Hypomagnesemia May Predict Better Survival and Reduced Nonrelapse Mortality in Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

BACKGROUND: Magnesium (Mg) is an essential element that is required as a cofactor for many cellular reactions, including immunologic pathways. The aim of this study was to investigate the potential impact of serum Mg levels on allogeneic hematopoietic stem cell transplantation (alloHSCT) outcomes. METHODS: Medical records of 340 alloHSCT recipients (median age: 45 [18-71] years; M/F: 210/130) were reviewed for this retrospective study. Serum Mg levels on days -28, -7, 0, +7, +14, +21, +30, +60, and +90 were included in the analysis. RESULTS: Serum Mg+14 levels predicted nonrelapse mortality (NRM) (P = .025) and had a significant impact on the development of mucositis (P = .027), fungal infection (P = .006), engraftment syndrome (P < .001), sinusoidal obstruction syndrome (SOS) (P = .001), cytomegalovirus (CMV) reactivation (P = .039), and acute graft vs host disease (GvHD) (P < .001). Based on the optimal threshold of serum Mg+14 level (1.33 mg/dL; area under the curve: 0.581 [0.515-0.648]; P = .018), the study group was divided into 2 subgroups as low- and high-Mg+14. The incidence of acute GvHD (P = .002), SOS (P = .013), engraftment syndrome (P = .013), CMV reactivation (P = .001), and Epstein Barr virus reactivation (P = .005) was significantly lower in low-Mg+14 group. The probability of overall survival (OS) was significantly better (P = .002), whereas NRM was lower in the low-Mg+14 group (P = .001). CONCLUSION: Hypomagnesemia seems to provide a considerable advantage for the post-transplant outcome, which may confirm its potential role in the immunologic microenvironment and adaptive immunity.

Impact of post-transplant cyclophosphamide (PTCy)-based prophylaxis in matched sibling donor allogeneic haematopoietic cell transplantation for patients with myelodysplastic syndrome: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT.

We retrospectively compared outcomes of 404 MDS patients undergoing 1st matched sibling donor allo-HCT receiving either PTCy-based (n = 66) or other "conventional prophylaxis" (n = 338; mostly calcineurin inhibitor + methotrexate or MMF). Baseline characteristics were balanced, except for higher use of myeloablative regimens in the PTCy group (52.3% vs. 38.2%, p = 0.047). Incidences of neutrophil (Day +28: 89% vs. 97%, p = 0.011) and platelet (Day +100: 89% vs. 97%, p < 0.001) engraftment were lower for PTCy-based. Day +100 cumulative incidences of grade II-IV and III-IV aGVHD, and 5-year CI of extensive cGVHD were 32%, 18% and 18% for PTCy-based and 25% (p = 0.3), 13% (p = 0.4) and 31% (p = 0.09) for the conventional cohort. Five-year OS (51% vs. 52%, p = 0.6) and GRFS (33% vs. 25%, p = 0.6) were similar between groups. Patients receiving PTCy had a trend to a lower cumulative incidence of relapse (20% vs. 33%, p = 0.06), not confirmed on multivariable analysis (p = 0.3). Although higher NRM rates were observed in patients receiving PTCy (32% vs. 21%, p = 0.02) on univariate analysis, this was not confirmed on multivariate analysis (HR 1.46, p = 0.18), and there was no resultant effect on OS (HR 1.20, p = 0.5). Based on these data, PTCy prophylaxis appears to be an attractive option for patients with MDS undergoing MSD allo-HCT.

In the era of Bortezomib-based Induction, intensification of Melphalan-based conditioning with Bortezomib does not improve Survival Outcomes in newly diagnosed Multiple Myeloma: a study from the Chronic Malignancies Working Party of the EBMT.

