scholarly journals Low Epression of MiR-18a Distinguishes Pediatric and Adult Acute Lymphoblastic Leukemia from Each Other

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4991-4991
Author(s):  
Neda Mosakhani ◽  
Mohamed El Missiry ◽  
Emmi Vakkila ◽  
Päivi Heikkilä ◽  
Sakari Knuutila ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Immune Cell ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Tissue Samples ◽  
Inflammatory Microenvironment ◽  
Qrt Pcr ◽  
Response To Chemotherapy ◽  
Pediatric All

Abstract In several adult solid cancers the presence or absence of an inflammatory microenvironment has turned out to be an important prognostic factor. Acute lymphoblastic leukemia (ALL) is seen in both adults and children but the response to chemotherapy and survival is significantly worse in adults than children. Therefore, we wanted to study whether the expression of immune system associated molecular markers would be different in adult and pediatric ALL patients at the time of diagnosis. IDO and FOXP3 were studied from paraffin embedded tissue samples by immunohistochemistry in 12 pediatric and 10 adult bone marrow samples. Inflammation associated miRNA analysis were performed in 19 adult and 79 pediatric ALL patients and involved miR-10, miR-15, miR-16, miR-17-92 cluster, miR-33, miR-146a, miR-150, miR-155, miR-181a, miR-222, miR-223, and miR-339. miRNAs were first analysed by Agilent's miRNA microarray and thereafter validated by qRT-PCR. miRNAs not expressed in at least 75% of one group of samples were excluded. Significance (p <0.05; q<0.1) of differential expression was estimated by t-test for those miRNAs with at least a 2.0 fold change. Sufficient RNA for qRT-PCR was available for 42 pediatric and 19 adult patients. The adult and pediatric ALL patients had quantitatively and qualitatively similar expression of IDO and FOXP3 in leukemic bone marrow samples (p=0.26 and 0.74, respectively). Out of studied miRNAs only miR-18a differed significantly in microarray analysis between adult and pediatric ALL being lower in children (FC -3.74; p 0,0037). Results were confirmed by qRT-PCR (upregulated in adults, FC 3.71, p 0.003161). The other members of the miR-17-92 cluster did not differ significantly. We conclude that pediatric and adult ALL patients have remarkably similar pattern of immune cell associated markers in bone marrow at diagnosis. This is in line with recent evidence that the outcome of the adult ALL patients can be significantly improved if treated with pediatric protocols. However, the low expression of miR-18a in pediatric ALL is interesting and demands further studies. Disclosures No relevant conflicts of interest to declare.

Detection of Five Common Fusion Oncogenes in Pakistani Children with Acute Lymphoblastic Leukemia and Their Association with Clinical Pattern and Treatment Outcome

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5124-5124
Author(s):  
Zafar Iqbal ◽  
Sabir Noreen ◽  
Aleem Aamer ◽  
Awan Tashfeen ◽  
Tahir Naeem ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
White Cell Count ◽  
Total Leukocyte Count ◽  
Age Group ◽  
Response To Chemotherapy ◽  
Pediatric All

