Extracorporeal photopheresis in the treatment of acute and chronic graft-versus-host disease: A position statement from the Turkish Society of Apheresis (TSA)

Graft versus host disease (GVHD) is still the most important cause of mortality and morbidity after allogeneic stem cell transplantation. Though perfect response rates are not achieved, steroids are still the first-line treat-ment. In the face of the presence of the drugs approved by FDA in recent years for acute and chronic GVHD as second-line therapy in the steroid-refractory group, there exists no standard approach. Extracorporeal photopheresis (ECP) with an immunomodulatory effect, is favored in the treatment of both acute and chronic steroid refractory GVHD as it does not increase the risk of relapses or infections. Having a low profile of side effects, ECP is also generally well-tolerated by patients. Being a time requiring procedure, the fact is that it is not able to be practiced in all health centers and requires central venous catheters in patients unfit for venous access may be enumerated among its shortcomings. No complete standard is available with respect to ECP application frequency-time; it varies from one center to another. The Turkish Society of Apheresis established the Turkish ECP (TECP) group and sought some answers to the questions regarding the use of ECP in the treatment of GVHD, and issued a position statement

SINGLE CENTER EXPERIENCE: IDA-FLAG TREATMENT IN PATIENTS WITH RELAPS / REFRACTORY ACUTE LEUKEMIA AND LYMPHOBLASTIC LYMPHOMA

Amaç: Primer refrakter ve/veya relaps akut lösemi olgularının yönetimi son derece zorolup sınırlı sayıda tedavi seçenekleri vardır ve bu hastalarda tam remisyon oranı düşükve remisyon süreleri çok kısadır. İda-FLAG rejimi erişkin relaps, refrakter vesekonder Akut Myeloblastik Lösemi, yüksek riskli Myelodisplastik Sendrom verelaps/refrakter Akut Lenfoblastik Lösemi olgularında yaygın olarak kullanılmakta vebu hastalarda ikincil remisyon için iyi bir seçenek olarak kabul edilmektedir.Gereç ve yöntem: Bu yazıda, merkezimizde İda-FLAG kemoterapisi uygulanan, yaşortalaması 43,5 (21-61) olan 13 relaps ve/veya refrakter akut lösemi ve 1 B hücrelilenfoblastik lenfomalı 14 hastanın sonuçları retrospektif olarak değerlendirilmiştir.Bulgular: Hastalardan 11'i ex olmuş (%78,6) 3 hastada (%21,4) ise komplet remisyonsağlanmıştır. Hastaların mortalite nedenleri incelendiğinde; 7 hasta sepsis, 2 hastahastalık progresyonu, 1 hasta kanama ve 1 hastada Tip I solunum yetmezliği nedeni ileex olmuştur. Bizim çalışmamızda en sık yan etki enfeksiyon olup, 10 hastada (%71)Grade III-IV olmak üzere hastaların tümünde enfeksiyon gelişmiştir.Sonuç: Bizim sonuçlarımız literatür verileri ile karşılaştırıldığında hastalarımızdakomplet remisyon oranı düşük, toksisite profili ise daha yüksek olarak bulunmuştur.Bu sonuçlarla Relaps/Refrakter Akut Lösemi olgularında ikincil remisyon indüksiyonuamacı ile kullanılan İda-FLAG rejiminin iyi bir seçenek olmadığıdüşünülmüştür.Objective: Management of primary refractory and/or relapsed patients with acutelymphoid and myeloid leukemias is difficult. Treatment options are limited andresponse rates and duration are not satisfactory. Ida-FLAG regimen is generallyaccepted as a good therapeutic option in adult patients with relapsed and/or refractoryleukemias in order to obtain remission.Material and method: In this paper, we have analyzed 13 patients with relapsedand/or refractory acute leukemia and one patient with B-cell lymphoblastic lymphoma who were treated with Ida-FLAG regimen retrospectively. Median age of the patientswas 43.5 year (min. 21 and max. 61).Results: Three patients had complete hematological remission (21.4%). Eleven of thepatients died (78.6%). Mortality reasons were sepsis in 7, disease progression in 2,severe disseminated bleeding in 1 and type one respiratory insufficiency in 1. The mostfrequent side effect of the regimen was grade lll-lV infections in 10 (71%) patients.Conclusion: Regarding both our results and data complete remission rate was verylow and toxicity was very high with Ida-FLAG regimen. These results indicate that Ida-FLAG is not a favorable regimen in this group of patients and there is a great need forimproving new treatment options

