Primary gastrointestinal aspergillosis: A case report and literature review

Invasive aspergillosis is a severe infection that generally involves the lungs. Primary gastrointestinal aspergillosis is the least common form of invasive aspergillosis. A patient aged 65 years developed a febrile neutropenic episode following an autologous stem cell transplant for plasmacytoid variant diffuse large B-cell gastric non-Hodgkin’s lymphoma. He had abdominal pain on the second day of the febrile neutropenic episode and ileus occurred on the sixth day. His general condition deteriorated despite broad spectrum antibiotics and caspofungin treatment, and intestinal perforation occurred on the nineteenth day of the febrile neutropenic episode. Pathological examination of the resected jejunum and ileum revealed mould hyphae compatible with aspergillus. The patient died due to massive gastrointestinal bleeding on the fifth post-operative day. Although a rare condition, primary gastrointestinal aspergillosis should be kept in mind while treating neutropenic patients with gastrointestinal symptoms

Sarcoidosis mimicking lymphoma on positron emission tomography-computed tomography in two patients treated for lymphoma: two case reports

<p>Abstract</p> <p>Introduction</p> <p>Sarcoidosis is a granulomatous disease that mostly involves the lungs. Its association with malignancies has been well documented. Several mechanisms have been proposed that may underlie this concurrence including triggering tumour antigens and defective cellular immunity.</p> <p>Case presentations</p> <p>We briefly review the literature on malignancy associated sarcoidosis and report two female lymphoma patients of 49 and 56 years of age who, during their course of disease, developed sarcoidosis that was misinterpreted as a lymphoma relapse on positron emission tomography-computed tomography.</p> <p>Conclusion</p> <p>We hypothesise that T cell dysfunction and exposure to tumour associated antigens might be the underlying mechanisms of development of sarcoidosis in patients with lymphoma. Positron emission tomography-positive lesions do not always indicate malignancy and therefore a tissue biopsy is always mandatory to confirm the diagnosis.</p

Comparison of efficacy and safety of generic plerixafor vs original plerixafor in the mobilization of myeloma patients

Introduction The commonest indication for an Autologous Stem Cell Transplantation (ASCT) is still Multiple Myeloma. A successful mobilization of hematopoietic stem cells (HSC) is a sine qua non of ASCT. The introduction of Plerixafor, which is a partial agonist of the alfa-chemokine receptor CXCR4 has added an important value and impact on mobilization. Plerixafor is successfully integrated into both growth factor-only and cyclophosphamide and growth factor mobilization strategies with significantly reducing the mobilization failure rate in myeloma patients. In addition, plerixafor + G-CSF has also been shown to successfully mobilize the majority of patients who previously failed to mobilize with either growth factor alone or in combination with chemotherapy. Even a Just-in-Time algorithm which induces plerixafor in patients who lacks a certain threshold of CD34 positive HSCs on the day of mobilization led to a cost-effective and successful mobilization with highly restricted rates of mobilization failure. In this study we tried to demonstrate the efficacy and safety of a novel generic Plerixafor (Pleksor - Gen Ilac) and to compare it with original one (Mozobil - Sanofi) in a retrospective manner. Method Patients who were transplanted in two centers who adopted the same mobilization standard operating procedures (SOP) were included in the study. An age and sex matched cohort of patients who received Mozobil (from 2020-2022 - Group A) were compared with the ones who received Pleksor (2021-2022 Group B) as a Just-in-Time conjunct to GCSF alone or chemo mobilization. Poor mobilization was defined as a final yield of 2 million CD34 positive HSCs per kg. Our aim was to collect enough stem cells for at least two ASCTs, thus our current SOP's indicated a minimum CD34 positive HSC threshold of at least 4 million per kg and an ideal HSC threshold of 6 million per kg. Results A total of 28 patients were included and they were equally distributed among Group A (n=14) and B (n=14). Median age of the patients at the time of mobilization were as follows, 60 (35-72) in Group A and 61 (38-70) in Group B. 14 patients who received Pleksor achieved a median yield of 8.40 million CD34 positive HSCs per kg (4.8-21) and the patients who received Mozobil have ended with a yield of 6.7 million CD34 positive HSCs per kg (4.5-13) (p=0.210). None of the patients in both groups were named to be a poor mobilizer according to the threshold of 2 million CD34 positive HSCs per kg but 3 of the patients in Group A and 2 of the patients in Group B ended with a yield of 6 million CD34 positive cells which was below to the ideal threshold for two transplants. Regarding lenalidomide exposure before mobilization, history of radiotherapy, line of the therapies received before mobilization, number of leukapheresis and the mobilization policy (chemo vs gcsf alone) there were no statistically significant difference between two groups (p=0.120, 0.702, 0.842, 0.769 and 0.420 respectively). The median neutrophil engraftment time in days were as follows for Group A and B, 11(10-14) vs 11 (10-16), p=0.541 and the median platelet engraftment time in days were 17 (10-30) in Group A and 16 (10-28) in Group B with a p value of 0.571. In none of the cases any specific side effects were noted which could be attributable to Pleksor or Mozobil. Conclusion Our study demonstrated a comparable efficacy of a generic form of Plerixafor when compared with the originator. This would lead to a decrease in the cost of total process of mobilization with a similar efficacy and toxicity profile. We are now planning to initiate a prospective trial to validate these results in a larger patient population. Up to our knowledge this is the first study comparing the efficacy of a generic Plerixafor in a sole myeloma patient cohort