Bortezomib (Vel)- Melphalan 200 mg/m2 (Mel200) (Vel-Mel) has been utilised to intensify conditioning in autologous hematopoietic stem cell transplantation (AHCT) for multiple myeloma (MM). This EBMT registry-based study compared Vel-Mel with Mel200 during upfront AHCT. Between 2010 and 2017, MM patients who received Vel-Mel (n = 292) conditioning were compared with 4,096 Mel200 patients in the same 58 centres. Pre-AHCT, compared to Mel200 patients, Vel-Mel patients had similar International Staging System (ISS) scores and cytogenetic risk profiles; a similar proportion had received bortezomib-based induction (85% and 87.3%, respectively) though they were younger with a better performance status. Vel-Mel patients were more likely to achieve CR post-induction (40.6% vs 20.3%, p < 0.001) and by day 100 of AHCT (CR/VGPR: 70.2 % vs. 57.2%, p < 0.001). There was no difference in 3-year PFS (49% vs 46%, p = 0.06) or early post-AHCT mortality. In multivariable analysis, Vel-Mel associated with inferior PFS (HR: 1.69 (1.27-2.25, p < 0.001) and OS (HR:1.46 (1.14-1.86,p = 0.002), similar to negative effects on PFS of advanced ISS (HR:1.56 (1.33-1.83, p < 0.001), high-risk cytogenetics (HR:1.43(1.18-1.74, p < 0.001) and poor post-induction response(<=PR)(HR: 1.43(1.25-1.62, p < 0.001) Overall, despite superior pre- and post-AHCT responses, there was no improvement in PFS or OS following Vel-Mel. This data supports the findings of the smaller prospective IFM study.

Clinical factors associated with autologous stem cell transplantation outcomes in multiple myeloma: upfront transplant with MEL200 remains the standard of care.

Autologous stem cell transplantation (ASCT) remains the mainstay of the treatment in newly diagnosed transplant-eligible multiple myeloma (MM) patients. This retrospective study was performed to investigate the potential prognostic markers which may modify transplant course in a total of 256 ASCT recipients [median age: 58 (30-74) years; male/female: 138/118], including pretransplant (PET0) and day + 60 (PET2) PET/CT assessments and comparative analysis of melphalan (Mel) dose. Better responses with significantly higher complete response/very good partial response rates were achieved in patients who proceeded to transplant within 301 days from diagnosis (p < 0.001). Patients who had received < 1.5 lines of treatment prior to transplant had significantly higher probability of overall survival (OS) (p = 0.004) and progression-free survival (PFS) (p < 0.001). The probability of OS was significantly higher in patients with low Eastern Cooperative Oncology Group (ECOG) performance score (PS = 0-1) (p = 0.003) and HCT-Comorbidity Index (HCT-CI = 0) (p = 0.011). The number of involved areas (p = 0.028) and maximum standardized uptake value (SUVmax) (p = 0.021) in PET0 represented significant impact on OS. The probabilities of OS (p < 0.001) and PFS (p = 0.01) were significantly better with Mel200 mg/m2 conditioning compared to Mel140 mg/m2. Conditioning with Mel200 mg/m2, early and upfront ASCT and low pretransplant treatment burden were found to be significantly associated with ASCT outcome in MM patients. Despite its predictor impact on survival and prognosis, further studies are warranted to standardize PET/CT-based response assessments before being used as a guide for treatment decisions in clinical practice.

ECP versus ruxolitinib in steroid-refractory acute GVHD - a retrospective study by the EBMT transplant complications working party.

Introduction: Extracorporal Photophoresis (ECP) is in clinical use for steroid-refractory and steroid-dependent acute GVHD (SR-aGVHD). Based on recent Phase-III study results, ruxolitinib has become the new standard of care for SR-aGVHD. Our aim was to collect comparative data between ruxolitinib and ECP in SR-aGVHD in order to improve the evidence base for clinical decision making. Methods: We asked EBMT centers if they were willing to participate in this study by completing a data form (Med-C) with detailed information on GVHD grading, -therapy, -dosing, -response and complications for each included patient. Results: 31 centers responded positively (14%) and we included all patients receiving alloSCT between 1/2017-7/2019 and treated with ECP or ruxolitinib for SR-aGVHD grades II-IV from these centers. We identified 53 and 40 patients with grades II-IV SR-aGVHD who were treated with ECP and ruxolitinib, respectively. We performed multivariate analyses adjusted on grading and type of SR-aGVHD (steroid dependent vs. refractory). At day+90 after initiation of treatment for SR-aGVHD we found no statistically significant differences in overall response. The odds ratio in the ruxolitinib group to achieve overall response vs. the ECP group was 1.13 (95% CI = [0.41; 3.22], p = 0.81). In line, we detected no statistically significant differences in overall survival, progression-free survival, non-relapse mortality and relapse incidence. Discussion: The clinical significance is limited by the retrospective study design and the current data can't replace prospective studies on ECP in SR-aGVHD. However, the present results contribute to the accumulating evidence on ECP as an effective treatment option in SR-aGVHD.

