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BRIEF REPORTDOI: 10.4274/tjh.galenos.2019.2019.0154Turk J Hematol 2020;37:116-120The Impact of Early Versus Late Platelet and Neutrophil Recoveryafter Induction Chemotherapy on Survival Outcomes of Patientswith Acute Myeloid LeukemiaAkut Myeloid Lösemili Hastalarda İndüksiyon Kemoterapisi Sonrası Erken ve Geç Trombositve Nötrofil İyileşmesinin EtkileriRafiye Çiftçiler¹, İbrahim C. Haznedaroğlu¹, Nilgün Sayınalp 1 , Osman Özcebe 1 , Salih Aksu 1 , Haluk Demiroğlu 1 ,Hakan Göker 1 , Ümit Yavuz Malkan 2 , Yahya Büyükaşık 11Hacettepe University Faculty of Medicine, Department of Hematology, Ankara, Turkey2Dışkapı Training and Research Hospital, Department of Hematology, Ankara, TurkeyAbstractObjective: The prognosis of patients with acute myeloid leukemia(AML) is affected by factors that are both patient- and diseasespecific.The aim of this study is to evaluate the impact of early versuslate platelet and neutrophil recovery after induction chemotherapyon survival outcomes of AML patients.Materials and Methods: A total of 181 patients with AML who weretreated in our tertiary center between 2001 and 2018 were evaluated.Neutrophil and platelet recovery times were accepted as the periodsfrom the beginning of induction chemotherapy to a neutrophilcount of ≥0.5x10 9 /L and a platelet count of ≥20x10 9 /L 3 days in arow, respectively. The median time to platelet recovery was 25 days(range=12-52) for all patients. Therefore, platelet recovery in thefirst 25 days was defined as early platelet recovery (EPR) and at ≥26days it was defined as late platelet recovery (LPR). The median timeto neutrophil recovery was 28 days (range=13-51) for all patients.Therefore, neutrophil recovery in the first 28 days was defined as earlyneutrophil recovery, and at ≥29 days it was defined as late neutrophilrecovery.Results: The 5-year overall survival (OS) rates for patients who hadEPR and LPR after induction chemotherapy were 62% and 23%,respectively (p<0.001). The 5-year disease-free survival (DFS) rates forpatients who had EPR and LPR after induction chemotherapy were57% and 15%, respectively (p<0.001).Conclusion: Short bone marrow recovery time may indicate betterhealthy hematopoiesis and marrow capacity associated with longerOS and DFS.Keywords: Acute myeloid leukemia, Platelet recovery, NeutrophilrecoveryÖzAmaç: Akut myeloid lösemili (AML) hastaların prognozu, hem hastayahem de hastalığa özgü faktörlerden etkilenmektedir. Bu çalışmanınamacı, indüksiyon kemoterapisi sonrası erken ve geç trombosit venötrofil iyileşmesinin akut myeloid lösemi hastalarının sağkalımsonuçları üzerindeki etkisini değerlendirmektir.Gereç ve Yöntemler: 2001-2018 yılları arasında üçüncü basamaksağlık merkezimizde tedavi edilen 181 AML hastası çalışmaya alındı.Nötrofil ve trombosit iyileşme süreleri, indüksiyon kemoterapisininbaşlangıcından itibaren sırasıyla 3 gün süreyle nötrofil sayısının0,5×10 9 /L’ye ve trombosit sayısının 20×10 9 /L’ye ulaşması olarak kabuledildi. Trombosit iyileşmesinin ortalama süresi tüm hastalar için 25gündü (12-52). Bu nedenle, ilk 25 günde trombosit iyileşmesi erkentrombosit iyileşmesi ve ≥26 gün geç trombosit iyileşmesi olaraktanımlandı. Nötrofil iyileşmesine kadar geçen ortalama süre tümhastalar için 28 gündür (13-51). Bu nedenle, ilk 28 günde nötrofiliyileşmesi erken nötrofil iyileşmesi ve ≥29 gün geç nötrofil iyileşmesiolarak tanımlandı.Bulgular: İndüksiyon kemoterapisi sonrası erken ve geç trombositiyileşmesi olan hastalar için 5 yıllık genel sağkalım sırasıyla %62 ve%23 olarak saptandı (p<0,001). İndüksiyon kemoterapisi sonrasıerken ve geç trombosit iyileşmesi olan hastalar için 5 yıllık hastalıksızsağkalım sırasıyla %57 ve %15 saptandı (p<0,001).Sonuç: Sonuç olarak, kısa kemik iliği iyileşme süresi, daha uzun genelve hastalıksız sağkalım ile ilişkili daha sağlıklı bir hematopoez/kemikiliği kapasitesini gösterebilir.Anahtar Sözcükler: Akut myeloid lösemi, Nötrofil iyileşmesi,Trombosit iyileşmesi©Copyright 2020 by Turkish Society of HematologyTurkish Journal of Hematology, Published by Galenos Publishing HouseAddress for Correspondence/Yazışma Adresi: Rafiye Çiftçiler, M.D., Hacettepe University Faculty of Medicine,Department of Hematology, Ankara, TurkeyPhone : +90 505 583 17 98E-mail : rafiyesarigul@gmail.com ORCID: orcid.org/0000-0001-5687-8531Received/Geliş tarihi: April 9, 2019Accepted/Kabul tarihi: September 2, 2019116
