The development of novel therapeutics in acute myeloid leukemia (AML) is driven by the need to improve efficacy and reduce toxicity. Clearly, elderly patients with AML represent a highly heterogeneous group, based on a wide array of disease- and patient-specific characteristics. Therefore, novel treatment strategies aimed at overcoming specific biologic modifiers of disease resistance will be paramount to successful therapy for some, whereas in others, the ability to administer a low-toxicity regimen on a chronic basis to achieve disease control may prove beneficial, perhaps even in the absence of complete responses. In addition, identifying genomic and proteomic expression patterns using an individual's unique neoplastic clone will likely optimize the ability to predict responders to novel therapies and identify new and relevant therapeutic targets. The development of reduced-intensity preparative regimens for allogeneic transplants has allowed physicians and patients to explore the option of long-term disease control. The risk–benefit ratio for this procedure will depend on the disease state, patient performance status, and comorbidities. However, current results underscore that age alone should no longer be a contraindication for allogeneic transplant with curative intent in these patients, and long-term disease control with good quality of life is possible and can be expected. Future trials combining the novel therapies described in this article and novel transplant technologies should allow more elderly patients with AML or myelodysplastic syndromes to experience long and productive lives.
Jeffrey E. Lancet and Sergio Giralt
Craig Sauter, W. Jeffrey Baker, Elizabeth Rodriguez, Silvia Willumsen, Barbara Morcerf, Kristi Gafford, Jessica Kennington, Richard Korman, Peter Yu, David Pfister, and Sergio Giralt
Background: Memorial Sloan Kettering Cancer Center (MSK) created the MSK Cancer Alliance in 2014, a dynamic and bidirectional collaboration with high-quality community providers to enhance access to state-of-the-art cancer care close to home. Hartford HealthCare Cancer Institute (HHC), joined the MSK Cancer Alliance as the first member in 2014. Research suggests that bone marrow transplant (BMT) is an underutilized definitive therapy (Yao et al, Biol Blood Bone Marrow Transplant 2013) for patients with hematologic malignancies and the timing of a referral for transplant has significant impact on patient outcomes (National Marrow Donor Program, available at: https://bethematchclinical.org/transplant-indications-and-outcomes/additional-outcomes/timing-impact-on-outcomes/). MSK and HHC developed the BMT Shared Care program to improve access to transplant, ensure BMT specialist consults for appropriate candidates occur during initial treatment planning, reduce burdensome travel for patients by facilitating care locally, and enhance seamless coordination between local oncologists and BMT providers from initial consult through post-transplant care. Methods: To achieve these goals, MSK and HHC physicians, nurses, and staff created a program that includes: HHC hiring a BMT nurse, who trained for 4 weeks at MSK, and works with MSK counterparts to create a streamlined referral process, pretransplant care at HHC, and travel logistics to MSK; MSK and HHC physicians hold virtual tumor boards to jointly evaluate patients and provide BMT consults at the optimal time; onsite lectures and observer-ships focused on advances in BMT, supportive care, and management of complications like graft versus host disease, leading to the integration of additional clinical services like infectious disease and dermatology; and research, including an MSK clinical trial open at HHC to identify and understand barriers to transplant in the community for patients with newly diagnosed or relapsed acute leukemia. Results: Since November 2015, HHC has referred 86 patients for BMT consult through this Shared Care program, with 35 patients transplanted or receiving immune effector cells (IEC) to date. Conclusions: The BMT Shared Care program effectively facilitates the referral and transplant of appropriate patients while allowing them to receive much of their pre- and post-transplant care in their local communities. Collaboration between BMT nurse coordinators and robust physician engagement are essential to this program. Future opportunities include expanding the use of telemedicine, enhancing electronic data sharing, quantifying and analyzing patient satisfaction, and expanding BMT research at HHC.
Ayman Saad, Marcos de Lima, Sarah Anand, Vijaya Raj Bhatt, Ryan Bookout, George Chen, Daniel Couriel, Antonio Di Stasi, Areej El-Jawahri, Sergio Giralt, Jonathan Gutman, Vincent Ho, Mitchell Horwitz, Joe Hsu, Mark Juckett, Mohamed Kharfan Dabaja, Alison W. Loren, MSCE, Javier Meade, Marco Mielcarek, Jonathan Moreira, Ryotaro Nakamura, Yago Nieto, Julianna Roddy, Gowri Satyanarayana, Mark Schroeder, Carlyn Rose Tan, Dimitrios Tzachanis, Jennifer L. Burns, and Lenora A. Pluchino
Hematopoietic cell transplantation (HCT) involves the infusion of hematopoietic progenitor cells into patients with hematologic disorders with the goal of re-establishing normal hematopoietic and immune function. HCT is classified as autologous or allogeneic based on the origin of hematopoietic cells. Autologous HCT uses the patient’s own cells while allogeneic HCT uses hematopoietic cells from a human leukocyte antigen-compatible donor. Allogeneic HCT is a potentially curative treatment option for patients with certain types of hematologic malignancies, and autologous HCT is primarily used to support patients undergoing high-dose chemotherapy. Advances in HCT methods and supportive care in recent decades have led to improved survival after HCT; however, disease relapse and posttransplant complications still commonly occur in both autologous and allogeneic HCT recipients. Allogeneic HCT recipients may also develop acute and/or chronic graft-versus-host disease (GVHD), which results in immune-mediated cellular injury of several organs. The NCCN Guidelines for Hematopoietic Cell Transplantation focus on recommendations for pretransplant recipient evaluation and the management of GVHD in adult patients with malignant disease.