scholarly journals Effectiveness of Dexamethasone compared with Prednisolone in Induction Therapy of Childhood Acute Lymphoblastic Leukemia

2016 ◽  
Vol 6 (1) ◽  
pp. 3-9
Author(s):  
Tofazzal Hossain ◽  
MA Mannan ◽  
Shamsoon Nahar ◽  
AKM Amirul Morshed ◽  
Shahnoor Islam ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
Blast Cell ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
Group A ◽  
Bone Marrow Study ◽  
Group B

Background: Corticosteroids are an essential component of treatment for acute lymphoblastic leukemia (ALL). Prednisolone is the most commonly used steroid. There is increasing evidence that, even in equipotent dosage for glucocorticoid effect, dexamethasone has enhanced lymphoblast cytotoxicity and penetration of central nervous system compared with prednisolone.Objectives: To determine the effect of dexamethasone and prednisolone and to compare them in induction therapy of ALL in Children.Material & Methods: A total of 60 newly diagnosed cases of ALL confirmed by bone marrow study, children of either sex with age >1 year were included in this study. Variables studied were age, sex, presenting features, neutrophil count, blast cell count, platelet count, bone marrow status at diagnosis, on D15 & D29 of induction and side effects.Results: Mean age of the patients of group A was 6.28 years & that of group B was 7.2 years. Out of all patients of group A 19 (63.3%) were male and 11 (36.7%) were female. In group B 21 (70.0%) patients were male and rests 9 (30.3%) were female. No statistically significant difference was observed in both groups in terms of age, sex & presenting features. After induction significant difference was observed in liver & spleen size at day 7 and day 15. All patients of both groups had M3 marrow status at diagnosis. Overall, in group A 93.3% patients achieved M1 marrow status (fewer than 5% blasts) and 6.7% had M2 marrow status (5-25% blasts) at day 15 of induction. On the other side 66.7% patients of group B achieved M1 status and 33.3% M2 status at day 15. Statistically significant difference was observed between groups on day 15 in term of achieved marrow status (p<0.05). No statistically significant difference was observed between groups in term of infection in difference days of induction. On day 16 of induction maximum incidence of infection was observed in both groups.Conclusion: Dexamethasone may be an effective alternative option to prednisolone for the treatment of acute lymphoblastic leukemia in children.J. Paediatr. Surg. Bangladesh 6(1): 3-9, 2015 (Jan)

scholarly journals Six-year experience with a comprehensive approach to the treatment of recurrent childhood acute lymphoblastic leukemia (ALL-REZ BFM 85). A relapse study of the BFM group

Blood ◽  
1991 ◽  
Vol 78 (5) ◽  
pp. 1166-1172 ◽  
Author(s):  
G Henze ◽  
R Fengler ◽  
R Hartmann ◽  
B Kornhuber ◽  
G Janka-Schaub ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Therapy Group ◽  
Lymphoblastic Leukemia ◽  
Cell Phenotype ◽  
Front Line ◽  
Extramedullary Relapse ◽  
Group A ◽  
First Relapse ◽  
Group B

Abstract Between April 1985 and March 1987 130 children and adolescents up to 18 years of age with first relapse of acute lymphoblastic leukemia (ALL) were registered on the stratified and randomized multicentric trial ALL- REZ BFM 85 designed for patients pretreated with intensive front-line therapies. Stratification criteria were time and site of relapse: bone marrow (BM) relapse on or up to 6 months after stopping front-line therapy (group A), BM relapse beyond 6 months after therapy (group B), and isolated extramedullary relapse at any time (group C). Treatment consisted of alternating courses of polychemotherapy including randomly administered high- or intermediate-dose methotrexate (HDMTX:12 g/m2 as 4-hour infusion; IDMTX: 1 g/m2 as 36-hour infusion). During maintenance therapy the patients received daily oral thioguanine and biweekly intravenous (IV) MTX. The overall second complete remission (CR) rate was 92% (groups A, B, and C: 88%, 92%, and 100%), and the probability of event-free survival (EFS) at 6 years is 0.31 +/- 0.04 (groups A, B, and C: 0.18 +/- 0.05, 0.30 +/- 0.07, and 0.72 +/- 0.11). HDMTX did not prove to be superior to IDMTX, which led to premature stopping of randomization. Risk factor analyses showed early relapse, particularly BM relapse within 18 months, and T-cell phenotype to be independent predictors of poor outcome. The incidence of central nervous system (CNS) relapses following BM relapse was 19%, indicating that reprophylaxis to the CNS with IV/intrathecal (IT) MTX was insufficient. For 17 children who received bone marrow transplantation in second CR from HLA-compatible siblings the EFS was 0.53 +/- 0.12 at 5 years. Their outcome was not influenced by the above-mentioned risk factors. With the proposed treatment regimen long-lasting second remissions can be achieved in about one third of patients even after intensive front- line treatment.

