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

Evaluation of prognostic factors associated with intensive care unit mortality in patients with hematopoietic stem cell transplantation

Background & objective: Although the outcome of patients admitted to ICUs have considerably improved in recent years, hematopoietic stem cell transplantation (HSCT) continues to be significantly associated with mortality.We studied the prognostic factors associated with ICU mortality after HSCT. The Acute Physiological and Chronic Health Evaluation II (APACHE II) was used as a prognostic scoring system.Methods: Within the scope of the research, the clinical and laboratory data of 52 patients who were admitted to the ICU after undergoing HSCT between 2013 and 2019 were analyzed retrospectively.Results: Mortality risk was found to be 4.22 times higher in patients who received mechanical ventilation (MV) within the first 24 h (P = 0.047), 18.37 times higher in patients who received total parenteral nutrition (TPN) support (P = 0.007), and 158.17 times higher in recipients of vasopressor drug support compared to those who did not (P < 0.001). It was found that a one unit increase in GCS score decreased mortality risk by 0.58 fold (P = 0.015). Additionally, a one unit increase in heart rate was found to increase mortality risk by 1.03 fold (P = 0.010). Whereas, one unit increases in systolic blood pressure or diastolic blood pressure decreased the mortality risk by 0.91 and 0.92 fold, respectively (P = 0.001 and P = 0.002). Mortality was not associated with APACHE II or graft-versus-host disease. Conclusion: Receiving MV, TPN or vasopressor treatment, and having lower GCS, higher heart rate, lower systolic and diastolic blood pressure were associated with an increase in the risk of ICU mortality in HSCT recipients admitted to the ICU

Vücut kitle indeksinin trombosit aferez donörlerinin trombosit sayıları ve donasyon sıklığı ile ilişkisi

Aim: The aim of this study was to investigate the demographic characteristics of platelet apheresis donors during the coronavirus disease 2019 (COVID-19) pandemic, to examine the association of platelet counts with blood groups and body mass index (BMI), and to characterize the effects of BMI on platelet apheresis donation. Material and Methods: In this retrospective study, the demographic characteristics of platelet apheresis donors admitted to our center between January 2020 and January 2021 were examined, and hemogram parameters, previous platelet donation frequencies, and blood groups information were recorded. The relationship between donors' platelet counts, blood groups, and BMI were analyzed. Results: There was no statistically significant relationship between the platelet counts and blood groups. Although platelet counts were higher in Rh positive donors, no statistically significant relationship was found between platelet counts and the Rh group (p=0.675). Even though the platelet counts were lower in low-weight donors, there was no statistically significant relationship between platelet count and BMI groups (p=0.134). The lower collected platelet counts of the normal group, compared to the obese group, was found to be statistically significant (p=0.001). The number of donations for the overweight group being higher than the normal and obese groups was found to be statistically significant (p=0.002). Conclusion: Even though the platelet count increases with obesity, it does not have any statistical significance in healthy platelet donors. In conclusion, obesity does not have an inverse relationship with platelet apheresis donation and high BMI should not be considered as a prognostic factor for donation.Amaç: Bu çalışmanın amacı, koronavirüs hastalığı 2019 (coronavirus disease 2019, COVID-19) pandemi döneminde trombosit aferez donörlerinin demografik özelliklerinin araştırılması, trombosit sayılarının kan grupları ve vücut kitle indeksi (VKİ) ile ilişkisinin gözden geçirilmesi ve VKİ’nin trombosit aferez bağışı üzerindeki etkisini karakterize etmektir. Gereç ve Yöntemler: Bu geriye dönük çalışmada Ocak 2020 ve Ocak 2021 tarihleri arasında merkezimize başvuran trombosit aferez donörlerinin demografik özellikleri incelendi ve hemogram parametreleri, daha önceki trombosit bağış sıklığı ve kan grubu bilgileri kaydedildi. Bağışçıların trombosit sayıları, kan grupları ve VKİ arasındaki ilişki analiz edildi. Bulgular: Trombosit sayıları ile kan grupları arasında istatistiksel olarak anlamlı bir ilişki bulunmamıştır. Trombosit sayıları Rh pozitif bağışçılarda daha yüksek olmakla birlikte trombosit sayıları ile Rh grubu arasında istatistiksel olarak anlamlı bir ilişki bulunmamıştır (p=0,675). Düşük kilolu donörlerde trombosit sayıları daha düşük olsa da trombosit sayısı ile VKİ grupları arasında istatistiksel olarak anlamlı bir ilişki yoktu (p=0,134). Obez grup ile karşılaştırıldığında, normal kilolu gruptaki daha düşük trombosit torba sayısı istatiksel olarak anlamlı olarak bulundu (p=0,001). Normal kilolu ve obez gruplara göre daha fazla sayıda olan, fazla kilolu gruba yapılan bağış sayısı istatistiksel olarak anlamlı olduğu bulundu (p=0,002). Sonuç: Trombosit sayısı obezite ile birlikte artsa da bu durum sağlıklı trombosit donörlerde istatiksel olarak bir anlamlılığa sahip değildir. Sonuç olarak, obezitenin trombosit aferez bağışı ile ters bir ilişkisi yoktur ve yüksek VKİ bağış için prognostik bir faktör olarak kabul edilmemelidir