Long-term Results of Imatinib Discontinuation in Patients with Chronic-phase Chronic Myeloid Leukemia: A National Multicenter Prospective Study

Objective: The discovery of imatinib was a milestone for chronic myeloid leukemia (CML). As the life expectancy of CML patients has approached that of the general population, research has shifted towards improving quality of life and economic considerations. After 2010, it was shown that some patients could maintain molecular response even after discontinuing imatinib. This national multicenter prospective cohort study aimed to observe the long-term consequences of discontinuing imatinib therapy in adult chronic-phase CML patients. Materials and Methods: We enrolled 41 CML patients from 4 different centers in this non-randomized single-arm trial. Molecular responses of all patients were re-evaluated using real-time polymerase chain reaction at a single center. The median follow-up time after imatinib discontinuation was 48 months (minimum-maximum: 6-81 months). Results: The rate of molecular relapse-free survival at 48 months was 33.2% (confidence interval: 48.2-18.2). Twenty-seven of 41 patients lost their major molecular response, treatment was started again, and deep molecular response was re-achieved with imatinib in all cases. There was no significant relationship between molecular relapse and clinical factors such as duration of treatment or molecular response status. Discontinuing imatinib resulted in savings of approximately 4,392,000 Turkish lira or 245,150 US dollars. Conclusion: Tyrosine kinase inhibitor discontinuation with close molecular monitoring is a safe option and provides important national economic benefits for chronic phase CML patients. This approach should be considered for all eligible patients. This is the first tyrosine kinase inhibitor discontinuation study from Türkiye.

The Effect of Granulocyte Colony-Stimulating Factor (G-CSF) on Early Complications and Graft-Versus-Host Disease (GVHD) in Allogeneic Stem Cell Transplantation (ASCT) Recipients.

Objectives Granulocyte colony-stimulating factor (G-CSF) is commonly used to accelerate neutrophil recovery after allogeneic stem cell transplantation (ASCT) in most transplant centers. There was no consensus on the optimal use of G-CSF after ASCT. Although we use G-CSF to minimize morbidity and mortality, G-CSF can increase the risk of graft-versus-host disease (GVHD). In our study, we want to show the effect of prophylactic G-CSF on infection frequency, neutrophil and platelet engraftment, the duration of neutropenia, the development of GVHD, hospitalization time, and transplant-related mortality (TRM) after ASCT. Materials and methods One hundred (71 males and 29 females) patients who did not receive G-CSF and 100 (58 males and 42 females) patients who received prophylactic G-CSF were included in the study. Results Age, diagnosis, the time between diagnosis and transplantation, preparation regimen, donor type, and the number of infused cluster of differentiation (CD) 34+ cells were not different in both groups (p>0.05). The frequency of female patients was higher in the group receiving G-CSF. Febrile neutropenia was more frequent in patients who did not receive G-CSF. Neutrophil engraftment and platelet engraftment were detected longer in patients not receiving G-CSF. The frequency of veno-occlusive disease (VOD) and hyperacute, chronic, and acute GVHD was not different in both groups (p>0.05). One hundred-day TRM and five-year overall survival (OS) were similar in the two groups (p>0.05). Conclusions Our study supports that G-CSF usage does not cause an increase in the frequency of GVHD and has a positive effect on the process by accelerating myeloid engraftment. In light of the data in our study, we can say that the use of G-CSF should be investigated in a randomized controlled clinical trial.

Preconditioning Modified-Easix as a Predictor of Prognosis in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