scholarly journals Aerobic training versus strength exercises on muscle strength and quality of life for children with acute lymphoblastic leukemia

2020 ◽  
Vol 25 (1) ◽  
Author(s):  
Doaa Mohamed ◽  
Faten Abd Alazim ◽  
Elham Salem ◽  
Nesreen Ali ◽  
Dina Elgalaly
Keyword(s):  
Quality Of Life ◽  
Acute Lymphoblastic Leukemia ◽  
Muscle Strength ◽  
Training Program ◽  
Aerobic Training ◽  
Lymphoblastic Leukemia ◽  
Significant Difference ◽  
Group A ◽  
Group B

Abstract Background The treatment for children and adolescents with acute lymphoblastic leukemia (ALL) can lead to multiple adverse effects, including poor physical capacity and muscle weakness. This study aimed to determine which is more effective, aerobic exercises or modified strength training program, on muscle strength and quality of life (QOL) for children with ALL. Results In terms of muscle strength, there was a significant difference (P < 0.05) in selected group of muscles elbow flexors, shoulder abductors, hip flexors, knee extensors, and ankle dorsiflexors at both sides in group B compared with group A, whereas there was no significant difference (P > 0.05) between groups on QOL. Conclusion The outcomes of the study showed that there was a significant difference in the selected group of muscles at both sides in group B compared with group A; thus, the modified strength training program is more effective for muscle strength of children with ALL than aerobic training, but there was no significant difference between them on QOL. Trial registration The clinical trial registered in clinicaltrials.gov with an identifier number NCT03147365

scholarly journals Six-year experience with a comprehensive approach to the treatment of recurrent childhood acute lymphoblastic leukemia (ALL-REZ BFM 85). A relapse study of the BFM group

Blood ◽  
1991 ◽  
Vol 78 (5) ◽  
pp. 1166-1172 ◽  
Author(s):  
G Henze ◽  
R Fengler ◽  
R Hartmann ◽  
B Kornhuber ◽  
G Janka-Schaub ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Therapy Group ◽  
Lymphoblastic Leukemia ◽  
Cell Phenotype ◽  
Front Line ◽  
Extramedullary Relapse ◽  
Group A ◽  
First Relapse ◽  
Group B

Between April 1985 and March 1987 130 children and adolescents up to 18 years of age with first relapse of acute lymphoblastic leukemia (ALL) were registered on the stratified and randomized multicentric trial ALL- REZ BFM 85 designed for patients pretreated with intensive front-line therapies. Stratification criteria were time and site of relapse: bone marrow (BM) relapse on or up to 6 months after stopping front-line therapy (group A), BM relapse beyond 6 months after therapy (group B), and isolated extramedullary relapse at any time (group C). Treatment consisted of alternating courses of polychemotherapy including randomly administered high- or intermediate-dose methotrexate (HDMTX:12 g/m2 as 4-hour infusion; IDMTX: 1 g/m2 as 36-hour infusion). During maintenance therapy the patients received daily oral thioguanine and biweekly intravenous (IV) MTX. The overall second complete remission (CR) rate was 92% (groups A, B, and C: 88%, 92%, and 100%), and the probability of event-free survival (EFS) at 6 years is 0.31 +/- 0.04 (groups A, B, and C: 0.18 +/- 0.05, 0.30 +/- 0.07, and 0.72 +/- 0.11). HDMTX did not prove to be superior to IDMTX, which led to premature stopping of randomization. Risk factor analyses showed early relapse, particularly BM relapse within 18 months, and T-cell phenotype to be independent predictors of poor outcome. The incidence of central nervous system (CNS) relapses following BM relapse was 19%, indicating that reprophylaxis to the CNS with IV/intrathecal (IT) MTX was insufficient. For 17 children who received bone marrow transplantation in second CR from HLA-compatible siblings the EFS was 0.53 +/- 0.12 at 5 years. Their outcome was not influenced by the above-mentioned risk factors. With the proposed treatment regimen long-lasting second remissions can be achieved in about one third of patients even after intensive front- line treatment.

