Background Outcomes of relapsed/refractory childhood acute leukemia remain poor. We analyzed the safety/efficacy of fludarabine, cytarabine, and granulocyte colony stimulating factor, with/without idarubicin (FLAG ± IDA) as salvage therapy compared with recent published results of novel therapies. Methods This retrospective study included children aged 1 to 15 years with relapsed/refractory acute leukemia who received FLAG ± IDA salvage therapy from January 2000 to December 2014. Patients with infant leukemia, mixed lineage leukemia, Philadelphia-positive acute leukemia, or secondary leukemia were excluded. Result Fifty patients were identified: 25 with acute lymphoblastic leukemia and 25 with acute myeloid leukemia. The median age at initiation of FLAG ± IDA was seven years. Site of relapse was the bone marrow in 29, isolated central nervous system in 11, and combined in 10 patients. FLAG ± IDA was used after first relapse in 68% and after multiple relapses in 32%. Complete remission was achieved in 34 (68%) patients. No variables predictive of complete remission were identified. Grade 3 or greater toxicity was observed in 96% and 6% died from toxicity. Toxicities included hematologic toxicity (96%), infection (52%), and enterocolitis (28%). Twenty-four of 50 (48%) patients achieved a sustained complete remission and survived to bone marrow transplantation. The five-year overall survival was 23.9% ± 6.9%. Patients achieving second complete remission and patients proceeding to bone marrow transplantation following second complete remission demonstrated significantly improved overall survival (p = 0.001). Conclusion Despite a 68% complete remission rate using FLAG ± IDA, only 48% of patients survived to bone marrow transplantation. The regimen was associated with 96% toxicity and only one in four patients was alive at five years. This underscores the need to find more effective lower toxicity salvage regimens.
Background: Pediatric Hodgkin lymphoma (HL) has been treated successfully with risk-adapted and response-adapted therapy. While risk factors like Ann Arbor staging system, B symptoms, bulky disease, and erythrocyte sedimentation rate were measured objectively, B symptoms are subjective tools. We evaluated whether the neutrophil-to-lymphocyte ratio (NLR) and inflammatory marker levels correlated with B symptoms and disease burden.Materials and Methods: We conducted a retrospective chart review of all children ≤ 14 years old with pathology-confirmed HL treated at our institution. Data included clinical and pathologic features, pretreatment erythrocyte sedimentation rate, ferritin levels; monocyte, neutrophil, and lymphocyte counts; and NLR. Optimum cutoffs of variables significantly associated with B symptoms were determined based on receiver operating characteristic curves.Results: Sixty-four patients were included in the analysis. Sixteen patients (25%) had B symptoms. Patients with B symptoms had higher ferritin levels (P < 0.0001), monocyte counts (P = 0.0060), neutrophil counts (P = 0.0003) and NLR (P < 0.0001), and lower lymphocyte counts (P = 0.0017). Multiple receiver operating characteristic curves were generated to identify the optimum cutoff. Sensitivities and specificities of NLR (cutoff, 3.5) and ferritin (cutoff, 173 ng/mL) were the highest (81.25% and 81.25% [P < 0.0001] and 89.36% and 75% [P < 0.0001], respectively). Patients with NLR > 3.5 and ferritin > 173 (ng/mL) had significantly higher stage, bulky disease, and B symptoms. NLR and ferritin are not predictive of worst outcome in the cohort analyzed.Conclusions: NLR and ferritin levels were associated with high disease burden and B symptoms. Therefore, these variables can be used as measurable tools for B symptoms that can help stratify patients with HL. Larger and prospective studies are needed to validate these findings.
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