Physical Address

304 North Cardinal St.
Dorchester Center, MA 02124

Preparative Regimens Used in Hematopoietic Cell Transplantation and Chimeric Antigen Receptor T-Cell Therapies

Hematopoietic Cell Transplant Preparative Regimens Goals of the Preparative Regimen Hematopoietic cell transplant (HCT) is a therapy that has the potential to cure or prolong the life of patients with hematologic malignancies as well as certain solid tumors and nonmalignant conditions. High-dose chemotherapy (HDC) preparative regimens are a critical part of the HCT process. The preparative regimen is administered before the HCT and is selected based…

Process and General Management of Patients Undergoing Chimeric Antigen Receptor Therapies

Introduction The introduction of chimeric antigen receptor (CAR) T-cell therapies represents the culmination of a decades-long journey to harness the immune system and exploit the antitumoral potential of immune cells to treat cancer. The first clinical experiences describing the administration of genetically engineered CD19-directed CAR T-cells (CART19) derived from patients’ own T lymphocytes for B-cell lymphoid neoplasms were published between 2011 and 2013. These pilot and…

Umbilical Cord Blood Transplantation

Introduction The first successful cord blood transplantation (CBT) was performed by Dr. Gluckman, Dr. Broxmeyer, and their colleagues for a patient with Fanconi anemia in 1989. Since then, the application of CBT has broadened to include both malignant and nonmalignant diseases, and cord blood has emerged as an essential alternative donor source in the practice of hematopoietic cell transplantation (HCT). CBT has become especially important because…

Haploidentical Hematopoietic Cell Transplantation

Introduction Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative treatment for various hematologic and immunologic disorders. Historically, selection of a suitable allo-HCT donor relied exclusively on degree of human leukocyte antigen (HLA) matching between the donor and the recipient to avoid the intense bidirectional immunologic reactions causing graft rejection and graft-versus-host disease (GHVD). However, a fully HLA matched related or unrelated donor cannot be identified in…

Transfusion Support During Hematopoietic Cell Transplantation

Blood products are essential during the peritransplant period. Patients receiving hematopoietic cell transplantation (HCT) require extensive transfusion support until appropriate platelet and red blood cell (RBC) engraftment ensures. The platelet lineage is considered engrafted when a patient’s platelet count is at least 20,000/µL after 3 consecutive days without platelet transfusion; neutrophil engraftment is defined by when the absolute neutrophil count (ANC) reaches > 500/µL for 2…

Patient and Donor Assessments in Preparation for Transplant

Introduction Hematopoietic cell transplantation (HCT) remains an essential therapeutic intervention for several high-risk hematologic neoplasms. HCT leads to durable responses and remissions for plasma cell neoplasms and indolent lymphomas and can be curative for aggressive lymphomas, acute leukemias, myelodysplastic syndromes, aplastic anemia, and myeloproliferative neoplasms, among other, less frequent indications. However, HCT, particularly allogeneic HCT (allo-HCT), is often associated with several early and late complications after…

Bayesian Statistical Methods in Stem Cell Transplantation and Cellular Therapy

Elements of Bayesian Statistics The main objects in a statistical model are observable data, which may include one or more outcomes, Y, possibly a vector, X, of patient covariates and treatments, and a parameter vector, θ. Parameters are unobserved conceptual objects, such as the probability of response, median survival time, effects of X on Y, or latent effects of individual patients or subgroups, such as disease…

Hematopoietic Cell Collection

Introduction The use of hematopoietic stem cells (HSCs) following conditioning chemotherapy in transplantation serves an important role to restore normal hematopoiesis and immune function. In allogeneic hematopoietic cell transplantation, the transplanted immune system has the additional therapeutic benefit of surveillance for the underlying malignant disease. Stem cells were initially collected from the bone marrow until the development of cord blood as a source and later peripheral…

Role of the Human Leukocyte Antigen System in Hematopoietic Stem Cell Transplantation

Introduction The human leukocyte antigen (HLA) system is the major histocompatibility complex (MHC) gene in humans. The HLA gene complex comprises about 3.6 Mb deoxyribonucleic acid (DNA) located on the short arm of chromosome 6 (6p21.3). It received its name because genes embedded in the complex play a major role in tissue graft rejection. The HLA system is highly polymorphic, with genes responsible for identifying self…

Hematopoietic Transplantation: Past, Present, and Future

Hematopoietic transplantation, commonly termed hematopoietic cell transplantation (HCT), involves engraftment of donor hematopoietic stem cells with subsequent regeneration of the blood and immune system. Transplants can be from another individual ( allogeneic ), a genetically identical twin ( syngeneic ), or patient's own cells ( autologous ). Cell sources for the transplant can be bone marrow, peripheral blood, or umbilical cord blood. The procedure for HCT…

