Outcomes of children and young adults with T-cell acute lymphoblastic leukemia/lymphoma who present in critical status.
Acute lymphoblastic leukemia
T cells
acute lymphoblastic lymphoma
adolescent
pediatric intensive care
pediatrics
Journal
Pediatric blood & cancer
ISSN: 1545-5017
Titre abrégé: Pediatr Blood Cancer
Pays: United States
ID NLM: 101186624
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
revised:
14
10
2021
received:
12
07
2021
accepted:
18
10
2021
pubmed:
9
1
2022
medline:
6
5
2022
entrez:
8
1
2022
Statut:
ppublish
Résumé
Patients with T-cell acute lymphoblastic leukemia and lymphoma (T-ALL/LLy) commonly present with critical features such as hyperleukocytosis and mediastinal mass, which complicates completing a diagnostic and staging workup and prevents clinical trial enrollment. Consecutive patients with T-ALL/LLy from 1999 to 2019 at the Children's Hospital of Philadelphia were analyzed for pediatric intensive care unit (PICU) admission and various high-risk features as well as clinical trial enrollment and outcome. We identified 153 patients newly diagnosed with T-ALL/LLy, 53 (35%) required PICU-level care within 24 hours and 73 (48%) within 7 days. Non-PICU patients had a significantly higher clinical trial enrollment rate (79.4%) versus PICU patients (56.1%, P = 0.016). Patients who enrolled on a clinical trial had similar relapse risk to those who did not enroll (relapse rate 20% vs 29%, P = 0.523). Nineteen patients were precluded from trial participation. Risk of relapse was increased for patients admitted to the PICU within 24 hours (26% vs 13%, P = 0.048). Forty-four patients with T-ALL presented with hyperleukocytosis, of which 30% relapsed versus 14% without (P = 0.082). Patients who underwent apheresis for hyperleukocytosis were statistically more likely to relapse (47% vs 15%, P = 0.007). Patients with elevated uric acid (20% vs 16%, P = 0.278), mediastinal mass (20% vs 14%, P = 0.501), or required emergent steroids (20% vs 16%, P = 0.626) had a similar relapse risk. A single second relapse patient survived. Almost half of T-ALL/LLy patients required PICU-level care at diagnosis, making enrollment on clinical trials challenging, but trial enrollment predicted better outcome. Physicians should balance maintaining eligibility with safety to offer patients all options.
Sections du résumé
BACKGROUND
Patients with T-cell acute lymphoblastic leukemia and lymphoma (T-ALL/LLy) commonly present with critical features such as hyperleukocytosis and mediastinal mass, which complicates completing a diagnostic and staging workup and prevents clinical trial enrollment.
PROCEDURE
Consecutive patients with T-ALL/LLy from 1999 to 2019 at the Children's Hospital of Philadelphia were analyzed for pediatric intensive care unit (PICU) admission and various high-risk features as well as clinical trial enrollment and outcome.
RESULTS
We identified 153 patients newly diagnosed with T-ALL/LLy, 53 (35%) required PICU-level care within 24 hours and 73 (48%) within 7 days. Non-PICU patients had a significantly higher clinical trial enrollment rate (79.4%) versus PICU patients (56.1%, P = 0.016). Patients who enrolled on a clinical trial had similar relapse risk to those who did not enroll (relapse rate 20% vs 29%, P = 0.523). Nineteen patients were precluded from trial participation. Risk of relapse was increased for patients admitted to the PICU within 24 hours (26% vs 13%, P = 0.048). Forty-four patients with T-ALL presented with hyperleukocytosis, of which 30% relapsed versus 14% without (P = 0.082). Patients who underwent apheresis for hyperleukocytosis were statistically more likely to relapse (47% vs 15%, P = 0.007). Patients with elevated uric acid (20% vs 16%, P = 0.278), mediastinal mass (20% vs 14%, P = 0.501), or required emergent steroids (20% vs 16%, P = 0.626) had a similar relapse risk. A single second relapse patient survived.
CONCLUSIONS
Almost half of T-ALL/LLy patients required PICU-level care at diagnosis, making enrollment on clinical trials challenging, but trial enrollment predicted better outcome. Physicians should balance maintaining eligibility with safety to offer patients all options.
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e29457Informations de copyright
© 2022 Wiley Periodicals LLC.
Références
Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med. 2015;373(16):1541-1552.
Han X, Bueso-Ramos CE. Precursor T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma and acute biphenotypic leukemias. Am J Clin Pathol. 2007;127(4):528-544.
Hunger SP, Lu X, Devidas M, et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the Children's Oncology Group. J Clin Oncol. 2012;30(14):1663-1669.
Winter SS, Dunsmore KP, Devidas M, et al. Improved survival for children and young adults with T-Lineage acute lymphoblastic leukemia: results from the Children's Oncology Group AALL0434 methotrexate randomization. J Clin Oncol. 2018;36(29):2926-2934.
Hayashi RJ, Winter SS, Dunsmore KP, et al. Successful outcomes of newly diagnosed T lymphoblastic lymphoma: results from Children's Oncology Group AALL0434. J Clin Oncol. 2020;38(26):3062-3070.
