The state of the art in the treatment of severe aplastic anemia: immunotherapy and hematopoietic cell transplantation in children and adults.

Acquired aplastic anemia (AA) is an immune-mediated bone marrow (BM) failure where marrow disruption is driven by a cytotoxic T-cell-mediated autoimmune attack against hematopoietic stem cells. The key diagnostic challenge in children, but also in adults, is to exclude the possible underlying congenital condition and myelodysplasia. The choice of treatment options, either allogeneic hematopoietic cell transplantation (alloHCT) or immunosuppressive therapy (IST), depends on the patient's age, comorbidities, and access to a suitable donor and effective therapeutic agents. Since 2022, horse antithymocyte globulin (hATG) has been available again in Europe and is recommended for IST as a more effective option than rabbit ATG. Therefore, an update on immunosuppressive strategies is warranted. Despite an improved response to the new immunosuppression protocols with hATG and eltrombopag, some patients are not cured or remain at risk of aplasia relapse or clonal evolution and require postponed alloHCT. The transplantation field has evolved, becoming safer and more accessible. Upfront alloHCT from unrelated donors is becoming a tempting option. With the use of posttransplant cyclophosphamide, haploidentical HCT offers promising outcomes also in AA. In this paper, we present the state of the art in the management of severe AA for pediatric and adult patients based on the available guidelines and recently published studies.

Inflammation-related mRNA expression in patients with multiple myeloma undergoing hematopoietic stem cell mobilization.

Mobilization of CD34+ cells is a key element in the therapy of patients with multiple myeloma (MM) undergoing autologous stem cell transplantation. The use of chemotherapy and the granulocyte colony-stimulating factor can significantly affect the expression of inflammation-related proteins and the migration of hematopoietic stem cells. We assessed the mRNA expression of selected proteins involved in the inflammatory landscape in patients with MM (n = 71). The study aimed to evaluate C-C motif chemokine ligands 3, 4, 5 (CCL3, CCL4, CCL5), leukocyte cell-derived chemotaxin 2 (LECT2), tumor necrosis factor (TNF), and formyl peptide receptor 2 (FPR2) levels in the course of mobilization and their role in the CD34+ collection efficacy. mRNA expression from peripheral blood (PB) plasma was evaluated by Reverse transcription polymerase chain reaction. We observed a deep decline in CCL3, CCL4, LECT2, and TNF mRNA expression on the day of the first apheresis (day A) compared with that at baseline. A negative correlation was observed between CCL3, FPR2, LECT2, TNF level, and the CD34+ cells count in PB on day A, and the number of CD34+ cells obtained at first apheresis. Our results indicate that the investigated mRNAs significantly alter and may regulate the migration of CD34+ cells during mobilization. Moreover, in the case of FPR2 and LECT2, the results obtained in patients differed from the murine models.

Real-world study of children and young adults with myeloproliferative neoplasms: identifying risks and unmet needs.

Myeloproliferative neoplasms (MPNs) are uncommon in children/young adults. Here, we present data on unselected patients diagnosed before 25 years of age included from 38 centers in 15 countries. Sequential patients were included. We identified 444 patients, with median follow-up 9.7 years (0-47.8). Forty-nine (11.1%) had a history of thrombosis at diagnosis, 49 new thrombotic events were recorded (1.16% patient per year [pt/y]), perihepatic vein thromboses were most frequent (47.6% venous events), and logistic regression identified JAK2V617F mutation (P = .016) and hyperviscosity symptoms (visual disturbances, dizziness, vertigo, headache) as risk factors (P = .040). New hemorrhagic events occurred in 44 patients (9.9%, 1.04% pt/y). Disease transformation occurred in 48 patients (10.9%, 1.13% pt/y), usually to myelofibrosis (7.5%) with splenomegaly as a novel risk factor for transformation in essential thrombocythemia (ET) (P= .000) in logistical regression. Eight deaths (1.8%) were recorded, 3 after allogeneic stem cell transplantation. Concerning conventional risk scores: International Prognostic Score for Essential Thrombocythemia-Thrombosis and new International Prognostic Score for Essential Thrombocythemia-Thrombosis differentiated ET patients in terms of thrombotic risk. Both scores identified high-risk patients with the same median thrombosis-free survival of 28.5 years. No contemporary scores were able to predict survival for young ET or polycythemia vera patients. Our data represents the largest real-world study of MPN patients age < 25 years at diagnosis. Rates of thrombotic events and transformation were higher than expected compared with the previous literature. Our study provides new and reliable information as a basis for prospective studies, trials, and development of harmonized international guidelines for the specific management of young patients with MPN.

