Increased Toxicity Among Adolescents and Young Adults Compared with Children Hospitalized with Acute Lymphoblastic Leukemia at Children's Hospitals in the United States

2021 ◽  
Author(s):  
Ajay Gupta ◽  
Rahul C. Damania ◽  
Ravi Talati ◽  
Mary Ann O'Riordan ◽  
Yousif H. Matloub ◽  
...  
Keyword(s):  
United States ◽  
Young Adults ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
The United States ◽  
Adolescents And Young Adults ◽  
Children's Hospitals ◽  
Children’S Hospitals

Frontline-Treatment Of Acute Lymphoblastic Leukemia (ALL) In Older Adolescents and Young Adults (AYA) Using a Pediatric Regimen Is Feasible: Toxicity Results of the Prospective US Intergroup Trial C10403 (Alliance)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3903-3903 ◽  
Author(s):  
Anjali S. Advani ◽  
Ben Sanford ◽  
Selina Luger ◽  
Meenakshi Devidas ◽  
Eric C. Larsen ◽  
...  
Keyword(s):  
Young Adults ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Specific Treatment ◽  
The United States ◽  
Adolescents And Young Adults ◽  
Motor Neuropathy ◽  
Age Cohorts ◽  
Age Related ◽  
Grade 3

Abstract Background Several retrospective trials suggest a superior outcome for adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) when they are treated with pediatric-inspired therapeutic regimens. C10403 is the largest prospective study to evaluate the feasibility of a pediatric regimen (Children’s Oncology Group (COG) AALL0232: COG0232) (Larsen et al. JCO 2011; 29(18) suppl: 3) in AYA ALL patients (pts) (16-39 yrs of age) treated by adult hematologist/ oncologists (HO). One objective was to identify age-related increases in specific treatment-related toxicities that may limit the applicability of these regimens. We describe here the adverse event (AE) profiles by age cohorts for pts enrolled on C10403 and compare them with data reported from the pediatric COG0232 trial in pts ≥ 16 yrs of age using the same regimen. In the COG study, AYA comprised 20% of enrolled pts, 66% were ages 16-21. Methods C10403 was a single arm study. All pts received treatment with the “PC” (prednisone/ ‘Capizzi’ methotrexate) Interim Maintenance (IM) arm from the AALL0232 regimen and were treated by adult HO. Descriptive statistics were used to summarize toxicities. For this report, we focused on Grade 3-5 events with at least a possible relationship to treatment. The comparison group from COG0232 included 159 pts randomized to the PC arm; however, in COG0232 slow responders received additional treatment compared to C10403 pts. Results Between Nov 2007 and Dec 2012, 318 pts in the United States 16-39 yrs of age were enrolled by 3 cooperative groups (CALGB, SWOG, ECOG). 61% were male; 74% white, 10% African American, and 16% Hispanic. The median age was 25 yrs, older than the COG0232 AYA pts. 14% were < 20, 58% 20-29, and 28% 30-39 yrs of age. Induction (indn) toxicities are summarized in Table 1. The rates of Grade 3-4 hyperglycemia, hyperbilirubinemia, pancreatitis, thrombosis, and febrile neutropenia during indn in the C10403 trial were higher than in AYAs treated on COG0232. However, indn mortality rates for C10403 and COG0232 were both low, 2%. Grade 3-5 AEs at any point during treatment are listed in Table 2. During IM, 5.6% of pts on C10403 developed Grade 3-4 mucositis. Grade 3-4 hypersensitivity reactions to peg-asparaginase declined from 12.9% to 7.9% after a C10403 protocol amendment to require premedication. There were no significant differences in the incidence of Grade 3-5 AEs by age cohort among C10403 pts except for increased incidences of neuropathy, osteonecrosis, and mucositis in pts ≥ 20 yrs old. In comparison, AYAs on COG0232 had higher rates of hypersensitivity (no premedication) and motor neuropathy and lower rates of thrombosis than the C10403 pts. Hepatic toxicities, incidence of pancreatitis and osteonecrosis were similar between the two studies. Toxicities were manageable by adult HO on C10403, and the overall treatment-related mortality rate on C10403 was low (3%). Attribution of toxicities to specific components of therapy, particularly peg-asparaginase, is being evaluated. Clinical outcomes of pts enrolled on C10403 are still being evaluated. Conclusions These data indicate that treatment with a pediatric regimen (C10403) is feasible when administered by adult HOs to an AYA population up to 40 years of age. C10403 can be used as a foundation for the design of successor trials in this pt population. (1) Larsen E, Salzer W, Nachman J, et al. Blood, Nov 2011; 118: 1510. Disclosures: Stone: Amgen: Consultancy.

Administration of Erwinia Asparaginase (Erwinase®) Following Allergy to PEG-Asparaginase In Children and Young Adults with Acute Lymphoblastic Leukemia Treated on AALL07P2 Achieves Therapeutic Nadir Serum Asparaginase Activity: A Report From the Children's Oncology Group (COG)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2134-2134
Author(s):  
Wanda Salzer ◽  
Barbara Asselin ◽  
Jeffrey Supko ◽  
Meenakshi Devidas ◽  
Nicole Kaiser ◽  
...  
Keyword(s):  
United States ◽  
Young Adults ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
The United States ◽  
E Coli ◽  
Clinical Allergy ◽  
Asparaginase Activity ◽  
Erwinia Asparaginase ◽  
Children And Young Adults

