How I Treat: Revisiting the myth of second remission in acute lymphoblastic leukemia in the era of immunotherapy

In 2013, we published a perspective entitled, "The myth of the second remission of acute leukemia," which underscored the dismal outcomes of relapsed acute leukemia in adults. We emphasized that only a minority of patients achieved second complete remission (CR2) after relapse and were subsequently eligible to receive a potentially curative allogeneic hematopoietic stem cell transplantation (HSCT). Hence, we urged the leukemia community not to delay HSCT in first complete remission (CR1) if indicated to avoid dire outcomes. Historically, poor outcomes resulted from suboptimal frontline therapy, inadequate risk stratification, and lack of effective agents to achieve CR2. In the past decade, remarkable progress has been made in the treatment paradigm of acute leukemia, most evidently in B-cell acute lymphoblastic leukemia. Key advancements include refinement of frontline treatment, incorporation of early immunotherapy, improved disease risk stratification based on molecular profiling and assessment of measurable residual disease, and discovery of highly effective salvage immunotherapies. These innovations have led to a high rate of cure by frontline therapy, precise selection for HSCT in CR1 for high-risk patients, and the reality of HSCT for patients in CR2. Here, we reexamine the myth of CR2 given the progress in the field.