GENERAL CLINICAL EVALUATION OF THE CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS

Amaç: Çalışmamızda 2000-2011 yılları arasında Dokuz Eylül Üniversitesi Tıp FakültesiHematoloj Bilim Dalı tarafından takip edilen 114 hastanın demografik verileri, tedaviendikasyonları, tedavi yanıtları ve total sağ kalım analizlerinin yapılması amaçlandı.Yöntemler: Kronik lenfoblastik lösemi tanısıyla takip edilen 114 hastanın verilerigeriye dönük olarak değerlendirildi.Bulgular: Hastaların 60'ı erkek (%52,6), 54'ü kadındı (%47,4). Ortanca yaş 64 olaraksaptandı. 61 hasta tedavisiz izlenirken 53 hasta tedavi aldı. Tanıdan ilk tedaviye kadargeçen süre ortalama 15,57 ay idi. İlk sıra kemoterapide en sık klorambusil kullanıldı(%62). Hastaların ilk sıra kemoterapi sonrası yapılan değerlendirmelerinde 40 hastadakısmi yanıt, 5 tam yanıt, 7 stabil hastalık ve 1 hastada progresyon izlendi veprogresyonsuz sağ kalım ortalaması 18 ay olarak bulundu. 25 hasta ikinci sırakemoterapi aldı. İkinci sıra kemoterapinin progresyonsuz sağ kalım ortalaması 6,23 ayolarak hesaplandı. 6 hastaya üçüncü sıra kemoterapi verildi ve üçüncü sıra kemoterapininprogresyonsuz sağ kalım ortalaması 5,5 ay idi. Çalışma sonunda 114hastanın ortalama toplam sağ kalım süreleri 92,8 ay olarak hesaplandı. Rai ve Binetevresi yüksek olan hastalarda tedavisiz sağ kalım ve progresyonsuz sağ kalımsürelerinin kısaldığı görüldü (p<0,05). Çalışma süresinde 14 hasta hastalık ilişkilinedenlerle 9 hasta hastalık dışı nedenlerle hayatını kaybetti.Sonuç: Hastalarımızın demografik özellikleri diğer çalışmalarla benzer iken tedavi alanhastalarda toplam sağ kalım süresinin daha kısa olmasının nedeni gelişmiş prognostikbelirteçlerin merkezimizde kullanılmaması, ilk sıra tedavilerde monoklonalantikorların yer almaması ve yetersiz hasta uyumu olabilir. Objectıve: Demographic features, treatment endications, responds to treatment of 114chronic lymphocytic leukemia patients observed in years of 2000-2011 on hematologydepartment of Dokuz Eylül University Medical Faculty have been analyzed in ourstudy.Methods: Features of 114 CLL patients were evaluated retrospectively.Results: In 60 patients were male (%52.6), 54 patients were female(%47.4). The medianage was 64. While 61 patients were being observed without treatment, 53 patients were under medical treatment. The therapy free survival was 15.57 months. Chlorambucilwas the most prefered drug on the first line therapy (%62). In the evaluation first linechemotherapy; partial remission for 40, complete remission for 5, stable disease for 7,progression for 1 patient was observed.Progression free survival was 18 months. 25patients have second line therapy. The progression free survival of the second linetherapy was 6.23 months. The third line therapy was given to 6 patients, theprogression free survival of the third line therapy was 5,5 months. At the end of thestudy overall survival was 92.8 months. For the patients whose Rai and Binet stage ishigh, therapy free survival and progression free survival 1 time is shorter (p<0.05).During the study deaths of the 14 patients were related to the CLL and 9 patientsrelated to another reasons.Conclusıon: Demographic features of patients are similar to other studies. Causes ofshorter survival time in therapy group may be related to lack of using modernprognostic markers in our center, lack of using monoclonal antibodies on the first linetherapy and poor patient adaptation to treatmen