Abstract Abstract 5124 Background & Objectives: Acute lymphoblastic leukemia (ALL) is a complex genetic disease involving many fusion oncogenes (FGs) (Xu et al., 2012). The frequency of various FO can vary in different ethnic groups & these FGs have important implications for prognosis & treatment outcome (van-Dongen et al, 1999). Methods: We studied FGs in 101 pediatric ALL patients using Interphase FISH & RT-PCR (van-Dongen et al, 1999), & their association with clinical features & treatment outcome. Results: Five most common FGs i. e. BCR-ABL [t(9;22)], TCF3-PBX1 [t(1;19)], ETV6-RUNX1 [t(12;21)], MLL-AF4 [t(4;11)] & SIL-TAL1 (del 1p32) were found in 89/101 (88. 1%) patients. Frequency of BCR-ABL was 44. 5% (45/101) (Table 1). BCR-ABL positive patients had a significantly lower survival (43. 73 ± 4. 24 weeks) (Figure 1)& higher white cell count as compared to others except patients with MLL-AF4. The highest relapse-free survival (RFS) was documented in ETV6-RUNX1 (14. 167 months) followed closely by those cases in which no gene was detected (13/100). RFS in BCR-ABL, MLL-ASF4, TCF-PBX4 & SIL-TAL1 was less than 10 months (7. 994, 3. 559, 5. 500 & 8. 080 months respectively) (Figure 2 & 3). BCR-ABL: Frequency of occurrence was directly proportional to age (3 less than 2 year age group, 16 in the 2–7 year age group & 26 in the older than 7 group. Total leukocyte count (TLC) was higher when compared to patients with other oncogenes. Organomegaly was not common. BCR-ABL positivity was associated with low remission rates & shortened survival. ETV6-RUNX1: The median age of the patients was 1. 85 years. The gene frequency was highest in patients younger than 2 years. TLC was not very high & patients had a good prognosis. MLL-AF4: 17 patients had MLL-AF4 gene rearrangement with a median age of 9 years. Five patients were younger than 2 years, two between 2 & 7 years, & ten patients were in the 7–15 age group. Majority of our patients were older unlike the usual occurrence where most of the patients are infants. TCF3-PBX1: This FG occurs in around 2% of patients. Only two female patients were diagnosed with this translocation. Both the patients were over 2 years of age. It was associated with an inferior outcome in the context of response to chemotherapy & a higher risk of CNS relapse although small numbers preclude any firm conclusions. SIL-TAL1: Patients were older than 2 years, with the majority falling in the age range 7 to 15 years. The immunophenotype data were available in all SIL-TAL1 patients showing this fusion gene was associated with T-ALL with organomegaly being observed frequently. Discussion & Conclusion: This is the first study from Pakistan correlating molecular markers with disease biology & treatment outcome in pediatric ALL. Our study revealed the highest reported frequency of BCR-ABL FO in pediatric ALL, in consistent with various other reports from Pakistan & rest of the world ((Iqbal & Akhtar, 2007; Faiz et al., 2011; (Gaynon et al., 1997; Iacobucci et al., 2012).) which, consequently, was associated with poor overall survival. The data indicates an immediate need for incorporation of tyrosine kinase inhibitors in the treatment of BCR-ABL+ pediatric ALL in this population & the development of facilities for stem cell transplantation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Long Term Results for Childhood Acute Lymphoblastic Leukemia: An Institutional Review

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5161-5161
Author(s):  
Huirong Mai ◽  
Ximin Fang ◽  
Xiuli Yuan ◽  
Xiaodong Wang ◽  
Sixi Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Severe Infection ◽  
Long Term Results ◽  
Term Survival ◽  
Institutional Review ◽  
Pediatric All

Abstract Objective s: To exam the outcomes of children with acute lymphoblastic leukemia (ALL) treated on Berlin-Frankfürt-Münster (BFM) International ALL- based protocol, GD 2008ALL protocol. Method s : In total, 274 patients with newly diagnosed ALL age 1 to 16 years were enrolled onto GD2008ALL protocol from July 1, 2008 to June 30, 2016. Five-year overall survival (OS) rates and even-free survival (EFS) rates were examined with additional analyses of causes of relapse and death. Results:The 5-year probabilities of OS and EFS were 90.8% and 86.9%. The 5-year EFS were 91.7% in SR group, 86.5% in IR group and 82.6% in HR group, respectively. Twenty-five patients were died. Reasons for mortality included 8 cases due to relapse of leukemia, seven cases due to severe infection, one case due to hepatic failure, one case due to intracranial hemorrhage from accident, eight cases abandoned after relapse. There were 29 cases relapsed, including 22 cases (75%) relapsed of the bone marrow alone, 1 case (3.6%) CNS relapsed alone, 2 cases (7.1%) testicular relapsed and 4 cases (14.3%) relapsed of bone marrow and extramedullary. Eleven patients survived after therapy for relapse, of which 7 had received HSCT, two out of the 7 had relapsed after HSCT, and continued on CART therapy. Four out of the 11 relapsed patients received relapsed ALLR3 protocol for treatment. All 11 patients remained in remission status. Conclusion:Our single institutional review of pediatric ALL treated on GD 2008ALL Protocol was tolerated and has good long term outcomes. Although relapse is a major factor affecting long term survival, there are still have options such as HSCT or immunotherapy available for these patients. Disclosures No relevant conflicts of interest to declare.

