Serum Leptin Level in Children with Acute Lymphoblastic Leukemia

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Manal Fawzy Ghozlan ◽  
Deena Samir Eissa ◽  
Nada Ahmed Hamed AbdelRahman
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Induction Chemotherapy ◽  
Lymphoblastic Leukemia ◽  
Response To Treatment ◽  
Main Function ◽  
Significant Relation ◽  
Anthropometric Measures ◽  
Serum Leptin ◽  
Post Induction

Abstract Background Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer .It is a disease of monoclonal proliferation of hematopoietic precursor cells of the lymphoid series within the bone marrow. Leptin is a peptide hormone which is predominantly produced by white adipose tissue. The main function of leptin in the human body is the regulation of energy expenditure and control of appetite .It is supposed to be involved in the pathogenesis of hematological malignancy through its proliferative, anti-apoptotic, and differentiating effects on hematopoietic neoplastic cells, in addition to its synergestic effect on vascular endothelial growth factor (VGEF) . Objectives To evaluate serum leptin level in children with acute lymphoblastic leukemia at diagnosis and at day 28 post induction chemotherapy,and to test the association between serum leptin levels and anthropometric measures of ALL patients and prognostic markers of ALL as age, gender, initial WBCS count, extramedullary infiltration to organs and CSF, cytogenetics, and response to treatment . Patients and Methods This is a case- control study performed at Clinical Pathology Department, Ain Shams University Hospitals. The study was conducted on 30 ALL pediatric patients admitted to Hematology & Oncology Unit, Pediatric Department, Ain Shams University Hospitals.The patients were evaluated at diagnosis before intake of chemotherapy and at day 28 post-induction chemotherapy, and 25 healthy controls matched with patients in age, sex, BMI. Results Serum leptin level is elevated in ALL patients at diagnosis as compared to controls .It has no significant relation with patients age, sex, BMI. It is elevated in patients who received cranial radiotherapy and those who relapsed. .However, it has no significant relation with clinical data (fever, lymphadenopathy and organomegaly) and laboratory characteristics (CBC, percentage of blasts infiltrating bone marrow and peripheral blood, immunophenotyping and cytogenetics) of ALL patients. Conclusion Data from our study showed that elevated leptin level in ALL patients can be considered a risk factor involved in ALL pathogenesis.It can be used as a biomarker for ALL diagnosis, a prognostic factor for ALL patients on chemotherapy, and a predicting factor for relapse.

Lack of Prognostic Significance of Absolute Lymphocyte Count After Intensive Induction Therapy in Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4909-4909
Author(s):  
Khaldoun J. Alkayed ◽  
Faris Madant ◽  
Abdulla Ibrahim ◽  
Hadeel Halasheh ◽  
Eman Khattab ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Induction Chemotherapy ◽  
Lymphocyte Count ◽  
Prognostic Value ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Absolute Lymphocyte Count ◽  
Prognostic Effect ◽  
Post Induction

Abstract Abstract 4909 Introduction: Previous work has shown that the function and number of lymphocytes are vital for the patient's immune system to mount an effective response against cancer cells. Multiple recent studies have demonstrated the prognostic value of absolute lymphocyte count (ALC) in a wide range of malignancies. In children with acute lymphoblastic leukemia (ALL), ALC during induction chemotherapy have been shown to be an independent predictor of adverse outcome, even in the era of minimal residual disease (MRD). Most of the previous studies used Children Oncology Group (COG) based regimens with 3 or 4 drugs induction. We hypothesized that with more intensive induction regimens with 5 or 7 drugs, ALC would lose its prognostic value due to more intensive chemotherapy induced leukopenia. Patients/methods: We reviewed 136 Jordanian pediatric patients (Arabic ethnicity) with newly diagnosed ALL, age 1–18 years, from 2007 to 2009. The patients were treated at a single institution on modified St. Jude total XIII and VX protocols, with a median follow up of 35 months (range: 2–54 months). The induction phase was composed of 7 drugs regimen. Variables analyzed included ALC at diagnosis, day15, day 36 end of induction chemotherapy and at time of post induction marrow recovery, white blood cells at diagnosis, age at diagnosis, gender, immunophenotype, cytogenetics, risk group and MRD status at end of induction. ALC at each time-point was evaluated for prognostic ability by univariate and multivariate analysis. Results: We found that ALC at day15, day 36 end of induction chemotherapy and at time of post induction marrow recovery failed to have any prognostic effect on event-free survival (EFS) or overall survival (OS). We analyzed ALC as continuous and dichomatous variable, but without any prognostic significance. In contrast to our hypothesis, children with ALL intensive induction regimen did not have profound lymphopenia, with ALC day15 median of 1260 cells/ml (range: 0–9450), ALC day36 median of 866 (range: 100–3476), and ALC (post induction marrow recovery) median of 1145 cells/ml (range: 85–9676). Our cohort confirmed several known prognostic factors in childhhod ALL. For EFS outcome we found MRD35, age, phenotype and risk group to have a significant prognostic effect with P values of (0.016, 0.005, 0.006, 0.001) respectively. For OS outcome we found both age and phenotype to have a significant prognostic P value of (0.006 and <0.001) respectively. Conclusions: In this study we failed to replicate the previous work that showed the independent prognostic value of ALC during induction therapy in childhood ALL. In contrast to our hypothesis, the reason for the lack of significance was not due to more profound lymphopenia. The lack of ALC prognostic significance in our cohort could be protocol related or patient population (ethnicity) related. Further studies are needed in children with ALL with different ethnic backgrounds to validate the previous work regarding ALC significance before its incorporation in ALL prognostic models, especially in middle or low income countries. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Clinical Utility of Morphological Evaluation of Day 14 Bone Marrow Biopsies in Acute Myeloid Leukemia Patients Undergoing Standard Induction Chemotherapy: Time to Change Practice?