Mitchell C, Richards S, Harrison CJ, Eden T. Long-term follow-up of the United Kingdom Medical Research Council protocols for childhood acute lymphoblastic leukaemia, 1980-2001. Leukemia. 2009;24(2):406-418.
Raetz EA, Teachey DT. T-cell acute lymphoblastic leukemia. Hematology. 2016;2016(1):580-588.
Attarbaschi A, Mann G, Dworzak M, Wiesbauer P, Schrappe M, Gadner H. Mediastinal mass in childhood T-cell acute lymphoblastic leukemia: significance and therapy response. Med Pediatr Oncol. 2002;39(6):558-565.
Kong SG, Seo JH, Jun SE, Lee BK, Lim YT. Childhood acute lymphoblastic leukemia with hyperleukocytosis at presentation. Blood Research. 2014;49(1):29.
Jaime-Pérez JC, Pinzón-Uresti MA, Jiménez-Castillo RA, Colunga-Pedraza JE, González-Llano Ó, Gómez-Almaguer D. Relapse of childhood acute lymphoblastic leukemia and outcomes at a reference center in Latin America: organomegaly at diagnosis is a significant clinical predictor. Hematology. 2017;23(1):1-9.
Meyer LK, Huang BJ, Delgado-Martin C, et al. Glucocorticoids paradoxically facilitate steroid resistance in T cell acute lymphoblastic leukemias and thymocytes. J Clin Invest. 2020;130(2):863-876.
Ravindranath Y, Kaplan J, Zuelzer WW. Significance of mediastinal mass in acute lymphoblastic leukemia (ALL). Pediatr Res. 1974;8(4):408-408.
Patel JL, Smith LM, Anderson J, et al. The immunophenotype of T-lymphoblastic lymphoma in children and adolescents: a Children's Oncology Group report. Br J Haematol. 2012;159(4):454-461.
Burkhardt B, Hermiston ML. Lymphoblastic lymphoma in children and adolescents: review of current challenges and future opportunities. Br J Haematol. 2019;185(6):1158-1170.
Prusakowski MK, Cannone D. Pediatric oncologic emergencies. Hematol Oncol Clin North Am. 2017;31(6):959-980.
Arceci RJ. Early postinduction intensification therapy improves survival for children and adolescents with high-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Yearbook of Oncology. 2009;2009:153-154.
Smock KJ, Agarwal AM, Lim MS, et al. Expression of Notch1 and mTOR pathway proteins in pediatric lymphoblastic lymphoma: a Children's Oncology Group report. J Hematopathol. 2014;7(1):9-14.
Hastings C, Gaynon PS, Nachman JB, et al. Increased post-induction intensification improves outcome in children and adolescents with a markedly elevated white blood cell count (≥200 × 109/l) with T cell acute lymphoblastic leukaemia but not B cell disease: a report from the Children's Oncology. Gr. Br J Haematol. 2014;168(4):533-546.
Ganzel C, Becker J, Mintz PD, Lazarus HM, Rowe JM. Hyperleukocytosis, leukostasis and leukapheresis: practice management. Blood Rev. 2012;26(3):117-122.
Korkmaz S. The management of hyperleukocytosis in 2017: do we still need leukapheresis?. Transfus Apher Sci. 2018;57(1):4-7.
Citrin R, Getz KD, Li Y, et al. The epidemiology of rasburicase use in paediatric patients with acute lymphoblastic leukaemia and non-Hodgkin lymphoma. Br J Haematol. 2018;184(4):684-688.
Hulst JM, Peters JW, van den Bos A, et al. Illness severity and parental permission for clinical research in a pediatric ICU population. Intensive Care Med. 2005;31(6):880-884.
Alahmad G. Informed consent in pediatric oncology. Cancer Control. 2018;25(1):107327481877372.
Horton TM, Lu X, O'Brien MM, et al. Bortezomib reinduction therapy to improve response rates in pediatric ALL in first relapse: a Children's Oncology Group (COG) study (AALL07P1). J Clin Oncol. 2013;31(15_suppl):10003-10003.
Faulk K, Anderson-Mellies A, Cockburn M, Green A. Assessment of enrollment characteristics for Children's Oncology Group upfront therapeutic clinical trials 2004-2015. J Clin Oncol. 2019;37(15_suppl):6564-6564.
Nguyen K, Devidas M, Cheng S-C, et al. Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children's Oncology Group study. Leukemia. 2008;22(12):2142-2150.
Freyer DR, Devidas M, La M, et al. Postrelapse survival in childhood acute lymphoblastic leukemia is independent of initial treatment intensity: a report from the Children's Oncology Group. Blood. 2011;117(11):3010-3015.
Berg SL, Blaney SM, Devidas M, et al. Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children's Oncology Group. J Clin Oncol. 2005;23(15):3376-3382.
Commander LA, Seif AE, Insogna IG, Rheingold SR. Salvage therapy with nelarabine, etoposide, and cyclophosphamide in relapsed/refractory paediatric T-cell lymphoblastic leukaemia and lymphoma. Br J Haematol. 2010;150(3):345-351.