scholarly journals Randomized Study of Pegasparagase (SS-PEG) and Calaspargase Pegol (SC-PEG) in Pediatric Patients with Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma: Results of DFCI ALL Consortium Protocol 11-001

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 175-175 ◽  
Author(s):  
Lewis B. Silverman ◽  
Traci M. Blonquist ◽  
Sarah K. Hunt ◽  
Samantha Kay-Green ◽  
Uma H. Athale ◽  
...  
Keyword(s):  
Single Dose ◽  
Acute Lymphoblastic Leukemia ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
Lymphoblastic Lymphoma ◽  
Remission Induction ◽  
Newly Diagnosed ◽  
Induction Dose ◽  
Post Induction ◽  
Significant Difference

Abstract Background: E.coli L-asparaginase (L-ASP) is an important component of treatment for childhood acute lymphoblastic leukemia (ALL), but the optimal preparation and dosing remain to be determined. Pegaspargase (SS-PEG) is a pegylated L-ASP formulation commonly used in frontline therapy. Calaspargase pegol (SC-PEG) is a novel formulation that uses the same ASP enzyme and PEG moiety as SS-PEG but a different linker molecule that is more hydrolytically stable, leading to a longer half-life. On Dana-Farber Cancer Institute (DFCI) ALL Consortium protocols, patients (pts) typically receive a single dose SS-PEG during induction, and then 15 doses every 2-weeks (wks) during post-induction in order to maintain therapeutic serum asparaginase activity (SAA), defined as ≥ 0.1 IU/mL, for 30 consecutive wks. We hypothesized that SC-PEG could be administered less frequently than SS-PEG during post-induction therapy with a similar SAA and toxicity profile. Methods: Between 2012-2015, pts aged 1-21 years with newly diagnosed ALL or lymphoblastic lymphoma (LL) were eligible to enroll on DFCI ALL Consortium Protocol 11-001. Pts were randomized at study entry to receive either SS-PEG (N=120) or SC-PEG (N=119), each given intravenously (IV) at a dose of 2500 IU/m2. Both groups received a single dose during multi-agent remission induction. Post-induction, pts assigned to SS-PEG received 15 doses every 2-wks and those assigned to SC-PEG received 10 doses every 3-wks along with other risk-stratified chemotherapy. Serum samples were obtained 4, 11, 18 and 25 days after the induction dose to determine SAA and prior to each post-induction dose (2 wks after each SS-PEG and 3 wks after each SC-PEG dose) to determine nadir SAA (NSAA) by a validated biochemical assay. Pts were switched to Erwinia asparaginase for Grade 2 or higher allergy or for silent inactivation (defined as 2 consecutive non-detectable NSAA). Asparaginase was permanently discontinued for pancreatitis and held for thrombosis (but re-started once the clot improved). End-induction minimal residual disease (MRD) was assessed in ALL pts by IGH/TCRPCR assay, with low MRD defined as < 0.001. Results: 239 eligible pts were enrolled (230 ALL and 9 LL). There were no significant differences in presenting characteristics between randomized arms. SAA during induction and NSAA during post-induction are displayed in Figure 1. SAA was similar for the two preparations at 4, 11 and 18 days after the induction dose, with SAA ≥ 0.1 IU/mL in ≥ 95% of pts at these time points on both arms. 25 days after the induction dose, SAA was higher with SC-PEG (median 0.298 IU/mL vs 0.056 for SS-PEG), with significantly more pts on SC-PEG arm with SAA ≥ 0.1 IU/mL (88% vs 15%, p<0.0001). Post-induction NSAA was similar between arms, with median NSAA ≥ 1.0 IU/mL (10-times higher than goal NSAA) at 7, 13, 19 and 25 wks after beginning the 30-wk post-induction asparaginase treatment. NSAA was ≥ 0.1 IU/mL in ≥ 98% of pts on both arms at each time point. Two pts on the SC-PEG arm (1.7%) and none on the SS-PEG arm met criteria for silent inactivation. There was no significant difference in rates of ASP-related allergy (p=1.00), pancreatitis (p=1.00), thrombosis (p=0.22) or infections (p=0.86) during induction or post-induction treatment (Table 1). Of 230 evaluable pts, 97% achieved CR, with no difference in proportion of pts with low end-induction MRD by randomized arm (91% SC-PEG vs 90% SS-PEG, p=1.00). Conclusion: During remission induction, a single dose of SC-PEG (2500 IU/m2) leads to more sustained SAA without excess toxicity or significant difference in the proportion of pts with low end-induction MRD. During post-induction therapy, SC-PEG can be given less frequently (every 3-wks) than SS-PEG (every 2-wks) with similar NSAA and toxicity. The high NSAA observed during post-induction therapy with each preparation suggests that a longer dosing interval and/or reduced dose may be feasible while still maintaining NSAA ≥ 0.1 IU/mL. Longer follow-up is necessary to determine event-free survival by randomized arm. Disclosures No relevant conflicts of interest to declare.

