Early molecular response in chronic myeloid leukemia patients predicts future response status

Abstract

Imatinib is the frontline therapy for chronic myeloid leukemia (CML) management. Most of the CML patients achieve major responses, but a proportion (nearly 25-35%) of them develop drug resistance. Molecular monitoring using quantitative real-time PCR at regular intervals according to European LeukemiaNet (ELN) helps in the assessment of long-term outcomes in imatinib-treated CML patients. Eighty-four CML patient samples (42 at diagnosis and 42 at 3-month intervals from the same patients) were analyzed for Bcr-Abl transcript levels. Quantification results revealed that the patients with <10% Bcr-Abl levels at 3 months had higher rates of complete cytogenetic response (CCyR) and optimal responses compared to patients with >10% Bcr-Abl levels (P < 0.0001). Patients with >10% Bcr-Abl levels were found to have 25.0% of suboptimal response and 3.57% of failure to imatinib at standard dose. Hence, the present study confirms that early molecular monitoring at 3 months after imatinib initiation helps in predicting the concurrent cytogenetic response and treatment optimization in CML patients.

Assessment of BCR-ABL1 Fusion Transcripts and Their Association with Response to Imatinib Treatment in Chronic Myeloid Leukemia Patients

“…Total RNA (1 μg) was reversely transcribed into complementary DNA using high-capacity reverse transcription kit (Applied Biosystems) and used for of BCR-ABL1 fusion transcript types [5,6] and expression analysis. [7] TKD mutations were analyzed in DNA using Sanger sequencing method. [8]…”

Molecular Response of Chronic Myeloid Leukaemia Patients to Tyrosine Kinase Inhibitors

“…12 Kagita et al observed their study the optimal response was 100 %, and no suboptimal response. 6 In this study it was observed that mean haemoglobin, total leukocyte count, platelet count, basophil, myelocyte were not statistically significant (p>0.05) when compared between BCR-ABL1 ≤10% (optimal) and BCR-ABL1>10 (warning) groups. However, mean typical cells was significantly higher in BCR-ABL1>10 (warning) group.…”

“…Kagita et al found, in their study, the median white cell count as 145 x 10 9 /L with range from 13.8 to 308 x l0 9 /L. 6 Marin et al found the median leukocyte count as 139.5 x 10 9 /L with range from 5.1 to 410.9 x 10 9 /L. 11 In our study the majority (46.7%) patients had platelet count ≤400 x 10 9 /L; the mean was 468.5±211.6 x 10 9 /L with range from 160.0 to 1000.0 x 10 9 /L.…”

“…Similarly, Kagita et al found their study the median age at presentation was 33 years with range 9-63 years. 6 In a study, Doval et al showed the mean age was 41 years with range from 18 to 66 years. 7 Bee et al observed in their study that the mean age was 45.5 years with range from 30.8 to 56.2 years.…”

“…10 Kagita et al showed mean Hb was 10.9 gm/dL with a range from 6.4 to 16 gm/dL. 6 Marin et al documented in their study that the median haemoglobin was 11.6 gm/dL with range from 6.99 to 16.0 gm/dL. 11 Similarly, Doval et al demonstrated the mean Hb (range grams) as 10.8 g/dl with range from 8.1 to 16.g/dl.…”