Bioimaging of Vascular Microenvironment Reveals Presence of Fli1a, Not VEGFR2, in Acute Lymphoblastic Leukemia Model in Syngeneic Zebrafish

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2551-2551
Author(s):  
Sergei Revskoy ◽  
Igor Mizgirev ◽  
Seth J. Corey
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Cellular Mechanisms ◽  
Bone Marrow Biopsies ◽  
Response To Chemotherapy

Abstract Abstract 2551 Despite great advances in the curability of children with acute lymphoblastic leukemia (ALL), outcomes for pediatric and adult patients with relapsed ALL remain poor. This highlights the need for new approaches to ALL treatment and novel tools for screening of potential therapeutics. Dysregulated angiogenesis has been implicated both in the pathogenesis of leukemia and development of chemoresistance. However, the complexity of the bone marrow microenvironment and the precise contributions by the various components cannot be easily dissected in cell lines, tissue blocks, or mouse models. For instance, leukemia-associated angiogenesis was mainly characterized by immunostaining of bone marrow biopsies. High resolution in vivo bioimaging of fluorescence-tagged tumors and their microenvironment has recently become feasible due to establishment of transplantable tumor models in clonal syngeneic zebrafish. We have applied this model to dissection of cellular mechanisms of angiogenesis during stages of progression of T-ALL, This novel animal model enables us to 1) track leukemic cell proliferation and dissemination in vivo in different temperio-spatial and vascular contexts, and 2) follow up on cellular angiogenic events in response to leukemia progression including those occurring in response to chemotherapy for leukemia. In zebrafish, angiogenesis is similar to that of mammals and has been well characterized by using VEGFR2 and Fli1a transgenic reporter systems. In embryos, the fli1a:EGFP expression pattern mirrors that of VEGFR2 fluorescence in vascular endothelial cells. However, later in the development, in larvae and adult fish, the pattern of Fli1a or VEGFR2 expression diverges. This divergence further extends to angiogenesis in areas adjacent to T-ALL with more prominent development of Fli1a vasculature. Leukemic patches are characterized by a microenvironment where Fli1a is predominant and VEGFR2 is absent. We are now using cyclophosphamide treatment of leukemic fish to dissect the role of microenvironment and whether angiogenic factors are modified. These data yield new insights into molecular mechanisms of leukemogenesis in conjunction with angiogenesis. Furthermore, our findings would have predicted the lack of efficacy of VEGFR inhibitors in leukemia therapy. Our model offers an advantage for cost-efficient in vivo large scale screening system for antiangiogenic drugs for acute leukemia. Disclosures: No relevant conflicts of interest to declare.

Acute Lymphoblastic Leukemia Blast Cells Stimulate the Autocrine Production of CCL2 and IL-8 in Bone Marrow Stromal Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2429-2429
Author(s):  
Jaira Ferreira de Vasconcellos ◽  
Nilson Ivo Tonin Zanchin ◽  
Angelo A. Cardoso ◽  
Silvia Regina Brandalise ◽  
José Andrés Yunes
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Cell Survival ◽  
Stromal Cells ◽  
Neutralizing Antibodies ◽  
Positive Impact ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Pediatric All

