İmatinib mesilat tedavisi altında olan kronik miyeloid lösemili hastalarda plazma imatinib konsantrasyonu ile sitogenetik remisyon arasındaki ilişkinin araştırılması
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Date
2010
Authors
Kaçan, Turgut
Journal Title
Journal ISSN
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Publisher
Uludağ Üniversitesi
Abstract
Kronik miyeloid lösemi (KML); Philadelphia (Ph) kromozomu olarak adlandırılan, 9 ve 22. kromozomlar arasında oluşan translokasyon t(9;22)(q34;q11) ve BCR-ABL ek geninin varlığı ile karakterize malign hematopoietik kök hücre hastalığıdır. İmatinib hızlı, tam oral biyoyararlanım ve dozun orantılı olarak dağılması gibi önemli farmakokinetik-farmakodinamik özelliklere sahiptir. İmatinibin KML tedavisine girmesi ile yeni bir milad oluşmuştur. Ancak imatinibin etkileyici sonuçlarına rağmen, başarısız olduğu veya yeterince başarılı olamadığı hasta grubu da mevcuttur.Bu özellikler nedeni ile çalışmamızda Uludağ Üniversitesi Tıp Fakültesi İç Hastalıkları Anabilim Dalı Hematoloji Bilim Dalı'nda takip edilen ve imatinib tedavisi altında olan kronik faz KML hastalarda plasma imatinib düzeyi ile sitogenetik remisyon arasındaki ilişkinin değerlendirmesi amaçlandı. Bu çalışmaya halen takip ve tedavi altında olan 58 kronik faz KML olgusu alındı. Olguların 35'i (%60.3) 400 mg/gün, 17'si (%29.3) 600 mg/gün ve 6'sı (%10.3) 800 mg/gün dozunda imatinib kullanmaktaydı. Toplam 58 olgunun 54'ünde (%93.1) tam sitogenetik yanıtın olduğu (TSY), 4 olguda ise (%6.9) tam sitogenetik yanıtın olmadığı saptandı. Hastaların 30'unda (%51.7) major moleküler yanıt (MMY) saptanırken, kalan 28 hastada (%48.3) MMY'ın olmadığı belirlendi. Ortalama imatinib plazma düzeyi 2381.53 ng/ml olarak tespit edildi. İstatistiksel yönden fark olmamakla birlikte, erkek olguların imatinib plazma düzeyi, kadınların plazma imatinib düzeyinden daha yüksek olarak belirlendi. TSY'ı olan hastaların ortalama imatinib plazma düzeyi 2417.66 ng/ml ve TSY'ı olmayan hastalar da ise ortalama düzey 1893.75 ng/ml olarak saptandı.Çalışmamızda; imatinib plazma düzeyinin gelişen tedavi yanıtında önemli olabileceği, ancak yalnız başına etkili faktör olmadığı, olağan şartlarda imatinib plazma düzeyinin ölçülmesinin bir faydası olmadığı, imatinib plazma düzey tetkikinin ferdileştirilmesi gerektiği, hematolojik veya sitogenetik yanıtsızlık gelişmesi durumunda nedenler araştırılırken imatinib plazma düzeyi tetkikinin de uygun olacağı sonuçları ortaya çıkmıştır.
Chronic myeloid leukemia (CML) is a malignant hematopoietic stem cell disorder that is characterized by the Philadelphia (Ph) chromosome caused by t (9; 22) (q34; q11) which results in fusion of BCR and ABL genes. Imatinib has favorable pharmacokinetic-pharmacodynamic characteristics, including rapid and complete oral bioavailability (98%) and a proportional dose-exposure relationship. Treatment of CML with imatinib has been a new revolution. Despite the impressive results of imatinib, however, have failed or was not successful enough group of patients is also available.Because of these properties, we aimed to determine the relationship between the cytogenetic remisson and plasma imatinib levels of patients with chronic phase CML who were treated with imatinib mesilat, applied to outpatient clinic of Uludag University Medical Faculty Internal Medicine Department Hematology Division. 58 patients with chronic phase CML who were still under follow-up and treated were included in this study. 35 of the patients (60.3%) 400 mg/day, 17 patients (29.3%) 600 mg/day, 6 patients (10.3%) 800 mg/day dose imatinib were used. 54 of 58 cases (%93.1) have complete cytogenetic response (CCR), while in 4 (6.9%) cases have not. Major molecular response (MMR) was determined in the 30 of the patients, the remaining 28 patients (48.3) were determined thay there is no MMR. The average plasma levels of imatinib was 2381.53 ng/ml. Despite the lack of statistical difference imatinib plasma levels of male patients were higher than womens. The average plasma levels of the patiens with CCR were determined as 2417.66 ng/ml and the patiens with no CCR were determined as 1893.75 ng/ml.In our study; It ıs suggested that imatinib plasma levels may be important in developing response to the treatment, but not alone and measuring imatinib plasma levels is not benefical in normal conditions, imatinib plasma level study should individually an also imatinib plasma level study should be advisable for investigating the causes in case of hematologic or cytogenetic unresponsiveness.
Chronic myeloid leukemia (CML) is a malignant hematopoietic stem cell disorder that is characterized by the Philadelphia (Ph) chromosome caused by t (9; 22) (q34; q11) which results in fusion of BCR and ABL genes. Imatinib has favorable pharmacokinetic-pharmacodynamic characteristics, including rapid and complete oral bioavailability (98%) and a proportional dose-exposure relationship. Treatment of CML with imatinib has been a new revolution. Despite the impressive results of imatinib, however, have failed or was not successful enough group of patients is also available.Because of these properties, we aimed to determine the relationship between the cytogenetic remisson and plasma imatinib levels of patients with chronic phase CML who were treated with imatinib mesilat, applied to outpatient clinic of Uludag University Medical Faculty Internal Medicine Department Hematology Division. 58 patients with chronic phase CML who were still under follow-up and treated were included in this study. 35 of the patients (60.3%) 400 mg/day, 17 patients (29.3%) 600 mg/day, 6 patients (10.3%) 800 mg/day dose imatinib were used. 54 of 58 cases (%93.1) have complete cytogenetic response (CCR), while in 4 (6.9%) cases have not. Major molecular response (MMR) was determined in the 30 of the patients, the remaining 28 patients (48.3) were determined thay there is no MMR. The average plasma levels of imatinib was 2381.53 ng/ml. Despite the lack of statistical difference imatinib plasma levels of male patients were higher than womens. The average plasma levels of the patiens with CCR were determined as 2417.66 ng/ml and the patiens with no CCR were determined as 1893.75 ng/ml.In our study; It ıs suggested that imatinib plasma levels may be important in developing response to the treatment, but not alone and measuring imatinib plasma levels is not benefical in normal conditions, imatinib plasma level study should individually an also imatinib plasma level study should be advisable for investigating the causes in case of hematologic or cytogenetic unresponsiveness.
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Keywords
Kronik miyeloid lösemi (KML), Plazma imatinib düzeyi, Sitogenetik remisyon, Chronic myeloid leukemia (CML), Plasma imatinib level, Cytogenetic remisson
Citation
Kaçan, T. (2010). İmatinib mesilat tedavisi altında olan kronik miyeloid lösemili hastalarda plazma imatinib konsantrasyonu ile sitogenetik remisyon arasındaki ilişkinin araştırılması. Yayınlanmamış uzmanlık tezi. Uludağ Üniversitesi Tıp Fakültesi.