Turk J Hematol: 40 (4)

Volume: 40 Issue: 4 - 2023


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RESEARCH ARTICLE
1.	Long-term Results of Imatinib Discontinuation in Patients with Chronic-phase Chronic Myeloid Leukemia: A National Multicenter Prospective Study Emine Merve Sava�, Seda Y�lmaz, Ay�e Asena Ba�er Dikyar, Z�beyde Nur �zkurt, Ramazan �cal, Ferda Can, Sezgin Pepeler, Lale Ayd�n Kaynar, Sanem G�k�en, Abdulkerim Y�ld�z, Murat Albayrak, Sema Karaku�, �zcan �eneli, M�nci Ya�c� doi: 10.4274/tjh.galenos.2023.2023.0194 Pages 236 - 241 Ama�: �matinib'in ke�fi, kronik myeloid l�semi (KML) i�in bir d�neme� olmu�tur. KML hastalar�n�n ya�am s�resi genel n�fusun ya�am s�resine yakla�t�k�a, ara�t�rmalar ya�am kalitesini art�rmaya ve ekonomik fakt�rlere odaklanm��t�r. 2010'dan sonra, baz� hastalar�n imatinib'i b�rakt�ktan sonra bile molek�ler yan�t� s�rd�rebildi�i g�sterilmi�tir. Bu ulusal �ok merkezli prospektif kohort �al��mas�, eri�kin kronik faz KML hastalar�nda imatinib tedavisinin sonland�r�lmas�n�n uzun vadeli sonu�lar�n� g�zlemlemeyi ama�lam��t�r. Gere� ve Y�ntem: Bu prospektif, randomize olmayan, �ok merkezli �al��maya d�rt farkl� merkezden 41 kronik faz KML hastas� dahil edildi. T�m hastalar�n molek�ler yan�tlar�, tek bir merkezde ger�ek zamanl� polimeraz zincir reaksiyonu kullan�larak yeniden de�erlendirildi. Tedavi kesilmesinden sonraki ortanca takip s�resi 48 ayd� (minimummaksimum 6-81 ay). Bulgular: K�rk sekizinci ayda molek�ler relapss�z sa�kal�m oran� %33,2 (g�ven aral��: 48,2-18,2) olarak hesapland�. 41 hastan�n 27�si maj�r molek�ler yan�t� kaybetti, tedaviye tekrar ba�land� ve t�m hastalarda imatinib ile derin molek�ler yan�t sa�land�. Molek�ler n�ks ile tedavi s�resi veya molek�ler yan�t�n derinli�i gibi klinik fakt�rler aras�nda ili�ki yoktu. �al��ma ile �u ana kadar toplamda yakla��k 4.392.000 T�rk liras� (TRY) veya 245.150 dolar (USD) tasarruf sa�land�. Sonu�: Kronik faz KML hastalar�nda yak�n molek�ler izlem ile tirozin kinaz inhibit�r� kesimi g�venli bir se�enektir ve �nemli ulusal ekonomik faydalar sa�lar. Bu yakla��m, t�m uygun hastalar i�in d��n�lmelidir. Bu �al��ma T�rkiye�de yap�lan ilk tirozin kinaz inhibit�r� kesilme �al��mas�d�r. Objective: The discovery of imatinib was a milestone for chronic myeloid leukemia (CML). As the life expectancy of CML patients has approached that of the general population, research has shifted towards improving quality of life and economic considerations. After 2010, it was shown that some patients could maintain molecular response even after discontinuing imatinib. This national multicenter prospective cohort study aimed to observe the long-term consequences of discontinuing imatinib therapy in adult chronicphase CML patients. Materials and Methods: We enrolled 41 CML patients from 4 different centers in this non-randomized single-arm trial. Molecular responses of all patients were re-evaluated using real-time polymerase chain reaction at a single center. The median follow-up time after imatinib discontinuation was 48 months (minimum-maximum: 6-81 months). Results: The rate of molecular relapse-free survival at 48 months was 33.2% (confidence interval: 48.2-18.2). Twenty-seven of 41 patients lost their major molecular response, treatment was started again, and deep molecular response was re-achieved with imatinib in all cases. There was no significant relationship between molecular relapse and clinical factors such as duration of treatment or molecular response status. Discontinuing imatinib resulted in savings of approximately 4,392,000 Turkish lira or 245,150 US dollars. Conclusion: Tyrosine kinase inhibitor discontinuation with close molecular monitoring is a safe option and provides important national economic benefits for chronic phase CML patients. This approach should be considered for all eligible patients. This is the first tyrosine kinase inhibitor discontinuation study from T�rkiye. Abstract \| Full Text PDF

