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Objective: Graft-versus-host disease (GvHD) is a common and serious complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), significantly impacting transplant efficacy. In the treatment of GvHD, numerous therapeutic approaches have been explored, with mesenchymal stem cells (MSCs) emerging as a prominent immunomodulatory option. We aimed to evaluate efficacy and outcomes of using MSCs for steroid refractory acute GVHD (SR-aGvHD) management., Materials and Methods: We retrospectively analyzed data from 36 patients' who received MSCs for treatment of SR-aGvHD following allo-HSCT between 2018 and 2024 from nine transplantation centers in Türkiye. The product consisted of umbilical cord-derived allogeneic MSCs, which were administered intravenously., Results: Our cohort was at the median age of 39 years (range: 19-61 years), with aGvHD diagnosed at a median of two months after allo-HSCT. More than half of the patients (58.3 %) classified as high-grade aGvHD according to the Minnesota risk scoring. Cord blood-derived MSCs were administered at a median dose of 3.45 (range: 0.8-5) million MSCs/kg, with a median of 3th (range: 2-5) line treatment. The rate of responses exceeding partial response (PR) was approximately 20 % at the first month, increasing to 24 % at the second month. The six-month survival rate was 33 %, with 46 % of mortality attributed to sepsis and 12.5 % related to GvHD. Multivariate analysis indicated that increasing age (≥35 years) and lower platelet counts (≤75 x10 9 /L) were associated with higher mortality (p < 0.05)., Conclusion: MSC therapy has shown promising potential in improving response rates in aGvHD treatment, with efficacy enhanced by younger age and higher platelet counts., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Many factors were identified for mobilization failure (MF) in autologous hematopoietic stem-cell transplantation. To our knowledge, this is the first study to investigate the efficacy of baseline inflammation indexes and neutrophil-to-lactate dehydrogenase (LDH) ratio to predict MF in multiple myeloma (MM) and lymphoma., Methods: A total of 240 patients with lymphoma or MM hospitalized between January 2014 and June 2022 for the first stem cell mobilization were included in this retrospective single-center study. We evaluated the impact of baseline demographic, clinical, and laboratory data (before granulocyte colony-stimulating factor and chemotherapy implementation), including neutrophil, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), neutrophil-to-C-reactive protein, and neutrophil-to-LDH ratios on MF., Results: A total of 240 patients were divided into successful (214 patients, 89.16%) and poor mobilizers (26 patients, 10.84%). Poor mobilizers had lower neutrophil, NLR, SII, and neutrophil-to-LDH ratios (P values were .001, .022, .001, and .001, respectively). Among these markers, only the neutrophil-to-LDH ratio was statistically low in both poor mobilizer MM and lymphoma patients. Receiving operator characteristic curve analysis was performed to evaluate neutrophil, SII, and neutrophil-to-LDH ratios for MF. Neutrophil-to-LDH ratio had the highest specificity (93.93%, for ≤9.904 cut-off) compared to the other two variables. Multivariate logistic regression analysis showed that neutrophil-to-LDH ratio ≤ 9.904 (cut-off) (odds ratio: 7.116, P = .001), neutrophil counts ≤3300/mm 3 (cut-off) (odds ratio: 3.248, P = .021), and lymphoma diagnosis (odds ratio: 2.674, P = .039) were independent risks for MF., Conclusion: The neutrophil-to-LDH ratio could be a novel marker in lymphoma and MM patients to predict the first MF. New studies should be conducted for the optimization of this index., (© 2023 Wiley Periodicals LLC.)

