Publication details
Využití vyšetření chemorezistence MTT testem u chronické B-lymfatické leukémie (B-CLL)
| Title in English | The use of MTT chemosensitivity/chemoresistance testing in B-CLL (chronic lymphocytic leukaemia) to individualise the patients cancer treatment. |
|---|---|
| Authors | |
| Year of publication | 2006 |
| Type | Article in Proceedings |
| Conference | II. Dny diagnostické, prediktivní a experimentální onkologie |
| MU Faculty or unit | |
| Citation | |
| Field | Oncology and hematology |
| Keywords | chemoresistance; chemosensitivity; in vitro testing; chronic lymfocytic leukemia |
| Description | Introduction: B-CLL is disease with a comparatively low malignity, which can, however, have a very variable course. Traditional prognostic systems (Rais or Binets classifications, chromosomal aberrations, mutation status of IgVH, ZAP-70, CD38), do not predict the chemosensitivity of the disease to the individual cytostatitics and corticosteroids. Because of the character of B-CLL and the patients characteristics (age, frequent intercurrences, previous treatments) a dilemma often occurs whether to start the therapy and which regimen is to be chosen from a variety of cytostatics with a high risk of complications and side effects. Methods and Results: To establish the proper treatment in justified cases, chemosensitivity/chemoresistance of the malignant B-cell population could be tested using in-vitro MTT-test (MTT, 3-4.5-dimethylasole-2-yl-2.5-diphenyl-tetrazolium). Two of presented cases will be given as a model example: Case 1: Man, born in 1940, in whom B-CLL was identified as clinical stage-I in 1994. In September 2005, another significant progression occurred and series 1st of chemotherapy in the CHOP regimen was started, the laboratory values being: leukocytes 203x109/l, lymphocytes 156x109/l. Before the series 2nd no signs of regression could be observed and the values being: leukocytes 214.9x109/l, lymphocytes 163.7x109/l. Therefore, peripheral blood was taken to examine the chemoresistance of leukocytic fraction of cells by the MTT-test. The test result proved the chemosensitivity only to fludarabine (EC50=0.31ug/ml, i.e the concentration in which 50% cancer cells survive; Cmax/%SC=20/0% - maximal tested concentration/%-surviving cells), a partial sensitivity to vincristine, etoposide and a resistance to prednisolone (EC50>0.2424ug/ml, Cmax/%SC=242.4/85.4%), dexamethasone (EC50=0.503ug/ml; Cmax/%SC=5/16.4%), daunorubicine (EC50>2ug/ml; Cmax/%SC=2/63.2%) and others. Based on these results, the chemotherapy was changed to fludarabine-monotherapy. The fludarabine series 1st resulted in the decrease of leukocytosis by 50%. After the series 3rd, the leukocytes value was 11.27x109/l, chemotherapy was interrupted and its effect persists. Case 2: Woman, born in 1922, in whom B-CLL was identified as a clinical stage-IV in 1992. Until 2003 the patient underwent treatment by 8 chemotherapy regimens and chemotherapy was always accompanied with complications and short stabilisation of the disease. Thanks to her good PS, the patient was proposed to undergo chemotherapy in the VAD regimen. Before the chemotherapy was started, the MTT-test was performed. The result proved an exceptional sensitivity of leukocytes to dexamethasone (EC50<0.0002ug/ml; Cmax/%SC=6/22.9%), a partial sensitivity to daunorubicine (EC50=0.02ug/ml; Cmax/%SC=2/5.26%) and fludarabine (EC50=0.521ug/ml; Cmax/%SC=20/10%) and a resistance to prednisolone (EC50=0.024ug/ml; Cmax/%SC=242.4/14.8%) and other cytostatics. Based on these results, the treatment regimen was changed for dexamethasone-monotherapy, which was started in November 2004. The first series of hormonal therapy caused a decrease of leukocytosis from 214.2x109/l to 53.73x109/l and this state persisted until March 2006. During all the treatment, the patient did not have any undesirable side effects; her physical condition and activity by the Kamofski index exceeded 80%. Unfortunately, the patient died in March 2006 as a result of dehydration associated with an acute campylobacterial enteritis. Conclusion: B-CLL represents a malignant disease which is easily accessible for laboratory analyses. Therefore, in justified cases, in vitro testing of chemoresistance/chemosensitivity can be successfully used to individualise the patients cancer treatment. |