Evaluation of Clinical & Haematological Response of Chronic Myeloid Leukemia Patients to Glivec Therapy in Sudan

Abstract

Background: In the last 20 years Chronic Myeloid Leukemia became one of the predominant cancer in men and women in Sudan, based on referral data from the Radiation & Isotopes Centre of Khartoum (RICK), the only cancer centre in Sudan. The genetic studies are the building blocks of the future and the development of Glivec provides a dramatic example of how the understanding of disease biology and genetic abnormality can lead to successful molecularly targeted treatments. In this study the effectiveness of the drug among Sudanese patients, individual response of patients and factors influencing the prognosis were examined in order to gain more insight on the use of Glivec in Sudan as first line treatment of CML. Design : A descriptive‐retrospective demographic & cross‐sectional study. Setting: In Radiation and Isotopes Centre of Khartoum (RICK), Khartoum, Sudan. Objectives: The overall aim of this study is to evaluate the effectiveness of Glivec treatment in Sudanese patients with CML based on haematologic and clinical remission. iv Materials and methods: The study covered CML (438pts) who took the drug since 2003, was conducted during the period from June 2007 to March 2008. 185 patient were selected randomly and subdivided into 2 groups according to response of therapy, namely to responders and non responders or deceased patients. CBC, bone marrow examination, PCR, renal and liver functions were assessed in all patients. Responders were sub‐divided into groups according to duration of therapy: 3 months, 6 months, 1 year, 2 years, 3 years and 4 years. Results: • The mean age of all patients was 53years with (46%) Females and (54%) Males. • Prognosis of CML patients who took the drug was impressive in that out of 438 only 51(11.8%) relapsed or died throughout the period of the study since 2003, while 308 (70.3%) were regularly taking treatment and coming to follow‐up. • An incidental diagnosis was made in 22 of the patients (15.8%), out of whom 12 patients (54.5%) were females. • The mean duration of illness and symptoms before diagnosis was 14 months, ranging from 1 ‐ 24months. • The most common symptoms were fatigue seen in 101 patients (72.6%) and fever in 56 patients (40%). Extramedullary involvement occurred in the form of splenomegaly in 79 patients (56.8%); hepatomegaly in 29 patients (20.8%) and lymphadenopathy in 4 patients (2.8%). • The median WBC of patients at initiation of therapy with Glivec was 193x109, Median Hb 10.3 g/dl, and median platelet count was 430x109. • Complete haematological and clinical response was reported in (86%) of patients and was achieved within 3 – 6 months from the start of therapy. • Glivec in general was well tolerated, only 37.4% experienced side‐effects • Out of 438 patients 30 patients (6.8%) died with resistance to drug; 11 patients of them (36.3%) due to primary resistance, 19 patients of them (63.3%) due to secondary resistance. • The type of encoded protein (210 or 190) and interruption of treatment are suggested as factors which can have an impact on survival of CML patients since (40%) of the deceased patients took the drug interruptedly and (54.5%) were 190 +ve patients. • Reticulin fibrosis was strongly associated with several poor prognostic features of the disease including huge splenomegaly, basophilia, anaemia and thrombocytosis. Conclusion: Although the results obtained with Glivec to date are truly impressive, longer follow‐up is necessary to draw definitive conclusions and to establish whether prevention or delay of blast crisis can be achieved, and whether an improved over‐all survival for the majority of patients can be obtained. Also, to help us pave the way for additional molecular targeted therapies and strategies in leukemia.