MULTİPLE MYELOMLU HASTADA GELİŞEN MALİGN PLEVRAL EFFÜZYON

Malign plevral effüzyon, multiple myelomda progresyonla karekterize ve geç gelişenbir komplikasyondur. Tanıdan sonra ortalama yaşam süresi 4 aydır ve sistemikkemoterapilere oldukça dirençlidir. Biz bu makalede 49 yaşında tanıdan 4 ay sonramalign plevral effüzyon gelişen ve solunum yetmezliği nedeniyle kaybedilen birhastayı sunuyoruz.Malign pleural effusion is a late and rare complication of multiple myeloma revealingthe progression. The mean survival time is four months after the diagnosis with a poorresponse to systemic chemotherapy.In this paper we mentioned about a 49 year old multiple myeloma patient in her fourthmonth of the diagnosis with a formation of malign pleural effusion just after inductionchemotherapy and died because of respiratory failure

SINGLE CENTER EXPERIENCE: RETROSPECTIVE ANALYSIS OF FOLLICULER LYMPHOMA

Amaç: Folliküler lenfoma, ikinci en sık görülen lenfoma türü olup, bütün non hodgkinlenfomaların %20-25'ini, yavaş seyirli (indolen) lenfomaların ise %70'ini oluşturur.Ortalama yaşam beklentisi yaklaşık 10 yıldır. Fakat beklenen yaşam süresi monoklonalantikorların keşfi ile uzamıştır.Yöntemler: Bu çalışmada, folliküler lenfomalı 28 hastanın klinikopatolojik özellikleri,tedavi modaliteleri ve yanıt oranları retrospektif olarak değerlendirilmiştir.Bulgular: Hastaların %39,3'ünde B semptomları ve %35,7'sinde kemik iliği tutulumumevcuttu. FLIPI skorlarına göre hastaların %37,5'i düşük, %21,4'ü orta ve %39,3'ü iseyüksek risk grubundaydı. Hastaların %32,1'i hastalığın erken evrelerinde idi.Hastaların %46,4'inde evre 1 ve %14,3'ünde evre 3 patolojik hastalık mevcuttu. %78,6hasta kemoterapi almıştı ve en çok kullanılan rejim de CVP (%53,6) idi. %14,3 hastadaradyoterapi uygulanmış ve hastaların %7,1' i tedavisiz izlenmişti. 9 hastada rituksimabilk sırada kullanılmış, 5 hastada ise ilk nükste kemoterapi ile birlikte uygulanmıştı. İlksıra kemoterapi sonrası; toplam remisyon oranı %74 olmakla birlikte hastaların%46,4'ünde tam yanıt, %25'inde ise kısmi yanıt gözlendi. Ortanca izlem süresi 32,8 ay(5-101 ay) ve ortanca hastalıksız sağ kalım 22,5 aydı (1-67 ay).Sonuç: Çalışmamızın sonuçları doğrultusunda, folliküler lenfomada başlangıçtedavisinde rituksimablı kemoterapi rejimleri ve remisyon sağlanan olgularda idamerituksimab tedavisinin akılcı bir hasta yönetimi olduğunu düşünmekteyiz. Objectıve: Follicular lymphoma is the second most common lymphoma comprising20-25% of all non hodgkin lymphomas and 70% of low grade lymphomas.Mediansurvival is around 10 years but survival rates were improved since the discovery ofmonoclonal antibodies.Methods: In this study, the clinicopathological features, the treatment modalities andthe response rates of 28 patients with follicular lymphoma were retrospectivelyanalyzed.Results: 39.3% of patients had b symptoms and the bone marrow involvement rate was35.7%. FLIPI scores; 35.7% of patients were in low risk group, 21.4% were in intermedi ate risk group and 39.3% were in high risk group. 32.1% of patiens were in early stagesof disease. 46.4% of patients had grade 1 and 14.3% had grade 3 pathologicdisease.78.6% of patients were treated with chemotherapy and the leading regimenwas CVP (53.6%) 14.3% of patients were treated with radiotherapy and 7.1% of patientswere followed without treatment.9 patients had rituximab as a firstline therapy and 5patients had rituximab after first relapse with adjunct to the chemotherapy. 4 patientshad rituximab as a maintanence therapy after remission. After firstline chemotherapy,with a total remission rate of 71.4,46.4% of patients had complete remission and 25%had partial remission.Median follow up time was 32.8 months (5-101 months) andmedian disease free survival was 22.5 months (1-67 months).Conclusion: We may conclude that the combination of rituximab with the firstlinetherapies and maintanence of rituximab after the first response is a rational way ofmanagement of follicular lymphoma with regard to the analysis of data obtained fromthis study