Osteoporosis in patients with hemophilia: Single-center results from a middle-income country

Increased number of patients with hemophilia have been identified to have osteoporosis at early ages. Low bone mineral density in the setting of hemophilia has been associated with decreased mobility, sedentary life style, on demand treatment or delayed prophylaxis, low body weight and viral infections. The aim of this study was to investigate the impact of hemophilia on bone health of adult patients living in a middle income country. A total of 61 adult patients with hemophilia who were followed at the Hematology Department of Cerrahpaşa Medical Faculty, Istanbul University-Cerrahpaşa were consecutively included in this study. Bone health of the patients was assessed using the bone mineral density (BMD) and vitamin D levels. Z and t scores are used for evaluation of BMD in patients with hemophilia aged < 50 and ≥ 50 years, respectively. Information on treatment and co-morbidities including viral diseases were obtained from the medical files of the recruited patients. Bone mineral density was found normal in 30, and low in 29 patients. Vitamin D levels were below 20 ng/ml in 46 patients. No significant relationship was found between the severity of hemophilia and bone density. Vitamin D levels were significantly lower in patients who had a history of joint intervention. Neither annual bleeding rate nor the treatment modality (on demand versus prophylaxis) were associated with the bone mineral density and vitamin D levels. Annual factor consumption was higher in patients whose bone mineral densities was low both in femoral and lumbar regions. The results of this study depicting the situation of adult hemophilia population from a middle income country show that bone mineral density and vitamin D levels were decreased in a considerable amount of patients at early ages

Do neutrophil-lymphocyte ratio and platelet-lymphocyte ratio have a role in determining mortality in intensive care patients undergoing plasmapheresis? Single-center experience

Introduction: Plasmapheresis is a frequently used procedure that removes the pathogenic components from circulation. We aimed to evaluate the relationship between plasmapheresis, neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR) and mortality in the intensive care unit (ICU) between 2014 and 2021. Methods: Forty-nine patients (27 females and 22 males) were included. Demographic characteristics, laboratory values of the day of admittance to the ICU, APACHE II scores, and length of stay were recorded. Results: The mean age was 52.73 ± 16.93. APACHE II value (p = 0.003; p < 0.01), NLR ratio (p = 0.001; p < 0.01) and PLR ratio (p = 0.001; p < 0.01) of the surviving group were lower than those of the deceased group, which was statistically significant. Conclusion: As high PLR and NLR levels suggest increased mortality in the ICU population, attention should be paid for increased NLR and PLR when plasmapheresis is decided on in the ICU

Rare side effect caused by atezolizumab, an immune checkpoint inhibitor: Cold agglutinin disease

Introduction Immune checkpoint inhibitors are drugs that are included in the guidelines of hematological and solid cancer treatments, give highly effective results and increase T cell functionality. However, these drugs can cause immune-related adverse events resembling autoimmune diseases. Case report A 50-year-old male patient was admitted to an external center with complaints of chest pain and dyspnea. Thoracic CT revealed a 97 x 58 mm mass in the left lung, and a diagnosis of Small Cell Lung Cancer (SCLC) was made by biopsy. The PET/CT performed for staging was also evaluated as extensive stage small cell lung cancer. It was decided to give a combination of atezolizumab and carboplatin-etoposide to the patient. Management and outcome: The patient completed 3 cycles without any problem. Discordance was detected in the hemogram of the patient who came to the control for the assessment of response and had a regression in the imaging. Hemoglobin 9.6 g/dl (N: 14-17.5) hematocrit 14.8% (N: 41-51) were detected in the hemogram. Agglutinins were seen in the peripheral smear performed. Cold agglutinin (+4 positive) and indirect coombs (+3 positive) were found positive. Atezolizumab was stopped and methylprednisolone was started. After 10 days of treatment, discordance improved and methylprednisolone was discontinued by decreasing to half dose every 5 days. Discussion With the increasing use of immune checkpoint inhibitors, the variety of side effects has increased and case reports have increased. After detection of cold agglutinin, IgG, cryoglobulin, mycoplasma pneumonia, hepatitis B, hepatitis C and HIV were found negative in the differential diagnosis, Our case appears to be immune checkpoint inhibitor-related Cold Agglutinin Disease (CAD). It should not be forgotten that immune checkpoint inhibitors, which are widely used, may cause CAD, and hemoglobin-hematocrit discordance should be paid attention to in routine controls