Early Tapering of Cyclosporine Is Feasible in Haploidentical Stem Cell Transplantation: A Single Center Experience.

INTRODUCTION: Cyclosporine-A (CsA) and post transplantation cyclophosphamide (PTCy) are common agents used for graft versus host disease (GVHD) prophylaxis in Haploidentical hematopoietic cell transplantation (haplo-HCT). However, the impact of CsA cessation timing in the posttransplant setting on clinical outcomes is uncertain. We aimed to investigate the impact of a novel approach that integrated early CsA cessation with PTCy utilization. PATIENTS AND METHODS: This study was a single arm retrospective study carried out at a tertiary referral hospital hematology and bone marrow transplantation center between 2009 and 2022. The patients who received haplo-HCT with ATG, PTCy and CsA as GVHD prophylaxis were included. CsA was planned for cessation starting at day 45 to day 60. Acute and chronic GVHD were evaluated and graded. CsA blood concentrations and its impact on acute and chronic GVHD was evaluated. RESULTS: Thirty-one patients composed of 19 (61.3%) male and 12 (38.7%) female patients with a median age of 31 years (20-58). Busulfan and TBI based conditioning regimens were the most utilized regimens. The majority of donors were first degree relatives. Stem cell origin was peripheral blood for all patients. GVHD prophylaxis consisted of ATG, CsA and PTCy. Acute GVHD was observed in 9 (29%) cases, whereas chronic GVHD was seen in 3 (9.7%) cases, with 2 of them having overlapping GVHD. Age, gender, number of chemotherapy lines, transplant characteristics, infused CD34 cell count, and engraftment durations were similar among patients with and without GVHD. Patients with GVHD had similar 1st, 2nd, 3rd and 4th week CsA concentrations compared to patients without GVHD (p > 0.05). The presence of GVHD was not associated with worse progression free survival and overall survival (p = 0.6, p = 0.5, respectively). CMV reactivation was more common in the GVHD group. CONCLUSION: In the current study, we did not find an impact of CsA concentration on GVHD and post-transplant outcomes in Haplo-HCT setting. Therefore, together with the use of PTCy, early CsA cessation can be an option; further studies are needed to understand all aspects of this approach.

Is an earlier strategy for harvesting peripheral blood stem cells in healthy allogeneic donors feasible?

INTRODUCTION: Peripheral blood stem cells (PBSC) mobilization with granulocyte colony stimulating factor (G-CSF) for healthy donors is generally performed at 5th day. However, earlier collection is sometimes feasible, raising the question of whether to initiate apheresis early to limit further G-CSF exposure, while considering the risk of mobilization failure. In the current study, we examined the factors predicting successful 4th day collection and developed a model that can be used practically. PATIENTS AND METHODS: The study was carried out by obtaining the data of PBSC mobilizations performed between January 2009 and September 2022 in our transplantation center. RESULTS: A total of 141 healthy donors with a median donor age of 32 (18-64) were included. Adequate mobilization was achieved in 115 (81.6 %) patients. Median peripheral CD34 + cell count was 69.4/µL in the adequate mobilization group and 46/µL in the mobilization failure group (p < 0001). Multivariate analysis revealed that donor/recipient weight ratio and the 4th day peripheral CD34 + cell count≥ 50/µL were independent markers for 4th day collection success. A predictive model of our center including these parameters was available with 0.765 sensitivity and 0.968 specificity [(AUC):0.948 (95 % CI, 0.90-0.99), p < 0.001]. CONCLUSION: The result of the current study shows that peripheral 4th day collection can be performed in selected donors, taking into account peripheral CD34+ cell count and donor/recipient weight ratio. In addition, using these indicators, new predictive models can be created that may assist clinicians in daily practice.

Efficacy and safety of plasmapheresis in symptomatic hyperviscosity and cast nephropathy: A Multicenter Experience in Turkey.