Cytomegalovirus (CMV) and Hepatitis B (HBV) reactivation during autologous stem cell transplantation: A single-center experience

Amaç: Sitomegalovirüs (CMV) reaktivasyonu allojenik hematopoetik kök hücre transplantasyo- nu sırasında sık görülür. Hepatit B reaktivasyonu (HBV), akut hepatit ve fulminan karaciğer yet- mezliği veya sadece HBV DNA düzeyinde artma şeklinde ortaya çıkabilir. Allojenik hematopoetik kök hücre nakli bağımsız bir risk faktörüyken, otolog hematopoetik kök hücre (HKH) alıcıları için risk ve nakil sürecine etkileri net bilinmemektedir. Çalışmamızda, geriye dönük olarak analiz etti- ğimiz otolog HKH alıcılarında CMV enfeksiyonu-engraftman ve hepatit B reaktivasyonu ilişkisini ortaya koymayı amaçladık. Hastalar ve Yöntem: Temmuz 2014-Aralık 2019 tarihleri arasında takip edilmiş olan toplamda 174 otolog KHN alıcı olan hasta değerlendirildi. CMV enfeksiyonuna bağlı organ tutulumları doku tanısı, görüntüleme ve klinik bulgularla doğrulandı. CMV enfeksiyonun tipi hastanın klinik izlemi, radyolojik raporları, hastanın tedavi alıp almamasına göre kopya sayısı seyri, virüsün herhangi bir dokunun patolojik incelemesinde tespit edilip edilmemesine göre değerlendirildi. Bulgular: Çalışmaya toplam 174 otolog KHN alıcı dahil edildi. CMV reaktivasyon oranı 18 has- tayla %10.3’tü. CMV reaktivasyonu olan olguların total Anti-HBc pozitif olma oranı, CMV negatif grubuna göre istatistiksel olarak anlamlı seviyede yüksek saptandı. CMV reaktivasyonu grubun- daki olguların HBV reaktivasyon oranı, CMV reaktivasyonu olmayan hasta grubundan istatistiksel olarak anlamlı seviyede yüksek saptandı. Sonuç: Otolog kök hücre nakli de viral reaktivasyonlar açısından dikkatli olunması gereken önemli bir tedavi tipini oluşturmaktadır.Objective: Cytomegalovirus (CMV) reactivation is a frequently encountered clinical condition during allogeneic hematopoietic stem cell transplantation. Hepatitis B reactivation (HBV) can occur asymptomatically only with re-emergence or increase in blood HBV-DNA levels, as well as in different clinical manifestations, including acute hepatitis and fulminant liver failure. While allogeneic hematopoietic stem cell transplantation is an independent risk factor, the risk for autologous hematopoietic stem cell (HSC) recipients and its effects on the transplantation process are not clear. In our study, we aimed to reveal the relationship between CMV reactivation and engraftment process and HBV reactivation in autologous HSC recipients. Patients and Methods: A total of 174 autologous HSC recipients who were followed-up between July 2014 and December 2019 were included in our study. Organ involvement due to CMV infection was confirmed by tissue pathology, imaging methods and clinical find- ings. The type of CMV infection was evaluated according to the patient’s clinical follow-up, radiological reports, the course of the copy number according to whether the patient received treatment, and whether the virus was detected in the pathological examination of any tissue. Results: The CMV reactivation rate was 10.3% with 18 patients. The rate of total Anti-HBc positivity in cases with CMV reactivation was found to be statistically significantly higher than in the CMV negative subgroup. The HBV reactivation rate of the patients in the CMV reactivation subgroup was found to be statistically significantly higher than the patient group without CMV reactivation. Conclusion: Autologous stem cell transplantation also constitutes an important type of treatment to be careful in terms of viral reacti- vation

Polatuzumab vedotin, rituximab, and bendamustine combination in relapsed or refractory diffuse large B-cell lymphoma: A real-world data from Turkey

