positive chronic myeloid leukemia (CML). In addition to PMF, the…

Allogeneic Hematopoietic Cell Transplantation in Myelodysplastic Syndrome Patients

Key Concepts Hematopoietic cell transplantation provides a curative therapy for patients with myelodysplastic syndrome. The clonal karyotype is the strongest predictor of posttransplant relapse. The availability of human leukocyte antigen (HLA)-matched related and unrelated donors, HLA-haploidentical donors, and umbilical cord blood helps identify donors for the majority of patients. As myelodysplastic syndrome is primarily a disease of older age and quality of life is a top…

Hematopoietic Cell Transplantation and Other Cellular Therapies for Chronic Lymphocytic Leukemia

Disclosures: FTA has provided consultancy to: Genentech, Astrazeneca, Abbvie, Janssen, Pharmacyclics, Gilead sciences, Kite pharma, Celgene, Karyopharm, MEI Pharma, Verastem, Incyte, Beigene, Johnson and Johnson, Dava Oncology, BMS, Merck, Cardinal Health, ADCT therapeutics, Epizyme. PRG has provided consultancy to: Pharmacyclics LLC, Kite pharma, BMS, Rafael Pharma and Cellectar Biosciences Background Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia in the West, with a median…

Chimeric Antigen Receptor T-Cell Therapy in Acute Lymphoblastic Leukemia

Introduction Acute lymphoblastic leukemia (ALL) is a heterogeneous group of hematologic malignancies with an annual age-adjusted incidence rate of 1.8 per 100,000 people in the United States, with an estimated 5690 new cases and 1580 deaths according to the most recent Surveillance, Epidemiology, and End Results data. Although remission rates for this malignancy are quite high and can reach up to 90%, relapse remains a challenge,…

Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Lymphoblastic Leukemia

Introduction Acute lymphoblastic leukemia (ALL) is a heterogeneous group of hematologic malignancies with an annual age-adjusted incidence rate of 1.73 per 100,000 people in the United States and with a median age of 14 years. It is estimated that 5690 new cases of ALL in adults and children will be diagnosed in the United States in 2021. With the use of modern risk-adapted chemotherapy over the…

Chimeric Antigen Receptor Therapy in Acute Myeloid Leukemia

Brief Overview of Acute Myeloid Leukemia Acute myeloid leukemia (AML) is a heterogeneous clonal disease of myeloid-stem and progenitor cells resulting from mutations, deletions, and epigenetic alterations in genes associated with cell differentiation, proliferation, and renewal. AML represents roughly 1% of all cancers; around 20,000 new cases and 11,000 deaths were projected to occur in the United States in 2021. AML encompasses a family of unique…

Hematopoietic Cell Transplantation in Adult With Acute Myeloid Leukemia

Introduction Acute myeloid leukemia (AML) is the commonest indication for allogeneic hematopoietic cell transplant (allo-HCT) worldwide with numbers rising since its inception 65 years ago. The majority of patients with AML enter complete (morphologic) remission (CR1) with induction therapy; however, the risk of relapse is considerable. With allo-HCT the relapse risk can be mitigated or completely abolished in all biologic subtypes of AML. Such remarkable contribution…

Radiobiologic Principles and the Role of Radiotherapy in Hematopoietic Cell Transplant and Chimeric Antigen Receptor T-Cell Therapy

Introduction Radiation therapy is an effective treatment for many hematologic malignancies in a variety of contexts. In this chapter, we provide a brief review of the mechanism of external beam radiation, discuss radiobiologic principles that guide radiation response and fractionation, and discuss toxicity most relevant in the treatment of hematologic malignancies. We then review the role of radiotherapy (RT) in the context of hematopoietic cell transplant…

Pharmacology of Drugs Used in Hematopoietic Cell Transplant and Chimeric Antigen Receptor Therapies

Introduction Medications used for hematopoietic cell transplant (HCT) and immune effector cell (IEC) therapies are often complex and carry numerous clinical considerations, including understanding of pharmacokinetic and pharmacodynamic principles, drug-drug interactions, adverse effects, and dose adjustment for organ dysfunction. This chapter will highlight commonly used medications for antimicrobial prophylaxis and treatment, graft-versus-host disease (GVHD) prophylaxis and treatment, IEC toxicity, and supportive care. Antimicrobial Agents Prophylactic antimicrobials…