Turk J Hematol 2020;37:116-120Çiftçiler R, et al: The Impact of Early Versus Late Platelet and Neutrophil RecoveryIntroductionThe clinical outcome of patients with acute myeloid leukemia(AML) varies across a wide spectrum, ranging from survival ofa few days to remission. Therefore, the prediction of outcomeis vital for those patients [1]. Prognosis of patients with AMLis affected by factors that are both patient- and diseasespecific.The most significant disease-specific prognosticfactors at the time of diagnosis of AML are cytogenetics andmolecular abnormalities [2]. On the other hand, the mostimportant patient-specific prognostic factor is age at diagnosis[3]. Estimating resistance to treatment in patients with AMLis extremely important for critical therapeutic decisions andfollow-up of the patient [4]. Very limited data are availableregarding the association between AML prognosis and bonemarrow recovery kinetics following induction chemotherapy[5,6,7]. The aim of this study was to evaluate the impact of earlyversus late platelet and neutrophil recovery after inductionchemotherapy on the survival outcomes of AML patients.Materials and MethodsStudy Design and Data CollectionThis study was performed in a retrospective manner. All clinicaldata were collected from hospital medical records. As a result ofthe application standards of the hospitals of Hacettepe MedicalSchool, it has been recognized from the patient records that allof the studied patients had given informed consent at the time ofhospitalization and before the administration of chemotherapyand other relevant diagnostic/therapeutic standards of care.Patient and Disease CharacteristicsNeutrophil recovery time (NRT) and platelet recovery time (PRT)were accepted as the periods from the beginning of inductionchemotherapy to a neutrophil count of ≥0.5x10 9 /L 3 daysin a row and a platelet count of ≥20×10 9 /L 3 days in a row(without transfusion support), respectively. The median time toplatelet recovery was 25 days (range=12-52) for all patients.Therefore, platelet recovery in the first 25 days was defined asearly platelet recovery (EPR) and at ≥26 days it was definedas late platelet recovery (LPR). The median time to neutrophilrecovery was 28 days (range=13-51) for all patients. Therefore,neutrophil recovery in the first 28 days was defined as earlyneutrophil recovery (ENR) and at ≥29 days it was defined as lateneutrophil recovery (LNR).In this study, patient inclusion criteria were as follows: age>18 years at the time of diagnosis, patients who receivedfirst induction chemotherapy, and achievement of completeremission after induction chemotherapy. Patients with refractoryAML and patients who were diagnosed with acute promyelocyticleukemia were not included in this study. All patients includedin the study received idarubicin (12 mg/m 2 IV push on each ofthe first 3 days of treatment) and Ara-C (100 mg/m 2 daily as acontinuous infusion for 7 days) as induction chemotherapy [8].Statistical AnalysesStatistical analyses were performed using SPSS 25 (IBM Corp.,Armonk, NY, USA). The variables were investigated usingvisual (histograms, probability plots) and analytical methods(Kolmogorov-Smirnov/Shapiro-Wilk tests) to determinewhether they were normally distributed or not. Statisticalcomparisons were made using chi-square tests for categoricaldata. The Student t-test for two independent samples was usedfor comparison of continuous numerical data. Survival analyseswere made using Kaplan-Meier tests. Multivariate analysis ofpredictors of survival was performed using the Cox regressiontest. Parameters with p≤0.10 in univariate tests were includedin the multivariate analysis, while p<0.05 was considered toindicate statistical significance.ResultsPatients’ CharacteristicsA total of 450 AML patients admitted to our hospital between2001 and 2018 were screened for this study. Patients withrefractory AML, patients who did not achieve completeremission after the first induction chemotherapy, and patientswho died during induction chemotherapy were not includedin the study. Patient characteristics are summarized in Table 1.There were 106 (57.9%) males and 77 (42.1%) females with amedian age of 44 (range=18-69) years at diagnosis. Karyotypeanalyses were available for 159 patients: 6 patients (3.7%) werein the favorable-risk group, 101 (63.5%) patients were in theintermediate-risk group, and 54 (33.9%) patients were in theadverse-risk group according to the European LeukemiaNetclassification [9]. The number of patients classified as havingEastern Cooperative Oncology Group performance status (ECOGPS) 0, 1, 2, and 3 were 4 (2.2%), 87 (48.1%), 78 (43.1%), and12 (6.6%), respectively [10]. According to periods, LPR was seenin fewer patients between 2011 and 2018 than in 2001-2010(p=0.01). Preexisting myelodysplastic syndrome or secondaryAML was seen more in patients with LPR than in patients withEPR (p=0.02).There were no statistically significant differences betweenthe two groups in terms of median age (p=0.10), sex (p=0.18),cytogenetic risk group (p=0.77), and ECOG PS (p=0.06). Mortality(66.3% vs. 30.4%, p<0.001) and relapse rate (47.2% vs. 29.3%p=0.01) were higher in patients who had LPR than EPR afterinduction chemotherapy. Nonrelapse mortality rate (NMR) washigher in patients who had LPR than EPR (28.1% vs. 9.8%,p=0.001). Major causes of NRM were infections (20 vs. 8), heartattack (3 vs. 0), acute renal failure (1 vs. 0), and graft-versushostdisease (1 vs. 0) in LPR and EPR patients, respectively.117
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