AML transformation and myeloid sarcoma in central nervous system in CMML patient

Myeloid sarkom inmatür granülositlerden oluşan ve nadir görülen bir tümördür. Hematolojik malignitelere eşlik edebileceği gibi miyeloproliferatif hastalıkların başlangıç semptomu olarak izlenebilir. Biz bu yazıda bilinç bulanıklığı ve gözünde şişlik yakınması ile başvuran Kronik Miyelomonositer Lösemi hastasında eş zamanlı gelişen AML-M4 ile frontal lob ve orbitada gelişen granülositik sarkom birlikteliği olan hastayı sunuyoruz. AML tedavisi ile hastanın beyin parankimi ve gözündeki lezyonlar belirgin geriledi. . Myeloid sarcoma is an uncommon tumor composed of immature granulocytes. It is described along with hematologic malignancies or it occurs as a first sign of myeloproliferative disorders incidently. In this paper we emphasize a Chronic Myelomonocytic Leukemia (CMML) patient with a swollen eye and unconsciousness presenting orbita and frontal lobe granulocytic sarcoma at the same time the AML-M4 transformation in bone marrow aspiration. By the treatment of AML the swollen eye and the lesion in the brain paranchim is regressed

EVALUATION OF CLINICAL PROGRESS AND THERAPY RESPONSE OF PATIENTS WITH IMMUNE THROMBOCYTOPENİC PURPURA; SINGLE CENTER EXPERIENCE

