Akut myeloid lösemili çocuk hastaların tedavileri ve prognozlarının değerlendirilmesi
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Dosyalar
Tarih
2019
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
AMAÇ: Akut myeloid lösemi (AML), kemik iliğinde myeloid serideki matürasyon defekti sebebiyle anormal lösemik blastik hücrelerinin birikimi ve normal kan hücrelerinin yapımının bozulmasıyla karakterize hematopoetik dokunun klonal heterojen hastalığıdır. AML çocuklarda önemli mortalite ve morbiditesi olmaktadır, hastaların standart bir protokole bağlı tedavi almalarına rağmen gelişen komplikasyonlar ve hastalar arası prognoz farklı seyretmektedir. Bunun sebebi çeşitli genetik ve çevresel faktörler olarak düşünülmektedir. Çalışmamızdaki amaç, akut myeloid lösemi tanısı alan çocuk hastalarda demografik özellikleri, genetik mutasyonların varlığı, enfeksiyon nitelikleri ve sıklığı, kardiyovasküler komplikasyonlar ve diğer komplikasyonların hastaların prognozları üzerine etkisini araştırmak. GEREÇ VE YÖNTEM: Çalışmamız geriye dönük olarak tasarlandı. Çalışmaya 2004 – 2018 yılları arasında Ege Üniversitesi Tıp Fakültesi Çocuk Hematoloji Bilim Dalında Akut Myeloid Lösemi tanısı alan 62 hasta çalışmaya alındı. Olguların yaş, tanı alma tarihleri, doğum tarihleri, cinsiyet, FAB sınıflandırılması, kardiyovasküler komplikasyonları, tedaviye başlama zamanı, kemoterapi protokolleri, relaps oranları, kemik iliği transplantasyon oranları, moleküler ve sitogenetik sonuçları değerlendirilmiştir. BULGULAR: Çalışmaya Akut Myeloid Lösemi tanısı alan 57 hasta dahil edildi. Olgularımızın cinsiyetler arası dağılımı %52.6'sı kız ve %47.4'ü erkek hasta saptandı. Çalışmaya dahil edilen en küçük hasta 1 yaşındayken, en büyük hasta 17 yaşında idi. Olguların ortalama tanı yaşı 10±5.49 saptandı, ortanca değer ise 9 idi. Ortalama yaş; kadın olgularda 15.83±6.19, erkek olgularda 13.74±5.86 saptandı. Hastaların ortalama beyaz küre sayısı 49023±72693/mm3 olup ortanca değer 18530/mm3 saptandı. Tanı anında beyaz küre sayısı 100.000/mm3'ün üzerinde olan 11 hasta vardı. Hastaların ortalama hemoglobin konsantrasyonu 7.96±1.64 g/dl olup ortanca değer 7.9 g/dl idi. Hemoglobin <7.0g/dl'nin altında olan 11 hasta mevcuttu. Hastaların ortalama trombosit sayısı 62896±53112/mm3 olup ortanca trombosit değeri 51700/mm3 saptandı. Hastaların trombosit <20.000/mm3'ün altında 10 hasta bulundu. Değerlendirilen 57 hastanın ortalama kemik iliği blast oranı ortalama %60,89±29.34 idi. En küçük değer %30 en büyük değer %100, ortanca değer %64 idi. En sık alt grup 19 hasta (%33.3) ile AML M2 idi. Bu grubu 17 hasta ile AML M7 (%28.1) ve 12 hasta (%21.1) ile AML M4/5 izlemekte idi. Kliniğimizde 57 hastadan 6'sında (%10.5) santral sinir sistemi tutulumu mevcuttu. Başvuru sırasında 4 hastada SSS dışı ekstramedüller tutulum vardı. Kemik iliğinin sitogenetik ve moleküler genetik açıdan incelenmesi 57 hastanın hepsinde yapılmıştır. Tanıda %52.6 (n=30) oranındaki hasta grubunda AML'ye özgü herhangi bir özel translokasyon saptanmadı. Hastaların %26.3'ünde (n=15) iyi prognostik özellik gösteren translokasyonlar, orta prognozlu translokasyonlar %5.4 (n=3), % 21.1'inde (n=12) ise kötü prognostik özelliğe sahip translokasyonlar gösterildi. Çalışma grubundaki 57 hastanın 5'ine (%8.8) AML BFM 98 protokolü, 18'ine (%31.6) AML BFM 2004 protokolü ve 34'üne (%59.6) AML BFM 2013 protokolü uygulanmıştı. Akut myeloid lösemili olguların 20 tanesi (% 35.1) 15. günde remisyona, 12 tanesi (%21.1) 28. günde, 5 tanesi (8.8) 33. günde ve 7 tanesi (%12.3) 58. günde remisyona girmiştir. Tanı alan 57 hastadan 2 hasta remisyona giremedi. Akut myeloid lösemi tanılı 57 hastadan 23'ünde (%40.4) relaps görüldü, bu hastaların relaps zamanları tanı anından itibaren ortalama 8.8±5.2 aydı. Kemik iliği transplantasyonu 57 hastadan 19 olguya (%33.3) allojenik ve 1 hastaya otolog KİT uygulanmıştır. SONUÇ: AML BFM 2013 protokolünde izlenen hastaların sağ kalımları daha önce kullanılan protokoller ile karşılaştırıldığında anlamlı olarak yüksek bulunmuştur. Kemoterapi protokolünün risk gruplarını belirleyen genetik faktörlerin tam olarak değerlendirilebilmesi sonuçların iyileşmesinde etkili olmuştur. Ancak sağ kalım halen beklenenin altında kalmıştır. Hasta sağ kalımda en olumsuz etki %40.4 oranı ile relaps hastalıktır. Relaps gelişiminde en önemli faktör uygun veriye ulaşım konusundaki sorunlardır. Kemoterapi sonrasında transplantasyon gerektiren hastaların uygun zamanın transplantasyona gidebilmesi durumunda relapsların azalması ve sağ kalımın iyileşmesi mümkün olabilecektir.