2.	Experience of Daratumumab in Relapsed/Refractory Multiple Myeloma: A Multicenter Study from T�rkiye Atakan Tekinalp, Ayfer Ged�k, Aydan Akdeniz, Esra Terzi Demirsoy, Vildan G�rsoy, M�zeyyen Aslaner Ak, Metin Ba�c�, Sema Se�ilmi�, Fatma Keklik Karada�, Ay�e Oru� Uysal, Ali Do�an, Sinan Demircio�lu, Ha�im Atakan Erol, Ceyda Aslan, Fahir �zkalemka�, �ehmus Ertop, Mehmet Da�l�, Mehmet Sinan Dal, G�ray Saydam, Mustafa Merter, Cihan Ural, �zcan �eneli doi: 10.4274/tjh.galenos.2023.2023.0029 Pages 242 - 250 Ama�: Bu �al��man�n amac�, relaps/refrakter multipl myelom (RRMM) tan�s� ile daratumumab (DARA) kullanan hastalar�n de�erlendirilmesidir. Gere� ve Y�ntem: �al��ma, �ok merkezli ve retrospektif olarak tasarland�. 01.02.2018-15.04.2022 tarifleri aras�nda en az iki k�r DARA kullanm�� olan 134 hasta �al��maya dahil edildi. Hastalar�n epidemiyolojik, hastal�k ve tedavi ile ili�kili �zellikleri ve tedavi ili�kili yan etkileri de�erlendirildi. Sa� kal�m analizleri yap�ld�. Bulgular: DARA tedavisine ba�lama ya��n�n ortancas� 60 (35-88) olup, hastalar�n 56�s� (%41,8) kad�n ve 48�i (%58,2) erkekti. DARA tedavisine ba�lama ve takip s�relerinin ortanca de�erleri s�ras�yla 41,2 (5,1-223) ve 5,7 (2,1-24,1) ayd�. DARA tedavisi sonras� genel yan�t oran� hastalar�n 75�inde (%55,9) ve �ok iyi k�smi yan�t veya daha iyisi hastalar�n 48�inde (%35,8) g�zlendi. T�m hastalar i�in genel sa�kal�m (OS) ve progresyonsuz sa�kal�m (PFS) s�ras�yla 11,6 (7,8-15,5) ve 8,0 (5,1-10,9) ayd�. DARA ve bortezomib-deksametazon (DARA-Vd) ile tedavi g�ren hastalarda OS, DARA ve lenalidomid-deksametazon (DARA-Rd) ile tedavi g�renlere g�re daha y�ksek bulundu (s�ras�yla 16,9 ve 8,3 ay; p=0,014). DARA-Rd tedavisi g�ren hastalar aras�nda, ekstramed�ller hastal�� olmayanlarda PFS, ekstramed�ller hastal�� olanlara g�re daha y�ksekti (NA�ya kar��l�k 3,7 ay; OR: 3,4; p<0,001). �nceki tedavilerin ortanca say�s� 3 (1-8) idi. DARA tedavisine erken d�nemde ba�laman�n OS ve PFS i�in bir avantaj sa�lad��, ancak istatistiksel olarak anlaml� olmad�� g�r�ld�. �nf�zyonla ili�kili reaksiyonlar 18 (%13,4) hastada g�zlendi. T�m reaksiyonlar ilk inf�zyon s�ras�nda meydana geldi ve reaksiyonlar�n �o�u 1 veya 2. derecedeydi (%94,5). N�tropeni ve trombositopeni s�kl�� DARA-Rd grubunda daha y�ksekti (%61,9�a kar�� %24,7, p<0,001 ve %42,9�a kar�� %15,7, p<0,001). Sonu�: �al��mam�z, RRMM hastalar�nda DARA kullan�m�yla ili�kin gerek ya�am verisi niteli�ini ta��maktad�r ve DARA�n�n erken d�nemde kullan�lmas�n� destekler niteliktedir. Objective: This study aimed to evaluate patients with relapsed/ refractory multiple myeloma (RRMM) who underwent daratumumab (DARA) therapy. Materials and Methods: This multicenter retrospective study included 134 patients who underwent at least two courses of DARA from February 1, 2018, to April 15, 2022. Epidemiological, disease, and treatment characteristics of patients and treatment-related side effects were evaluated. Survival analysis was performed. Results: The median age at the start of DARA was 60 (range: 35-88), with 56 patients (41.8%) being female and 48 (58.2%) being male. The median time to initiation of DARA and the median follow-up time were 41.2 (5.1- 223) and 5.7 (2.1-24.1) months, respectively. The overall response rate after DARA therapy was 75 (55.9%), and very good partial response or better was observed in 48 (35.8%) patients. Overall survival (OS) and progressionfree survival (PFS) for all patients were 11.6 (7.8-15.5) and 8.0 (5.1-10.9) months, respectively. OS was higher for patients undergoing treatment with DARA and bortezomib-dexamethasone (DARA-Vd) compared to those undergoing treatment with DARA and lenalidomide-dexamethasone (DARA-Rd) (16.9 vs. 8.3 months; p=0.014). Among patients undergoing DARA-Rd, PFS was higher in those without extramedullary disease compared to those with extramedullary disease (not achieved vs. 3.7 months; odds ratio: 3.4; p<0.001). The median number of prior therapies was 3 (1-8). Initiation of DARA therapy in the early period provided an advantage for OS and PFS, although it was statistically insignificant. Infusion-related reactions were observed in 18 (13.4%) patients. All reactions occurred during the first infusion and most reactions were of grade 1 or 2 (94.5%). The frequency of neutropenia and thrombocytopenia was higher in the DARA-Rd group (61.9% vs. 24.7%, p<0.001 and 42.9% vs. 15.7%, p<0.001). Conclusion: Our study provides real-life data in terms of DARA therapy for patients with RRMM and supports the early initiation of DARA therapy. Abstract \| Full Text PDF

