Sami Felimban

A pilot study of prophylactic ciprofloxacin during delayed intensification in children with acute lymphoblastic leukemia

We hypothesized that prophylactic administration of an appropriate antibiotic following each delayed intensification (DI) in children with acute lymphoblastic leukemia (ALL) would reduce the episodes of fever and bacteremia associated with neutropenia, and hence reduce both the rate and duration of hospitalization.

Circadian rhythm of granulocyte-macrophage colony-stimulating factor in normal subjects and neutropenic hospitalised patients

BackgroundGranulocyte-macrophage colony-stimulating factor (GM-CSF), one of the haemopoietic growth factors, has rarely been detected in human serum. It has, therefore, been suggested that a paracrine model can explain its behaviour where the substance is produced and acts locally. An alternative explanation might be due to blood sampling time with GM-CSF concentrations undetectable at the nadir of secretion.HypothesisWe hypothesised that endogenous production of GM-CSF in humans is subject to diurnal rhythm.MethodsBlood samples were obtained from 17 healthy individuals and 17 neutropenic hospitalised patients with haematological malignancies on myelosuppressive therapy at 6, 12, 18 and 24 hours. In the neutropenic patients, samples were collected at the nadir of the neutrophil count (ANC <0.2 × 109/L). Serum was assayed for GM-CSF levels using an enzyme-linked immunosorbent assay method.ResultsThere were significant differences in the mean levels of GM-CSF within the two groups (P<0.001). In normal subjects, peak GM-CSF levels were reached at six hours (mean = 10.1 pg/ml). Peak levels were reached in hospitalised neutropenic patients at 18 hours (mean = 13.7 pg/ml). The difference between the peak GM-CSF levels in the two groups was not significant (P=0.11). On factorial design analysis, there was a significant interaction between the time of blood collection and the subject groups (P<0.001).ConclusionsOur data are consistent with a diurnal secretion pattern for GM-CSF in both normal and neutropenic patients. As this finding might have practical implications, including timing of administration of GM-CSF in neutropenic patients, further studies are suggested.

Identifying causes of variability in outcomes in children with acute lymphoblastic leukemia treated in a resource-rich developing country.

The outcome of children with acute lymphoblastic leukemia (ALL) in developing countries is less favorable than in developed countries, primarily due to resource constraints. However, it is unknown whether the therapeutic results differ. Thus, we hypothesized that outcomes in resource‐rich developing countries would be similar to those in industrialized regions.

Comparison of clinical trial versus non-clinical trial treatment outcomes of childhood acute lymphoblastic leukemia using comparable regimens

Objectives: Treatment regimens tested in major clinical trials, conducted by cooperative groups, are often adapted as standard of care by cancer centers with the hope to replicate the treatment outcomes reported in these landmark studies. It is therefore postulated that applying clinical trial regimens in a non-clinical trial setting yield similar outcomes. The aim of the present study was to explore this hypothesis in the context of childhood acute lymphoblastic leukemia (ALL) in our institution. Methods: We retrospectively evaluated 224 consecutive pediatric ALL cases treated between January 2001 and December 2007. Standard-risk (SR) patients were treated on CCG-1991 (regimen OD) while high-risk (HR) patients were treated on CCG-1961 (regimen D). Results were compared with those of the equivalent regimen in the original clinical trials. Statistical analysis was carried using chi-square or Fishers exact test, Kaplan–Meier and log-rank tests. Results: Comparison of treatment outcomes revealed that SR patients had inferior 5-year overall survival (OS) of (89.0 ± 2.9 vs. 96.0% ± 0.9%); event-free survival of (82.3 ± 3.5 vs. 88.7% ± 1.4%); and relapse rate of (15.8 vs. 9.3% (P = 0.034)) compared to patients treated in the clinical trial. However, no statistically significant difference in treatment outcomes was observed between HR patients. Conclusions: Despite using comparable regimens, suboptimal outcomes were noted in SR patients implying that similar treatments do not necessarily yield similar outcomes. This underscores the need to evaluate outcomes of adapted regimens to identify areas that need further improvement in centers not enrolling patients on prospective collaborative clinical trials.

Does the early intensification of intrathecal therapy improve outcomes in pediatric acute lymphoblastic leukemia patients with CNS2/TLP+ status at diagnosis?

