Challenges faced in the treatment of acute lymphoblastic leukemia in adolescents and young adults

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Although the survival rate for pediatric patients with acute lymphoblastic leukemia (ALL) has substantially improved over the last half century, patients in the adolescent and young adult (AYA) age-group (15 to 30 years) have not attained the same benefit. There is a controversy over which regimens should be used to treat AYA patients: pediatric-inspired regimens or adult-inspired ones.

AYA patients typically benefit more from pediatric regimens than from adult regimens, as demonstrated in clinical trials where AYA patients are included in the pediatric age group or the adult age group. In the United States, a retrospective analysis of 321 patients age 16 to 20 years who were treated on trials from either the Children’s Cancer Group (CCG) or Cancer and Leukemia Group B (CALGB) demonstrated improved event-free survival and overall survival for those treated on CCG trials compared with those who participated in CALGB studies.

Patients enrolled in CALGB studies also had a higher CNS relapse rate, suggesting that the pediatric practice of aggressive CNS-targeted therapy may aid in the prevention of CNS relapse. In addition, higher cumulative doses of nonmyelosuppressive agents may decrease the occurrence of systemic disease relapse.

Furthermore, whether to use hematopoietic cell transplantation (HCT) in AYAs with ALL in first complete remission is unclear. AYA patients treated with a pediatric-inspired regimen and HCT had a lower cumulative incidence of relapse than those who did not undergo HCT, but they also had higher nonrelapse mortality. Thus, there may not be a general benefit to HCT in first complete remission for all AYA patients.

Clinical Oncology in Adolescents and Young Adults

Abstract: The survival rate for children with acute lymphoblastic leukemia (ALL) has dramatically improved over the last 50 years. However, for those in the adolescent and young adult (AYA) age-group of 15–30 years with ALL, there has not been the same degree of improvement. Historically, pediatric and adult providers have utilized different treatment approaches based on clinical trials. However, studies that have compared the outcome of AYA patients with ALL treated on pediatric or adult clinical trials have generally shown substantially better outcomes for this patient population treated with the pediatric trials. Additionally, hematopoietic stem cell transplantation has been considered as part of intensified therapy for AYA patients with ALL. Herein, we review the outcomes with chemotherapy alone and with hematopoietic stem cell transplantation, and explore the challenges faced in determining the ideal therapy for the AYA population of patients.

Keywords: adolescent young adult oncology, leukemia, hematopoietic stem cell transplantation

INTRODUCTION

Acute lymphoblastic leukemia (ALL) is a multifaceted disease in its biological pathogenesis, with variety of populations affected and numerous epidemiological factors.¹ The treatment regimens are typically intense and involve many chemotherapeutic agents that carry a multitude of toxicity risks. However, the improvement in the prognosis for children diagnosed with ALL has been one of the great success stories for the 20th and early 21st centuries for cancer care. While only 30% of children diagnosed with ALL survived in 1970, more than 85% survive today, with some populations of patients having a .95% survival at 5 years. Unfortunately, the same cannot be said for young adults between 15 and 30 years of age with ALL, which, for the purposes of this review, we will consider to be the adolescent and young adult (AYA) population. For the patients in this age-group, the prognosis has been less promising and can vary from 35% to 75% disease-free survival at 5 years, depending on the leukemic subtype and therapy utilized.^2–4 Efforts to improve the prognosis for this group of patients have been challenging, and controversy between pediatric and adult oncologists regarding the optimal treatment has contributed to a lack of clarity over a standard approach to care. This includes a discrepancy among some providers regarding the utilization of hematopoietic stem cell transplantation (HSCT). Here, we review many of the issues that need to be considered in determining the ideal treatment course for AYAs with ALL.

BACKGROUND

ALL develops as a result of deregulation in various pathways in the cell cycle that serve to control cell survival and proliferation.^1,5 ALL in particular is characterized by an uncontrollable proliferation of malignant cells with an arrest of normal lymphoid progenitor cell development.⁶ As a result, normal bone marrow cells are replaced by malignant lymphoblasts, thereby inhibiting homeostatic hematogenous and immune functions.^7,8 In ALL, examination of the bone marrow will most likely reveal a hypercellular and homogenous population of blasts.⁹

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Acute Lymphoblastic Leukemia Adolescents and Young Adults Hematologic Cancers Publishers Alliance Research

Challenges faced in the treatment of acute lymphoblastic leukemia in adolescents and young adults

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INTRODUCTION

BACKGROUND

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