scholarly journals PROGNOSTIC VALUE OF PROTEASE ACTIVATED RECEPTOR-1 IN EGYPTIAN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA

2014 ◽  
Vol 6 (1) ◽  
pp. e2014029 ◽  
Author(s):  
Adel Abd Elhaleim Hagag
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Flow Cytometric Analysis ◽  
Newly Diagnosed ◽  
Negative Group ◽  
Positive Group ◽  
Egyptian Children ◽  
Wide Range ◽  
Protease Activated Receptor 1

Background: Acute Lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor cells that proliferate and replace the normal hematopoietic cells of the bone marrow. Protease-activated receptor 1 (PAR-1), is atypical member of this family of receptors that mediate cellular responses to thrombin and related proteases. PAR1 is expressed by a wide range of tumor cells and can promote tumor growth, invasion and metastasis. The aim of this work was to study the role of PAR-1 expression in newly diagnosed ALL patients. Patients and methods: This study was conducted on 44 children with newly diagnosed ALL who were admitted to Hematology Unit, Pediatric department, Tanta University Hospital including 24 males and 20 females with their age ranged from 4-17 years and their mean age value of 9.06±3.26 who were divided into two groups; PAR-1 positive group (18 patients) and PAR-1 negative group (26 patients). All patients were subjected to complete history taking, thorough clinical examination, bone marrow aspiration and flow cytometric analysis for detection of PAR-1 expression by malignant cells. Results: PAR-1 was positive in 18 cases (41%) and negative in 26 cases (59%) of studied patients. This study showed no significant relation between PAR-1 expression and age, sex and most of the clinical data including hepatomegaly, splenomegaly and purpura while generalized lymphadenopathy was significantly higher in PAR-1 positive group. PAR-1 positive expression was associated with some bad prognostic laboratory parameters including higher hemoglobin, higher white blood cells, higher peripheral blood and bone marrow blast cells, higher serum LDH and lower platelets count. No significant association was detected between PAR-1 expression and immunophenotyping. There were significantly higher remission rates in PAR-1 negative group and significantly higher relapse and death rates in PAR-1 positive group. Conclusion: From this study, it could be concluded that PAR-1 expression on ALL cells represents an important adverse prognostic factor. Recommendations: PAR-1 expression should be routinely investigated for better prognostic assessment of ALL patients at diagnosis and should be taken in consideration in designing future therapeutic strategies based on patients- specific risk factors.

