Issue Archive

Treatment for patients with acute myeloid leukemia (AML) is being transformed for some patients, as targeted agents increase complete remission rates and survival when appropriately applied. Although the efficacy of newer regimens has been established in major clinical trials, use in routine practice is often challenging, and careful choices need to be made. Associate Editor Selina M. Luger introduces this case-based How I Treat series designed to provide guidance in those circumstances. Wei et al discuss how to maximize the benefits when the venetoclax-azacitidine regimen was indicated, while Issa and colleagues discuss differentiation therapy, highlighting how the clinical course for patients varies from what is seen with intensive chemotherapy-based induction regimens. Green and Wang tackle the challenge of managing patients with secondary AML. Finally, Roboz and Canaani outline how maintenance can benefit selected patients not undergoing allogeneic transplant, while exploring the many unanswered questions that arise in clinical practice.

Treatment for patients with acute myeloid leukemia (AML) is being transformed for some patients, as targeted agents increase complete remission rates and survival when appropriately applied. Although the efficacy of newer regimens has been established in major clinical trials, use in routine practice is often challenging, and careful choices need to be made. Associate Editor Selina M. Luger introduces this case-based How I Treat series designed to provide guidance in those circumstances. Wei et al discuss how to maximize the benefits when the venetoclax-azacitidine regimen was indicated, while Issa and colleagues discuss differentiation therapy, highlighting how the clinical course for patients varies from what is seen with intensive chemotherapy-based induction regimens. Green and Wang tackle the challenge of managing patients with secondary AML. Finally, Roboz and Canaani outline how maintenance can benefit selected patients not undergoing allogeneic transplant, while exploring the many unanswered questions that arise in clinical practice.

Treatment for patients with acute myeloid leukemia (AML) is being transformed for some patients, as targeted agents increase complete remission rates and survival when appropriately applied. Although the efficacy of newer regimens has been established in major clinical trials, use in routine practice is often challenging, and careful choices need to be made. Associate Editor Selina M. Luger introduces this case-based How I Treat series designed to provide guidance in those circumstances. Wei et al discuss how to maximize the benefits when the venetoclax-azacitidine regimen was indicated, while Issa and colleagues discuss differentiation therapy, highlighting how the clinical course for patients varies from what is seen with intensive chemotherapy-based induction regimens. Green and Wang tackle the challenge of managing patients with secondary AML. Finally, Roboz and Canaani outline how maintenance can benefit selected patients not undergoing allogeneic transplant, while exploring the many unanswered questions that arise in clinical practice.

Treatment for patients with acute myeloid leukemia (AML) is being transformed for some patients, as targeted agents increase complete remission rates and survival when appropriately applied. Although the efficacy of newer regimens has been established in major clinical trials, use in routine practice is often challenging, and careful choices need to be made. Associate Editor Selina M. Luger introduces this case-based How I Treat series designed to provide guidance in those circumstances. Wei et al discuss how to maximize the benefits when the venetoclax-azacitidine regimen was indicated, while Issa and colleagues discuss differentiation therapy, highlighting how the clinical course for patients varies from what is seen with intensive chemotherapy-based induction regimens. Green and Wang tackle the challenge of managing patients with secondary AML. Finally, Roboz and Canaani outline how maintenance can benefit selected patients not undergoing allogeneic transplant, while exploring the many unanswered questions that arise in clinical practice.

Treatment for patients with acute myeloid leukemia (AML) is being transformed for some patients, as targeted agents increase complete remission rates and survival when appropriately applied. Although the efficacy of newer regimens has been established in major clinical trials, use in routine practice is often challenging, and careful choices need to be made. Associate Editor Selina M. Luger introduces this case-based How I Treat series designed to provide guidance in those circumstances. Wei et al discuss how to maximize the benefits when the venetoclax-azacitidine regimen was indicated, while Issa and colleagues discuss differentiation therapy, highlighting how the clinical course for patients varies from what is seen with intensive chemotherapy-based induction regimens. Green and Wang tackle the challenge of managing patients with secondary AML. Finally, Roboz and Canaani outline how maintenance can benefit selected patients not undergoing allogeneic transplant, while exploring the many unanswered questions that arise in clinical practice.

Combinations of targeted agents have supplanted DNA-damaging chemotherapy-based regimens for chronic lymphocytic leukemia (CLL), although the optimal regimens are still being defined. In this month’s CME article, Fürstenau and colleagues report results from the German CLL study group phase 2 trial of zanubrutinib, obinutuzumab, and venetoclax in relapsed CLL. The authors found that after 6 combination cycles, all patients showed response, irrespective of whether they had previously received any of these agents, and 52.5% of patients had undetectable minimal residual disease (uMRD) in the blood. Thus far, progression is uncommon, and the proportion of patients with uMRD continues to improve with ongoing follow up, indicating that this is a promising regimen.

Despite our extensive knowledge, major questions remain about the regulation of blood cell production from hematopoietic stem cells (HSCs). Singh and colleagues synthesized murine cellular and expression level data with mechanistic mathematical models to quantify and compare specific regulatory processes that drive shifts in lineage contributions during hematopoiesis, particularly in the context of inflammation or aging. The authors show how the well-recognized myeloid prominence in these situations arises through a combination of HSC differentiation bias and myeloid-primed progenitor cell proliferation.

The introduction of rituximab, the first therapeutic monoclonal antibody for hematological malignancies, dramatically improved outcomes in many CD20 lymphomas, but recurrence and resistance remain problems. Baskar et al reveal an innovative approach to improving rituximab treatment, exploiting the deposition of C3d on the surface of B cells during CD20 antibody therapy, thus creating a neoantigen for selective targeting. In xenografted mouse models, the authors showed that novel C3d antibodies can be combined with CD20 antibodies to eradicate resistant CD20+ lymphomas, opening prospects for analogous approaches clinically.

Chronic graft-versus-host disease (cGVHD) remains the major complication limiting the success of allogeneic stem cell transplantation, with fibrotic change in multiple organs leading to loss of function being a common but poorly understood feature. To address this, Baumrin et al describe the development and initial validation of the newly proposed Lee Symptom Scale for Skin Sclerosis, a patient-reported outcome instrument of 55 items specifically developed for adult patients with cGVHD-associated skin sclerosis. Use of this instrument during clinical trials should enhance and accelerate the development of better preventative and therapeutic interventions.