AİM: Acute myeloid leukemia (AML) is a clonal heterogeneous disease of hematopoietic tissue characterized by the accumulation of abnormal leukemic blastic cells and disruption of normal blood cell production due to a maturation defect in the myeloid series in the bone marrow. Acute myeloid leukemia has significant mortality and morbidity in children, although complications and inter-patient prognosis are different, although patients receive treatment based on a standard protocol. This is thought to be due to various genetic and environmental factors. The aim of this study was to investigate the demographic characteristics, presence of genetic mutations, infectious characteristics and frequency, cardiovascular complications and other complications on the prognosis of children with acute myeloid leukemia. Material and Methods: Our study was designed retrospectively. The study included 62 patients diagnosed with acute myeloid leukemia in the Department of Pediatric Hematology, Ege University School of Medicine between 2004 and 2018. Age, diagnosis date, birth date, sex, FAB classification, cardiovascular complications, time to start treatment, chemotherapy protocols, relapse rates, bone marrow transplantation rates, molecular and cytogenetic results were evaluated. Results: Fifty seven patients with acute myeloid leukemia were included in the study. The gender distribution of our cases was 52.6% female and 47.4% male. The youngest patient was 1 year old and the oldest patient was 17 years old. The mean age at diagnosis was 10 ± 5.49, and the median age was 9 years. Average age; 15.83 ± 6.19 in female patients and 13.74 ± 5.86 in male patients. The mean white blood cell count of the patients was 49023 ± 72693/mm3 and the median value was 18530/mm3. There were 11 patients with a white blood cell count of more than 100,000/mm3 at the time of diagnosis. The mean hemoglobin concentration of the patients was 7.96 ± 1.64 g/dl and the median value was 7.9 g/dl. There were 11 patients with hemoglobin <7.0 g/dl. The mean platelet count of the patients was 62896 ± 53112/mm3 and the median platelet count was 51700/mm3. Ten patients were found to have platelets <20,000/mm3. The mean bone marrow blast rate of the 57 patients evaluated was 60.89 ± 29.34%. The minimum value was 30%, the maximum value was 100%, and the median value was 64%. The most common subgroup was AML M2 with 19 patients (33.3%). This group was followed by AML M7 (28.1%) with 17 patients and AML M4 with 12 patients (21.1%). In our clinic, 6 (10.5%) of 57 patients had central nervous system involvement. At admission, 4 patients had extramedullary involvement without CNS. Cytogenetic and molecular genetic examination of bone marrow was performed in all 57 patients. No specific translocation specific to AML was detected in the 52.6% (n = 30) patient group. In 26.3% (n = 15) of the patients, translocations with good prognostic characteristics, translocations with moderate prognosis were seen in 5.4% (n = 3), and in 21.1% (n = 12) translocations with poor prognostic characteristics were shown. Of the 57 patients in the study group, 5 (8.8%) AML BFM 98 protocol, 18 (31.6%) AML BFM 2004 protocol and 34 (59.6%) AML BFM 2013 protocol were applied. 20 (35.1%) of the patients with acute myeloid leukemia had remission on the 15th day, 12 (21.1%) on the 28th day, 5 (8.8) on the 33rd day and 7 (12.3%) on the 58th day. Of 57 patients diagnosed, 2 patients could not enter remission. Of 57 patients diagnosed with acute myeloid leukemia, 23 (40.4%) had relapse, with a mean of 8.8 ± 5.2 months from the time of diagnosis. Bone marrow transplantation Allogeneic HSCT was applied in 19 patients (33.3%) from 57 patients and autologous in 1 patient. Conclusion: The survival rates of the patients followed in the AML BFM 2013 protocol were significantly higher compared to the previously used protocols. The complete evaluation of the genetic factors determining the risk groups of the chemotherapy protocol was effective in improving the results. However, survival still remains below expectations. The most negative effect on patient survival is relapse with a rate of 40.4%. The most important factor in the development of relapse is the problem of access to appropriate data. If the patients who require transplantation after chemotherapy can go to transplantation at the appropriate time, relapses will decrease and survival will be improved.