SIRT1-SIRT7 Expression in Patients with Lymphoproliferative Disorders Undergoing Hematopoietic Stem Cell Mobilization.

Sirtuins are involved in the fate of hematopoietic stem cells (HSCs), including their metabolism, stress response, differentiation, migration, and apoptosis. The aim of this study was to explore SIRT1-7 expression during HSC mobilization. The study included 50 patients with lymphoproliferative disorders (39 multiple myeloma, 11 lymphoma). Samples were taken before mobilization (day 0) and on the day of first apheresis (day A). The sirtuin expression was evaluated by the Droplet Digital PCR (ddPCR) method. A significant increase of the SIRT1, SIRT2, SIRT3, SIRT5, SIRT6, and SIRT7 levels measured at day A as compared to baseline was observed. The study revealed a positive correlation between SIRT5, SIRT6, and SIRT7 expression and the CD34+ peak value in peripheral blood and the number of CD34+ cells collected on day A. Patients from the SIRT7 "high expressors" group collected more CD34+ cells on day A than "low expressors". Upregulated expressions of SIRT3 and SIRT7 on the day of first apheresis were observed in patients in complete remission status (CR) as compared to the non-CR group. Our results suggest that the investigated sirtuins may influence the HSC migration and hematopoietic landscape during mobilization. SIRT5, SIRT6, and SIRT7 may be associated with the efficacy of HSC mobilization.

Alterations in microRNA Expression during Hematopoietic Stem Cell Mobilization.

microRNAs play an important role in the regulation of gene expression, cell fate, hematopoiesis, and may influence the efficacy of CD34+ cell mobilization. The present study examines the role of hsa-miR-15a-5p, hsa-miR-16-5p, hsa-miR-34a-5p, hsa-miR-126-3p, hsa-miR-146a-5p, hsa-miR-155-5p, and hsa-miR-223-3p in the course of hematopoietic stem cell mobilization. The numbers of CD34+ cells collected in patients with hematological malignancies (39 multiple myelomas, 11 lymphomas) were determined during mobilization for an autologous hematopoietic stem cell transplantation. The miRNA level was evaluated by RT-PCR. Compared to baseline, a significant decline in hsa-miR-15a-5p, hsa-miR-16-5p, hsa-miR-126-3p, hsa-miR-146a-5p, and hsa-miR-155-5p was observed on the day of the first apheresis (day A). An increase was observed only in the expression of hsa-miR-34a-5p. On day A, a negative correlation was found between hsa-miR-15a-5p and hsa-miR-146a-5p levels and the number of CD34+ cells in peripheral blood. A negative correlation was observed between hsa-miR-146a-5p and the number of collected CD34+ cells after the first apheresis. Good mobilizers, defined according to GITMO criteria, demonstrated a lower hsa-miR-146a-5p level on day A than poor mobilizers. Patients from the hsa-miR-146a-5p "low expressors" collected more CD34+ cells than "high expressors". Our results suggest that the investigated miRNAs, especially hsa-miR-146a-5p, may influence the efficacy of HSC mobilization.

Salvage autologous hematopoietic stem cell transplantation for multiple myeloma performed with stem cells procured after previous high dose therapy - a multicenter report by the Polish Myeloma Study Group.

