Immunophenoty ping of childhood non-hodgkin lymphowa in Iraq

number: 
531
إنجليزية
Degree: 
Imprint: 
Medicine
Author: 
Abdul-Razak H. Ahmed
Supervisor: 
Dr. Nidhal Abdul-Muhymen
Dr. Al-Nassir Ibrahim J.
year: 
2001
Abstract:

Forty-eight child with Non-Hodgkin's Lymphomas (31 small non-cleaved cell malignant lymphoma (SNCL), 7 lymphoblastic malignant lymphoma (LB), 5 Large cell malignant lymphoma (LC) (one diffuse large, one -anaplastic large cell lymphoma and three immunoblastic malignant lymphoma), and 5 diffuse mixed cells malignant lympnoma (MC)), their diagnosis based on clinical and histopathological examination and forty-eight age & sex-matched, apparently healthy controls were included in this prospective study. Blood samples and biopsies were taken from patients and only blood sample was taken from control group. Investigations including Complete Blood Picture, Erythrocytes Sedimentation Rate, and serological tests including auto-antibodies, rheumatic factors detection, total serum protein, serum albumin, serum globulin, serum calcium, serum uric acid and viral serologjy (EBV, HBV, HCV, HSV, measles, Rubella and CMV) were done for patients and control group. Specific and non-specific, cell mediated and humoral mediated immune response were assessed by studying the production and functional assessment of the complements and immunoglobulins, and by enumeration and functional assessment of lymphocytes and neutrophils of all patients and controls. Prognostic evaluation by detection of soluble sCD30, sCD44, sB2MG and serum LDH in patients sera were done. The results of patient and control groups were compared and statistically studied for any significant differences. NHL were Classified according to their cell of origin, and evaluation of prognostic features like: the proliferative activity (using Ki-67) and ability to metastasized (using CD44-homing receptor) by immunostaining of 33 paraffin-embedded tissue sections, and in-vitro prediction of tumor response to chemotherapy were done. The studied sample comprises l8 boys and 20 girls, there was no significant difference regarding the incidence between sexes. The mean age was (7.67±0.82) years for all patients. The mean age of SNCL was (5.67 ± 0.6) was significantly lower than the mean age of other patient groups and also lower than that of such group in previous studies, this indicates that the SNCL occurs at an early age. The mean body weight of patient groups was significantly lower than that of the controls. Patients were referred from all parts of Iraq with a significant number (47.91%) of them were from the southern provinces where the depleted Uranium was used intensively at that area diirmg the 1991 aggression. Most (91.66%) of the patients were presented with extra-nodal disease and (89.58%) of the patients were presented with advanced stages (III&IV) at the time of diagnosis, the disease have a rapid and aggressive course with poor response to chemotherapy. Twenty seven percent of the patients were died with a mean survival of (5 months). Death was due to unavailability of important chemotherapy as a result of embargo, failure to response to available chemotherapy, involvement of CNS and/or bone marrow, infections, surgery and tumor lysis. Most of the patients have abnormal N/L ratio, high ESR, mild eosinophilia with hypo-proteinaemia, decreased calcium level and increased serum uric acid level and highly association with positive EBV serology. Specific and non-specific, cell mediated and humoral mediated immune response were assessed and when compared to that of the controls revealed a significant decrease of C3 and hemolytic activity (CH50) of alternative and classical pathways, while the C4 level was found to be within normal range. Immunoglobulins assessment revealed a multi-phasic results with numerous Ig disorders. There was no significant difference in the percent of neutrophile between patient and control groups and slightly impaired neutrophil functions was noticed in NHL patients. Assessment of peripheral bloojd lymphocyte sub-population reveal a marked reduction of CD3+ and CD4+ subsets of lymphocyte and there was no significant difference between patient and control groups in CD 19+ and CD56+ lymphocytes, although CD56 was found to be higher in patients. While CD8+ cells was significantly higher in patient groups. In addition, impaired lymphocyte response to poly-clonal mitogens in term of MI, BI and MTT-assay values was noticed. Immunostaining of thirty-three tissue sections, revealed that 29 (87.87%) patient were B-cell malignant lymphoma,' 3 (9.1 %) were T-cell malignant lymphoma and one (3.03 %) patient was Ki-positive anaplastic large cell lymphoma. Prognostic evaluation of the proliferative activity (using Ki-67) and ability to metastasized (using CD44-homing receptor) by immunostaining of 33 paraffin-embedded tissue sections, revealed that 20 (60.6%) were strongly, 10 (30.3%) were moderately and 3 (9.1%) were weakly stained with Ki-67. Twenty-six (78.78%) were positive and 7 (21.22%) were negatively stained withCD44. While, prognostic evaluation by detection of soluble sCD30, sCD44, sB2MG and serum LDH in patients sera, revealed 25 (52.1%), 27 (56.25%), 25 (52.1%) and 38 (79.2%) of the patients have elevated serum level respectively. In-vitro prediction of tumor response to chemotherapy (cyclo-1 phosjpHamide, adriamycin) alone or in combination with S2-complex or verapamil was studied by MTT-assay and cytogenetic analysis, revealed that adriamycine gave a significantly higher cytotoxicity when compared with other cytotoxic drugs, S2-complex has no cytoioxic activity and when combined with adriamycine gave a comparable result to that of combination of adriamycine with verapamil.