BACKGROUND AND OBJECTIVES: Cast nephropathy (CN) and hyperviscosity (HV), which we encounter in plasma cell diseases, are serious clinical manifestations that increase mortality and morbidity if not managed well in the early period. Therapeutic plasma exchange (TPE) procedures based on the removal of patient plasma is a frequently preferred treatment modality. TPE is recommended at varying levels of evidence for the treatment of CN and HV in plasma cell disorders. MATERIAL AND METHODS: A total of 61 patients, 50 with multipl myeloma (MM) and 10 with Waldenström macroglobulinemia (WM), who underwent TPE for CN and HV, were included in our multicenter, and retrospective study. RESULTS: A statistically significant decrease was found in all disease-related biochemical markers, which were measured 1 week after the application of TPE added to standard medical treatment (IgG; p < 0.001, IgM; p = 0.004, IgA; p = 0.14, kappa light chain; p < 0.001, lambda light chain; p < 0.001, ß-2 microglobulin; p < 0.001, total protein; p < 0.001, albumin; p < 0.001, LDH; p = 0.02, creatine; p < 0.001, hemoglobin; p = 0.010). Clinically, all 11 patients who underwent TPE for HV responded. While a partial response (PR: 80 %) was obtained in 40 of 50 MM patients with CN, no response was obtained in 10 patients (non-response: 20 %). CONCLUSION: In conclusion, it was observed that TPE reduced all biochemical markers related to HV and CN, while making a significant contribution to clinical improvement. We believe that adding TPE to the standard treatment in this patient group will reduce mortality and morbidity in the early period and have a positive effect on survival in the long term.

Does myeloma genetic have an effect on stem cell mobilization?

BACKGROUND: Autologous stem cell transplantation (ASCT) after induction treatment is the standard of care. Our understanding of myeloma genetics has been very limited and its effect to stem cell mobilization is not widely investigated. We aimed to investigate the effect of genetic abnormalities on stem cell mobilization in myeloma. METHODS: The data of 150 MM patients who underwent stem cell mobilization at our center between 2009-2020 were included and analyzed retrospectively. Pre-treatment bone marrow cytogenetics and fluorescence in situ hybridization tests were performed for each patient. RESULTS: Groups were divided into two as patients with normal cytogenetic and abnormal cytogenetic. No difference observed between groups regarding age, gender and ECOG (p = 0.4; p = 0.2; p = 0.3). Groups were similar concerning myeloma characteristics, received treatment and treatment response. Median CD34+ cells/kg harvested was 444(2-11.29) in normal cytogenetic group whereas it was 4,8(2.4-8.6) in abnormal cytogenetic group(p = 0.2). Optimal CD34+ cells level achievement was 73 (67 %) in normal cytogenetic group while it was 25(71.4 %) in abnormal cytogenetic group(p = 0.6). Neutrophil and platelet engraftment durations were similar among cytogenetic groups (p = 0.7; p = 0.9). R-ISS based groups were also did not differ regarding harvested CD34+ cells and achievement optimal CD34 level (p = 0.79, p = 0.74). Engraftment durations for neutrophil and platelet were comparable between R-ISS based groups (p = 0.59, p = 0.65) CONCLUSIONS: Here we were not able to find any impact of genetic abnormalities on stem cell mobilization in myeloma patients. Expanded studies can aid to identify the effect of particular genetic anomalies on the stem cell mobilization.

Recovery of Symmetrical Peripheral Gangrene of Limbs in a Patient After Performing Hemoadsorption in Septic Shock.

We report a 42-year-old patient who had Hodgkin lymphoma and developed bilateral symmetrical peripheral gangrene (SPG) in the feet and hands, which occurred during septic shock after autologous hematopoietic stem-cell transplantation. SPG is a rare but severe complication of disseminated intravascular coagulation (DIC) and is frequently associated with sepsis. The pathophysiology of SPG includes DIC-mediated intravascular thrombosis and thrombotic occlusion of microcirculation, resulting in low blood flow. Sepsis-induced hypotension has been suspected as one of the other causes of SPG, and it is thought to be aggravated by vasopressor treatments given for hypotension. Our patient first experienced coldness, paleness, and cyanosis in his body's acral parts, and then SPG later developed in both his feet and hands. Septic shock management was performed with cytokine hemoadsorption, broad-spectrum antibiotics, and massive fluid replacement rapidly. The patient fully recovered without the need for amputation. Hemoadsorption is an extracorporeal cytokine-adsorption method for removing excess cytokines. Prompt management of septic shock and early monitoring of peripheral ischemia are essential to avoid SPG.

Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience.

Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, in approximately one-third of the responding patients, the disease relapses following completion of therapy. One of the drugs that have been approved for the treatment of relapsed/refractory cHL is nivolumab, an immune check point inhibitor that shows its effects by blocking the programmed death 1 (PD-1) receptor. In this study, we present a retrospective "real-life" analysis of the usage of nivolumab in patients with relapsed/refractory cHL that have joined the named patient program (NPP) for nivolumab, reflecting 4 years of experience in the treatment of relapsed/refractory cHL. We present a retrospective analysis of 87 patients (median age, 30) that participated in the NPP in 24 different centers, who had relapsed/refractory cHL and were consequently treated with nivolumab. The median follow-up was 29 months, and the median number of previous treatments was 5 (2-11). In this study, the best overall response rate was 70% (CR, 36%; PR, 34%). Twenty-eight of the responding patients underwent subsequent stem cell transplantation (SCT). Among 15 patients receiving allogeneic stem cell transplantation, 9 patients underwent transplantation with objective response, of which 8 of them are currently alive with ongoing response. At the time of analysis, 23 patients remained on nivolumab treatment and the rest discontinued therapy. The main reason for discontinuing nivolumab was disease progression (n = 23). The safety profile was acceptable, with only nine patients requiring cessation of nivolumab due to serious adverse events. The 24-month progression-free and overall survival rates were 58.5% (95% CI, 0.47-0.68) and 78.7% (95% CI, 0.68-0.86), respectively. Eighteen patients died during the follow-up and only one of these was regarded to be treatment-related. With its efficacy and its safety profile, PD-1 blockers became an important treatment option in the heavily pretreated cHL patients.

Inferior prognosis in poor mobilizing myeloma patients.

INTRODUCTION: Induction treatment followed by autologous stem cell transplantation (ASCT) has been accepted as the standard treatment for multiple myeloma (MM) patients. Granulocyte colony stimulating agent (G-CSF), chemotherapy or agents likes plerixafor are being used for the mobilization of stem cells from bone marrow. In this study, we evaluated the impact of the mobilization methods on the outcome of MM patients after ASCT. METHOD: The data of 205 MM patients who underwent ASCT at our center between December 2009 and January 2019 were retrospectively analyzed. Patients were divided into 2 groups as good mobilizers (patients who were mobilized with G-CSF alone) and poor mobilizers (patients who were failed to mobilize with G-CSF alone and mobilized with G-CSF + cylophosphomide or G-CSF + plerixafor). RESULTS: The median progression free survival (PFS) was 18.27 ± 3.22 months in good mobilizers and 14.22 ± 3.7 months in poor mobilizers. In G-CSF + cyclophosphamide method median PFS was 15.4 ± 4.9 months wheras it was only 4 months in G-CSF + plerixafor method. We did not find a statistically significant difference between good and poor mobilizers regarding median PFS (p: 0.342). The median overall survival (OS) was found 34.48 ± 4.2 months in good mobilizers and 15.13 ± 5.78 months in poor mobilizers. In G-CSF + cyclophosphamide method median OS was 17 ± 14.01 months wheras it was 10.66 ± 7.68 months in G-CSF + plerixafor method. We found a statistically significant difference between good and poor mobilizers regarding median OS (p: 0.007*). CONCLUSION: Our study shows that difficulty in stem cell mobilization is correlated with worse outcome.

The effect of serum vitamin B12, folate, ferritin levels and transferrin saturation on stem cell mobilization in allogeneic donors.

