Issue Archive

Pegasparaginase is a key drug in curative regimens for acute lymphoblastic leukemia (ALL), but has unique toxicities that may be unfamiliar to adult hemato-oncologists. Using 5 cases of adults with ALL who were treated with pediatrically inspired regimens, Aldoss and Douer illustrate the management of several pegasparaginase-associated adverse effects and guide whether and how to continue the drug.

Avadomide is a novel cereblon-modulating drug that both kills lymphoma cells directly and stimulates T cells and natural killer cells. Carpio et al describe the safety and preliminary efficacy of avadomide in relapsed diffuse large B-cell lymphoma (DLBCL) and how immune cell composition is associated with differential responses. The companion article by Risueño et al details a new gene expression classifier that discriminates DLBCL based on tumor and immune-cell composition and that may assist in identifying patients most likely to respond to immunomodulatory therapy, such as avadomide.

Avadomide is a novel cereblon-modulating drug that both kills lymphoma cells directly and stimulates T cells and natural killer cells. Carpio et al describe the safety and preliminary efficacy of avadomide in relapsed diffuse large B-cell lymphoma (DLBCL) and how immune cell composition is associated with differential responses. The companion article by Risueño et al details a new gene expression classifier that discriminates DLBCL based on tumor and immune-cell composition and that may assist in identifying patients most likely to respond to immunomodulatory therapy, such as avadomide.

Aberrant MYC activity is a major driver of B-cell lymphomagenesis. However, if it is left unchecked, this oncogenic signal also drives cells to apoptosis. Nguyen et al reveal the important role of MNT, another component in the MYC transcription factor network, in the establishment and maintenance of MYC-driven lymphomas, and point to it as a future target for therapy.

Mutations in the RNA splicing factors SF3B1, SRSF2, and U2AF1 are common in myeloid neoplasms and usually occur at specific hotspots. Pangallo et al studied rare and private mutations in these genes and demonstrated that most of them are also pathogenic, frequently phenocopying hotspot mutations.

Ofori-Acquah et al report findings that are important to understanding the pathophysiology of sickle cell disease (SCD)–related kidney injury. Using both human samples and murine models, they identified acquired hemopexin deficiency as a risk factor for acute kidney injury in SCD and hemopexin replacement as a potential therapy.

Jodele et al detail their experience with 64 pediatric patients with stem cell transplant–associated thrombotic microangiopathy (TA-TMA) and end organ damage treated with the complement blocker eculizumab. They report improved outcomes with brief, intensive therapy in comparison with historical controls.

Mollé et al investigated the patterns of weight gain associated with ruxolitinib therapy in patients with myeloproliferative neoplasms, defined high-risk groups for treatment-acquired obesity, and defined a plausible mechanism in mouse models.