Salvage autologous hematopoietic stem cell transplantation (auto-HSCT) constitutes a therapeutic option for a group of well-selected patients with relapsed multiple myeloma (MM). However, if an insufficient number of stem cells were harvested and stored before the first auto-HSCT, stem cells need to be remobilized. Patients diagnosed with MM who following relapse after auto-HSCT, had remobilization and afterward, auto-HSCT with remobilized cells were included in this retrospective analysis. Thirty-three patients, 61% males, the median age 61 years, were included. With a median follow-up of 1.8 years, 2-year progression-free survival was 56.2%, non-relapse mortality 4.8%. The 2-year cumulative incidence of t-MDS was 4.9%. Factors important for the outcome were: the quality of response, previous radiotherapy, the time between the first and salvage auto-HSCT. To conclude, salvage auto-HSCT performed with cells procured after the previous auto-HSCT can be efficacious in relapsed MM, especially if a sufficiently long response had been obtained to the first auto-HSCT(s).

The role of NF-κB and Smac/DIABLO proteins in the treatment response and survival of acute myeloid leukemia patients.

INTRODUCTION: The misbalance between a family of inhibitor of apoptosis proteins (IAP), regulated by the nuclear factor kappa B (NF-κB) and their natural antagonist second mitochondrial-derived activator of caspases/direct IAP binding protein with low pI (Smac/DIABLO) are important to biology of acute myeloid leukemia (AML). MATERIAL AND METHODS: The aim of the study was to assess NF-κB and Smac/DIABLO proteins expression in blasts of 109 newly diagnosed AML patients using the multicolor flow cytometry and evaluate their influence on AML patients outcome. RESULTS: Expression of NF-κB and of Smac/DIABLO proteins were found in 95% and 98% of the patients, respectively. A negative correlation between Smac/DIABLO and NF-κB was observed. Age < 60 years old as well as higher Smac/DIABLO expression were associated with a higher probability of complete response achievement in the multivariate analysis. Longer overall survival (OS) in the univariate and multivariate analyses was influenced by age < 60 years old, a favorable or intermediate-risk karyotype and high Smac/DIABLO expression. Additionally, in the survival analysis of the subgroups, the patients aged < 60 years old, with high Smac/DIABLO expression, lower NF-κB expression and < 50% of bone marrow blasts who were treated with standard treatment had better OS. CONCLUSIONS: Lower NF-κB and higher Smac/DIABLO expression may influence AML patients outcome.

Stem cell mobilization in multiple myeloma patients relapsing after previous autologous hematopoietic stem cell transplantation: A multicenter report by the Polish Myeloma Study Group.

BACKGROUND: Salvage autologous hematopoietic stem cell transplantation (autoHSCT) may be used to treat relapse of multiple myeloma occurring after previous autoHSCT. When insufficient number of hematopoietic stem cells was stored from the initial harvest, remobilization of stem cells is necessary. PURPOSE: The analysis of stem cell remobilization after previous autoHSCT. PATIENTS AND METHODS: Fifty-eight patients, 60% males, median 59 years, were included. Median time interval between autoHSCT and remobilization was 42 months. The first remobilization was performed mostly after chemotherapy: cyclophosphamide (33%), cytarabine (43%), and etoposide (19%). RESULTS: The first remobilization was successful in 67% patients. About 19% patients required plerixafor rescue, among whom it allowed for successful harvesting in 14%. Use of cyclophosphamide, cytarabine, and etoposide allowed for successful remobilization in 53%, 84%, and 55% patients, respectively. Patients treated with cytarabine had the highest yield of CD34+ cells (median 7.5 × 106 /kg vs 5.8 and 2.4 for etoposide and cyclophosphamide, P = .001). Higher percentage of patients was able to collect ≥2 × 106 CD34+ cells/kg during one leukapheresis after cytarabine (76% vs 21% for cyclophosphamide vs 36% for etoposide, P = .001). Cytarabine use was associated with lower risk of remobilization failure OR = 0.217, P = .02. Toxicity comprised mostly hematological toxicity (thrombocytopenia and neutropenia). One patient succumbed to septic shock. CONCLUSION: Remobilization after previous autoHSCT is feasible only in a proportion of patients. Cytarabine is associated with the highest rate of successful mobilization and the highest yield of mobilized CD34+ cells. The toxicity requires careful surveillance of these patients.