Bone Marrow Transplantation or G-CSF Treatment Can Accelerate Recovery of Injured Spinal Cord in Mice.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4181-4181
Author(s):  
Damianos Sotiropoulos ◽  
Eleni Siotou ◽  
Evangelia Athanasiou ◽  
Christos Kalpouzos ◽  
Panayotis Kaloyannidis ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Control Group ◽  
Significant Difference ◽  
Cord Injury ◽  
Group A ◽  
B Mice ◽  
The Mean ◽  
Group B

Abstract Mice, unlike rats and humans, have a self recovery mechanism of spinal cord injury. Whether the hematopoietic system is involved in this mechanism is under investigation. In this study we tested whether bone marrow cells transplanted or mobilized by a growth factor in mice with spinal cord injury, can accelerate the recovery. C57bl/6 female mice 10 to 12 weeks of age underwent spinal cord incision in an open operation. The injury was performed as a complete transection including the dura mater and the whole circumference of the cord at the T10-T11 intervertebral space with a micro scalpel (No 11). Group A mice received 200μg/kg/day G-CSF subcutaneously for 7 days, starting 24 hours after operation. Group B mice received 106 light density bone marrow cells from C576bl/6 donor mice intravenously 24 hours after operation. Control group mice received no treatment. Histological evaluation was performed at 48 hours, 1 week, 3 weeks and 5 weeks postoperatively. Paraffin embedded longitudinal samples of spinal cord were cut as serial sections. Spinal cord damage was estimated by measuring the maximum diameter of the area of axonal damage and disruption of astrocytic network using immunostaining for neurofilaments and GFAP. Antibodies against CD68 were applied to identify macrophage aggregations. All measurements were performed by morphometric photo analysis. The volume of fibroblastic infiltration was estimated using a grading system (0–7), based on Van Gieson stain for connective tissue. Functional deficits and recovery over time were evaluated by testing hind limb reflex and coordinated motor function (Kuhn and Wrathal functional tests, modified by Seki et al, 2002). All tests have been videotaped. Outcome scores at 48 hours, 1 week, 3 weeks and 5 weeks postoperatively for the control group, group A and group B mice were analyzed with the Mann-Whitney U test. 48 hours post operatively all mice in all groups were paralyzed in both hind limbs. Gradual improvement was observed in all groups. At week 3 there was a significant difference between the mean scores of functional tests for both treated groups (A and B) compared with the mean scores of the control group. Statistically significant difference (p&lt;0,05) was observed in 5 out of 7 tests for group A and in 3 out of 7 tests for group B. Same difference between Group A mice and control group mice was observed by 5 weeks, while group B had no statistically significant difference. No animal in any of the groups had a complete recovery 5 weeks postoperatively. Spinal cord in control group mice showed a gradually increase of fibroblastic infiltration until 5 week which entirely separated the two ends of the cord. In group A and group B mice a significant decrease of fibroblastic infiltration was observed at week 5 compared with week 3. Macrophage aggregations were evident at weeks 1 and 5 but not at week 3 in all groups. In conclusion our results indicate that light density bone marrow transplanted cells or G-CSF treatment can accelerate spinal cord injured mice recovery. It is possible that this is associated with a decrease in fibroblastic infiltration of spinal cord. Macrophage aggregation may also play an important role in the mechanism of recovery in mice, while in rats a different reaction including cavitation and delayed demyelination prohibits neurological recovery.

Study on Gene Exppression Profiling Associated with Prognosis in AML (M2a).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4360-4360
Author(s):  
Fan Yi Meng ◽  
Jiaming Tang ◽  
Wenli Ma
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Mononuclear Cells ◽  
Bone Marrow Mononuclear Cells ◽  
Oligonucleotide Microarrays ◽  
Newly Diagnosed ◽  
Standard Chemotherapy ◽  
Group A ◽  
Group B ◽  
Refractory Aml

