Does Previous Interferon Use Have Negative Effect on Imatinib Response in Chronic Myeloid Leukemia (CML)? A Single Center Study.
Authors: Yenerel Mustafa , Diz-Kucukkaya Reyhan , Demirel Naciye , Ayer Mesut , Yavuz Selim , Besisik Sevgi , Aktan Melih , Nalcaci Meliha , Sargin Deniz , Atamer Tanju , Pekcelen Yuksel , Dincol Guncag 
Published: April 2020

Aim: Effectiveness of imatinib in CML was evaluated on a cohort of 104 patients with a median 29 months of observation time, recruited between 3/2002 and 2/2006.

Patients and methods: 104 patients diagnosed as having CML between 1990–2006 were included in this study. Their median age was 44 years (19–77) and 55% of patients were male. Imatinib was used in a dose of 400mg/day for chronic phase and 600mg/day for accelerated and blastic phase. In chronic phase patients with no cytogenetic response in 1 year and in accelerated or blastic phase patients with no hematologic response in 3 months, doses were increased to 600mg/day and 800 mg/day respectively. Interferon (IFN) treatment had been used as α-IFN 5 MIU/m2 daily combined with or without monthly courses of cytosine arabinoside (Ara-C) 20 mg/m2 for 10 days in 50 patients before imatinib. Cytogenetic response (CR) was monitored on bone marrow metaphases collected at baseline, 3, 6, 9 and 12 months during the first year, and every 6 months thereafter. CR was quantified by 20 metaphases Ph in bone marrow: 0% as complete (CCR), 1–35% major as (MjCR) and &gt; 95% as imatinib failure. Molecular response followed by PCR in bone marrow samples. We stratified the patients according to previous IFN treatment in two groups. CML patients who were treated with imatinib as a first line therapy were analyzed as Group I. Other patients who were treated initially with IFN and ara-C and those were switched to imatinib because of intolerance or unresponsiveness were accepted as Group II.

Results: Age, sex distribution and disease phases of both groups were quite similar. Therapy responses are summarized in Table 1. Hematological response (HR) was seen in 90,4 % of the patients (94/104) in median 54 days (11–149) for Group I and 41 days (15–193) for Group II. There wasn’t any difference according to the time elapsed for HR (p=0,79). Cytogenetic data were interesting in our patients. As a total result, CR were achieved in 77,8 % of the patients in median 5,1 months (84 days– 2,7 years). CR rate was significantly higher in Group I (p=0.019). When we compared two groups according to early cytogenetic response in first 6 months, Group I had also much better results (p=0.049). CCR were achieved 35,6 % of the patients (37/104) and there wasn’t any difference between the groups (p=0,25). Molecular response was achieved in 19,2% of the patients followed by PCR (19/87) and there was no significant difference (p=0,15). We conclude that imatinib is highly effective as a first line agent in CML patients. Advanced disease age probably is the most important factor for the lower response rates in the second group. But, the role of previous IFN therapy should also be questioned. As a summary, imatinib should be used in every CML patient without any delay in order to get higher and sooner CR.

Tablo 1. Imatinib response of the 104 patients with CML. HR (p=0.89) CR (p=0.019) MjCR in 6 months(p=0.049) CCR(p=0.25) Mol. Response(p=0,15) Imatinibfailure (p=0.03) Imatinib Follow-up Group I 90,7% (49/54) 77,8% (42/54) 57,4% (31/54) 40,7% (22/54) 30% (12/40) 22,2% (12/54) 22,1 months (3,7 months -3,5 yrs) Group II 88% (44/50) 56% (28/50) 38% (19/50) 30% (15/50) 17% (8/47) 40% (20/50) 3 years (9months-5,1 yrs)