Abstract The interactions of Acute Lymphoblastic Leukemia (ALL) blasts with bone marrow (BM) stromal cells have a positive impact on leukemia cell survival and resistance to chemotherapy. ALL stimulates BM stromal cells, which reciprocally promotes leukemia cell survival. To identify molecules critically involved in leukemia–microenvironment crosstalk, we performed gene expression profiling analyses of primary BM endothelial cells (BMEC) and BM mesenchymal stem cells (BMMSC) following stimulation by primary ALL cells. Leukemia stimulation of BM stromal cells upregulates the expression of several inflammatory chemokines, including CCL2 and IL-8/CXCL8. Secretion of these molecules was confirmed by ELISA assays of in vitro co-culture experiments and in BM plasma samples from pediatric ALL patients. Most primary ALL samples were found to express mRNA for CCR2 and CXCR1/CXCR2, which are the cognate receptors for CCL2 and IL-8, respectively. Primary ALL cells expressing at least one myeloid marker (CD13, CD15 or CD33) exhibited increased mRNA expression of CCR2 (p = 0.02). Leukemia cells from most patients express CCL2 and IL-8 chemokines (ELISA test) but at lower levels than that of BMEC and BMMSC. In vitro functional studies revealed that the proliferation, survival and migration of primary ALL cells co-cultured with BM stromal cells were not affected by addition of CCL2, IL-8 or of neutralizing antibodies to these chemokines. On the other hand, both chemokines were found to enhance BMEC and BMMSC survival in serum-free medium and to increase their proliferation in serum-starved conditions. Interestingly, CCL2 and IL-8 affected endothelial morphogenesis as shown in Matrigel assays. Since CCL2 and IL-8 have suppressive effects in normal hematopoiesis but do not seem to affect primary ALL cells, it is possible that these chemokines may contribute to the establishment of survival/proliferative selective advantage for ALL cells in the leukemic BM microenvironment. In addition, CCL2 and IL-8 seems indirectly to contribute to ALL cell survival by stimulating the supporting BM stromal cells. Finally, preliminary results showed that standard risk pediatric ALL patients with BM plasma levels below 577pg/ml have better survival rates than those with higher CCL2 levels (p = 0.08). In conclusion, this work suggests a significant role for the chemokines CCL2 and IL-8 in the leukemia/microenvironment crosstalk in human ALL, and suggests that these molecules may represent valuable targets for therapeutic intervention in this cancer. Supported by: CNPq, FAPESP.

Acute Lymphoblastic Leukemia with Mature Appearing Lymphocytes: First Chinese Case Report and Literature Review

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4896-4896
Author(s):  
QiGuo Zhang ◽  
Jian Ouyang ◽  
Jianyong Li
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Poor Response ◽  
Chromosome 8 ◽  
Leukemic Cells ◽  
Fish Analysis ◽  
Ki 67 ◽  
Diffuse Infiltration ◽  
Response To Chemotherapy

Abstract Objective: To increase the knowledge and understanding of acute lymphoblastic leukemia with maturation(ALLm). Method: One ALLm case with clinical manifestation, bone marrow morphology, immunophenotype and cytogenetic results were presented and related literatures were reviewed. Result: The patient was a fifty-five year old women, the haematological feature was Pancytopenia. There were 12% lymphoblasts and 82.5% mature appearing lymphocytes in the bone marrow smear. The mature appearing leukemic cells could not be separated clearly by gating. However, the immunophenotypes of mature-appearing leukemic cells(Low FSC and Low CD45) and lymphoblasts were the same. Both results were CD33+CD34+CD19+CD22+HLA−DR+CD5−CD7−CD10−CD13−CD14−CD15−CD20−CD25−CD45−CD71−CD11b−CD103−CD117−. Bone marrow biopsy showed hypercellularity with diffuse infiltration of lymphocytes, The results were CD34++,TdT++,Pax-5+++,CD43++,CD3+(scatter),CD5+(scatter),CD20−,CD10+,CyclinD1−, lymphoblasts Ki67+, mature-appearing leukemic cells ki-67-. FISH analysis of the bone marrow revealed about 1% cells with a signal pattern suggesting loss of one copy of chromosome 8. After VDP, MA, AAG and HAG regimens Complete remission was not achieved. Conclusion: ALLm is a special morphological variant of acute lymphoblastic leukemia, most mature appearing cells are in resting G0 phase and this could be the reason why ALLm has a poor response to chemotherapy.