Abstract Abstract 2134 Introduction: L-asparaginase is a vital component of multi-agent chemotherapy for children and young adults with acute lymphoblastic leukemia (ALL). In the United States, there are 2 asparaginase preparations approved by the Food and Drug Administration, native E. coli (Elspar®) and PEG-asparaginase (Oncaspar®). PEG-asparaginase is the most commonly utilized asparaginase product due to its longer half-life and decreased immunogenicity. However, the incidence of clinical allergy to PEG-asparaginase approaches 20%, with repeated administration. Due to cross reactivity with native E. coli asparaginase, there is no FDA-approved preparation available for patients who develop clinical allergy to PEG-asparaginase. A third preparation, Erwinia asparaginase (Erwinase®), derived from Erwinia chrysanthemi, is not commercially available in the United States. The optimal dosing of Erwinase® necessary to obtain nadir asparaginase activity > 0.1 IU/mL similar to that obtained after conventional dosing of PEG-asparaginase is unknown. Patients and Methods: We hypothesized that substitution of Erwinase® 25,000 IU/m2 × 6 doses intramuscularly (IM) on a Monday/Wednesday/Friday schedule in children and young adults with ALL would provide a 48 hour nadir serum asparaginase activity ≥ 0.1 IU/mL, and effectively deplete plasma asparagine, a surrogate marker of asparaginase activity. Eligible patients on COG study AALL07P2 were >1 to <30 years of age, concurrently enrolled on a frontline COG ALL treatment study, and had documented ≥ grade 2 allergy (NCI Common Terminology Criteria 3.0) to PEG-asparaginase. Results: A total of 55 eligible/evaluable patients were enrolled from February 2008 to April 2010. Blood samples were obtained at scheduled time points during Erwinase® therapy and assayed for serum asparaginase activity and asparagine concentration in plasma. Nadir serum asparaginase activity ≥ 0.1 IU/mL was achieved in 49/53 patients (92.5%) at 48 hours after dosing and in 46/52 patients (88.5%) at 72 hours after dosing. Plasma asparagine was significantly depleted (<1.0 μM) in all 49 patients for whom samples were satisfactorily obtained. Grade 2–3 allergic reaction and grade 1–2 hyperglycemia related to Erwinase® were reported in 5 and 3 patients, respectively. There were no reports of hemorrhage, thrombosis, pancreatitis, or death. Conclusion: Erwinase® as administered using the AALL07P2 regimen was well tolerated and achieved nadir serum asparaginase activity at both 48 and 72 hours after dosing that was similar to that achieved with PEG-asparaginase. We conclude that following allergy to PEG-asparaginase, Erwinase® 25,000 IU/m2 × 6 doses IM on a Monday/Wednesday/Friday schedule can be substituted for a single dose of PEG-asparaginase. Disclosures: Supko: EUSA Pharma: Research Funding. Plourde: EUSA Pharma: Employment. Winick: EUSA Pharma: EUSA Advisory Board.

scholarly journals THE EPIDEMIOLOGY OF PEDIATRIC MENISCAL ALLOGRAFT TRANSPLANTATION IN THE UNITED STATES

2021 ◽  
Vol 9 (7_suppl3) ◽  
pp. 2325967121S0004
Author(s):  
Haley E. Smith ◽  
Madeline M. Lyons ◽  
Neeraj M. Patel
Keyword(s):  
United States ◽  
Pediatric Population ◽  
The United States ◽  
National Database ◽  
Control Group ◽  
Meniscal Allograft Transplantation ◽  
Children's Hospitals ◽  
Allograft Transplantation ◽  
Meniscal Allograft ◽  
Children’S Hospitals

Background: Meniscal allograft transplantation (MAT) is an option to slow the progression of degenerative disease in the setting of substantial meniscal deficiency. This may be especially important in children and adolescents, but there is little literature on MAT in this population. Hypothesis/Purpose: The purpose of this study was to evaluate the epidemiology of MAT in the pediatric population, with specific attention to regional and demographic trends. Methods: The Pediatric Health Information System, a national database consisting of 49 children’s hospitals, was queried for all patients undergoing MAT between 2011 and 2018. Demographic information was collected for each subject as well as data regarding previous and subsequent surgeries. The database was also queried for all meniscus surgeries (including repairs and meniscectomies) performed during the study period. Demographic and geographic data from this control group were compared to that of children undergoing MAT. Univariate analysis was followed by purposeful entry multivariate regression to adjust for confounding factors. Results: A total of 27,168 meniscus surgeries were performed in 47 hospitals, with MAT performed 67 times in 17 hospitals. Twelve patients (18%) underwent a subsequent procedure after transplantation. In multivariate analysis, each year of increasing age resulted in 1.1 times higher odds of having undergone MAT rather than repair or meniscectomy (95% CI 1.03-1.1, p=0.002). Patients that underwent transplantation had 2.0 times higher odds of being female (95% CI 1.2-3.3, p=0.01) and 2.0 times higher odds of being commercially insured (95% CI 1.1-3.6, p=0.02). MAT was performed most frequently in the Northeast (4.9/1000 meniscus surgeries) and least often in the South (1.1/1000 meniscus surgeries, p<0.001). Furthermore, transplantation was more likely to be performed in larger cities. The median pediatric population of cities in which MAT was performed was 983,268 (range 157,253-3,138,870) compared to 662,290 (range 4,420-4,311,500) in cities where it was not (p=0.04). Conclusion: In the United States, patients that underwent MAT were older, more likely to be female, and have commercial insurance than those undergoing meniscus repair or meniscectomy. MAT was only done in 17/47 children’s hospitals that perform meniscus surgery and was most frequently performed in the Northeast and in larger cities. These trends highlight the need for further research, especially regarding differences along the lines of sex and insurance status.

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