Small cell lung cancer

CLINICAL PEARLS In practice, small cell lung cancer (SCLC) is classified using the Veterans’ Administration Lung Study Group system as either limited-stage, if all disease can be encompassed within one tolerable radiotherapy port, or extensive-stage. Genomically, SCLC is characterized by near universal functional loss of the tumor suppressors RB1 and TP53 and lacks actionable genomic alterations. SCLC is characterized by an initial response to chemotherapy or…

Immunotherapy

CLINICAL PEARLS In patients with no contraindications, immunotherapy monotherapy or its use as part of combination therapy is the mainstay of treatment in non−small cell lung cancer (NSCLC). Testing for PD-L1 expression is essential to help guide treatment decisions. Unlike chemotherapy, responses to immunotherapy can take several weeks, which must be taken into consideration when assessing responses to treatment. Prompt recognition and treatment of immune-related adverse…

Other molecular cohorts including ROS1, BRAF, HER2, MET, NTRK, RET, KRAS

CLINICAL PEARLS Molecular profiling of tissue is now recommended during the initial workup of advanced non–small cell lung cancer. Patients may be eligible for targeted therapies to driver mutations other than EGFR and anaplastic lymphoma kinase as early as first line. Implementation of different testing platforms in clinic is essential in ensuring patients receive optimal treatment, including ongoing clinical trials. ROS-1, BRAF, RET, MET exon 14…

Diagnosis and treatment of anaplastic lymphoma kinase (ALK) rearranged non−small cell lung cancer

CLINICAL PEARLS Testing for ALK rearrangement can be performed by using immunohistochemistry, fluorescence in-situ hybridization, and next-generation sequencing. All patients with stage 4 non–small cell lung cancer with adenocarcinoma histology should be tested for an ALK rearrangement. Next-generation ALK tyrosine kinase inhibitors are the preferred first-line therapy. At the time disease progression after next-generation ALK tyrosine kinase inhibitors, lorlatinib and chemotherapy-based treatment are options. Brain imaging…

Epidermal growth factor receptor –mutated non–small cell lung cancer: a clinical approach

CLINICAL PEARLS All patients with advanced, nonsquamous, non−small cell lung cancer (NSCLC) should undergo epidermal growth factor receptor (EGFR) mutation testing as a part of a broader molecular panel (e.g., targeted next-generation sequencing panel). EGFR tyrosine kinase inhibitors (TKIs) are standard first-line therapy for advanced EGFR -mutated NSCLC, with >2 decades of data showing an improvement in progression-free survival when compared with platinum-based chemotherapy. Osimertinib, a…

Second-line therapy in advanced non–small cell lung cancer

CLINICAL PEARLS For immunotherapy-naïve patients, second-line anti-PD-1/PD-L1 inhibitors are preferred over cytotoxic chemotherapy due to improved efficacy and tolerability. For patients with disease progression on first-line immunotherapy monotherapy, second-line cytotoxic chemotherapy with platinum doublet is appropriate. For patients with progression on first-line immunotherapy/platinum combinations, second-line docetaxel remains the most appropriate standard of care combination. Clinical trial enrollment remains strongly encouraged where available, particularly for patients with…

First-line therapy

CLINICAL PEARLS In advanced non−small cell lung cancer, when an actionable oncogenic driver is present, regardless of the PD-L1 tumor proportion score (TPS), targeted therapy is the preferred option. In the absence of an oncogenic driver, currently PD-L1 TPS drives decision making. For those with PD-L1 TPS ≥50% and no contraindication to immunotherapy, immunotherapy monotherapy is the preferred option, although chemoimmunotherapy combinations may be considered. In…

Locally advanced non–small cell lung cancer

CLINICAL PEARLS Locally advanced non–small cell lung cancer (NSCLC) is a heterogeneous entity, which can be divided broadly into patients with resectable and unresectable disease. Select cases of locally advanced NSCLC (including superior sulcus tumors) are amenable to surgical resection, frequently after administration of preoperative chemotherapy or chemoradiation, and these patients are best managed in a multidisciplinary setting. In patients with unresectable locally advanced NSCLC, the…

Oligometastatic disease

CLINICAL PEARLS Stage IV NSCLC is a heterogeneous disease, reflected in reclassifications seen in the eighth edition of the TNM staging system. Oligometastatic disease, described as an isolated metastasis or limited metastases in a single or limited number of organs, is now classified separately from other stage IV manifestations. The most commonly used criteria are five or fewer total metastases in up to three separate organs.…

Surgically resectable disease

CLINICAL PEARLS Surgical resection plays a key role in curative-intent treatment of patients with stages I, II, and IIIA NSCLC. Prior to resection, patients should be assessed for mediastinal lymph node involvement by PET/CT, and pathological nodal assessment by EBUS or mediastinoscopy should be considered in all but the smallest and most peripheral tumors. Patients with N2 disease detected preoperatively should undergo induction therapy and be…