3.	Immune Thrombotic Thrombocytopenic Purpura in Elderly Patients: The Roles of PLASMIC and French Scores Mehmet Baysal, Fehmi Hindilerden, Elif G�ls�m Umit, Ahmet Muzaffer Demir, Fatma Keklik Karada�, G�ray Saydam, Seval Akp�nar, Burhan Turgut, Vildan �zkocaman, Fahir �zkalemka�, Rafiye �ift�iler, Can �zl�, Sinan Demircio�lu, Y�ld�z �pek, Reyhan Diz K��kkaya doi: 10.4274/tjh.galenos.2023.2023.0295 Pages 251 - 257 Ama�: Son y�llarda, imm�n trombotik trombositopenik purpura (iTTP) y�netiminde g�nl�k uygulamalara yeni geli�meler eklenmi�tir. �zellikle klinik skorlama sistemleri klinisyenlere klinik karar verme ve erken tan�da yard�mc� olabilir. Ancak, ya�l� hastalar genellikle daha fazla organ tutulumu ve al��lmad�k �ekillerde ba�vurabilmektedir. �leri ya��n bu klinik tahmin skorlama sistemleri �zerindeki etkisi belirsizdir. Bu ba�lamda, PLASMIC ve French skorlar�n�n 60 ya� ve �zeri hastalarda kullan�labilirli�ini de�erlendirdik. Gere� ve Y�ntem: 2014 ile 2022 y�llar� aras�nda on merkezde iTTP olas� tan�s� alan 60 ya� �st� hastalar retrospektif olarak de�erlendirildi. PLASMIC ve French skorlar�n� hesaplad�k ve verilerimizi trombotik mikroanjiyopati ile ba�vuran gen� hastalar�n tek merkezli analiziyle kar��la�t�rd�k. Bulgular: �al��mam�z 60 ya� �st� 30 hasta ve 60 ya� alt� 28 hastadan olu�an kontrol grubunu i�eriyordu. French skoru ≥1�in tan�sal duyarl�l�� ve �zg�ll�� ya�l� hastalarda kontrol grubuyla kar��la�t�r�ld��nda daha d��kt� (s�ras�yla %78,9�a kar�� %100 ve %18,2�ye kar�� %57,1). PLASMIC skoru ≥5�in tan�sal duyarl�l�� ve �zg�ll��, �al��ma grubu ve kontrol grubu i�in s�ras�yla %100�e kar�� %95 ve %27,3 ve %100 idi. �al��mam�zda ya�l� hastalarda kontrol grubuyla kar��la�t�r�ld��nda daha y�ksek �l�m oran� saptand� (%30 vs %7,1 p-de�eri =0,043). Sonu�: S�n�rl� say�da hastada (n=6) sonu�lar�m�z rit�ksimab�n mortaliteyi azaltabildi�ini g�stermektedir. Ya�l� hastalarda iTTP i�in klinik �ng�rme skorlamalar�n�n g�venilirli�inin daha az olabilece�i g�z �n�ne al�nd��nda, sonu�lar�n yorumlanmas�nda daha dikkatli olunmal�d�r. Objective: In recent years, new developments have been incorporated into daily practice in the management of immune thrombotic thrombocytopenic purpura (iTTP). In particular, clinical scoring systems could help clinicians with clinical decision-making and early recognition. However, older patients frequently present with more organ involvement and in unusual ways. The ways in which age could affect these clinical prediction scoring systems remain unclear. We evaluated the use of PLASMIC and French scores in patients over 60 years of age. Materials and Methods: We performed a retrospective crosssectional analysis of patients over 60 years of age with a presumptive diagnosis of iTTP between 2014 and 2022 at 10 centers. We calculated PLASMIC and French scores and compared our data with a singlecenter analysis of younger patients presenting with thrombotic microangiopathy. Results: Our study included 30 patients over 60 years of age and a control group of 28 patients younger than 60 years. The diagnostic sensitivity and specificity of a French score of ≥1 were lower in older patients compared to the control group (78.9% vs. 100% and 18.2% vs. 57.1%, respectively). The diagnostic sensitivity and specificity of a PLASMIC score of ≥5 were 100% vs. 95% and 27.3% vs. 100% for the study group and control group, respectively. Our study showed a higher mortality rate in older patients compared to the control group (30% vs. 7.1%, p=0.043). Conclusion: For a limited number of patients (n=6), our results showed that rituximab can reduce mortality. Given that the reliability of clinical prediction scores for iTTP in older patients may be lower, more caution must be undertaken in interpreting their results. Abstract \| Full Text PDF