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1004-1004 ◽  
Author(s):  
Yehuda E. Deutsch ◽  
German Campuzano-Zuluaga ◽  
Matthew P Salzberg ◽  
Alexandra Gomez Arteaga ◽  
Justin M. Watts ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Predictive Value ◽  
Chromosomal Abnormalities ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Response To Treatment ◽  
Bone Marrow Biopsies ◽  
Count Recovery

Abstract Introduction Early bone marrow (BM) evaluation (during aplasia or at “day 14” (D14)) in patients with AML undergoing conventional induction therapy has been adopted from clinical practice in pediatric acute lymphoblastic leukemia (ALL). While it has been shown that early persistence of AML correlates with decreased complete remission (CR) rates and overall survival (OS), unlike in ALL, there are no data to indicate that early initiation of re-induction therapy based on these findings will positively influence outcome. In fact, early re-induction, especially in older patients, may increase morbidity and mortality from prolonged cytopenias, infectious complications, and longer hospital stays. Moreover, it can be challenging to determine the nature of scattered blasts identified in a hypocellular BM at D14, as they may represent normal recovering marrow elements or malignant blasts. Even if malignant, the chemosensitivityof these cells will only be fully determined by later assessment of the BM at the time of expected count recovery (“day 28”). For these reasons, early re-induction therapy may not be advisable. In this retrospective study, we sought to evaluate the validity of D14 BM assessments as post-therapy prognostication to guide treatment decisions in AML. Methods We conducted a retrospective institutional study (2006-2014) of AML patients undergoing routine induction chemotherapy where diagnostic, interim (around D14) and recovery (D21-42) BM evaluations were available for review. Clinical information and pathology data were retrieved from our institutional database. Responses at D14 were categorized morphologically into three categories: optimal response (OR, blasts ≤5%), indeterminate response (IR, blasts 6-19%), and residual leukemia (RL, blasts ≥20% or a relative decrease in blast count from baseline of <20%). Published response criteria were used to define responses at marrow recovery. Suboptimal response (SOR) at D14 was defined as either IR or RL during the assessment period. Mann-Whitney's U test was used to compare non-normally distributed variables. The Fisher's exact test was employed to assess for associations between response to treatment at D14 and likelihood of recovering in CR. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of a D14 BM to predict CR were calculated for patients that were observed without re-induction. Results Evaluable patients (n=98) had a mean age of 51 years (20-73), and 45% were male. The median BM blast percentages at diagnosis, D14 and recovery were respectively 54.5%, 0% and 2.5% (Figure 1). There was a significantly greater absolute decrease in blast percentage from diagnosis to D14 in patients who recovered in CR compared to those who did not achieve CR (median: 53.5% vs 23.0%, P = 0.001). In patients that got early re-induction therapy for SOR at D14, the relative differential in baseline and D14 BM blasts was significantly lower compared to patients with D14 SOR who did not get re-induction therapy (median: 21.8% vs 77.8%, P=0.004) Ninety patients did not receive early re-induction therapy. Of these, 86 (95.6%) achieved CR and 4 patients (4.4%) recovered counts with residual leukemia. Fourteen (14.3%) patients were classified as SOR at D14. Of these, 6 (6.7%) did not receive re-induction therapy and 4 of these 6 patients (67%) achieved a CR. Eight patients received early re-induction therapy based on SOR at D14 (IR = 2, RL = 6); of these, 4 patients (50%) achieved CR at count recovery. Achieving an OR at D14 was predictive of achieving CR at recovery (sensitivity = 95.3%, PPV = 97.6%). However, not achieving an OR at D14 had low specificity (50%) and NPV (33.3%) for achieving CR (P = 0.021). Conclusions Our results indicate that a SOR at the D14 BM evaluation does not uniformly identify patients with primary induction failure (low NPV) and should not be used to dictate the timing of re-induction therapy. We confirmed the PPV of achieving an OR at D14 as previously reported, but we argue that no additional prognostic data is provided by an OR at D14, beyond what can already be predicted by pre-treatment variables (e.g., age and chromosomal abnormalities). We suggest that the D14 BM should be omitted from the routine evaluation of AML patients during induction therapy outside the context of a clinical trial. Figure 1 Figure 1. Progression and percentage of blasts at diagnosis, day 14 and recovery assessments (n = 98). Disclosures No relevant conflicts of interest to declare.