INTRODUCTION: Peripheric blood derived stem cells are used in 75 % of allogeneic stem cell transplantations. Iron, vitamin B12 and folate involve in hematopoiesis. Therefore serum levels of iron, vitamin B12 and folat may effect stem cell mobilization. We aimed to analyze the effects of iron status, vitamin B12 and folate levels on peripheric blood stem cell mobilization in healthy donors. METHOD: The mobilization results of 218 allogeneic donors were analyzed retrospectively. RESULTS: In 64 donors, serum ferritin level was <15 µg / L and transferrin saturation was <20 %. When we compared the donors with iron deficiency to the donors without iron deficiency, the number of collected CD34 + cell was significantly higher in donors without iron deficiency. We did not find any impact of serum vitamin B12 and folate level on CD34+ cells collected. CONCLUSION: Our study shows that serum ferritin and transferrin saturation have a greater effect on the amount of CD34+ cells collected from donors than serum vitamin B12 and folate levels. Consequently, when compliance tests of allogeneic donors are performed, the evaluation of vitamin B12 and folate levels is not necessary; whereas iron deficiency must be assessed and -if possible- corrected before apheresis is performed.

Evaluation of neutropenia-related outcomes in Hodgkin's lymphoma patients with moderate or severe neutropenia who received ABVD chemotherapy without using granulocyte-colony stimulating factor.

OBJECTIVE: To evaluate the possible neutropenia-related effects of administering adriamycin [doxorubicin], bleomycin, vinblastin, dacarbazine (ABVD) chemotherapy in Hodgkin's lymphoma patients with moderate or severe neutropenia without granulocyte-colony stimulating factor supplementation. METHODS: This study evaluated neutropenia-related outcomes and the need for granulocyte-colony stimulating factor use during the periods between chemotherapy rounds. Forty-three rounds of ABVD chemotherapy were evaluated in the study. The outcomes that could be related to neutropenia were analyzed. In addition, rounds of ABVD chemotherapy given in the presence of severe neutropenia were compared with ABVD chemotherapy rounds given in the presence of moderate neutropenia in terms of neutropenia-related outcomes and the need for granulocyte-colony stimulating factor use. The study only included patients with classical Hodgkin's disease (lymphoma). Patients with a final neutrophil count of <1 × 103 cells/µL (<1000 cells/µL) prior to chemotherapy round and those receiving ABVD chemotherapy for Hodgkin's lymphoma were included in the study. RESULTS: We observed that none of the patients with moderate neutropenia before the start of chemotherapy round needed granulocyte-colony stimulating factor, and four patients with severe neutropenia prior to the start of chemotherapy round required granulocyte-colony stimulating factor. However, there was no statistically significant relationship between the severity of neutropenia (in terms of moderate and severe) before chemotherapy and granulocyte-colony stimulating factor requirement after chemotherapy (p> 0.05). Furthermore, none of the patients included in the study had bleomycin-related lung toxicity during the treatment periods included in the study. CONCLUSION: Administering ABVD chemotherapy to patients with moderate neutropenia seems to be safe.

Does microbial contamination influence the success of the hematopoietic cell transplantation outcomes?

INTRODUCTION: Microbial contamination can be a marker for faulty process and is assumed to play an important role in the collection of hematopoietic progenitor cell (HPC) and infusion procedure. We aimed to determine the microbial contamination rates and evaluate the success of hematopoietic cell transplantation (HCT) in patients who received contaminated products. PATIENTS-METHODS: We analyzed microbial contamination records of HPC grafts between 2012 and 2015, retrospectively. Contamination rates of autologous donors were evaluated for at three steps: at the end of mobilization, following processing with dimethyl sulfoxide, and just before stem cell infusion. Grafts of allogeneic donors were assessed only before HCT. RESULT: A total of 445 mobilization procedures were carried out on 333 (167 autologous and 166 allogeneic) donors. The microbiological contamination of peripheral blood (323/333 donations) and bone marrow (10/333 donations) products were analyzed. Bacterial contamination was detected in 18 of 1552 (1.15 %) culture bottles of 333 donors. During the study period 248 patients underwent HCT and among these patients microbial contamination rate on sample basis was 1.3 % (16/1212). Microbial contamination detected in nine patients (7 autologous; 2 allogeneic). In 8 of 9 patients, a febrile neutropenic attack was observed. The median day for the neutropenic fever was 4 days (0-9). None of the patients died within the post-transplant 30 days who received contaminated products. CONCLUSION: The use of contaminated products with antibiotic prophylaxis may be safe in terms of the first day of fever, duration of fever, neutrophil, platelet engraftment and duration of hospitalization.

