How I treat acute lymphoblastic leukemia in older adolescents and young adults

Abstract

At the intersection between children and older adults, the care of adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) poses unique challenges and issues beyond those faced by other age groups. Although the survival of AYA patients is inferior to younger children, growing evidence suggests that AYA patients have improved outcomes, with disease-free survival rates of 60% to 70%, when treated with pediatric-based approaches. A holistic approach, incorporating a multidisciplinary team, is a key component of successful treatment of these AYA patients. With the appropriate support and management of toxicities during and following treatment, these regimens are well tolerated in the AYA population. Even with the significant progress that has been made during the last decade, patients with persistence of minimal residual disease (MRD) during intensive therapy still have a poor prognosis. With new insights into disease pathogenesis in AYA ALL and the availability of disease-specific kinase inhibitors and novel targeted antibodies, future studies will focus on individualized therapy to eradicate MRD and result in further improvements in survival. This case-based review will discuss the biology, pharmacology, and psychosocial aspects of AYA patients with ALL, highlighting our current approach to the management of these unique patients. (Blood. 2015;125(24):3702-3710)

Progress and Prospects in Pediatric Leukemia

“…27,28 Moreover, there is a much higher incidence of Phþ and Ph-like ALL in this age group. Multiple studies have shown that AYAs do better when treated on pediatric regimens, with OS approaching 70%, compared to that of approximately 40% on adult therapy regimens.…”

“…Multiple studies have shown that AYAs do better when treated on pediatric regimens, with OS approaching 70%, compared to that of approximately 40% on adult therapy regimens. 27,29,30 In the face of ever improving outcomes with chemotherapy, the role of hematopoietic stem cell transplantation (HSCT) in pediatric leukemia has steadily declined. 31 There is currently no role for HSCT in patients newly diagnosed with ALL who respond well to chemotherapy, regardless of risk group.…”

Phase 2 study of intensified chemotherapy and allogeneic hematopoietic stem cell transplantation for older patients with acute lymphoblastic leukemia

“…[3][4][5][6] However, the effect of therapeutic intensification in older adults has not been extensively studied, and this population is often excluded from clinical trials or transplantation studies. We now demonstrate that an intensified multi-agent approach can lead to promising results in older adults.…”

How is the Ph-like signature being incorporated into ALL therapy?

“…A phase 2 trial of ruxolitinib in combination with multi-agent chemotherapy [hyper-CVAD, high-dose methotrexate and cytarabine, POMP maintenance] in children ≥10 years and adults with relapsed/refractory JAK-mutant ALL is also ongoing at MDACC (NCT02420717) [46]. In this study, patients with JAK pathway-mutant Ph-like ALL are initially treated with up to three weeks of ruxolitinib monotherapy with subsequent addition of multi-agent chemotherapy for those patients with suboptimal response to single-agent ruxolitinib.…”