Extramedullary manifestations in acute lymphoblastic leukemia in children: a systematic review and guideline-based approach of treatment
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Mahdi Shahriari1, Nader Shakibazad2,1, Sezaneh Haghpanah1
1Hematology Research Center, Shiraz University of Medical Sciences Shiraz, Iran.
Insights
Extramedullary involvement in childhood acute lymphoblastic leukemia (ALL) can delay diagnosis. Recognizing these varied symptoms, including musculoskeletal and renal issues, is crucial for early detection and improved survival rates in pediatric ALL.
Area of Science:
- Pediatric Hematology Oncology
- Clinical Pediatrics
- Leukemia Research
Background:
- Acute lymphoblastic leukemia (ALL) in children can present with extramedullary manifestations, often leading to diagnostic delays.
- Understanding these unusual presentations is critical for timely intervention in pediatric ALL cases.
Purpose of the Study:
- To review and analyze the extramedullary manifestations of acute lymphoblastic leukemia (ALL) in children.
- To highlight the importance of recognizing these diverse symptoms for prompt diagnosis and treatment of pediatric ALL.
Main Methods:
- A comprehensive literature search was conducted across multiple databases using keywords related to ALL and its atypical presentations in children.
- Inclusion criteria focused on case reports, case series, and studies detailing extramedullary ALL in pediatric populations.
- Eighty-seven studies were analyzed for extramedullary features, patient demographics, treatment, and prognostic factors.
Main Results:
- The most frequent initial extramedullary signs were musculoskeletal (19.5%), particularly bone symptoms and hypercalcemia.
- Other common extramedullary involvements included renal (19.5%), hepatic (13.8%), orbital (11.5%), and neurological (9%) systems.
- Dermatological, oral, hypereosinophilia, abdominal, and pericardial manifestations were also observed with varying frequencies.
Conclusions:
- Clinicians need to be aware of the wide spectrum of extramedullary presentations of ALL in children to prevent diagnostic delays.
- Early identification of these atypical signs can significantly improve the chances of survival for pediatric patients with ALL.
Objective:
Acute lymphoblastic leukemia (ALL) may present with signs and symptoms related to extramedullary involvement, therefore, leads to delayed diagnosis of ALL in children. This study aims to consider the extramedullary manifestations of ALL in children and their proper treatment.
Method:
The databases were searched for all relevant subjects including "acute lymphoblastic leukemia", "clinical presentation", "unusual presentation", "childhood acute lymphoblastic leukemia", "presenting features of ALL", "extramedullary presentation", and "atypical presentation" from April 1968 to June 2020. The Inclusion criteria for this review study were all cases reported, case series, and studies about extramedullary presentations of ALL in pediatrics. Eighty-seven studies had inclusion criteria. All reported studies were analyzed given their extramedullary presentations, age, sex, treatment option, and prognostic factors. A two-sided P-value less than 0.05 was considered statistically significant.
Result:
In this review study, the extramedullary initial signs and symptoms of ALL were related to musculoskeletal system 17 (19.5%) especially bony symptoms and hypercalcemia. The additional extramedullary presentations of ALL in order of frequency include; renal involvement, 17 (19.5%), hepatic symptom 12 (13.8%), orbital presentation 10 (11.5%), neurologic signs 8 (9%), dermatological manifestations 5 (5.8%), oral presentations 5 (5.8%), hypereosinophilia 5 (5.8%), abdominal manifestation 3 (3.5%), pericardial involvement 2 (2.3%), and the other miscellaneous presentations 3 (3.5%).
Conclusion:
The clinicians must become familiar with these extramedullary presentations of ALL in pediatrics to avoid the delayed diagnosis of this disease and increase the probable chance of survival by early detection.
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