4.	Comparison of Capillary Zone Electrophoresis with High-pressure Liquid Chromatography in the Evaluation of Hemoglobinopathies �zlem �ak�r Madenci, �zlem H�rmeydan, Asuman Or�un, Fatma Erdo�mu� doi: 10.4274/tjh.galenos.2023.2023.0114 Pages 258 - 265 Ama�: Hemoglobinopatilerin de�erlendirilmesinde HbA2 �l��m� a��s�ndan kapiller zone elektroforezi (CZE) ve y�ksek bas�n�l� s�v� kromatografisi (HPLC) y�ntemleri kar��la�t�r�ld�. Gere� ve Y�ntem: Hemoglobinopatisi olmayan (n=321), β-talasemi ta��y�c�s� (n=113) ve yayg�n (Hb D-Punjab, E, C, S/A, S/S) ve nadir (Hb S/D, O-Arap, Lepore, G-Coushata, Setif, Hamadan, Q-Iran ve H) varyantlar� (n=21) olan hastalarda CZE ile HPLC kar��la�t�r�ld�. HbA2 i�in referans aral�� CZE taraf�ndan belirlendi. Bulgular: Hemoglobinopatisi olmayan hastalarda HPLC ve CZE ile medyan (2,5-97,5 persentil) de�erleri HbA i�in s�ras�yla %97,4 (97,0-98,0) ve %97,5 (96,6-98,4) (p=0,060), HbA2 i�in %2,4 (1,6-3,0) ve %2,5 (1,6-3,1) bulundu (p<0,001). HbA2 i�in referans aral�� CZE ile %1,6-3,1 idi. HbA2 i�in y�ntem kar��la�t�rma �al��mas�nda sabit hata 0,255 (CI; 0,062-0,448) ve Bias %0,10 (LOA; 0,33-0,53) bulundu ve CZE ile daha y�ksek sonu�lar elde edildi. Y�ntemler aras�nda g��l� bir korelasyon elde edildi (r=0,782). Klinik tan� a��s�ndan iki y�ntem m�kemmel uyum g�sterdi (κ=0.911). Her iki y�ntem de ortak varyantlar� tespit etti ve benzer �ekilde tan�mlad�. HPLC ile HbH ve CZE ile HbS/D d��ndaki t�m nadir varyantlar, her iki y�ntemle de ayr� pikler olarak saptand�. Sonu�: β-talasemi hastalar�n�n �n tan�mlamas�nda her iki y�ntem de uyum i�indeydi. Her iki y�ntemle farkl� Hb varyantlar� saptand�, ancak HbA2 �l��mlerinde olas� bir metodolojik etkile�im s�z konusuydu. CZE, hemoglobinopatilerin de�erlendirilmesi i�in g�venilir ve basit bir alternatiftir. Rutin laboratuvar prati�inde fazla say�da teknik mevcut oldu�undan, HbA2 �l��m�n�n standardizasyonuna �ncelik verilmelidir. Objective: The capillary zone electrophoresis (CZE) and highperformance liquid chromatography (HPLC) methods were compared in terms of HbA2 measurement for the assessment of hemoglobinopathies. Materials and Methods: CZE was compared with HPLC for the evaluation of patients without hemoglobinopathy (n=321), with β-thalassemia trait (n=113), and with common (HbD-Punjab, E, C, S/A, and S/S) and rare (HbS/D, O-Arap, Lepore, G-Coushata, Setif, Hamadan, Q-Iran, and H) variants (n=21). The reference range for HbA2 was determined by CZE. Results: Among patients without hemoglobinopathy, the median (2.5th-97.5th percentiles) values were 97.4% (97.0-98.0%) and 97.5% (96.6-98.4%) for HbA (p=0.060) and 2.4% (1.6-3.0%) and 2.5% (1.6-3.1%) for HbA2 (p<0.001) by HPLC and CZE, respectively. The reference range for HbA2 was 1.6-3.1% by CZE. In the comparison of methods for HbA2, there was a constant error of 0.255 (confidence interval: 0.062-0.448) and bias of 0.10% (limit of agreement: 0.33- 0.53), and higher values were obtained with CZE. A strong correlation was observed between the methods (r=0.782). Interrater agreement was almost perfect for clinical diagnosis (κ=0.911). The two methods detected and identified the common variants similarly. All rare variants, except HbH by HPLC and HbS/D by CZE, were detected as separate peaks by both methods. Conclusion: The two methods were in agreement regarding the preliminary identification of β-thalassemia patients. Different Hb variants were detected by both methods but with possible methodological interference for HbA2 measurements. CZE is a reliable and simple alternative for the evaluation of hemoglobinopathies. The standardization of HbA2 measurements should be prioritized as more techniques become available in routine laboratory practice. Abstract \| Full Text PDF