Background: Passenger lymphocyte syndrome (PLS) causes immune-mediated hemolysis in solid and bone marrow transplant recipients. Donor-derived antibodies against the recipient erythrocyte drive the pathogenesis. It is a rare entity in kidney transplantation, and most of the cases are self-limited., Case Presentation: A 36-year-old woman presented with fatigue 13 days after living donor renal transplantation. The operation was uneventful, and she was discharged with normal graft functions on the 11th day of transplantation Findings were consistent with cold agglutinin disease at her admission. However, the cold agglutinin test was negative. Eventually, she was diagnosed with PLS. Refractory intravascular hemolysis and frank hemoglobinuria were also present in the patient. Hemolysis was resistant to steroids, intravenous immunoglobulin (IVIG), and Rituximab. Because of life-threatening anemia related to refractory PLS, mycophenolate and tacrolimus were interrupted. However, hemolysis persisted. Following that, immunoadsorption (IA) treatment was obtained. Unfortunately, graft loss occurred due to rejection despite the resolution of PLS after IA., Conclusion: PLS is a rare and usually self-limited entity. Our case was an atypical refractory PLS that resembled cold agglutinin disease. Also, frank hemoglobinuria was observed related to severe intravascular hemolysis. These features have not been described before in PLS, to the best of our knowledge. Additionally, IA treatment had never been reported in the literature for PLS, as far as we know. Treatment and management could be a challenge in refractory PLS. Rituximab, IVIG, and extracorporeal treatments could be beneficial. It should be borne in mind that refractory PLS can cause graft and patient loss., (Copyright © 2022 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Thalassemia intermedia (TI) patients may need a transfusion during physiological stress conditions, such as pregnancy. We present a case of a female TI patient with emerging transfusion-refractory anaemia during pregnancy, which resolved after splenectomy performed simultaneously with cesarean delivery. A 26-year pregnant woman at 29th gestational weeks was referred with a diagnosis of TI due to emerging anaemia which was refractory to transfusion. Splenectomy at term was decided to improve anaemia, and transfusion response. A preterm infant was delivered by cesarean section due to threatened preterm labour. Once the uterine incision was closed, an open splenectomy was performed. Postoperative follow-up was uneventful. To the best of our knowledge, the present case is the first open splenectomy performed during cesarean delivery as a salvage option for the management of transfusion-refractory anaemia. Key Words: Thalassemia intermedia, Splenectomy, Pregnancy, Hemolytic anaemia.

Intraoperative cell salvage (ICS) system performs autologous transfusion by filtering and reinfusing the shed blood into corporeal circulation during the surgery. Especially for pregnant Jehovah's Witnesses, the ICS system could be a life-saving intervention. This report describes the successful use of intravenous iron therapy and ICS during the cesarean delivery of a Jehovah's Witness diagnosed with placenta previa totalis who refused to receive any type of blood or blood product transfusion. Intravenous iron treatment initiated in the preoperative period can reduce the need for blood and blood product transfusion. The ICS system provides recognised advantages; however, its utilisation requires high technology equipment and skilled health staff. Key Words: Jehovah's witness, pregnancy, Iron therapy, Intraoperative cell salvage.

Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) is a treatment option with growing performance for leukaemia, aplastic anaemia and genetic disorders. The frequency of MHC (Major Histocompatibility Complex) gene locus recombination is increased at loci close to the telomeres and in the female gender. The aim of the present study is to document the recombination events by pedigree diagrams with the primary goal to determine the frequency of recombination in a different ethnic population from mostly reported studies., Methods: Altogether 9545 allogeneic HSCT recipients and their family-based potential donors (n:36231) were included in this retrospective study., Results: Recombinations were determined in 118 (F/M:50/68) out of 9545 families enrolled on the study. These were present in 40 of the patients and 78 of healthy donors. The frequency of recombinations was 0.42% and 0.22%, in patients and donors, respectively. Of the 118 recombinations, 60 were detected in A locus (13 inpatients), 14 in B locus (3 inpatients) and 42 in DR locus (22 inpatients). In our study, due to recombinations in HLA (Human Leukocyte Antigen)-A,-B,-DR loci, we found that some patient-donor pairs became 6/5 matched instead of 6/6 (n:45), eliminating the allogeneic HSCT possibility for the patients from the full-matched siblings., Conclusion: To our knowledge, this is the first study reporting the recombination frequencies in HLA loci among Turkish population and thus, providing informative data to the clinicians regarding the cross-over possibilities in Turkish patients with haematological malignancies., (© 2021 John Wiley & Sons Ltd.)

Background and Objectives: Extracorporeal photopheresis (ECP) is a treatment strategy in steroid-refractory chronic graft-versus-host disease (cGvHD). In this study, we aimed to share our multicenter experience using ECP in our steroid-refractory cGvHD patients., Materials and Methods: In this multicenter observational retrospective study with the participation of four Turkish transplant centers, 100 patients with the diagnosis of steroid-refractory cGvHD who underwent ECP were analyzed. All ECP procedures were performed with the off-line system., Results: Severe cGvHD was observed in 77 % of the patients. 50 % of the patients had more than 1 organ involvement. The overall response rate in cGvHD was 58 %, and the complete response (CR) rate was 35 %. The skin was the most involved organ, with a response rate of 61.2 % (CR rate 30.6 %) in cGvHD. At a median 13 months (1-261) follow-up, overall survival (OS) was 41 % (n = 41) and the mortality rate was 59 % (n = 59). Median overall survival (OS) was 2 months for non-responders and 91 months for responders (p < 0.001). Significant OS differences were observed for patients responding to ECP in cGvHD (HR = 4.1, p = 0.001) patients., Conclusions: ECP is a good therapeutic alternative and could be used earlier in patients with steroid-resistant cGvHD., (Copyright © 2021. Published by Elsevier Ltd.)