Allogeneic hematopoietic stem cell transplantation (alloHCT) is associated with severe complications, most of which share a common physiopathological background characterized by endothelial dysfunction. A novel risk assessment model, endothelial activation and stress index (EASIX), has been introduced as a predictor of endothelial activation. This retrospective study was performed to evaluate the predictive impact of EASIX/modified-EASIX (mEASIX) on transplant outcome. Medical records of 398 alloHCT recipients [median age: 43(17-71) years; M/F: 243/155] were examined. EASIX/mEASIX were calculated at specific time points before and after transplantation. EASIX/mEASIX were significantly associated with transplant complications including engraftment syndrome, sinusoidal obstruction syndrome, febrile neutropenia and transplant associated thrombotic microangiopathy. The probability of overall survival was significantly higher in low-preconditioning mEASIX (day -7) group (37% vs 25.2%; p = 0.008; HR: 2.057; 95% CI: 1.208-3.504). The probabilities of day30 mortality (2.9% vs 19.4%; p = 0.017; HR: 7.028; 95% CI: 1.418-34.836), day100 mortality (9% vs 33%; p = 0.004; HR: 4.469; 95% CI: 1.619-12.336) and non relapse mortality (44.8% vs 61.4%; p = 0.005; HR: 2.551; 95% CI: 1.318-4.941) were lower in low-preconditioning mEASIX (day -7) group. This retrospective cohort analysis demonstrates the significant impact of EASIX/mEASIX on transplant complications and survival. Prospective analyses are mandatory to assess the predictive role of EASIX/mEASIX in clinical practice.

Is flow cytometry useful in determining central nervous system involvement in patients with hematological malignancy? Analysis with a prospective cohort.

Central nervous system (CNS) involvement occurs in approximately 5-15% of patients in hematological malignancies. Early diagnosis and treatment is essential for a successful approach to CNS involvement. The gold standard method for diagnosis is cytological evaluation, but its sensitivity is low. Flow cytometry (FCM) from cerebrospinal fluid(CSF) is another method used to identify small groups of cells with abnormal phenotype. In our study, we compared FCM and cytological findings in the evaluation of CNS involvement in our patients with hematological malignancies. 90 patients [58 males, 32 females] were included in the study. CNS involvement was positive in 35(%38.9) patients, negative in 48(%53.3) patients, and suspicious (atypical) in 7(%7.8) patients by flow cytometry and it was positive in 24(%26.7) patients, negative in 63(%70) patients, and atypical in 3(%3.3) patients by cytology. While the sensitivity and specificity were found to be respectively 68.5% and 100% by cytology, it was found to be 94.2% and 85.4% by flow cytometry. Flow cytometry, cytology and MR findings were significantly correlated with each other in both prophylaxis (p < 0.001) and patients with prediagnosis of CNS involvement. Although the gold standard diagnostic method in the diagnosis of CNS involvement is cytological, its sensitivity is low and it can give false negative results at a rate of 20-60%. Flow cytometry is an ideal objective and quantitative method for identifying small groups of cells with abnormal phenotype. Flow cytometry can be used routinely in the diagnosis of CNS involvement in patients with hematological malignancies with cytology, since it can detect fewer malignant cells, has a higher sensitivity, and provides easy and faster results.

[Comparison of the Results of Galactomannan and Beta Glucan Antigen Tests in the Suspicion of Invasive Pulmonary Aspergillosis]. / Invaziv Pulmoner Aspergilloz Süpheli Hastalarda Galaktomannan ve Beta Glukan Antijen Testlerinin Karsilastirilmasi.

Opportunistic fungal infections are an important cause of morbidity and mortality in immunocompromised patients. Invasive aspergillosis (IA) has an important place among these infections with ~ 250.000 cases annually. Reducing the mortality rate due to invasive aspergillosis is possible with early diagnosis and treatment of the disease. Because of the low sensitivity in microscopic examination, the time consuming of culture growth, and the difficulties in distinguishing colonization/infection, serological methods are frequently used in the diagnosis of invasive aspergillosis. The aim of this study was to determine the diagnostic performance of galactomannan and beta glucan tests for the diagnosis of invasive pulmonary aspergillosis (IPA). Sixty patients, followed up with the suspicion of invasive pulmonary aspergillosis in Gazi University Hospital were included in the study. The clinical classification of the patients was made according to the revised European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) criteria. A total of 10 patients were classified as probable invasive aspergillosis and 20 patients were classified as possible invasive fungal disease. Demographic data of the patients and various risk factors were recorded. One hundred and thirty serum and nine bronchoalveolar lavage (BAL) fluid samples were studied with Plateliaᵀᴹ Aspergillus Ag (Bio-Rad, France), Dynamiker Aspergillus Galactomannan and Dynamiker Fungus (1-3)-beta-D-Glucan (Dynamiker, China) kits. Sensitivity and specificity values were calculated according to U.S. Food and Drug Administration (FDA) approved Plateliaᵀᴹ Aspergillus Ag test. According to this study, the most important risk factors in the development of IPA were the use of steroids and immunomodulatory drugs. The sensitivity of the galactomannan test in the probable group was 77.8%, the specificity was 96.7%, the sensitivity of the beta glucan test was 61.1%, and the specificity was 92.6%. When these two tests were evaluated together, it was observed that the sensitivity in the probable group increased to 83.3% and the specificity decreased to 89.3%. The combined use of galactomannan and beta glucan tests increases the diagnostic sensitivity. Although the presence of prolonged neutropenia is an important risk factor for IA, the use of steroids and immunomodulatory drugs should be kept in mind in non-neutropenic patients.