Is neutropenic fever an obstacle to effective stem cell harvesting?

INTRODUCTION: Autologous stem cell transplantation (ASCT) is a well-established consolidation treatment for many hematologic cancers which delivers prolonged survival. A subset of patients' adequate stem cell harvest is not achievable with a solitary use of granulocyte colony-stimulating agents (G-CSF). Generally, chemomobilization is employed for patients failing G-CSF and its most feared complication febrile neutropenia (FN). MATERIALS AND METHODS: Here, we aimed to investigate the impact of the FN in chemomobilization on apheresis outcomes and engraftment. One hundred and eighty-three patients with the diagnosis of lymphoma or myeloma who underwent chemomobilization between 2015 and 2020 were included in the study. RESULTS: Forty-three patients experienced FN. All patients received G-CSF. All myeloma patients were mobilized with 4 g/m2 cyclophosphamide, but it was heterogeneous for lymphoma patients. The precollection blood counts, harvested CD34+ hematopoietic stem cells (HSCs)/kg, apheresis count, and engraftment durations were recorded. Preapheresis leukocyte and platelet were lower in the FN group (P = 0,004 and P = 0,001). Peripheral CD34 HSCs and total harvested CD34 HSCs were similar among groups (P = 0.25 and P = 0.9). More apheresis was needed in the FN group, but it was not significant (P = 0.07). Undergoing ASCT was similar (P = 0.7); however, platelet and neutrophil engraftment durations were slower in the FN group (P = 0.05 and P = 0.001). CONCLUSION: Harvesting sufficient CD34+ HSCs from patients with FN is still feasible; however, FN treatment should begin promptly, and further apheresis sessions may be required.

HBV-related events after allogeneic hematopoetic stem cell transplantation in a center from Turkey.

To investigate the frequency of hepatitis B virus (HBV)-related events after allogeneic HCT in a moderate endemic area for HBV infection. The data of 197 patients who underwent allogeneic hematopoetic stem cell transplatation (HCT) from September 2003 through December 2010 were reviewed retrospectively with respect to HBV-related events. Resolved HBV infection was described as negative HBsAg, positive HBcAb, and positive HBsAb. Latent HBV infection was defined in patients with HBcAb positivity in the abscence of HBV DNA and HBsAb. Hepatitis B naive patients are defined as the patiens with no serological or molecular marker related to HBV. Seropositive patients were the patients with positive HBsAg and HBV-DNA. Median age was 28 (range, 15-64) years, with 128 male and 69 female patients. Median follow-up of the cohort was 8 (range, 0.5-78) months. We detected HBV-related events in 7 (3.6 %) recipients after allogeneic HCT. Five (71.4 %) of these events were HBV reactivation, while two cases (28.6 %) had acute hepatitis B infection. Four of the five reactivations were in the seropositive group (80 %), while one ocurred in a patient with resolved hepatitis. Two patients who developed acute hepatitis B were HBV naive and previously immunized patients, respectively. Hepatitis B virus reactivation remains a problem in seropositive patients and might require more effective treatment strategies.

Adverse impact of hyperferritinemia and transfusion dependency on treatment success in myelodysplastic syndrome.