Background: RhD typing has remained of primary importance, as being the leading cause of hemolytic disease of the newborn. Among Rh system's 55 blood group antigens, RhD is the most immunogenic. We aimed with this study to determine weak D/partial D variant frequency in blood donors who were admitted to our blood center and have serologically designated blood group weak D., Materials and Methods: We screened blood donors who admitted between 2011 and 2017 to our blood center. Sixty-seven serologically weak D phenotyped donors have participated in the study. These donors' samples were studied further by Polymerase Chain Reaction Sequence- Specific Primers (PCR-SSP) for determining D variants., Results: Weak D phenotype was detected in 228(0.12 %) out of 177,554 donors. Sixty-seven of them agreed to take part in the study. The frequency of weak D and partial D was 68.7 % (n = 46), and 22.4 % (n = 15), in order. The most encountered weak D and partial D variant was type 15 and DFR type, respectively., Conclusions: The prevalence of serologically weak D phenotypes varies by race and ethnicity. Turkey is a country covering a mixture of European and Asian DNA with different ethnic groups. Thus, our research as giving the overall distribution of RHD variants from the largest city of Turkey, which may reflect the general ethnic background of the country, would help to the establishment of a databank for blood banking. This paper is the first molecular study on RHD variants in Turkey. New molecular research would be more reliable and precise., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: In countries where frontline drug approval is limited to first-generation proteasome inhibitors or immunomodulatory drugs, relapses have been both more frequent and less durable. We investigated real world data on the efficacy and safety of daratumumab monotherapy among patients with relapsed refractory multiple myeloma (RRMM) from Turkey using a prospective early access program., Patients and Methods: A total of 42 patients with RRMM after a minimum of 3 previous lines of proteasome inhibitor/immunomodulatory drug-based treatments were included from 25 centers across Turkey. Daratumumab monotherapy was administered intravenously at a dose of 16 mg/kg weekly (cycles 1-2), on alternate weeks (cycles 3-6), and monthly thereafter., Results: The median daratumumab monotherapy duration was 5.5 months (range, 0.2-28.7 months). The overall response rate was 45.2%, including 14 (33.3%) partial responses, 4 (9.5%) very good partial responses, and 1 (2.4%) complete response. The median duration of response was 4.9 months. The median progression-free survival (PFS) was 5.5 (95% confidence interval, 2.6-8.4 months) with 12- and 18-month PFS rates of 35.7% and 31.0%, respectively. The median overall survival was not reached; the 12- and 18-month overall survival rates were 64.3% and 59.5%, respectively. The depth of response had a significant effect on PFS (log-rank test, P = .026). Overall, of the 76 adverse events reported, 33 (43.4%) were grade ≥ 3; only 4 (9.52%) were grade 3 infusion-related reactions. No infusion-related reactions or adverse events led to treatment discontinuation., Conclusion: The present findings from our daratumumab early access program have confirmed the efficacy and safety profile of daratumumab monotherapy in heavily pretreated Turkish patients with RRMM., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

After allogeneic hematopoietic stem cell transplantation, risk factors for cytomegalovirus (CMV) reactivation include pretransplantation donor and recipient CMV serologic status and posttransplantation development of acute graft-vs-host disease (aGvHD). Human leukocyte antigen (HLA) allele type is an additional factor in CMV infection. The present study included 108 patients who received an allogeneic stem cell graft from an HLA-identical sibling between 1993 and 2004. All recipients and donors were typed for HLA-A, HLA-B, and HLA-DR alleles using serologic or molecular methods. All recipients received grafts because of a hematologic disease from HLA full-matched donors. In pretransplantation seropositive patients with aGvHD, no significant difference was observed in patients who developed CMV infection compared with those without CMV infection. Seropositive patients without aGvHD but with posttransplantation CMV infection demonstrated a higher incidence of HLA-A30, HLA-B40, and HLA-DRB1*15 compared with those without CMV infection. In conclusion, it seems that certain HLA alleles may have either a protective or predisposing role in CMV reactivation, which might be helpful in estimating the risk of aGvHD and designing individualized therapy.