Risk factors for ICU mortality in patients with hematological malignancies: a singlecenter, retrospective cohort study from Turkey.

BACKGROUND: Patients with hematological malignancies (HM) often require admission to the intensive care unit (ICU) due to organ failure, disease progression or treatment-related complications, and they generally have a poor prognosis. Therefore, understanding the factors affecting ICU mortality in HM patients is important. In this study, we aimed to identify the risk factors for ICU mortality in our critically ill HM patients. METHODS: We retrospectively reviewed the medical records of HM patients who were hospitalized in our medical ICU between January 1, 2010 and December 31, 2018. We recorded some parameters of these patients and compared these parameters by statistically between survivors and nonsurvivors to determine the risk factors for ICU mortality. RESULTS: The study included 368 critically ill HM patients who were admitted to our medical ICU during a 9-year period. The median age was 58 (49-67) years and 63.3% of the patients were male. Most of the patients (43.2%) had acute leukemia. Hematopoietic stem cell transplantation (HSCT) was performed in 153 (41.6%) patients. The ICU mortality rate was 51.4%. According to univariable analyses, a lot of parameters (e.g., admission APACHE II and SOFA scores, length of ICU stay, some laboratory parameters at the ICU admission, the reason for ICU admission, comorbidities, type of HM, type of HSCT, infections on ICU admission and during ICU stay, etc.) were significantly different between survivors and nonsurvivors. However, only high SOFA scores at ICU admission (OR:1.281, p = 0.004), presence of septic shock (OR:17.123, p = 0.0001), acute kidney injury (OR:48.284, p = 0.0001), and requirement of invasive mechanical ventilation support during ICU stay (OR:23.118, p = 0.0001) were independent risk factors for ICU mortality. DISCUSSION: In our cohort, critically ill HM patients had high ICU mortality. We found four independent predictors for ICU mortality. Yet, there is still a need for further research to better understand poor outcome predictors in critically ill HM patients.

Comparison of maintenance regimens in Acute Promyelocytic Leukemia patients.

Maintenance therapy in APL is still a standard especially in high-risk patients treated with chemotherapy+ATRA combination whereas the role of the maintenance therapy in low-risk patients is controversial. This study aims to compare the efficacy and toxicity of ATRA monotherapy and ATRA+MTX+ 6-MP combination as the maintenance treatment for 2 years in APL patients who achieved molecular complete response after induction and consolidation with ATRA+chemotherapy. A total of 71 patients from 4 different centers were included in this study. After a median follow-up of 54 months (5-180 months), the 5-year RFS was 89 % in the ATRA monotherapy arm, the 5-year RFS was 78.5 % in the combined treatment arm (p = 0.643, HR:1.3, 95 % CI: 0.35-5.3). Hematological toxicity in all grades and Grade III/IV hematological toxicity was observed significantly more in the combined treatment arm than in the ATRA monotherapy arm (All grades: 76.9 % vs 18.9 %, p < 0.001; Grade III/IV: 20.5 % vs. 3.1 %, p = 0.035). Hepatotoxicity at all levels was significantly higher in the combined treatment arm than in the ATRA monotherapy arm (61.5 % vs 25 %, p = 0.002). Our study concluded that two years of ATRA monotherapy and combined maintenance therapy, both of which were found to be similar in terms of disease control and long term survival, ATRA Monotherapy could be a safer maintenance treatment option since both hematological and non-hematological toxicities were observed less often in the ATRA monotherapy arm.

International Forum: The Turkish perspective on apheresis activity: The Turkish apheresis registry report.