BACKGROUND: Myelodysplastic syndrome (MDS) is characterized by peripheral cytopenias and dysplasia in one or more cell lines in the bone marrow. A significant proportion of patients require blood product support due to symptomatic anemia and/or thrombocytopenia during the course of their disease. This retrospective study was planned to evaluate the transfusion requirement of MDS patients and the role of ferritin in predicting transfusion requirement and response to treatment. METHODS: We retrospectively reviewed the records of 35 MDS patients [median age: 66 (22-84); male/female: 21/14]. The World Health Organization (WHO) criteria was used for disease classification and International Prognostic Scoring System (IPSS) for risk stratification. RESULTS: A total of 22 patients (62.8%) required transfusions during follow-up. While all the 22 patients received packed red blood cells (PRBCs), only 8 patients (22.9%) required platelet transfusion(s). Although no significant relationship was demonstrated between transfusion dependency and disease progression, patients who responded to disease-specific treatment were exposed to less PRBC transfusions compared to non-responders (p=0.04). Treatment response was found to be better in patients who had lower serum ferritin levels at diagnosis (p=0.004). A total of 11 patients were followed for a minimum of 24months. Transfusion load was not different among these patients with respect to disease subtype, IPSS risk score and treatment protocol in the first and second 12-month interval. Median overall survival of the cohort was 26.3 (0.4-160.3) months and median progression free survival was 24.9 (0.4-160.3) months. CONCLUSION: The present report underlines the association of baseline hyperferritinemia and transfusion dependency with treatment success in MDS. Even in patients treated with new generation agents, the vicious impact of transfusion load seems to be the tender spot of the MDS puzzle. The prognostic impact of baseline hyperferritinemia should be validated with further studies.

The effect of pre-conditioning immunoglobulin and absolute lymphocyte count on the outcomes of allogeneic hematopoietic cell transplantation.

INTRODUCTION: The prevention of mortality and morbidity related to the increasingly used allogeneic hematopoietic cell transplantation (allo-HCT), along with the effects of pre- and post-transplant immune status on transplant outcomes, have become the focus of the studies conducted on this subject in recent years. In parallel, this study was designed to investigate the effects of pre-conditioning immunoglobulin (pre-conditioning-Ig) and pre-conditioning absolute lymphocyte count (pre-conditioning-ALC) levels on transplant outcomes. METHODS: This study was designed as a retrospective, observational and cross-sectional study. The objective of the study is to investigate the effects of pre-conditioning-Ig and ALC levels primarily on the rate of patients with febrile neutropenia (FEN) and the duration of FEN and length of hospital stay (LoS), and secondarily on acute graft-versus-host disease (aGVHD), cytomegalovirus (CMV) viremia, and mortality in the acute leukemia patients who underwent allo-HCT. RESULTS: A total of 104 acute leukemia patients, of whom 55 had acute lymphoblastic leukemia (ALL) and 49 had acute myeloid leukemia (AML), were included in the study. Compared to the AML group, the median pre-conditioning-IgG, IgA, and IgM levels were found to be significantly lower in the ALL group (11.3 vs. 6.6, p < 0.001; 1.8 vs. 0.9, p < 0.001; and 0.7 vs. 0.4, p < 0.001; respectively). But, there was no significant difference between the groups in pre-conditioning-Ig and ALC levels and transplant outcomes. However, subgroup analysis revealed that high pre-conditioning-ALC levels were significantly correlated with aGVHD levels (Odds Ratio: 1.02; p = 0.034) and low pre-conditioning-IgM levels were significantly correlated with increased mortality rate (Hazard Ratio: 0.08; p = 0.042) in AML patients. CONCLUSION: The significant difference determined between the ALL and AML groups in pre-conditioning-Ig levels was not reflected on the effects of pre-conditioning-Ig and ALC levels on transplant outcomes. However, we observed that pre-conditioning-IgM and ALC levels have an impact on transplant outcomes in AML patients.

Real-world data on the effectiveness and safety of Ixazomib-Lenalidomide-Dexamethasone therapy in relapsed/refractory multiple myeloma patients: a multicenter experience in Turkey.