PERSPECTIVE IN HEMATOLOGY
5.	Change in Polycythemia Vera Treatment: Ropeginterferon Alfa-2b in Light of Current Trials Heinz Gisslinger doi: 10.4274/tjh.galenos.2023.2023.0419 Pages 266 - 268 Ropeginterferon alfa-2b (RopegIFN), polisitemia vera (PV) hastal��nda etkili bir sitored�ksiyon sa�lar. Son analizler, uzun vadeli RopegIFN tedavisinin, PV'li hastalar� i�in �nemli olan tedavi hedeflerini kar��lad��n� g�stermektedir. Bu hedefler aras�nda iyi bir ya�am kalitesi, hastal��n ilerlemesinin yava�lat�lmas� ve uzun s�reli olaydan ba��ms�z sa�kal�m bulunmaktad�r. Veriler, RopegIFN�nin erken d�nem PV tedavisi ile ikinci basamak tedavi ve sonras�nda kullan�m�n� desteklemektedir. Ropeginterferon alfa-2b (RopegIFN) enables effective cytoreduction in polycythemia vera (PV). Recent analyses suggest that long-term RopegIFN therapy fulfills treatment goals important to patients with PV including good quality of life, the slowing of disease progression, and long event-free survival. Data support the use of RopegIFN in both early PV therapy and second-line and beyond. Abstract \| Full Text PDF