We aimed to compare the cytogenetic and molecular analyses in the assessment of imatinib mesylate response in patients suffering the chronic phase of chronic myelocytic leukemia who were refractory to alpha-interferon treatment. A total of 117 patients in the chronic phase of chronic myelocytic leukemia were included. The patients were treated with 400 mg/day imatinib mesylate. Bone marrow samples were obtained for the cytogenetic and molecular analyses. Patients without the Ph chromosome were defined as complete cytogenetic responders. Partial cytogenetic response was determined when the Ph chromosome was detected in 1-35% of the cells. Molecular response was determined by quantitative real-time reverse transcriptase polymerase chain reaction (QR-PCR) and defined as no detection of BCR-ABL mRNA. The frequencies of complete and partial cytogenetic response were 29% (n = 34) and 15% (n = 18), respectively. No cytogenetic response was achieved in 56% (n = 65) of the patients. Molecular response was achieved in 62% (n = 21) and 33% (n = 6) of the complete and partial cytogenetic responders, respectively. All of the 65 patients with no cytogenetic response were also molecular nonresponders. We conclude that there is reasonable agreement between the cytogenetic and molecular analyses. Both methods are complementary in the assessment of response to therapy.

Invasive pulmonary aspergillosis (IPA) poses major management problems for clinicians caring for patients with haematological diseases. The clinical courses of patients with IPA who had been hospitalised in Hematology Unit, Bone Marrow Transplantation Unit and Infectious Diseases and Clinical Microbiology Unit between 1998 and 2005, the efficacy and adverse effects and costs of antifungal drugs (conventional amphotericin B deoxycholate, liposomal amphotericin B, amphotericin B lipid complex and caspofungin) used in the therapy of these patients were analysed in this study. Ninety-three patients with IPA were reviewed retrospectively. Mean age of the patients was 40.4 +/- 15.1 years (range 14-70 years). Fifty-eight male patients and 35 female patients were included in the study. Manageable hypopotassemia, nausea/vomiting and headache were the most commonly observed side-effects during antifungal (AF) therapy. While it was not found to be statistically significant with regard to the mean time to resolution of fever (P = 0.8), it was found to be statistically significant with regard to radiological regression at 30th day, and mean duration of therapy between patients who were dead or alive (P < 0.05, P < 0.001). Total cost of AF therapy for 93 patients was found to be US$4 461 824 (minimum US$387-maximum US$279 023). Of this amount, US$4 272 845 represents the payment for AF drugs, US$188 979 the payment for other expenditures. Mean cost of therapy for a patient with IPA was found to be US$49 336. Although it seemed to be difficult, investigations should primarily focus on providing standardisation of parameters relating to the duration of AF therapy. Despite the less-than-optimal safety profile of CAB, it often remains to be the preferred first line option for the treatment of fungal infections because of its broad spectrum, activity and low acquisition cost.

Whole-body scintigraphy with Technetium-99m 2-methoxy-isobutyl-isonitrile ((99m)Tc-MIBI) has been proposed as a useful method for demonstrating the areas of active bone marrow infiltration in multiple myeloma (MM). In this study, we compared the (99m)Tc-MIBI scan with magnetic resonance imaging (MRI), skeletal X-ray survey, and biochemical markers of disease activity in MM to determine its potential in predicting the extension of the disease. Twenty-four myeloma patients had undergone to the (99m)Tc-MIBI scan. Only two patients showed negative results in the (99m)Tc-MIBI scan; one had clinically active disease, and the other was on remission. MRI was performed to 18 clinically active patients, and 16 of them showed positive myelomatous bone marrow involvement. No significant difference was found between the (99m)Tc-MIBI scan and MRI in predicting the extension of bone marrow infiltration in MM (p = 0.11). (99m)Tc-MIBI scores were correlated with bone marrow neoplastic plasma cell ratio (p = 0.005), serum paraprotein level (p < 0.001), serum lactate dehydrogenase (p = 0.031), and beta-2 microglobulin (p = 0.045). The (99m)Tc-MIBI scan showed disease activity better than the skeletal X-ray survey (x2 = 5.299, p = 0.021). A significant decrease was found in posttreatment (99m)Tc-MIBI scores of the patients with positive overall response (p = 0.016). The (99m)Tc-MIBI scan is a noninvasive test that can show the extension of the disease in MM. It seems that the (99m)Tc-MIBI scan and MRI show extension and intensity of the myelomatous bone marrow infiltration equally well. The (99m)Tc-MIBI scan can be an alternative to MRI when it is not available or if there is any limitations for its usage.

