Patterns of care and outcomes in adolescent and young adult acute lymphoblastic leukemia: a population-based study

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Abstract

<p id="d13728685e185"> <div class="list"> <a class="named-anchor" id="d13728685e187">  </a> <ul class="so-custom-list"> <li id="d13728685e188"> <div class="so-custom-list-content so-ol"> <p class="first" id="d13728685e189">Two-thirds of AYA ALL are treated in the adult cancer setting; one-quarter of AYAs in this setting receive front-line pediatric ALL therapy. </p> </div> </li> <li id="d13728685e191"> <div class="so-custom-list-content so-ol"> <p class="first" id="d13728685e192">Survival was superior for AYA ALL patients treated in pediatric cancer settings and in NCI-designated cancer centers. </p> </div> </li> </ul> </div> </p><p class="first" id="d13728685e196">Adolescents and young adults (AYAs, 15-39 years) with acute lymphoblastic leukemia (ALL) represent a heterogeneous population who receive care in pediatric or adult cancer settings. Using the California Cancer Registry, we describe AYA ALL patterns of care and outcomes over the past decade. Sociodemographics, treatment location, and front-line therapies administered to AYAs diagnosed with ALL between 2004 and 2014 were obtained. Cox regression models evaluated associations between ALL setting and regimen and overall survival (OS) and leukemia-specific survival (LSS) for the entire cohort, younger AYA (<25 years), and AYAs treated in the adult cancer setting only. Of 1473 cases, 67.7% were treated in an adult setting; of these, 24.8% received a pediatric ALL regimen and 40.7% were treated at a National Cancer Institute (NCI)–designated center. In multivariable analyses, front-line treatment in a pediatric (vs adult) setting (OS HR = 0.53, 95% confidence interval [CI], 0.37-0.76; LSS HR = 0.51, 95% CI, 0.35-0.74) and at an NCI/Children’s Oncology Group (COG) center (OS HR = 0.80, 95% CI, 0.66-0.96; LSS HR = 0.80, 95% CI, 0.65-0.97) were associated with significantly superior survival. Results were similar when analyses were limited to younger AYAs. Outcomes for AYAs treated in an adult setting did not differ following front-line pediatric or adult ALL regimens. Our population-level findings demonstrate that two-thirds of AYAs with newly diagnosed ALL are treated in an adult cancer setting, with the majority receiving care in community settings. Given the potential survival benefits, front-line treatment of AYA ALL at pediatric and/or NCI/COG-designated cancer centers should be considered. </p><p id="d13728685e202"> <div class="fig panel" id="absf1"> <a class="named-anchor" id="absf1">  </a> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/3300002e-830b-4c04-aa6c-d854e1b0abdc/PubMedCentral/image/advances014944absf1"/> </div> <div class="panel-content"/> </div> </p>

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In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993).

Anthony H Goldstone, Susan M Richards, Hillard M Lazarus … (2008)

An international collaboration was set up to prospectively evaluate the role of allogeneic transplantation for adults with acute lymphoblastic leukemia (ALL) and compare autologous transplantation with standard chemotherapy. Patients received 2 phases of induction and, if in remission, were assigned to allogeneic transplantation if they had a compatible sibling donor. Other patients were randomized to chemotherapy for 2.5 years versus an autologous transplantation. A donor versus no-donor analysis showed that Philadelphia chromosome-negative patients with a donor had a 5-year improved overall survival (OS), 53% versus 45% (P = .01), and the relapse rate was significantly lower (P < or = .001). The survival difference was significant in standard-risk patients, but not in high-risk patients with a high nonrelapse mortality rate in the high-risk donor group. Patients randomized to chemotherapy had a higher 5-year OS (46%) than those randomized to autologous transplantation (37%; P = .03). Matched related allogeneic transplantations for ALL in first complete remission provide the most potent antileukemic therapy and considerable survival benefit for standard-risk patients. However, the transplantation-related mortality for high-risk older patients was unacceptably high and abrogated the reduction in relapse risk. There is no evidence that a single autologous transplantation can replace consolidation/maintenance in any risk group. This study is registered at http://clinicaltrials.gov as NCT00002514.