Polatuzumab vedotin (Pola) with bendamustine and rituximab (BR) is a promising option for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We analyzed the data of 71 R/R DLBCL patients who had been treated with Pola-BR in the named patient program from March 2018 to April 2021 from 32 centers in Turkey. All patients received up to six cycles of Pola 1.8 mg/kg, rituximab 375 mg/m2 on day 1, and bendamustine 90 mg/m2 on days 1–2 of each cycle. Median age at Pola-BR initiation was 55 (19–84). The overall response rate was 47.9%, including 32.4% CR rate when a median of 3 cycles was applied. With a median follow-up of 5 months, the median OS was 5 months. Grade 3–4 neutropenia and thrombocytopenia were the most common hematological toxicities. The real-world data from our cohort showed the Pola-BR is an effective option with a manageable toxicity profile

Türkiye akademik CAR-T hücre (ISIKOK-19) klinik çalışması ön raporu: Ürün karakterizasyonu ve klinik uygulama sonuçları

Objective: Chimeric antigen receptor T (CAR-T) cell therapies have already made an impact on the treatment of B-cell malignancies. Although CAR-T cell therapies are promising, there are concerns about commercial products regarding their affordability and sustainability. In this preliminary study, the results of the first production and clinical data of an academic CAR-T cell (ISIKOK-19) trial in Turkey are presented. Materials and Methods: A pilot clinical trial (NCT04206943) designed to assess the safety and feasibility of ISIKOK-19 T-cell therapy for patients with relapsed and refractory CD19+ tumors was conducted and participating patients received ISIKOK-19 infusions between October 2019 and July 2021. The production data of the first 8 patients and the clinical outcome of 7 patients who received ISIKOK-19 cell infusions are presented in this study. Results: Nine patients were enrolled in the trial [5 with acute lymphoblastic leukemia (ALL) and 4 with non-Hodgkin lymphoma (NHL)], but only 7 patients could receive treatment. Two of the 3 participating ALL patients and 3 of the 4 NHL patients had complete/ partial response (overall response rate: 72%). Four patients (57%) had CAR-T-related toxicities (cytokine release syndrome, CAR-T-related encephalopathy syndrome, and pancytopenia). Two patients were unresponsive and had progressive disease following CAR-T therapy. Two patients with partial response had progressive disease during follow-up. Conclusion: Production efficacy and fulfillment of the criteria of quality control were satisfactory for academic production. Response rates and toxicity profiles were also acceptable for this heavily pretreated/refractory patient group. ISIKOK-19 cells appear to be a safe, economical, and efficient treatment option for CD19+ tumors. However, the findings of this study need to be supported by the currently ongoing ISIKOK-19 clinical trial.Amaç: Kimerik antijen reseptör T (CAR-T) hücre uygulamaları B-hücreli malignitelerin tedavisinde etkili olmaktadır. CAR-T hücre uygulamalarının sonuçları umut vaadedici olsa da, ticari CAR-T ürünlerinin yükek maliyetleri nedeniyle ulaşılabilirlik açısından ciddi sorunlar yaşanmaktadır. Bu ön raporda, Türkiye’deki ilk akademik CAR-T hücre çalışmasının üretim ve klinik uygulama sonuçları sunulmuştur. Gereç ve Yöntemler: Relaps refrakter CD 19+ hematolojik maligniteli hastalarda ISIKOK-19 T-hücre tedavisinin güvenliği ve etkinliğini değerlendirmek amacıyla yürütülen klinik çalışmaya (NCT04206943) Ekim 2019-Temmuz 2021 tarihleri arasındaki hastalar dahil edilmiştir. Bu raporda ilk 8 hastanın üretim bilgileriyle, ISIKOK-19 hücre infüzyonu yapılan 7 hastanın klinik sonuçları sunulmuştur. Bulgular: Çalışmaya toplam 9 hasta dahil edilmiştir (5 akut lenfoblastik lösemi [ALL] ve 4 non-hodgkin lenfoma [NHL]), ancak sadece 7 hastaya hücre infüzyonu yapılabilmiştir. Hücre infüzyonu alan 3 ALL hastasından 2’sinde ve 4 NHL hastasının 3’ünde tam/kısmi cevap gözlenmiştir (toplam yanıt oranı %72). Dört hastada (%57) CAR-T ilişkili toksisite (sitokin salınım sendromu, immün efektör hücre ilişkili nörotoksisite sendromu ve pansitopeni) tespit edilmiştir. İki hastada ise CAR-T hücre uygulaması sonrası cevapsızlık ve progresif hastalık izlenmiştir. Kısmi cevap veren hastalardan 2’sinde de takip sırasında progresif hastalık tespit edilmiştir. Sonuç: Akademik CAR-T üretimimiz, üretim etkinliği ve kalite kontrol kriterlerinin tam olarak karşılanması açısından tatmin edici sonuçlara sahiptir. Çalışmaya dahil edilen hastaların tedavi yükü hesaba katıldığında tedaviye cevap oranı ve toksisite profili açısından da sonuçlar kabul edilebilir düzeydedir. Bu sonuçlarla, ISIKOK-19 hücrelerinin güvenli, ekonomik ve etkili bir tedavi seçeneği olduğu düşünülebilir. Ancak bu ön sonuçların halen devam eden ISIKOK-19 klinik çalışmasıyla desteklenmesi beklenmektedir