Renal insufficiency is a common complication early after hematopoietic stem cell transplantation (HSCT). Renal function as measured by creatinine clearance (CrCl) was prospectively evaluated in 47 patients undergoing allogeneic (n=22) or autologous (n=25) HSCT during the first 100 days. Renal dysfunction was classified as follows: Grade 0 (<25% decline in CrCl), Grade 1 (>or=25% decline in CrCl but <2 x increase in serum creatinine), Grade 2 (>or=2 x rise in serum creatinine but no need for dialysis) and Grade 3 (>or=2 x rise in serum creatinine and need for dialysis). Thirty-three patients (70%) had Grade 1-3 renal dysfunction. Renal dysfunction was more common after myeloablative allogeneic HSCT (91%) than autologous HSCT (52%) (P=0.004), and was associated with a high risk of mortality (P=0.039). Sepsis in autologous HSCT patients and cyclosporine toxicity in allogeneic HSCT patients were associated with renal dysfunction. We conclude that autologous and allogeneic HSCT differ in the likelihood and causes of renal dysfunction.

Background: Procalcitonin (PCT) represents a new marker of systemic inflammatory reactions to bacterial infections. The main aim in this study was to determine the diagnostic value of PCT in predicting the clinical severity of febril neutropenic attacks, compare it with that of C-reactive protein (CRP), and clarify its importance in culture-positive attacks., Methods: Between February 2001 and April 2002, 36 patients who were neutropenic due to various hematologic disorders and febrile were entered into the study. Blood samples were obtained on the first day of fever for the measurement of serum PCT and CRP levels., Results: In clinically severe neutropenic fever attacks, means of serum PCT and CRP levels were measured as 0.93+/-1.33 ng/mL and 67+/-24 mg/L, while they were 0.37+/-0.23 ng/mL and 32+/-19 mg/L in clinically mild ones (p = 0.033 and p < 0.001). On the other hand, no statistical significance was found between culture-positive and negative attacks when either serum PCT or CRP levels were taken into consideration (p = 0.133 and p = 0.141). The specificity and positive predictive value of the serum PCT test for severe febrile neutropenia was higher than that of the serum CRP test (0.80 vs. 0.57 and 0.50 vs. 0.39). However, sensitivity and negative predictive value for CRP were higher than the values for PCT (1.00 vs. 0.40 and 1.00 vs. 0.73). Diagnostic value and positive likelihood ratio of CRP for severe febrile neutropenia were higher than those of PCT (71 vs. 67 and 2.32 vs. 2.00)., Conclusions: PCT and CRP are comparable with each other in prediction of the clinical severity of febrile neutropenic attacks. Furthermore, serum CRP levels correlate with the duration of fever.

We aimed to evaluate the diagnostic values of soluble transferrin receptor (sTfR) concentration, transferrin-ferritin index (soluble transferrin receptor concentration/log ferritin), ferritin levels and other related parameters in geriatric patients with anemia of chronic disease (ACD) and iron deficiency (IDA). Forty-four elderly subjects (median age 73 [63-94]) and twenty healthy subjects (median age 49 [44-56]) were enrolled into this study, divided into four groups: twenty middle aged healthy subjects (group A), fifteen elderly patients with IDA (group B), fourteen elderly patients with ACD (group C) and fifteen nonanemic geriatric subjects (group D). Hemoglobin, mean corpuscular volume, serum iron concentration and transferrin saturation levels of the patients in IDA group were found significantly lower than those in both non-anemic group and healthy subjects. Serum sTfR concentrations of the patients in IDA group were significantly higher than those in non-anemic geriatric group, ACD group and healthy subjects. Transferrin-ferritin index of the patients with IDA was significantly higher than that in non-anemic geriatric and ACD group. Serum ferritin levels of the patients in IDA group did not show any differences when compared with the other groups. Serum ferritin was highly specific for IDA (95%) when compared with ACD, although its sensitivity was low (38%). STfR values were negatively correlated with both transferrin and ferritin levels (p = 0.042 r = -0.40; and p = 0.034 r = -0.41, respectively). In conclusion, serum soluble transferrin receptor and transferrin-ferritin index may be used together with serum ferritin to distinguish the iron deficiency state in the elderly.