Abstract Objectives We aimed to determine whether the addition of two extra intrathecal methotrexate (ITM) doses during induction in acute lymphoblastic leukemia (ALL) patients eliminate the prognostic significance of CNS2/TLP+ status. Methods We retrospectively analyzed 224 patients according to the central nervous system (CNS) involvement at diagnosis: CNS1, CNS2, or CNS3. Patients with CNS2/TLP+ received two additional ITM doses during induction. Patients were treated according to the Childrens Cancer Group (CCG)-1991/1961 protocols between January 2001 and December 2007. Results The 5-year relapse-free survival (RFS) rates for the ALL patients in the CNS1, CNS2, and CNS3 groups were 80.4 ± 3.0, 100, and 73.5 ± 11.3%, respectively; a non-significant difference was observed between the groups (P = 0.063). However, the patients with CNS2 had significantly better survival compared with the CNS3 patients (P = 0.03). The 5-year cumulative incidence of relapse (CIR) rates for the three groups were 17 (95% confidence interval (CI): 11.9–22.9), 0, and 18.8% (95% CI: 4.3–41.1), respectively; (P = 0.214) and those of isolated or combined CNS relapse were 9.6 (95% CI: 5.8–14.5), 0 and 6.3% (95% CI: 0.3–25.8), respectively (P = 0.424). Conclusions This study shows that the intensification of ITM therapy during induction improves outcomes in patients with CNS2/TLP+ status and eliminates its prognostic significance. This suggests that early intensification using CNS-directed therapy is beneficial in controlling minimal CNS disease.

Sickle cell disease : splenectomy and thrombocytosis

A 12-year-old boy with sickle cell disease (SCD) presented to the emergency department of our hospital with pain in the back and right leg and inability to walk. This visit was his first to our hospital and no previous laboratory results were available. His blood test results were WBC count, 10.8 ¥ 10 per L; Hb level, 9.4 g per dL; Hct level, 30.3 percent; PLT count, 1352 ¥ 10 per L; reticulocyte count, 3.3 percent; and hemoglobin S (HbS) level, 90.7 percent. The patient had splenectomy at the age of 6 years.Considering the HbS level,previous history of stroke,and multiple episodes of vasoocclusive crises, automated erythrocytapheresis was performed with a commercially available leukoreduction system (COBE Spectra LRS system, Gambro BCT, Inc., Lakewood, CO). The procedure was programmed to achieve an end Hct of 28 percent and fraction of RBCs remaining (FCR) of 30 percent. Four leukoreduced RBC units collected in sterile bags (MacoPharma, Mouvaux, France) and stored in SAGM and CPD anticoagulant preservative solution were used as replacement fluid. A total of 1570 mL of replacement was used including 270 mL of ACD. The procedure was carried out according to standard erythrocytapheresis procedures for the COBE Spectra, with no rinseback and no divert waste step. Post-RBC exchange results were WBC count, 13.9 ¥ 10 per L; Hb level, 9.7 g per dL; Hct level, 29.5 percent; and PLT count, 388 ¥ 10 per L. The removal of PLTs associated with RBC or plasma exchange is well established. Patients can lose up to 30 percent of their circulating PLTs at the end of these procedures. In our patient, however, approximately 70 percent of PLTs were removed during the RBC exchange, perhaps due to the exceptionally high initial PLT count (1352 ¥ 10/L). This excessive removal of PLTs is shown in Figs. A and B. Figure A shows a post-RBC exchange container, the plasma is thickly turbid due to the large amount of suspended PLTs. Figure B taken after 36 hours of gravity sedimentation at room temperature of the same bag shows clear plasma on the top, PLT-containing turbid plasma in the middle, and a thick layer of settled PLTs above the RBCs (see arrow).

Transfusion medicine illustrated. Sickle cell disease: splenectomy and thrombocytosis.

A 12-year-old boy with sickle cell disease (SCD) presented to the emergency department of our hospital with pain in the back and right leg and inability to walk. This visit was his first to our hospital and no previous laboratory results were available. His blood test results were WBC count, 10.8 ¥ 10 per L; Hb level, 9.4 g per dL; Hct level, 30.3 percent; PLT count, 1352 ¥ 10 per L; reticulocyte count, 3.3 percent; and hemoglobin S (HbS) level, 90.7 percent. The patient had splenectomy at the age of 6 years.Considering the HbS level,previous history of stroke,and multiple episodes of vasoocclusive crises, automated erythrocytapheresis was performed with a commercially available leukoreduction system (COBE Spectra LRS system, Gambro BCT, Inc., Lakewood, CO). The procedure was programmed to achieve an end Hct of 28 percent and fraction of RBCs remaining (FCR) of 30 percent. Four leukoreduced RBC units collected in sterile bags (MacoPharma, Mouvaux, France) and stored in SAGM and CPD anticoagulant preservative solution were used as replacement fluid. A total of 1570 mL of replacement was used including 270 mL of ACD. The procedure was carried out according to standard erythrocytapheresis procedures for the COBE Spectra, with no rinseback and no divert waste step. Post-RBC exchange results were WBC count, 13.9 ¥ 10 per L; Hb level, 9.7 g per dL; Hct level, 29.5 percent; and PLT count, 388 ¥ 10 per L. The removal of PLTs associated with RBC or plasma exchange is well established. Patients can lose up to 30 percent of their circulating PLTs at the end of these procedures. In our patient, however, approximately 70 percent of PLTs were removed during the RBC exchange, perhaps due to the exceptionally high initial PLT count (1352 ¥ 10/L). This excessive removal of PLTs is shown in Figs. A and B. Figure A shows a post-RBC exchange container, the plasma is thickly turbid due to the large amount of suspended PLTs. Figure B taken after 36 hours of gravity sedimentation at room temperature of the same bag shows clear plasma on the top, PLT-containing turbid plasma in the middle, and a thick layer of settled PLTs above the RBCs (see arrow).