Türkiye’ den hematolojik parametrelerin en büyük referans aralığı çalışması: Bir vaka-kontrol araştırması

Objectives: Accurate, reliable laboratory reference ranges are essential for effective clinical evaluation and monitoring. We present robust reference ranges established for hematology parameters using the Sysmex XT2000i analyzer. Methods: Blood samples were taken from 17409 healthy adults (19 to 49 years, 51.4% men and 48.6% women) and routine hematology analysis performed. Patients were assessed as healthy on the basis of a medical history and routine medical examinations. Serum hematinic assays (vitamin B12, folate, iron and ferritin) were also analyzed in order to exclude the potential anemia existence. Results: There was a statistically significant difference (p&lt;0.001) between men and women, with the former showing higher CBC values, except WBC, neutrophil and platelet counts compared to females. Several differences were observed when compared to previously established values from Turkey, most notably in leucocytes and platelets. Our findings for CBC parameters, except leucocyte count and MCV are in general agreement with previously published data from more limited trials undertaken in other countries. Conclusions: In spite of the uncontrolled factors influencing hematological values, this study permitted to establish the new hematological reference values in Turkey, especially living near sea level. In the absence of previously detailed investigated hematological reference values in Turkey, we offered to use these results for clinical management of Turkish patients and interpretations of laboratory data for research purpose.Amaç: Doğru, güvenilir laboratuvar referans aralıkları etkili klinik değerlendirme ve izleme için gereklidir. Biz hematoloji parametreleri için belirlenmiş mevcut referans aralıklarını Sysmex XT2000i analizörü kullanarak sunuyoruz.Yöntemler: kan örnekleri 17409 sağlıklı erişkinden (yaş aralığı, 19 ile 49 yıl arasında, %51,4 erkek ve %48,6 kadın) alındı ve rutin hematoloji analizi yapıldı. Hastalar, tıbbi geçmişleri ve rutin muayenelerine dayanarak sağlıklı olarak değerlendirildi. Serum hematinik testleri (vitamin B12, folat, demir ve ferritin) de çalışılarak potansiyel anemi varlığı hariç tutuldu. Bulgular: Kadın ve erkek arasında belirgin istatistiksel farklılık (p<0,001) olup erkeklerde kadınlara göre tam kan sayımı parametreleri, beyaz küre hücreleri, nötrofil ve trombositler hariç daha yüksekti. Daha önce Türkiye'den bildirilen değerler ile karşılaştırıldığında başta lökositler ve trombositler olmak üzere birçok farklılıklar tespit edildi. Tam kan sayımı parametreleri bulgularımız, diğer sınırlı sayıda katılımcının yer aldığı ülkelerden elde edilen yayınlanmış verilere göre kıyaslandığında ise lökosit sayısı ve MCV hariç genel bir uyumluluk içindeydi. Sonuçlar: Hematolojik değerleri etkileyen kontrol edilemeyen faktörlerin aksine, bu çalışmada, Türkiye' de özellikle deniz seviyesinde yaşayanlar için yeni hematolojik referans değerlerinin oluşturulmasına izin vermiştir. Türkiye'de daha önce ayrıntılı incelenen hematolojik referans değerleri yokluğundan dolayı, bu sonuçların Türk hastaların klinik açıdan yönetimleri ve araştırma amaçlı laboratuvar verilerinin yorumlanması adına kullanılmasını öneriyoruz

Spontaneous regression of a systemic ALK (+) anaplastic large cell lymphoma carrying ALK gene rearrangement that developed after PPD tuberculin skin test

Here we report an ALK ( ) ALCL carrying ALK gene rearrangement that developed after a PPD tuberculin skin test, which spontaneously regressed after an excisional lymph node biopsy and is still in complete remission more than 5 years later without treatment. Written informed consent was obtained from the patient for publication of this manuscript and accompanying images

Epidemiology and clinical features of febrile neutropenic episodes: Three years experience at hematology wards

..

The interactive educational approach in management of anxiety related to bone marrow transplantation

..