Early Responses to Chemotherapy of Normal and Malignant Hematologic Cells Are Prognostic in Children With Acute Lymphoblastic Leukemia

2005 ◽  
Vol 23 (10) ◽  
pp. 2264-2271 ◽  
Author(s):  
Stephen J. Laughton ◽  
Lesley J. Ashton ◽  
Edward Kwan ◽  
Murray D. Norris ◽  
Michelle Haber ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Induction Chemotherapy ◽  
Lymphoblastic Leukemia ◽  
Intensive Therapy ◽  
Prognostic Significance ◽  
Molecular Techniques ◽  
Response To Treatment ◽  
Relapse Prediction ◽  
Risk Of Relapse

Purpose Improved cure rates for children with acute lymphoblastic leukemia (ALL) have resulted from better relapse prediction, using clinical and laboratory features at diagnosis, and more intensive therapy in high-risk patients. More recently, measurements of the variation in the response of malignant lymphoblasts to chemotherapy in vivo have further improved relapse prediction. It is unknown whether the variation in the response of nonmalignant hematologic cells after chemotherapy correlates with the response of lymphoblasts or risk of relapse. Patients and Methods We retrospectively evaluated myelosuppression during induction and consolidation chemotherapy in 227 children uniformly treated for ALL on consecutive Australian and New Zealand Children's Cancer Study Group protocols. The early response to treatment was assessed in a representative subset (n = 62) by determining minimal residual disease (MRD) level by molecular techniques on the end-of-induction bone marrow sample. Results We found that a slow rate of myeloid recovery at the end of induction chemotherapy, reflected in a low absolute neutrophil count (ANC), was highly predictive of relapse (P < .0001). Additionally, patients with a high end-of-induction MRD level had a high risk of relapse (P = .001). Multivariate analysis confirmed the independent prognostic significance of MRD and ANC at the end of induction chemotherapy (P < .05). There was no significant association between other measures of myelotoxicity and MRD or relapse. Conclusion We conclude that the responses of normal myeloid cells and malignant lymphoblasts to chemotherapy predict outcome by distinct mechanisms. While these results are promising, their use in the clinical setting needs to be examined in a future randomized controlled trial.

Blast Percentage of Bone Marrow Aspirate on Day 14 of Induction Chemotherapy Predicts Adult Acute Lymphoblastic Leukemia Treatment Outcomes

2018 ◽  
Vol 139 (4) ◽  
pp. 220-227 ◽  
Author(s):  
Han-Seung Park ◽  
Dae-Young Kim ◽  
Eun-Ji Choi ◽  
Jung-Hee Lee ◽  
Je-Hwan Lee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Treatment Outcomes ◽  
Induction Chemotherapy ◽  
Lymphoblastic Leukemia ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Adult Acute Lymphoblastic Leukemia

The prognosis of adult acute lymphoblastic leukemia is much worse than that of pediatric acute lymphoblastic leukemia, even when patients achieve complete remission. Early response to treatment can be an important alternative indicator of treatment outcomes. The purpose of our current study was to identify the prognostic value of the blast percentage of the induction interim bone marrow, which might predict relapse-free survival and overall survival in patients with adult acute lymphoblastic leukemia. A retrospective analysis was performed on 80 adult patients diagnosed with Philadelphia chromosome-negative acute lymphoblastic leukemia from 1994 to 2011. Complete remission was observed in 75 (93.8%) patients after induction chemotherapy. On multivariate analysis, a reduction of blasts to a level of 5% or less in the induction interim bone marrow and CD20 positivity were significant prognostic predictors of relapse-free survival (hazard ratio, HR = 2.88, p = 0.006, and HR = 2.67, p = 0.010) and overall survival (HR = 2.10, p = 0.033, and HR = 2.39, p = 0.013). The blast percentage of the induction interim bone marrow may be a useful prognostic factor to predict outcome.