A multicenter, retrospective, observational study was conducted to explore effectiveness and safety of ixazomib plus lenalidomide with dexamethasone (IRd) in relapsed/refractory multiple myeloma (RRMM) patients following at least ≥ two lines of therapy. Patients' treatment responses, overall response rate, progression-free survival rate, and adverse events were recorded. Mean age of 54 patients was 66.5 ± 9.1 years. There were 20 patients (37.0%) with progression. Median progression-free survival was 13 months in patients who received a median of three therapy lines in a 7.5-month follow-up period. Overall response rate was 38.5%. Of 54 patients, 19 (40.4%) had at least one adverse event, and nine (19.1%) had an adverse event of at least grade 3 or more. Of 72 adverse events observed in 47 patients, 68% were grade 1 or 2. Treatment was not stopped in any patient due to adverse events. IRd combination therapy was effective and safe in heavily treated RRMM patients.

Prognostic role of pre-transplantation serum C-reactive protein levels in patients with acute leukemia undergoing myeloablative allogeneic stem cell transplantation.

The aim of this study was to identify indicators of outcome prior to transplantation in allogeneic hematopoietic stem cell transplantation (HCT). Clinical data of 106 patients with acute leukemia were retrospectively analyzed. We examined the role of pre-conditioning serum C-reactive protein (CRP) and ferritin levels, HCT-CI and European Group for Blood and Marrow Transplantation (EBMT) scores on transplant toxicities, transplant-related mortality (TRM), progression-free survival (PFS), and overall survival (OS). High pre-conditioning serum CRP levels showed a positive correlation with higher EBMT scores (p < 0.001), HCT-CI (p = 0.004), and ferritin levels (p < 0.001). In univariate Cox regression analysis, serum CRP ≥10 mg/L, serum ferritin ≥1500 ng/mL, and HCT-CI ≥3 had a significant adverse effect on OS. Serum CRP ≥10 mg/L and HCT-CI ≥3 predicted increased risk of TRM in univariate analysis. Multivariate Cox regression analysis showed that HCT-CI score ≥3 independently predicted increased risk of TRM and CRP ≥10 mg/L predicted increased risk of disease progression. Although CRP lost its significance on TRM in multivariate analysis, as an inexpensive and readily available serum biomarker of inflammation, the prognostic role of pre-transplant CRP levels should be analyzed in selected diseases and increased number of patient groups.

Evaluation of multiple myeloma patients presenting with renal failure in a university hospital in the year 2010.

BACKGROUND: The aim of this cross-sectional study was to evaluate multiple myeloma patients presenting with renal failure in a University hospital. METHODS: The records of all the patients diagnosed with multiple myeloma in the departments of hematology and nephrology at Gazi University Hospital between January 2010 and January 2011 were reviewed retrospectively. Renal failure was defined as a serum creatinine level of ≥2 mg/dL. Median age was 63 (range 37-80) years, with 13 male and 17 female patients. RESULTS: Eight (26.7%) of the 30 patients had renal failure and 4 (50%) patients with renal failure required renal replacement therapy with hemodialysis after admission. Renal functions recovered in four (50%) of the eight patients after treatment. In one of the eight patients (12.5%) creatinine levels improved, but did not reach the level defined as reversal of renal failure. The renal functions of the three (37.5%) patients did not improve and they remained on chronic hemodialysis program during which one of them died due to a cerebrovascular accident and one other patient was lost due to follow-up. CONCLUSION: A substantial proportion of myeloma patients referred with renal failure might enjoy a disease-free survival and could be saved from chronic renal replacement therapy with prompt diagnosis and treatment in the era of new-generation anti-myeloma agents which provide fast and effective responses. Multiple myeloma should be considered in the differential diagnosis of acute renal failure even in the absence of hyperglobulinemia and hypercalcemia.

Flow cytometric evaluation of cell cycle regulators (cyclins and cyclin-dependent kinase inhibitors) expressed on bone marrow cells in patients with chronic myeloid leukemia and multiple myeloma.