IMAGES IN HEMATOLOGY
6.	Epithelial Cells in a Peripheral Blood Smear Phebe Enni Lee, Gloria Yuquan Chen, Eng Soo Yap doi: 10.4274/tjh.galenos.2023.2023.0268 Pages 269 - 270 Abstract \| Full Text PDF

7.	Erythrophagocytosis by Blasts and Numerous Cytoplasmic Granules in a Child with De Novo T-lymphoblastic Leukemia Fang Long, Wenwen Song, Xue Li, Li Li, Ting Li, Yun Zhang doi: 10.4274/tjh.galenos.2023.2023.0242 Pages 271 - 272 Abstract \| Full Text PDF

8.	Round Promyelocyte Cells with Round Nuclei: Clues to the Diagnosis of ZBTB16-RARA Acute Promyelocytic Leukemia Yang Su, Jiwei Zhao, Xiaoming Fan, Wei Yang, Jinlin Liu doi: 10.4274/tjh.galenos.2023.2023.0181 Pages 273 - 274 Abstract \| Full Text PDF

LETTER TO EDITOR
9.	ChatGPT as a Way to Enhance Parents� Communication in Cases of Oncological Pediatric Diseases Filipe Prazeres doi: 10.4274/tjh.galenos.2023.2023.0326 Pages 275 - 277 Abstract \| Full Text PDF

10.	Diagnostic Accuracy of Serum Galactomannan Assay in Children with Acute Myeloid Leukemia: Effect of the Revised EORTC/ MSGERC 2020 Criteria G�lhadiye Avcu, Nihal Karada�, �ebnem �nen G�ktepe, Dilek Ye�im Metin, Deniz Y�lmaz Karap�nar doi: 10.4274/tjh.galenos.2023.2023.0285 Pages 278 - 280 Abstract \| Full Text PDF

11.	Clinical and Biological Characteristics of 14 Adult Cases of NUP98-NSD1+ Acute Myeloid Leukemia Yan-jun Sun, Wei Wang, Shen-qi Lu, Li-rong Li doi: 10.4274/tjh.galenos.2023.2023.0340 Pages 281 - 283 Abstract \| Full Text PDF

12.	Effect and Safety of Orelabrutinib and Lenalidomide Plus R-mini CDOP in Relapsed/Refractory Aggressive B-cell Non-Hodgkin Lymphoma Ying Shang, Hongyu Zhao, Daqi Li doi: 10.4274/tjh.galenos.2023.2023.0263 Pages 284 - 285 Abstract \| Full Text PDF

13.	Genetic Analysis of Prekallikrein Deficiency in a Consanguineously Married Chinese Family Yuan Chen, Meina Liu, Mingshan Wang, Huilin Chen, Bile Chen doi: 10.4274/tjh.galenos.2023.2023.0351 Pages 286 - 287 Abstract \| Full Text PDF

14.	A Turkish Patient with Aceruloplasminemia Found to Have a Novel Pathogenic Variant Presenting with High Ferritin Level and Microcytic Anemia Hande �zkalayc�, Meral Uluk�yl� Meng��, Naz G�leray Lafc�, Ay�eg�l �zt�rk Kaymak doi: 10.4274/tjh.galenos.2023.2023.0270 Pages 288 - 290 Abstract \| Full Text PDF

INDEX
15.	Author Index Pages E1 - E4 Abstract \| Full Text PDF

16.	Subject Index Pages E5 - E14 Abstract \| Full Text PDF

17.	Advisory Board of This Issue Page E15 Abstract \| Full Text PDF

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