Therapeutic apheresis is an extracorporeal treatment that selectively removes abnormal cells or harmful substances in the blood that are associated with or cause certain diseases. During the last decades the application of therapeutic apheresis has expanded to a broad spectrum of hematological and non-hematological diseases due to various studies on the clinical efficacy of this procedure. In this context there are more than 30 centers performing therapeutic apheresis and registered in the apheresis database in Turkey. Herein, we, The Turkish Apheresis Registry, aimed to analyze some key articles published so far from Turkey regarding the use of apheresis for various indications.

Safety and efficacy of autologous stem cell transplantation in dialysis-dependent myeloma patients-The DIADEM study from the chronic malignancies working party of the EBMT.

The role of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) in the treatment of myeloma (MM) patients with severe and/or dialysis-dependent renal impairment remains uncertain. We report on the outcomes of 110 patients (median age 57 years) who had become dialysis-dependent pre-ASCT and who underwent a first ASCT between 1997 and 2017. Sixty-three (57%) patients had light chain MM. All patients required dialysis (94% hemodialysis and 6% peritoneal). Forty-four of 71 (62%) patients received bortezomib-based induction regimens and 42 (39%) patients had achieved at least a very good partial response (VGPR) pre-ASCT. Melphalan dosing was as follows: ≤140 mg/m2 (82%), and >140 mg/m2 (18%). The median PFS after ASCT was 35 months (95% CI: 21.5-42.2) and the median OS 102 months (95% CI: 70.4-129.1). At 1, 2, and 5 years after ASCT, 8% (95% CI 3-14%), 13% (6-20%), and 20% (12-29%) of patients, respectively, had achieved dialysis independence. In multivariate analyses of OS and PFS including age at ASCT, response at ASCT, and year of ASCT, younger age at ASCT and better response at ASCT (CR/VGPR/PR vs. MR/SD/progression) were significantly associated with better OS and PFS.

Exercise capacity, physical activity and quality of life in patients with newly diagnosed hematologic malignancies: a cross-sectional study.

OBJECTIVE: The aims of this study were to compare pulmonary function, exercise capacity, physical activity levels, quality of life, respiratory muscle strength and endurance, dyspnea in patients with newly diagnosed hematologic malignancies and controls. METHODS: Twenty-three patients and 20 healthy controls were included. Pulmonary function, exercise capacity, physical activity level, quality of life, respiratory muscle strength [maximum inspiratory (MIP), expiratory pressure (MEP)], respiratory muscle endurance, and dyspnea were evaluated. RESULTS: Patients' six-minute walk test distance, PEF, MIP, MEP, respiratory muscle endurance, total and active energy expenditure, physical activity duration, average MET's, number of steps, functional, social function, general health status scores were lower; dyspnea, symptom, fatigue subscales scores were higher compared with controls (p < .05). CONCLUSIONS: Although pulmonary function is preserved, exercise capacity, respiratory muscle strength and endurance, physical activity, quality of life were impaired in patients. Individualized pulmonary rehabilitation programs should be performed in the early stage of the disease.

Is comprehensive geriatric testing guiding in the identification of multiple myeloma patients who are candidates for autologous stem cell transplantation? A prospective analysis.

Multiple myeloma (MM) is a hematological malignancy of older adults. This study aimed to investigate the differences in performance, comorbidity scores, and comprehensive geriatric assessment (CGA) before and after induction therapy in newly diagnosed MM patients, as well as the factors that may be associated with improved performance status after induction therapy. Thirty-seven consecutive patients aged 50 years and older, who were newly diagnosed with MM, were included in the study. The patients underwent performance status evaluation and CGA when first diagnosed and after 4 cycles of induction chemotherapy. The performance status of 11 patients (40.7%) changed after induction therapy. Improvement in performance status was significantly lower in patients who were frail according to the Fried frailty criteria and IMWG scores (60% vs. 25%, p = 0.04), (30.0% vs. 6.2%, p = 0.02), taking more than 2 medications due to comorbidities (p = 0.01, confidence interval 0.06-0.09) and those with renal involvement (80.0% vs. 18.7%, p = 0.002). Those with bone involvement were more prevalent among the patients whose performance status improved (87.5% and 50.0%, p = 0.03). This study demonstrated that performance status might improve after induction therapy. Results suggest that CGA before induction therapy can predict performance status change. These results might have implications for predicting at the time of diagnosis, whether an MM patient can be a transplant candidate after induction therapy.

