The authors have declared that no competing interests exist.
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.
LDH levels were evaluated on 65 diagnosed Algerian children and compared to healthy control.
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.
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.
Lymphoma is a group of malignancies characterized by malignant cell infiltrations of the lymphatic 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
Lactate dehydrogenase (LDH), a cytoplasmic enzyme, reversibly catalyzes the conversion of pyruvate to lactate, which is the last step of glycolysis. Even under normal oxygen concentrations in malignancies, pyruvate transformation to lactate is upregulated
In this study, serum LDH level was measured in Algerian children with lymphoma and itsrelation with clinical presentation, stage of the disease and response to therapy was investigated in patients with Hodgkin's and non-Hodgkin's lymphoma.
This study was carried out with blood samples taken from 65 children, 32 NHL and 33 HD. The mean age was 11 years, while age range between 4 and 18 years. The mean age at disease onset was 7 ranging from 1 to 12 years. Patients came from the Department of Hematology, University Hospital Center of Beni Messous, Algeria. They had already a confirmed histologic diagnosis of lymphoma. The clinical data of age, gender, stage of disease and histologic subtype were recorded. Patients were treated for 14 weeks with LBM 2001 group B protocol (Prednisone, cyclophosphamide, vincristine, MTX) for non-Hodgkin's lymphoma and ABVD protocol (Adreamycien, bleomycin, vinblastine And dacarbazine) for hodgkin's disease. The patients received, according to their stage, two or three cures. The control group consisted of 75 unrelated healthy subjects, with no chronic or autoimmune disease and no personal or family history. The mean age was 13 years (
Characteristics | Patients (n=65) | |
HL (n=33) | NHL (n=32) | |
Age (years) | ||
Mean | 11 | 11 |
Range | 18-Apr | 18-Apr |
Age at disease onset (years) | ||
Mean | 7 | 7 |
Range | 12-Jan | 13-Feb |
Gender | 72.72 | 78.12 |
Male (%) | 27.27 | 21.87 |
Female (%) | ||
Histological types | - | 37.5 |
Thoracic (%) | - | 46.87 |
Abdominal (%) | - | 15.62 |
Maxillary (%) | 54.54 | - |
Nodular sclerosis (%) | 18.18 | - |
Lymphocyte-rich (%) | 27.27 | - |
Mixed cellularity (%) | 0 | - |
Lymphocyte-depleted (%) | ||
Stage | 24.24 | 15.62 |
I (%) | 51.51 | 37.5 |
II (%) | 24.24 | 46.87 |
III (%) | 0 | 0 |
IV (%) |
Analysis of LDH concentration shows that the serum LDH level was significantly higher in untreated children with both hodgkin’s and non hodgkin’s lymphomas compared to control group (p<0.001). Furthermore, this level increased during disease growth time. When HL and NHL patients were separately studied against the control group the difference was significantly high, more remarkably in NHL patients. On the other hand, the mean serum LDH level in NHL patients was significantly higher than that of HL (646.72±51.02 vs. 557.85±44.16 , p=0.01)
The effect of chemotherapeutic treatment on serum LDH level in HL and NHL patients is shown in
The relation of extent of the disease represented by stage of lymphoma to the mean serum LDH level is shown in
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 significantly lower in lymphoma patients compared to control (p<0.001)(
Pearson correlation analysis of serum LDH among HL and NHL patient groups showed no correlation between serum LDH levels and biochemical or hematological parameters (
NHL | HL | |
PAL | 0.03 | -0.12 |
ALT | 0.09 | 0.32 |
AST | -0.04 | 0.03 |
Alb | -0.03 | 0.08 |
UA | 0.22 | 0.26 |
Urea | -0.04 | 0.22 |
Creat | -0.18 | -0.08 |
WBC | -0.08 | 0.1 |
RBC | -0.03 | -0.14 |
Hb | -0.12 | -0.03 |
Platelets | 0.35 | 0.29 |
ESR | -0.18 | -0.19 |
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)
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
Protein kinases, various hormones and growth factors have been shown to regulate LDH gene expression
In addition, the tumor cells may produce LDH enzyme to respond to the increase of lactic acid, resulting in oxidtive reductive reaction to become pyruvic acid. High LDH level describes high aggressiveness and proliferation of the tumor cells. Therefore, LDH level in NHL is a marker of cell turnover and correlated with tumor burden. Several studies showed correlation between LDH level and the result of therapy. High LDH level often provides less response to the result of therapy, often relapses, and has a potential of metastasis
Lactate efflux provokes a local inflammatory response that attracts immune cells such as macrophages, which secrete cytokines and growth factors that drive tumor cell growth and metastasis
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.
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.