Abstract Objective: to explore genes related to the prognosis of AML (M2a). Methods: 6 newly diagnosed AML were involved in this experiment and were divided into 2 groups. Group A: 3 AML (M2a) patients with continuous complete remission (CCR1) less than 6 months; Group B: 3 AML (M2a) patients with CCR1 more than 12 months. Bone marrow mononuclear cells were separated and mRNA was purified and labeled with Cy3 and Cy5 respectively, which were used to hybridize against the Agilent human 1B 60mer oligonucleotide microarrays. Results: in the 20173 genes tested, 22 genes were found to be expressed differently between these two groups, among them 10 genes were up-regulated in group A, and 12 genes were up-regulated in group B. Conclusion: with microarray assay, 22 genes including APP were found to be differently expressed in AML (M2a) treated with standard chemotherapy. These genes may be early indicators for the diagnosis as well as prognosis of the refractory AML.

Infectious Central Venous Line Complications During Induction Therapy for Newly Diagnosed Acute Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4322-4322
Author(s):  
Rebecca Cook ◽  
Roger Berkow
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Acute Leukemia ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
Wound Dehiscence ◽  
Newly Diagnosed ◽  
Central Venous ◽  
Central Lines ◽  
Picc Line

Abstract Abstract 4322 Introduction: Childhood acute leukemia treatment requires central venous lines (CVL) for instillation of chemotherapy and blood products. Ideally, a proper white cell count (WBC) and absolute neutrophil count (ANC) ensure proper healing of CVLs, but this is challenging in children with acute leukemia. We sought to investigate the CVL complication rate in newly diagnosed children with acute leukemia during their induction therapy, and determine if the degree of neutropenia at the time of CVL placement correlated with the number of CVLs lost due to infection, wound dehiscence, or thrombosis. Methods: We conducted a retrospective chart review of children diagnosed with leukemia between January 2007 and December 2009 and recorded leukemia type, WBC and ANC at diagnosis and at the time of CVL placement, the type of CVL placed (external line, subcutaneous port) or placement of peripherally inserted central (PICC) line. We recorded complications, including infection, line malfunction, wound dehiscence, and thrombosis within their induction therapy phase. Results: Ninety-five children were evaluable, including 68 children with precursor B acute lymphoblastic leukemia (pre B ALL), 19 with acute myelogenous leukemia (AML), and 8 with T-cell acute lymphoblastic leukemia (T cell ALL). Ninety-eight CVLs were placed in 94 children (1 child died of complications of APML before initiation of therapy). There were 77 subcutaneous ports and 21 external lines placed. Eleven patients received PICC lines for various reasons (ex – sedation risk due to large mediastinal mass or altered mental status due to leukocytosis, coagulopathy, refractory thrombocytopenia, previously placed PICC line at outside hospital). ANC at the time of CVL insertion was reviewed: ANC<500 in 39 central lines, 500–1000 in 29 central lines, and >1000 in 30 central lines. Only 1 central line was removed due to wound dehiscence in a child with T cell ALL, and 2 central lines were removed for cellulitis in children with pre B ALL, and all these patients had ANC<500 at the time of line insertion. Two of the 98 central lines developed an associated thrombosis (1 CVL associated extensive arm venous thrombus and 1 external line with small atrial thrombus at tip of catheter), as opposed to 2 of the 11 PICC lines placed (both extensive arm venous thrombi). Seventeen positive blood cultures occurred during the first month of induction (15 from central lines and 2 from PICC lines), and all infections cleared with antibiotics except for 1 patient with PICC-associated venous thrombosis and persistent MRSA bacteremia. One subcutaneous port had to be revised after 3 days due to deep insertion and difficultly accessing; this child had ANCs<500 during each surgery and healed without complications. Three external lines were removed due to malfunction (2 with ANC<500, 1 with ANC 500–1000 at time of insertion). Conclusions: Nearly 40% of CVLs were placed in times of severe neutropenia (ANC<500), and only 3 were lost due to cellulitis or wound dehiscence. No CVL was lost due to persistent bacteremia compared to 1 PICC line. There was an increased incidence of thrombosis in PICC lines (2 of 11 placed) compared to external lines or ports (2 of 98 lines placed). We failed to see an increased risk of infection due to degree of neutropenia at the time of CVL insertion. Disclosures: No relevant conflicts of interest to declare.