Triptolide Induces Apoptosis In Acute Lymphoblastic Leukemia Cells by Inhibition of the Oncoprotein MDM2

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4934-4934
Author(s):  
Mei Huang ◽  
Lubing Gu ◽  
Muxiang Zhou
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Biological Action ◽  
Leukemic Cells ◽  
Transcriptional Level ◽  
Antitumor Effects ◽  
Mdm2 Expression ◽  
Pediatric All ◽  
Chinese Plant

Abstract Abstract 4934 Triptolide, a nature product derived from the Chinese plant Tripterygium wilfordii, is reported to exhibit antitumor effects in a broad range of cancers. Recent studies indicate that the antitumor activity of triptolide is associated with its biological action to inhibit expression of many oncoproteins and anti-apoptotic or survival factors that were expressed in the cancer cells. Herein, we demonstrate that triptolide induces apoptosis in a subgroup of acute lymphoblastic leukemia (ALL) cells that overexpress MDM2 oncoprotein by inhibiting the MDM2 expression. In pediatric ALL, overexpression of MDM2 by leukemic cells is typically associated with a wild-type (wt) p53 phenotype and resistance to conventional chemotherapeutic drugs such as doxorubicin. In the present study, we evaluated the role of triptolide in regulating MDM2 and in inducing apoptosis, as compared to doxorubicin, using ALL lines and primary ALL samples. In contrast to doxorubicin, which induced p53 activation and a subsequent upregulation of MDM2, triptolide strongly induced persistent inhibition of MDM2 followed by a steady-state activation of p53, which resulted in potent apoptosis of the MDM2-overexpressing ALL cells tested, even if they were doxorubicin-resistant. We discovered that triptolide's inhibition of MDM2 in ALL cells occurred at the post-transcriptional level through inhibition of mRNA synthesis. Because p53 function is inhibited by MDM2 in chemoresistant/MDM2-overexpressing ALL cells, potent killing of these cells by triptolide suggests that this naturally-derived agent may be a novel therapeutic for refractory ALL. Disclosures: No relevant conflicts of interest to declare.

Successful Engrafment After HLA Identical Granulocyte Transfusion As Support Therapy in a Septic Shock Patient with Acute Lymphoblastic Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4507-4507
Author(s):  
Roberto Ovilla ◽  
Claudia Barrera-Carmona ◽  
Nicolas Guzman-Bouilloud ◽  
Elizabeth Buganza-Torio ◽  
Rosa Jimenez-Alvarado ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Septic Shock ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Transplant ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Immunosuppressive Treatment ◽  
Marrow Transplant ◽  
Granulocyte Transfusion ◽  
Shock State

