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Ara-C fever and infections after high-dose ara-C treatment in pediatric lymphoid malignancies
Torben Ek1, Mirka Pinkava, Jonas Abrahamsson
1Department of Pediatrics, Goteborg University, Goteborg, Sweden. torben.ek@medfak.gu.se
Insights
High-dose cytarabine (Ara-C) causes fever in most children with leukemia or lymphoma. Infections are common due to neutropenia, but serious complications are rare, even without growth factor support.
Area of Science:
- Pediatric Oncology
- Hematology
- Pharmacology
Background:
- High-dose cytarabine (HDAC) is a key treatment for acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) in children.
- Understanding HDAC-related fever and infection risk is crucial for managing pediatric cancer patients.
Purpose of the Study:
- To determine the incidence and characteristics of fever associated with HDAC.
- To evaluate the frequency and severity of infections following HDAC in pediatric ALL and NHL patients.
Main Methods:
- Retrospective review of 169 HDAC courses in 57 pediatric patients (ages 1.8-17.8 years).
- Analysis of C-reactive protein (CRP) and procalcitonin (PCT) levels in febrile patients.
- Assessment of myelosuppression (neutropenia, thrombocytopenia) and lymphopenia.
Main Results:
- Fever occurred in 67% of HDAC courses, often with elevated CRP.
- Profound neutropenia (99%) and thrombocytopenia (92%) were common.
- Infections occurred after 55% of courses, with a low incidence of severe complications (e.g., viridans streptococcal septicemia).
- Corticosteroids were found to inhibit fever.
Conclusions:
- HDAC-induced fever is frequent and can complicate the interpretation of inflammatory markers like CRP and PCT.
- Profound neutropenia and lymphopenia are primary drivers of infection risk.
- Despite high infection rates, the risk of life-threatening complications from HDAC in pediatric lymphoid malignancies is low, even without prophylactic G-CSF.
Abstract:
The objective of this study was to examine the incidence and characteristics of Ara-C-related fever and the frequency and severity of infections after single-drug, high-dose Ara-C treatment (HDAC) in children treated for acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL). A retrospective review was performed of 169 courses of HDAC administered to 57 patients (age 1.8-17.8 years). Procalcitonin values (PCT) were analyzed in a subgroup of 16 patients. Fever during HDAC occurred in 113 of 169 (67%) cases. C-reactive protein (CRP) was elevated in the febrile patients (median 38 mg/L [range 3-150]). PCT was elevated (>0.5 ng/mL) during HDAC in 4 of the 16 evaluated patients. Corticosteroids could inhibit fever (P < 0.001). Myelosuppression after HDAC was prominent: 99% developed neutropenia (<0.5 x 10/L) and 92% thrombocytopenia (<25 x 10/L). An early lymphopenia (median 0.1 x 10/L [range 0.01-0.68]) was seen during the first week. G-CSF was used after 12 of the 169 HDAC courses. A febrile episode occurred after 93 of the 169 (55%) HDAC courses, with no need for intensive care and no deaths. The incidence of viridans streptococcal septicemia was 2 of the 169 cases. Ara-C fever is common, and evaluation with inflammation markers is complicated by the fact that HDAC can induce a moderate release of both CRP and PCT. Profound neutropenia and lymphopenia are causative factors for the high incidence of infections, but the risk of life-threatening complications after HDAC in children in remission of lymphoid malignancies is low, even without prophylactic use of colony-stimulating factors.
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