Pentoxifylline During Steroid Window At Induction To Remission Increases Apoptosis In Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2623-2623
Author(s):  
Oscar Gonzalez-Ramella ◽  
Jimenez-Lopez Xochiquetzatl ◽  
Sergio Gallegos-Castorena ◽  
Pablo Ortiz-Lazareno ◽  
Jose Manuel Lerma-Diaz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Cancer Cells ◽  
Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Control Group ◽  
Induction Phase ◽  
Study Group ◽  
Significant Difference

Abstract Introduction Acute lymphoblastic leukemia (ALL) is the most common cancer diagnostic in children, and it represents the second death cause in this population. Despite advances in the treatment of childhood ALL, there are small portion of patients whom still succumb to this disease. A reduced apoptosis in cells plays an important role in carcinogenesis. This phenomenon is an important component in the cytotoxicity induced by anticancer drugs. A currently challenge is the chemotherapy resistance of tumor cells, inhibiting the apoptosis induced by chemotherapy. Pentoxifylline, (PTX) has been studied for its role on increase of apoptosis on cancer cells by different pathways. Our group has reported its efficacy in vitro and ex vivo in increasing apoptosis induced by chemotherapy drugs such as adriamycin and cisplatin in fresh leukemic human cells, lymphoma murine models and cervical cancer cells. We conducted a phase 1 controlled randomized trial to evaluate the efficacy of adding PTX to the steroid window during the remission induction phase in new diagnosed children with ALL. Methods We included all children from both sexes from 9 months to 17 years old during October 2011 to December 2012. Patients were divided into 3 groups, the first one as a non-malignant control group (NL group) included children with a non-hematology disease in which bone marrow aspiration (BMA) was mandatory in order to reach the diagnosis. The second one, the ALL control group whom received prednisone (PRD group) for the steroid window at 40mg/m2/day PO from day -7 to day 0; and then the third one (PTX group), the study group which included children receiving the steroid phase with PRD as early described, plus PTX at 10mg/kg/day IV divided in 3 doses, at the same days as recommended in our treatment protocol (Total Therapy XV). For all 3 groups a BMA was performed at diagnosis, for PRD group as well as PTX group, a second BMA was also collected at day 0. Apoptosis was evaluated by means of Annexin V Apoptosis Detection Kit FITC/PI (eBioscience¨, San Diego, CA, USA) in 1×106 bone marrow mononuclear cells. We measured minimal residual disease (MRD) by flow cytometry at day 14 to demonstrate complete remission in leukemic patients. Statically analysis was performed by U Man Whitney. Results We enrolled 32 patients: 10 in NL group; 11 in PRD group; and 11 in PTX group. The median age of all groups was 6 years (range 9 months-17 years). In PRD group, patient 1 abandoned treatment after administration of day 0, nevertheless the second BMA sample was collected. Patient number 7 died at day 4 due to complications from tumor lysis syndrome. Consequently, in these patients we were not able to measure MRD and BM aspiration at day 14. Except one patient in PRD group, all achieved complete remission at day 14. We did not find any significant difference between NL group and PRD and PTX groups before intervention (U=32 p=0.7; U=28.5 p=0.48 respectively). There was no significant difference between treatment groups before intervention (U= 37 p=0.79). However, after treatment we found an important difference between PRD and PTX groups, we observed an increase in apoptosis in PTX group in comparison with PRD group (U=17.5 p=0.04). There were no adverse effects during treatment. Conclusions The present study is the first one that shows the efficacy of PTX in increasing apoptosis induced by PRD in new ALL diagnosed children, whom have not received any treatment yet. This might be helpful, not only in patients with relapse, but to increase the overall cure rate in ALL. Further studies are needed to prove this hypothesis. With this objective, our study group is already planning a second trial were PTX will be given during all remission induction phase. Experimental reports strongly suggest that PTX induces inhibition of the transcription factor NF-ĸB, by inhibiting survival gens and facilitating apoptosis. To prove it, we are currently processing these patients' samples to know their genetic expression. Disclosures: No relevant conflicts of interest to declare.

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