Amaç: İmmun Trombositopeni (İTP), trombositlere karşı oluşan otoantikorların trombositlerin yaşam sürelerini kısaltması sonucu gelişen ve trombositopeni ile seyreden edinsel bir hastalıktır. Trombositopeninin derecesine bağlı olmak üzere, sıklıkla, purpurik deri lezyonları, mukozal kanamalar, nadiren iç organ kanamaları gibi hayatı tehdit eden kanamalar gelişir. Yöntemler: Bu çalışmada 1988 - 2011 yılları arasında tedavi ve takiplerine merkezimizce devam edilen 76 hastanın sonuçları retrospektif olarak değerlendirilmiştir. Bulgular: 76 hastanın 49'u kadın (%64,5), 27'si erkek (%35,5) olup, ortanca yaş 50,7 (19 - 83 yıl) idi. Olguların 20'si tedavisiz takip edilmiş, tedavi uygulanan 56 olgunun 53'ünde (%92) ise başlangıç tedavisi olarak 1 mg/kg metil prednizolon uygulanmıştı. Bu hastaların 24'ünde (%44,6) tam yanıt, 13'ünde (%23,2) yanıt elde edilmiş ve 17 (%31,5) olguda ise yanıt alınamamıştı. Steroide yanıt vermeyen ya da yanıt sonrası nüks eden hastalara splenektomi uygulanmıştı (37 hasta). Bu hastalardan 33'ünde tam yanıt, 2'sinde yanıt elde edilirken, 2 hastada yanıt alınamadı. Toplamda 8 hastaya Rituksimab verildi. 3 hastada tam yanıt, 2 hastada yanıt alındı. 3 hastada ise yanıt elde edilemedi. Sonuç: ITP hastalarında başlangıç prednizolon tedavisi ve splenektomi, olguların çoğunda etkili bir tedavi seçeneği olmakla birlikte, bu tedavilere cevap vermeyen refrakter ITP olgularında ise ritüksimab kullanımı etkili bir tedavi seçeneğidir. Objective: Immune thrombocytopenia (ITP) is an autoimmune thrombocytopenic disease characterized by destruction of platelets mainly at spleen in reticuloendothelial system. The initiation of ITP is mostly insidious, usually defined with mild to moderate history of hemorrhage. Rarely, life threatining bleeding episodes are documented. Methods: 76 ITP patients diagnosed at Dokuz Eylul University Faculty of Medicine Hospital from 1988 to 2011 are included in this retrospective study. Results: 49 of 76 (64.4%) patients were female and 27 patients diagnosed as ITP were male (35,5%) (F/M: 1.81). At diagnosis the median age of patients was 50.7 (Interval; 19 - 83). 20 patients were followed without any treatment. 53 of 56 patients (92%) in treated group received 1 mg/kg methyl prednisolone. 24 patients (44.6%) achieved complete response after initial steroid therapy, 13 patients (23.2%) were followed with partial response and 17 patients (31.5%) had no response. Splenectomy was applied to patients that were not responded or relapsed after steroid treatment. After splenectomy 33 patients achieved complete response, 2 patients achieved partial response and 2 patients were followed as nonresponders to splenectomy. Totally 8 patients received rituximab. 3 of 8 patients (37.5%) were complete responders, 2 of 8 patients (25%) were partial responders on the other hand 3 of 8 patients (37.5%) were nonresponders. Conclusion: Most of the patients are successfully treated with steroids or splenectomy. Hence, in relapsed and refractory ITP after splenectomy rituximab is an effective treatment option

PERIPHERAL BLOOD STEM CELL TRANSPLANTATION FOR LYMPHOMA PATIENTS: SINGLE CENTER EXPERIENCE

Amaç: Birinci sıra tedaviye yeterli yanıt vermeyen yada relaps olan Hodgkin ve Non-Hodgkin lenfomalı hastalarda ikinci sıra tedavi sonrası otolog periferik kök hücre(OKIT) destekli yüksek doz kemoterapi yaygın olarak kullanılmaktadır. Biz buçalışmada Dokuz Eylül Üniversitesi Tıp Fakültesi Hematoloji Bilim dalı tarafından2005-2009 yılları arasında izlenen ve periferik kök hücre nakli yapılan 45 lenfomahastasını sunmayı amaçladık.Gereç ve yöntemler: Hastaların yaşları 19-67 arasında ve yaş ortalamaları 38,87 idi.Tanılarına bakıldığında %24,4'ü Diffüz Büyük B hücreli NHL, %35,6'sı NodülerSklerozan Hodgkin Lenfoma, %17,8'i miks sellüler Hodgkin lenfoma, %8,9'u lenfoblastiklenfoma idi.Bulgular: Hastaların %90'ına OKIT destekli yüksek doz tedavi, %10'una ise allogeneikkök hücre nakli uygulandı. Nakil sonrası hastaların son yapılan değerlendirmelerinde45 hastanın 13'ünün komplet remisyonda, 2'sinin progresif hastalık, 2'sinin parsiyelyanıtlı, 3'ünün stabil hastalık olduğu görüldü. 12 hasta hastalık ilişkili, 2'si hastalık dışınedenlerle ve 11 hastada sepsis nedeni ile kaybedildi.Sonuç: Otolog periferik kök hücre destekli yüksek doz tedavi ile özellikle platin bazlıtedaviye yanıt veren lenfoma hasta gurubunda yüz güldürücü sonuçlar alınmaktadır.Objective: Peripheral Blood Stem Cell Transplantation (PBSCT) following intensiveconditioning chemotherapy has improved the survival in relapsed Hodgkin's disease(HD) and non- Hodgkin's lymphoma (NHL). In this study we aim to present 45relapsed refractory lymphoma patients who had peripheral blood stem celltransplantation and were observed between 2005 and 2009 by Dokuz Eylül UniversityFaculty of Medicine Hematology Department.Material and methods: The age range of 45 pateients that were included in this studywas between 19 and 67, and the mean age is 38,87... When we look at subtypes, 24.4%diffuse large B-cell NHL, 35.6% Nodular Sclerozan Hodgkin\\\'s Lymphoma, 17.8% mixed cellula rity Hodgkin\\\'s lymphoma, and 8.9% were diagnosed as lymphoblastic lymphoma.Results: 90% of the patients were treated with high-dose chemotherapy withautologous PBSCT, to the 10% of the pateients allogeneic PBSCT from full matchedrelatives was applied.. Recent evaluation of 45 patients, 13 patients were CR (28.9%), 2have progressive disease, 2 PR, 3 were classified as SD. Associated with the disease in12 patients, 2 of them for reasons other than illness, and 11 patients had died of sepsis.Conclusion: PBSCT following intensive conditioning chemotherapy has improved thesurvival in relapsed-refractory lymphoma patients

