CML and Imatinib Mesylate: Response Related to Karyotype.
Authors: Rubio-Martinez Araceli , Recasens Valle , Odero Maria D. , Rubio-Felix Daniel , Calasanz Maria J. , Mayayo Pilar , Giralt Manuel , Giraldo Pilar 
Published: April 2020

Background: Imatinib mesylate (STI571), as a specific inhibitor for tyrosine kinase product of oncoprotein Bcr/Abl. Efficacy of Imatinib is questioned when other cytogenetics abnormalities associated to t(9;22) are present. We describe our experience in CML patients treated with Imatinib in one centre, evaluating hematological (HR) and cytogenetic response (CR) related to kariotype.

Patients and methods: 28 patients diagnosed as having CML, 1990–2005, Imatinib 400–800 mg/d, were stratified according to cytogenetic abnormalities: Group A: t(9;22) typical in 19 patients, Group B: patients with t(9;22) and different genomic rearrangement associated: 9. At diagnosis were classified in stages Kantarjian score and the cytogenetic study (kariotype, % metaphases Ph, FISH and PCR/RT-PCR in bone marrow (BM) and peripheral blood (PB)). HR was evaluated monthly and CR in BM every 3–6 months. In patient with complete cytogenetic response (CCR) we performed follow-up in PB by RT-PCR every 3 months and a cytogenetic study in BM once a year. Cytogenetic response (CR) was quantified by n° metaphases Ph in BM: 0% CCR, 1–35% partial (PCR), 36–95% minor (MCR) and &gt; 95% failure (F). Molecular response (MR): normal kariotype (Bcr/Abl negative and RT-PCR&lt;5 copies). Statistical analysis: Chi-cuadrado and Kaplan-Meier survival test.

Results: 18 M /10 F (2 died by blast crisis), mean age 50 (range 30–72), Kantarjian score: A group (4: 2pts, 3: 5pts, 2: 5pts, 1: 7 pts). Mean time on therapy: 26.46 m (1–51 ). Previous therapy: α-interferon 7, α-interferon/pegilated 1, α-interferon/α-interferon+citarabine 3, α-interferon+citarabine 6. Imatinib as first line: 11. When Imatinib started: accelerated phase 3, chronic phase 23 and chronic phase post-blast crisis2. The results of therapy are in table I. We have not observed statistically significant differences (s.s.d) in MR (p=.577) and in OS (p=.581) between group A and B with the same doses. Two patients that had started therapy with Imatinib 800 mg/day (group A) reached MR three months later. In group B one patient 12 months after got MR surprisingly developed a ALL Ph’, he received chemotherapy plus Imatinib 800 mg/day and 6 months later he is in CCR.

Conclusions: Three months after Imatinib therapy HR was 100% in both groups. One year undergoing therapy CR response was higher in A group (81% vs 50%). Nevertheless the n° of MR obtained in patients with complex karyotypes receiving Imatinib 400 mg/day has been high (33.3%) and without s.s.d.with those with classical translocation.

Hematological and Cytogenetic response to Imatinib Months N.E.P. A Group (19) N.E.P. B Group (9) 1 19 HR : 100% 9 HR :78% 3 10 HR:100%. CR 7 (70%): 4CCR(2MR), 2PRC, 1MRC, 3F. 3 HR: 100%. CR 2 (67%): 2MCR, 1F 6 16 HR: 94%. CR: 12 (75%), 7CCR (3MR), 3PRC, 2MCR, 4F 6 HR: 86%. CR 4 (67%): 3CCR, 1MCR, 2F 12 16 HR: 94%. CR 13 (81%): 11CCR (6MR), 2PRC, 3 F 4 HR: 100%. CR 2 (50%): 2CCR (1MR), 2F 18 13 HR: 100%. CR 12 (92%): 10CCR (6MR), 2PRC, 1F 5 HR: 80%. CR 3(60%): 3CCR (2 MR), 2F 24 13 HR: 93%. CR 12 (92%): 10CCR (7MR), 2PRC, 1F 6 HR: 83%. CR : 4 (67%): 3CCR (3 MR*), 1PRC, 2F 36 4 HR: 100%. CR 3 (75%): 2CCR (1MR), 1PRC, 1F 5 HR: 60%. CR 2 (40%): 2CCR (2MR), 3F 48 2 HR: 100%. CR 1 (50%): 1 PRC,1F 0 MR:N 10 (52,6%). Mean time : 12 m (3–24 m). Imatinib : 488,88 mg/d, Months in MR : mean 15.8 (9–21m) 3 (33.3%). Mean time : 18 months (12–26 m). Imatinib : 400 mg/day. Months in MR : mean 18 (12–26 m)