Eltrombopag may induce bone marrow fibrosis in allogeneic hematopoietic stem cell transplant recipients with prolonged thrombocytopenia.

Poor graft function (PGF) and secondary failure of platelet recovery (SFPR) are significant causes of transplant related morbidity and mortality. Although thrombopoietin receptor agonists (TPO-RA), particularly Eltrombopag (EPAG), have been reported to be efficacious in the treatment of prolonged thrombocytopenia, potential long term adverse effects remain to be elucidated. This retrospective study was performed to determine the efficacy and toxicity profile of TPO-RAs in allogeneic hematopoietic stem cell transplant (alloHCT) recipients. Medical records of 27 patients [median age: 55(21-73) years; male/female: 15/12] who received posttransplant EPAG for SFPR or PGF were analysed. Eltrombopag was started on day 110(33-670) after transplant. Median initial dose was 25(25-50) mg/day which was properly escalated to a maximum dose of 75(50-100) mg/day. Duration of the treatment was median 120(31-377) days. Overall response rate (ORR) was 59.3% in the study population. Time-to-treatment response was 42(3-170) days. Mild-to-moderate bone marrow fibrosis was detected in the posttreatment biopsies of 12/22 patients (54.5%), 9 of whom did not represent any grade of myelofibrosis in their inital biopsies. The grade of posttreatment fibrosis was significantly increased when time-to-treatment response was longer (p = 0.008). Long term use of TPO-RAs may be considered as a potential cause of myelofibrosis in alloHCT recipients.

Comparison of daily oral iron replacement therapy with every other day treatment in female reproductive age patients with iron-deficiency anemia.

Iron-deficiency anemia (IDA) is accepted as the most common cause of anemia in the world. The main goals of iron replacement therapy are to normalize the hemoglobin level and to replace iron stores. Current guidelines for treating iron deficiency recommend daily divided doses of iron to increase absorption. Hepcidin is a key regulator of systemic iron balance and acts in harmony with intracellular iron metabolism. Daily dosing and divided doses may increase serum hepcidin and decrease iron absorption. In this study, it was aimed to compare the effectiveness of daily and every other day oral iron replacement therapy in women of reproductive age with iron-deficiency anemia. We included premenopausal female patients aged between 18 and 50 years with iron-deficiency anemia. Forty patients were given oral iron therapy at a daily dose of 2*80 mg (iron sulfate). Forty-three patients were given iron treatment at a dose of 2*80 mg (iron sulfate) every other day. After 2 months of oral iron therapy, there was a significant improvement in hemoglobin, mean corpuscular volume, serum iron, total iron-binding capacity, and transferrin saturation in both groups. The values of hemoglobin, serum iron, transferrin saturation, and ferritin significantly increased at the end of the treatment for both groups. Although the median hepcidin level on the 15th-day measurement in the every other day treatment group was higher than that in the daily treatment group, there was no significant difference. As a result, the patients' compliance with the treatment can be increased by offering treatment every other day instead of daily, since it provides similar treatment effectiveness.

Autologous hematopoietic cell transplantation for relapsed multiple myeloma performed with cells procured after previous transplantation-study on behalf of CMWP of the EBMT.

Autologous hematopoietic cell transplantation (auto-HCT) may be performed in multiple myeloma (MM) patients relapsing after a previous auto-HCT. For those without an adequate dose of stored stem cells, remobilization is necessary. This retrospective study included patients who, following disease relapse after the first auto-HCT(s), underwent stem cell remobilization and auto-HCT performed using these cells. There were 305 patients, 68% male, median age at salvage auto-HCT was 59 years. The median time to relapse after the first-line penultimate auto-HCT(s) was 30.6 months, the median follow-up after salvage auto-HCT 31 months. The 2- and 4-year non-relapse mortality (NRM) after the salvage auto-HCT was 5 and 9%, the relapse incidence 56 and 76%, respectively. Overall survival (OS) after 2 and 4 years was 76 and 52%, progression-free survival (PFS) 39 and 15%. In multivariable analysis an increasing interval between the penultimate auto-HCT and relapse was associated with better OS and PFS, later calendar year of salvage auto-HCT with better OS. In conclusion, salvage auto-HCT performed with cells remobilized after a previous auto-HCT was associated with acceptable NRM. The leading cause of failure was disease progression of MM, which correlated with a shorter interval from the penultimate auto-HCT to the first relapse.