Pretreatment with ibrutinib reduces cytokine secretion and limits the risk of obinutuzumab-induced infusion-related reactions in patients with CLL : analysis from the iLLUMINATE study

The online version contains supplementary material available at 10.1007/s00277-021-04536-6

Clinical outcomes and treatment patterns of primary central nervous system lymphoma: Multicenter retrospective analysis

Objectives: Primary central nervous system lymphoma (PCNSL) is a rare malignant disease with poor prognosis. Its low incidence leads to challenges in decision-making for treatment. As a matter of fact, there is still no consensus on the appropriate treatment modalities. In this context, the objective of this study is to investigate and comparatively assess the efficacies of several treatment modalities in the treatment of PCNSL. Methods: Thirty-four patients diagnosed with PCNSL at 5 different hematology centers between 2007 and 2021 were included in the study. Patients’ data from all five centers were collected retrospectively. Since ibrutinib is not approved for this indication in Turkey, consent for off-label use of ibrutinib is obtained from each patient. Ethics committee ap-proval was obtained on June 9, 2021 with decision number 2021/18-05. Results: The median age of the patients was 59 (min.: 22, max.: 78) years. The male-to-female ratio was 1.26/1. Nineteen (55.9%) patients had Eastern Cooperative Oncology Group (ECOG) performance score of ≥2. Fifteen (44.1%) patients had normal lactate dehydrogenase (LDH) levels and only 14.7% of the patients had B symptoms at the time of diagnosis. Magnetic resonance imaging (MRI) revealed a single mass lesion in 14 (41.2%) patients. As an induction therapy, meth-otrexate-based regimen was administered in 29 (85.3%) patients. Only 14 of the 34 patients received 4 or more cycles of high-dose methotrexate (MTX). About 32.4% of the patients received radiation therapy (RT) during follow-up as a part of induction therapy. Five patients received only RT due to poor performance status. Ibrutinib was administered in 5 patients for refractory disease. It was determined that four or more cycles of MTX treatment increased progression-free survival (PFS) (p=0.031) and overall survival (OS) (p=0.012). Moreover, RT improved PFS (p=0.023). Considering that the complete response achieved by induction therapy influences long-term survival, achievement of the best response to the treatment regimens administered in combination with new agents may prolong survival (PFS: p=0.01, OS: p=0.023). Conclusion: The findings of this study indicate that the initial response to treatment is crucial. Additionally, it was found that high-dose MTX treatment should be administered for 4 cycles or more in order to achieve the best results. Furthermore, it was determined that ibrutinib monotherapy was well-tolerated in our patients with relapsed/refractory disease, with excellent clinical benefits. In conclusion, a combination therapy consisting of high-dose MTX, ibrutinib, and rituximab appears to be a promising initial treatment approach in appropriate patients