Unusual complication of sickle cell crisis

A 6-year-old Saudi boy with sickle cell anemia had cough, fever, chest pain, and anemia. A chest x-ray showed a slight opacity in the left lower lobe. A diagnosis of pneumonia with sickle cell crisis was made. Despite broad-spectrum antibiotics, he had increased respiratory distress requiring ventilatory support. A repeat chest x-ray revealed a left pleural effusion and mediastinal shift (Fig. 1). Insertion of a chest tube produced only a small volume of serosanguinous fluid that was sent out for smear and culture. Two exchange transfusions were undertaken to reduce pulmonary sickling. Computerized axial tomography of the chest showed extensive consolidation (Fig. 2). Examinations of the pleural fluid and specimens from bronchoalveolar lavage and cerebrospinal fluid showed no organisms and all cultures were negative. However, the

High-dose methotrexate vs. Capizzi methotrexate for the treatment of childhood T-cell acute lymphoblastic leukemia

Sixty-three children (1–14 years of age) newly diagnosed with T-cell acute lymphoblastic leukemia were treated from January 2001 to December 2014. Patient outcomes were evaluated based on the regimen received; Capizzi methotrexate (C-MTX) vs. high-dose methotrexate (HDMTX). Complete remission (CR) was achieved in 54 of 60 (90.0%) patients and 3 patients died during induction. The 5-year overall survival (OS) and disease-free survival (DFS) were 88.3 ± 6.5% and 85 ± 7.5%, respectively. Post-induction, 35 patients were treated with HDMTX and 25 with C-MTX. There was no difference in OS or DFS for patients treated with HDMTX vs. C-MTX (P > 0.05 for both). Central nervous system involvement (CNS3) was associated with inferior survival outcomes compared to Non-CNS3 patients (OS, CNS3 73.3 ± 9.1% vs.non-CNS3 93.2 ± 2.6%, (P = 0.045) and DFS, CNS3 66.7 ± 10.4% vs. non-CNS3 90.9 ± 3.1% (P = 0.0163)). Delayed radiation in CNS3 was associated with relapse (P = 0.0037) regardless of regimen. Thus optimization of CNS-directed therapy for patients with CNS3 is needed.

Sickle cell disease: splenectomy and thrombocytosis: TRANSFUSION MEDICINE ILLUSTRATED

A 12-year-old boy with sickle cell disease (SCD) presented to the emergency department of our hospital with pain in the back and right leg and inability to walk. This visit was his first to our hospital and no previous laboratory results were available. His blood test results were WBC count, 10.8 ¥ 10 per L; Hb level, 9.4 g per dL; Hct level, 30.3 percent; PLT count, 1352 ¥ 10 per L; reticulocyte count, 3.3 percent; and hemoglobin S (HbS) level, 90.7 percent. The patient had splenectomy at the age of 6 years.Considering the HbS level,previous history of stroke,and multiple episodes of vasoocclusive crises, automated erythrocytapheresis was performed with a commercially available leukoreduction system (COBE Spectra LRS system, Gambro BCT, Inc., Lakewood, CO). The procedure was programmed to achieve an end Hct of 28 percent and fraction of RBCs remaining (FCR) of 30 percent. Four leukoreduced RBC units collected in sterile bags (MacoPharma, Mouvaux, France) and stored in SAGM and CPD anticoagulant preservative solution were used as replacement fluid. A total of 1570 mL of replacement was used including 270 mL of ACD. The procedure was carried out according to standard erythrocytapheresis procedures for the COBE Spectra, with no rinseback and no divert waste step. Post-RBC exchange results were WBC count, 13.9 ¥ 10 per L; Hb level, 9.7 g per dL; Hct level, 29.5 percent; and PLT count, 388 ¥ 10 per L. The removal of PLTs associated with RBC or plasma exchange is well established. Patients can lose up to 30 percent of their circulating PLTs at the end of these procedures. In our patient, however, approximately 70 percent of PLTs were removed during the RBC exchange, perhaps due to the exceptionally high initial PLT count (1352 ¥ 10/L). This excessive removal of PLTs is shown in Figs. A and B. Figure A shows a post-RBC exchange container, the plasma is thickly turbid due to the large amount of suspended PLTs. Figure B taken after 36 hours of gravity sedimentation at room temperature of the same bag shows clear plasma on the top, PLT-containing turbid plasma in the middle, and a thick layer of settled PLTs above the RBCs (see arrow).