Abstract Abstract 4507 A 53 years old male started in February 2010 with ecchymosis, petechiae and spontaneous gum bleeding. He was diagnosed with acute lymphoblastic leukemia, and was started on HYPER-CVAD, in combination with anti-tumoral lysis syndrome measures and antimicrobial, antiviral y antifungal prophylaxis. After finishing HYPER-CVAD phase A, he developed severe myelosuppression even with the use of G-CSF, 72 hours later he presented with abdominal cramping, fever up to 38.2°C and hypotension, with a high clinical suspicion of neutropenic colitis; his mean arterial pressure average was 45 mmHg, he was started on intravenous colloids, dobutamine and norepinephrine drips. Because of severe myelosuppression, septic shock and myocardial depression, a granulocyte transfusion without previous mobilization was performed with an identical sibling donor with concomitant use of granulocytic colony stimulation factor. Severe myelosuppression was maintained during 7 days, however shock state was reversed some hours after performing granulocyte transfusion, without infectious signs, 36 hours later a mononuclear cell infusion was performed from the same donor, with previous 2 days G-CSF mobilization. A gradual increase in leukocyte number appeared, with 400, 900 and finally 1900. A new bone marrow aspiration was performed, where hematopoietic recovery was confirmed from his sister's cells with confirmation by karyotype and microsatellites. He was then considered bone marrow grafted HLA compatible. On April 2010 he presented with acute diarrheic syndrome secondary to a CMV infection, he was started on ganciclovir and intravenous immunoglobulin. On May he presented an Aspergillus pneumonia that was treated both clinically with antifungal therapy and surgically with thoracoscopy to remove the fungi lesion. On October 2010 he started with graft versus host manifestations on the skin and in the liver. He started immunosuppressive treatment with Prednisone and Sirolimus. On November he developed anogenital herpes zoster infection. After this complication, every GVHD manifestation ceded. Now, 28 months post-bone marrow transplant he presents full remission with no evidence of leukemia. Granulocyte transfusion is an uncommon technique. Preferably it should be done with and identical donor. In this case report, the justification of the procedure was to be able to achieve a remission from a potentially irreversible septic shock; this was successfully done, in an unexpected clinical scenario with severe life threatening, and in a casual manner, the patient achieved a successfully bone marrow transplant, and now 30 months post-granulocyte infusion the patient is free from any evidence of disease. Disclosures: No relevant conflicts of interest to declare.

Aggravated Bone Density Decline after Symptomatic Osteonecrosis in Children with Acute Lymphoblastic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2260-2260
Author(s):  
Marissa den Hoed ◽  
S.M.F. Pluijm ◽  
Mariël L. Te Winkel ◽  
Hester A. de Groot-Kruseman ◽  
Marta Fiocco ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Acute Lymphoblastic Leukemia ◽  
Side Effects ◽  
Bone Mineral ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Bone Destruction ◽  
Mineral Density ◽  
Pediatric All ◽  
Cessation Of Treatment

Abstract Background: Osteonecrosis (ON) and decline of bone mineral density (BMD) are serious side effects during and after treatment of childhood acute lymphoblastic leukemia (ALL). It is unknown whether ON and low BMD co-occur in the same patients, and whether these two osteogenic side effects can influence each other’s development during pediatric ALL treatment. Methods: BMD and the incidence of symptomatic ON were prospectively assessed in 466 patients with ALL (4-18 years of age) treated according to the dexamethasone-based Dutch Child Oncology Group-ALL9 protocol. Symptomatic ON was defined as persistent pain in arms or legs not caused by vincristine administration, and confirmed by magnetic resonance imaging. Bone mineral density of the lumbar spine (BMDLS) (n=466) and of the total body (BMDTB) (n=106) were measured by dual X-ray absorptiometry at ALL diagnosis, after 32 weeks of treatment, at cessation of treatment (109 weeks) and 1 year after cessation of treatment. BMD was expressed as age-matched and gender-matched standard deviation scores (SDS; Z-score). Multivariate linear mixed models were adjusted for age at diagnosis. Results: Thirty patients (6.4%) suffered from ON. At cessation of treatment, mean BMDLS was -1.28 SDS (SD: 1.27, n=332; p<0.01) and BMDTB was -0.74 SDS (SD: 1.29, n=65; p<0.01) lower in ALL patients compared to their healthy peers. At baseline, BMDLS and BMDTB did not differ between patients who developed or who did not develop ON (mean BMDLS ON+: -0.90 vs. ON-: -1.14, p=0.36; mean BMDTB ON+: 0.07 vs. ON-: 0.25 p=0.65). At cessation of treatment, patients with ON seem to have a trend for a lower mean BMDLS (ON+: -1.68 vs. ON-: -1.31, p=0.18) and they have a lower mean BMDTB (ON+: -1.91 vs. ON-: -0.59, p=0.01) than patients without ON. Multivariate analyses showed that BMDTB change during follow-up was significantly different for patients with ON than without ON (interaction group time, p=0.04). Between BMD measurements before and after the diagnosis, patients with ON seemed to have a more rapid decline of BMDTB than in patients of the same age without ON (mean BMDTB difference -1.13 vs. -0.62, p=0.10). Conclusion: We conclude that symptomatic ON and low BMD during antileukemic treatment co-occur in pediatric ALL patients. BMD status at ALL diagnosis does not seem to precede ON. However, the development of ON seems to aggravate BMD decline during antileukemic treatment, most likely due to bone destruction and the advised physical immobilization. Disclosures No relevant conflicts of interest to declare.