Prognostic importance of measuring early clearance of leukemic cells by flow cytometry in childhood acute lymphoblastic leukemia

Blood ◽  
2002 ◽  
Vol 100 (1) ◽  
pp. 52-58 ◽  
Author(s):  
Elaine Coustan-Smith ◽  
Jose Sancho ◽  
Frederick G. Behm ◽  
Michael L. Hancock ◽  
Bassem I. Razzouk ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Acute Lymphoblastic Leukemia ◽  
Induction Chemotherapy ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cell ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Remission Induction

Abstract Early clearance of leukemic cells is a favorable prognostic indicator in childhood acute lymphoblastic leukemia (ALL). However, identification of residual leukemic cells by their morphologic features is subjective and lacks sensitivity. To improve estimates of leukemia clearance, we applied flow cytometric techniques capable of detecting 1 leukemic cell in 10 000 or more normal cells and prospectively measured residual leukemia in bone marrow samples collected on day 19 of remission-induction chemotherapy from 248 children with newly diagnosed ALL. In 134 samples (54.0%), we identified at least 0.01% leukemic cells (0.01%-&lt; 0.1% in 51 samples [20.6%], 0.1%-&lt; 1% in 36 [14.5%], and ≥ 1% in 47 [19.0%]). Among 110 children treated within a single chemotherapy program, the 5-year mean ± SE cumulative incidence of relapse or failure to achieve remission was 32.2% ± 6.5% for the 59 patients with 0.01% residual leukemic cells or greater on day 19 and 6.0% ± 3.4% for the 51 patients with less than 0.01% leukemic cells (P &lt; .001). The prognostic value of day-19 bone marrow status defined by flow cytometry was superior to that defined by morphologic studies and remained significant after adjustment for other clinical and biologic variables. Lack of detectable leukemic cells on day 19 was more closely associated with relapse-free survival than was lack of detectable residual disease at the end of remission induction (day 46). Thus, approximately half of the children with ALL achieve profound clearance of leukemic cells after 2 to 3 weeks of remission-induction chemotherapy, and these patients have an excellent treatment outcome.

scholarly journals Bone Marrow Recovery by Morphometry during Induction Chemotherapy for Acute Lymphoblastic Leukemia in Children

PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0126233 ◽  
Author(s):  
Tuong-Vi Nguyen ◽  
Anna Melville ◽  
Shriram Nath ◽  
Colin Story ◽  
Stuart Howell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Induction Chemotherapy ◽  
Lymphoblastic Leukemia ◽  
Leukemia In Children

scholarly journals Unusual Presentation with Orbital Mass in a Child with Precursor B-Cell Acute Lymphoblastic Leukemia

2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
Lalita Sathitsamitphong ◽  
Rungrote Natesirinilkul ◽  
Worawut Choeyprasert ◽  
Pimlak Charoenkwan
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Ct Scan ◽  
B Cell ◽  
Induction Chemotherapy ◽  
Lymphoblastic Leukemia ◽  
Intracranial Extension ◽  
Orbital Mass ◽  
Orbital Involvement ◽  
The Right

Orbital involvement is one of the extramedullary manifestations in acute leukemia. It is common in acute myeloid leukemia, but rare in acute lymphoblastic leukemia (ALL). We described a 3-year-old girl who presented with progressive proptosis of the right eye and was later diagnosed with precursor B-cell ALL. Initial blood count showed Hb 6.9 g/dL, WBC 42,000/mm3, lymphoblast 50%, and platelet count 185,000/mm3. Bone marrow aspiration revealed 90% lymphoblasts with positivity for CD10, CD19, CD20, CD22, and HLA-DR markers. Computed tomography (CT) scan of the brain and orbit revealed a homogeneous enhancing mass involving the right orbit with intracranial extension. The cytogenetic study showed 46,XX chromosomes. After 4 weeks of induction chemotherapy for very high-risk ALL, although the bone marrow was in remission, the proptosis was partially resolved. CT scan confirmed a decrease in size of the right orbital mass and degree of intracranial extension. Unfortunately, the patient abandoned the treatment after the induction chemotherapy. The actual incidence of orbital involvement in ALL is unknown. Previous case reports describe diverse manifestations of orbital involvement in ALL. The involvement may be unilateral or bilateral, may occur at first diagnosis or at relapse, and may be seen in isolation or with other systemic symptoms. There is no standard treatment protocol. Chemotherapy with or without radiotherapy is generally suggested. The role of upfront hematopoietic stem cell transplantation remains inconclusive. The previously reported prognosis of ALL with orbital involvement is poor.

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