Issue Archive

Mycosis fungoides and Sézary syndrome are heterogeneous diseases for which novel targeted therapies are being incorporated into treatment. In this Perspective, Khodadoust et al describe this new generation of therapies and place them in the context of the need for sequential therapy in most patients. They discuss the current approach to treatment selection as well as speculating on the future of molecularly guided therapy.

Asparaginases are a key component of acute lymphoblastic leukemia therapy, but shortages of Erwinia-derived asparaginase and hypersensitivity and inactivation of Escherichia coli–derived products threaten its availability. Maese and colleagues present results of a phase 2/3 study of recombinant Erwinia asparaginase, demonstrating efficacy in achieving therapeutic levels with a toxicity profile that is comparable to other asparaginases.

Hypomorphic alleles for the recombination activation genes RAG1 and RAG2 lead to severe immunodeficiency syndromes. Schuetz et al report on a retrospective analysis of transplant outcomes in 60 patients with this rare disorder. Overall survival at 4 years was 67.5%, with poor survival predicted by active infection, organ damage, and T-cell depletion of the graft. Patients diagnosed by newborn screening with early transplant had 100% survival, supporting early transplantation for these patients.

Second malignancies after childhood acute lymphoblastic leukemia (ALL) are rare. Elitzur and colleagues present a retrospective survey of 85 patients who developed non-Hodgkin lymphoma (NHL) following chemotherapy for pediatric ALL. Over 80% occurred during or within 6 months of maintenance therapy. The majority had features characteristic of immunodeficiency-associated NHL, and 65% were associated with Epstein-Barr virus (EBV). This previously unheralded association has implications for posttreatment monitoring and therapy of secondary NHL.

Extramedullary infiltration (EMI) in patients with acute myeloid leukemia (AML) is associated with poor prognosis. Yang et al investigated a patient with extensive leukemia cutis and demonstrated a complement C1Q⁺ subset of cells within the skin and the bone marrow. Subsequent studies reveal that C1Q overexpression is commonly seen in AML with EMI and relapse. C1Q is both a poor prognostic marker in AML and is associated with EMI, offering a potential novel therapeutic target.

In this month’s CME article, Arends and colleagues report that clonal hematopoiesis (CH) is associated with an increased risk of recurrent stroke, myocardial infarction, and all-cause mortality in patients with first ischemic stroke. Patients with CH have higher levels of proinflammatory cytokines, and the increased risk associated with CH is partially mitigated by a germline variant of the IL-6 receptor, suggesting that modulation of the proinflammatory profile may lower the risk of recurrent events.