LDL Discordance in Pediatric Survivors of Acute Lymphoblastic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 6003-6003
Author(s):  
Galit Rosen ◽  
Gabriel Q Shaibi
Keyword(s):  
Cardiovascular Disease ◽  
Acute Lymphoblastic Leukemia ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Cardiovascular Disease Risk ◽  
Heart Association ◽  
Cardiac Risk ◽  
Cardiac Events ◽  
Pediatric All

Abstract Background: Survivors of childhood acute lymphoblastic leukemia (ALL) have a four-fold excess risk of mortality secondary to cardiovascular events compared to the general population. While it is well-known that LDL has a role in atherogenesis and subsequent cardiac events, recent studies consistently show that LDL particle number (LDLp) is a stronger, independent predictor of coronary heart disease in adults compared to LDL-cholesterol (LDLc), especially when the values are discordant. There is emerging evidence that LDL discordance also occurs in children. We studied this phenomenon in pediatric ALL survivors and identify associated risk factors. Methods: Complete data were available from 64 patients enrolled in the Phoenix Children’s Hospital pediatric cancer survivorship registry. Patients were 12.9±3.5 years of age (range: 7.7-22.7 years) with a mean time off therapy of 5.5±2.6 years (range 2.3-11.4 years). LDLc and LDLp were assessed by NMR spectroscopy. Patients were assessed by a registered dietician for calcium, fat, and fruit intake as well as physical activity. Ideal LDLc and LDLp were defined as <160 mg/dL and <1600 nmol/L, respectively, based on American Heart Association guidelines for people with standard cardiac risk. Discordance was classified based on ideal vs. not-ideal status for each parameter. Results: Mean BMI was 22.7±5.7 kg/m2 (range 14-38 kg/m2); mean BMI percentile was 73.1±26.1% (0.9-99.5%) with 42% of patients considered overweight or obese at the time of evaluation. Mean LDLc and LDLp were 79±25.5 mg/dL (29-164 nmol/L) and 1124±517 nmol/L (411-2837 nmol/L), respectively, with 89% (n=56) of survivors exhibiting ideal LDLc and 47% (n=30) of survivors exhibiting ideal LDLp. In a subgroup of patients with ideal LDLc, 40.6% (n=26) exhibited not-ideal LDLp and were classified as discordant. Regression analysis showed that after adjusting for age and gender, BMI (p<0.00001) and LDLc (p<0.00001) were significant independent predictors of LDLp while lifestyle factors and time off therapy were not significant predictors of LDLp. When patients were grouped as concordant (ideal LDLc and LDLp, n=30) or discordant (ideal LDLc and elevated LDLp, n=25), BMI was 17.6% higher in the discordant group (25.0±5.4 kg/m2 vs. 20.6±5.0 kg/m2, p=0.003). Conclusion: In this population of pediatric ALL survivors, LDLc measurements may not provide a complete assessment of cardiovascular disease risk. Given that LDLp is an early predictor of cardiovascular outcomes, conventional lipid testing may underestimate the true cardiovascular disease risk in ALL survivors. Survivors may benefit from early, expanded screening and targeted intervention. Further studies should focus on the broader pathophysiology of cardiovascular disease in pediatric ALL survivors. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document