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Nonadherence to oral mercaptopurine and risk of relapse in Hispanic and non-Hispanic white children with acute lymphoblastic leukemia: a report from the children's oncology group.

Mary Relling, Smita Bhatia, George Schaible … (2012)

Systemic exposure to mercaptopurine (MP) is critical for durable remissions in children with acute lymphoblastic leukemia (ALL). Nonadherence to oral MP could increase relapse risk and also contribute to inferior outcome in Hispanics. This study identified determinants of adherence and described impact of adherence on relapse, both overall and by ethnicity. A total of 327 children with ALL (169 Hispanic; 158 non-Hispanic white) participated. Medication event-monitoring system caps recorded date and time of MP bottle openings. Adherence rate, calculated monthly, was defined as ratio of days of MP bottle opening to days when MP was prescribed. After 53,394 person-days of monitoring, adherence declined from 94.7% (month 1) to 90.2% (month 6; P < .001). Mean adherence over 6 months was significantly lower among Hispanics (88.4% v 94.8%; P < .001), patients age ≥ 12 years (85.8% v 93.1%; P < .001), and patients from single-mother households (80.6% v 93.1%; P = .001). A progressive increase in relapse was observed with decreasing adherence (reference: adherence ≥ 95%; 94.9% to 90%: hazard ratio [HR], 4.1; 95% CI,1.2 to 13.5; P = .02; 89.9% to 85%: HR, 4.0; 95% CI, 1.0 to 15.5; P = .04; < 85%: HR. 5.7; 95% CI, 1.9 to 16.8; P = .002). Cumulative incidence of relapse (± standard deviation) was higher among Hispanics (16.5% ± 4.0% v 6.3% ± 2.2%; P = .02). Association between Hispanic ethnicity and relapse (HR, 2.6; 95% CI, 1.1 to 6.1; P = .02) became nonsignificant (HR, 1.8; 95% CI, 0.6 to 5.2; P = .26) after adjusting for adherence and socioeconomic status. At adherence rates ≥ 90%, Hispanics continued to demonstrate higher relapse, whereas at rates < 90%, relapse risk was comparable to that of non-Hispanic whites. Lower adherence to oral MP increases relapse risk. Ethnic difference in relapse risk differs by level of adherence-an observation currently under investigation.

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6MP adherence in a multiracial cohort of children with acute lymphoblastic leukemia: a Children's Oncology Group study.

Smita Bhatia, Wendy Landier, Lindsey Hageman … (2014)

Durable remissions in children with acute lymphoblastic leukemia (ALL) require a 2-year maintenance phase that includes daily oral 6-mercaptopurine (6MP). Adherence to oral 6MP among Asian-American and African-American children with ALL is unknown. We enrolled 298 children with ALL (71 Asian Americans, 68 African Americans, and 159 non-Hispanic whites) receiving oral 6MP for the maintenance phase. Adherence was measured electronically for 39 803 person-days. Adherence declined from 95.0% (month 1) to 91.8% (month 5, P < .0001). Adherence rates were significantly (P < .0001) lower in Asian Americans (90.0% ± 4.9%) and African Americans (87.1% ± 4.4%), as compared with non-Hispanic whites (95.2% ± 1.3%). Race-specific sociodemographic characteristics helped explain poor adherence (African Americans: low maternal education [less than a college degree: 78.9%, vs at least college degree: 94.6%; P < .0001]; Asian Americans: low-income households [<$50 000: 84.5%, vs ≥$50 000: 96.7%; P = .04]; households without mothers as full-time caregivers [85.6%] vs households with mothers as full-time caregivers [97.2%; P = .05]). Adherence rate below 90% was associated with increased relapse risk (hazard ratio, 3.9; P = .01). Using an adherence rate <90% to define nonadherence, 20.5% of the participants were nonadherers. We identify race-specific determinants of adherence, and define a clinically relevant level of adherence needed to minimize relapse risk in a multiracial cohort of children with ALL. This trial was registered at www.clinicaltrials.gov as #NCT00268528.