AİM: Acute myeloid leukemia (AML) is a clonal heterogeneous disease of hematopoietic tissue characterized by the accumulation of abnormal leukemic blastic cells and disruption of normal blood cell production due to a maturation defect in the myeloid series in the bone marrow. Acute myeloid leukemia has significant mortality and morbidity in children, although complications and inter-patient prognosis are different, although patients receive treatment based on a standard protocol. This is thought to be due to various genetic and environmental factors. The aim of this study was to investigate the demographic characteristics, presence of genetic mutations, infectious characteristics and frequency, cardiovascular complications and other complications on the prognosis of children with acute myeloid leukemia. Material and Methods: Our study was designed retrospectively. The study included 62 patients diagnosed with acute myeloid leukemia in the Department of Pediatric Hematology, Ege University School of Medicine between 2004 and 2018. Age, diagnosis date, birth date, sex, FAB classification, cardiovascular complications, time to start treatment, chemotherapy protocols, relapse rates, bone marrow transplantation rates, molecular and cytogenetic results were evaluated. Results: Fifty seven patients with acute myeloid leukemia were included in the study. The gender distribution of our cases was 52.6% female and 47.4% male. The youngest patient was 1 year old and the oldest patient was 17 years old. The mean age at diagnosis was 10 ± 5.49, and the median age was 9 years. Average age; 15.83 ± 6.19 in female patients and 13.74 ± 5.86 in male patients. The mean white blood cell count of the patients was 49023 ± 72693/mm3 and the median value was 18530/mm3. There were 11 patients with a white blood cell count of more than 100,000/mm3 at the time of diagnosis. The mean hemoglobin concentration of the patients was 7.96 ± 1.64 g/dl and the median value was 7.9 g/dl. There were 11 patients with hemoglobin <7.0 g/dl. The mean platelet count of the patients was 62896 ± 53112/mm3 and the median platelet count was 51700/mm3. Ten patients were found to have platelets <20,000/mm3. The mean bone marrow blast rate of the 57 patients evaluated was 60.89 ± 29.34%. The minimum value was 30%, the maximum value was 100%, and the median value was 64%. The most common subgroup was AML M2 with 19 patients (33.3%). This group was followed by AML M7 (28.1%) with 17 patients and AML M4 with 12 patients (21.1%). In our clinic, 6 (10.5%) of 57 patients had central nervous system involvement. At admission, 4 patients had extramedullary involvement without CNS. Cytogenetic and molecular genetic examination of bone marrow was performed in all 57 patients. No specific translocation specific to AML was detected in the 52.6% (n = 30) patient group. In 26.3% (n = 15) of the patients, translocations with good prognostic characteristics, translocations with moderate prognosis were seen in 5.4% (n = 3), and in 21.1% (n = 12) translocations with poor prognostic characteristics were shown. Of the 57 patients in the study group, 5 (8.8%) AML BFM 98 protocol, 18 (31.6%) AML BFM 2004 protocol and 34 (59.6%) AML BFM 2013 protocol were applied. 20 (35.1%) of the patients with acute myeloid leukemia had remission on the 15th day, 12 (21.1%) on the 28th day, 5 (8.8) on the 33rd day and 7 (12.3%) on the 58th day. Of 57 patients diagnosed, 2 patients could not enter remission. Of 57 patients diagnosed with acute myeloid leukemia, 23 (40.4%) had relapse, with a mean of 8.8 ± 5.2 months from the time of diagnosis. Bone marrow transplantation Allogeneic HSCT was applied in 19 patients (33.3%) from 57 patients and autologous in 1 patient. Conclusion: The survival rates of the patients followed in the AML BFM 2013 protocol were significantly higher compared to the previously used protocols. The complete evaluation of the genetic factors determining the risk groups of the chemotherapy protocol was effective in improving the results. However, survival still remains below expectations. The most negative effect on patient survival is relapse with a rate of 40.4%. The most important factor in the development of relapse is the problem of access to appropriate data. If the patients who require transplantation after chemotherapy can go to transplantation at the appropriate time, relapses will decrease and survival will be improved.
Açıklama
Anahtar Kelimeler
Akut Myeloid Lösemi, Çocuk, Relaps, Kemik İliği Nakli, Acute Myeloid Leukemia, Relapse, Bone Marrow Transplantation
