Increased Level of Lactate Dehydrogenase Correlates with Disease Growth in Algerian Children with Lymphoma

Objective: This study aimed to evaluate the relation of Lactate dehydrogenase (LDH) levels with stage of the disease and it role in monitoring tumor response to therapy in lymphoma patients. Methods. LDH levels were evaluated on 65 diagnosed Algerian children and compared to healthy control. Results: Our results revealed that LDH levels were significantly higher in untreated children with both hodgkin’s and non hodgkin’s lymphomas compared to control. Moreover, it was observed that the higher is the stage of disease, the more serum LDH level will be. However, there was a significant fall in serum LDH activity by completion of the chemotherapeutic courses. Conclusion: LDH plays an important role in tumor initiation and maintenance. The elevated serum LDH may reflect, release of the enzyme from malignant cells and suggest that they may reflect tumor burden and therefore correlate with disease progression. J O U R N A L O F H E M A T O L O G Y A N D O N C O L O G Y R E S E A R C H ISSN NO: 2372-6601 Review Article DOI : 10.14302/issn.2372-6601.jhor-17-1473 Corresponding author: R. Raache, Université des Sciences et de la Technologie Houari Boumediene (USTHB), Alger, Algérie, Email : raache_ipa@yahoo.fr

and nodular sclerosis (NS) 2 .NHL refers to a group of diverse tumors derived from cells of lymphocytic lineage.
It occurs as clonal proliferations of single cells at any stage of lymphocyte development.In children, lymphoblastic lymphoma, Burkitt lymphoma and anaplastic large-cell lymphoma predominate 3 .There is male predominance in childhood NHL, except for primary   The survival rate for five years after the treatment was 93.75%.The analysis of LDH levels of diagnosed patients against their survival rates, showed that those with higher LDH levels were exposed to early relapse of their disease.However, there was no significant correlation between LDH level before the treatment with survival rate.
Liver and kidney function tests and blood cell count in total HD and NHL patients were compared to control.The levels of albumin and hemoglobin were si-gnificantly lower in lymphoma patients compared to control (p<0.001)(Figure.4).However, the total WBC count and Erythrocyte sedimentation rate were significantly higher in lymphoma patients compared to control (p<0.001)(Figure.5).
Pearson correlation analysis of serum LDH among HL and NHL patient groups showed no correlation between serum LDH levels and biochemical or hematological parameters (Table .2).

Discussion
Among biochemical parameters, lactate dehydrogenase (LDH) represents a very valuable enzyme in patients with malignant lymphomas.The serum level has been considered as very important in the evaluation of disease extension in non-Hodgkin's lymphomas (NHL) and Hodgkin's disease (HD) 13 .
In this study, we have analazed the relation between serum LDH level, stage and response to treatment on 33 patients with HL and 32 patients with NHL.The LDH level was significantly elevated in lymphoma patients compared to control.This finding agrees with that, reported by other investigators 14,15 .This intense LDH level observed in patients during cancerous conditions may be the result of high glycolytic rate 16 .In fact, the high glycolytic rate is important for rapidly proliferating cancers not only as a major energy source but also to provide such cells with precursors for nucleotide and lipid biosynthesis 17 .
Similar to results of many previous studies 18,19 ,   30,31 .Indeed, the inflammatory response is often necessary for tumor progression, and elevated numbers of inflammatory cells, such as tumor-associated macrophages, connote poor prognosis 31 .Furthermore, lactate in the tumor cell milieu impairs the adaptive immune response, disabling immune surveillance [32][33][34][35] .
Thus, lactate also appears to promote tumorigenesis via non-tumor cell mediated effects on the inflammatory and immune responses.

Conclusion
Lactate dehydrogenase (LDH) plays an important role in tumor initiation and maintenance since its ability to function in anaerobic metabolism helps cancer cells grow even after their rapid proliferation leads to low-oxygen conditions in the tumor microenvironment.The elevated serum LDH could be used to select patients who will benefit from more intensified treatment.

Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
system.It represents the third most common cancer in children and has classically been divided into two distinct groups : Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL).HL is a common lymph node cancer of germinal center B-cell origin, which is characterized by malignant Hodgkin and Reed-Sternberg (HRS) cells mixed with a dominant background population of reactive lymphocytes and other inflammatory cells 1 .The most accepted histologic classification, the Rye classification system, defines four histologic subtypes of HL : lymphocytic predominace (LP), mixed cellularity (MC), lymphocytic depletion (LD),

Figure 5 .
Figure 5. Increased Total WBC count and ESR in patients.

Table 1 :
Clinical characteristics of lymphoma patientsThe effect of chemotherapeutic treatment on serum LDH level in HL and NHL patients is shown in figure2.As illustrated, there was a significant fall in serum LDH activity by completion of the chemotherapeutic courses in both HL and NHL groups of patients (360.85 ± 15.36 vs. relation of extent of the disease represented by stage of lymphoma to the mean serum LDH level is shown in figure3.It was observed that the higher is the stage of disease, the more serum LDH level will be.This difference was notably high among NHL groups.In fact, The

Table . 2
: Correlation between LDH, biochemical and hematological parameters Protein kinases, various hormones and growth factors have been shown to regulate LDH gene expression 20,21 .In most cases, these factors induce a shift towards A-subunit containing isoenzymes which can