OBJECTIVE: The aim of this study was to use flow cytometry to analyze the expression of cell cycle-regulating elementswith low and high proliferative signatures in patients with malignant diseases. MATERIAL AND METHODS: Cyclin D, E, A, and B, and cyclin-dependent kinase inhibitor (CDKI) p16 and p21 levels weremeasured via flow cytometry in patients with chronic myeloid leukemia (CML) (n = 16) and multiple myeloma (MM)(n = 13), and in controls (n = 15). RESULTS: The distributions of the cell cycle S phase were 10, 63%, 6, 72% and 3, 59%; for CML, MM and controlpatients, respectively. Among all the cyclins expressed during the S phase, cyclin D expression was the lowest in the CMLpatients. Distribution of cyclins and CDKIs during the G2/M phase was similar in the MM and control groups, whereascyclin expression was similar during all 3 phases in the MM and CML groups. CONCLUSION: Elevated cyclin expression during cell cycle phases in the CML and MM patients was not associatedwith elevated CDKI expression. This finding may increase our understanding of the mechanisms involved in theetiopathogenesis of hematological malignancy.

Could blood groups have prognostic significance on survival in patients with diffuse large B cell lymphoma?

The prognostic importance of the ABO blood group in non-Hodgkin lymphoma is largely unknown. We aim to investigate the prognostic significance of blood groups on the survival in diffuse large B-cell lymphoma (DLBCL) patients. 412 people (206 DLBCL patients and 206 healthy donors) were included. The blood group types of patients treated at our center from 2009 to 2019 were analyzed retrospectively and compared to the results from healthy thrombocyte donors. The distribution of the ABO blood groups was as follows: blood type A (45.2%), B (9.7%), O (38.8%), and AB (6.3%). We found no statistically significant difference between patients and the control group in terms of ABO and Rhesus blood group distribution (p = 0.27 and p = 0.45, respectively). The median follow-up time was 18 months (0-116). In the Cox regression analysis ABO blood groups, and Rh group were not significant predictors of survival in patients with DLBCL, whereas ECOG score, IPI score, Ann-Arbor stage, and LDH level were found significant. Receiving R-CHOP as the first-line treatment was associated with better survival in the multivariate analysis. No statistically significant difference was found between the control and DLBCL patient groups regarding the distribution of ABO and Rh blood groups.

Factors affecting survival in elderly patients with diffuse large B-Cell lymphoma.

INTRODUCTION: Diffuse large B cell lymphoma (DLBCL) has an increasing incidence in elderly patients with poorer prognosis than in younger patients. Clinicians should clearly identify the characteristics and prognostic factors of elderly patients. We analyzed the outcome of elderly DLBCL patients, especially factors affecting survival in real-life clinical practice. MATERIALS AND METHODS: The data of 330 DLBCL patients at our center were retrospectively evaluated by dividing three groups; younger than 65 years, between 65-79 years, and 80 years and older. We examined the factors affecting survival in DLBCL patients ≥ 65 years old. RESULTS: The median age of the patients was 61 years (range 16-87). 192 (58.2 %) of our patients were younger than 65 years old, 112 (33.9 %) were between 65-79 years, and 26 (7.9 %) patients were 80 years old or older. The median follow-up was 15 (1-120) months. Median PFS was 38 months in the 65-79 years group, ten months in the ≥ 80 years group; meanwhile, median OS was 43 months in the 65-79 years group, 25 months in the ≥80 years group. The number of patients who relapsed within 12 months of the first-line treatment was 69 (35.9 %) in the <65 years group, it was 60 (53.6 %) in 65-79 years group, and 22 (84.6 %) in ≥80 years group (p < 0.001). The median OS was 9 (7.1-10.9) months in DLBCL patients older than 65 years old who relapsed within 12 months. Early relapse, failure to achieve CR after first-line chemotherapy, and high IPI score were associated with poor survival in patients ≥ 65 years old (p:0.001). CONCLUSION: Advancing age was a poor prognostic factor for survival of DLBCL. Relapsing within the first year, or failure to achieve complete remission were associated with poorer survival of the elderly DLBCL patients. R-CHOP is the standard treatment in DLBCL, and the best responses are obtained regardless of age. Due to difficulty in receiving standard treatments, novel treatment modalities are needed for better outcomes in elderly patients with DLBCL.