Allogeneic Hematopoietic Stem Cell Transplantation for Paroxysmal Nocturnal Hemoglobinuria: Multicenter Analysis by the Polish Adult Leukemia Group.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the sole potential cure for paroxysmal nocturnal hemoglobinuria (PNH); however, the data on its utility in PNH are limited. This retrospective analysis of patients with PNH who underwent allo-HSCT in 11 Polish centers between 2002 and 2016 comprised 78 patients with PHN, including 27 with classic PNH (cPNH) and 51 with bone marrow failure-associated PNH (BMF/PNH). The cohort was 59% male, with a median age of 29 years (range, 12 to 65 years). There was a history of thrombosis in 12% and a history of hemolysis in 81%, and 92% required erythrocyte transfusions before undergoing allo-HSCT. No patient received eculizumab, and 26% received immunosuppressive treatment. The median time from diagnosis to allo-HSCT was 12 months (range, 1 to 127 months). Almost all patients (94%) received reduced-toxicity conditioning, 66% with treosulfan. The stem cell source was peripheral blood in 72% and an identical sibling donor in 24%. Engraftment occurred in 96% of the patients. With a median follow-up of 5.1 years in patients with cPNH and 3.2 years in patients with BMF/PNH, 3-year overall survival (OS) was 88.9% in the former and 85.1% in the latter (P = not significant [NS]). The 3-year OS for patients with/without thrombosis was 50%/92% (P = NS) in the cPNH group and 83.3%/85.3% (P = NS) in the BMF/PNH group. The 3-year OS for in the BMF/PNH patients with/without hemolysis was 93.9%/62.9% (hazard ratio, .13; P = .016). No other factors impacted OS. After allo-HSCT, the frequency of the PNH clone was reduced to 0%, <1%, and <2.4% in 48%, 48%, and 4% of cPNH patients and in 84%, 11%, and 5% of BMF/PNH patients, respectively. The frequency of acute graft-versus-host disease (GVHD) grade II-IV was 23%, and the cumulative 1-year incidence of extensive chronic GVHD was 10.8% in the BMF/PNH group and 3.7% in the cPNH group. Allo-HSCT is a valid option for PNH patients, effectively eliminating the PNH clone with satisfactory overall survival and acceptable toxicity. Reduced-toxicity conditioning with treosulfan is effective and safe in patients with cPNH and BMF/PNH.

Early induction intensification with cladribine, cytarabine, and mitoxantrone (CLAM) in AML patients treated with the DAC induction regimen: a prospective, non-randomized, phase II study of the Polish Adult Leukemia Group (PALG).

We present the results of a prospective, non-randomized phase 2 trial in which 253 AML patients (pts) under 60 years old received DAC (Daunorubicin + AraC + Cladribine) as first induction followed by CLAM (Cladribine + AraC + Mitoxantrone) as early second induction on day 16 based on bone marrow (BM) blasts on day 14 (D14). The CR/CRi rate after a single course of DAC was 83% for pts with D14 BM blasts less than 10%. Forty-six pts had >10% BM blasts on D14, of whom 35 received CLAM with rates of CR/CRi 60% and early death (ED) 23%. The remaining 11 pts were not fit to receive CLAM, with rates of CR/CRi 28%, PR 18%, and ED 18%. Median OS was 7.2 versus 7.5 months, respectively. The overall CR/CRi rate was 77% after the first induction, with final CR/CRi rate 80% after DAC reinduction for pts who achieved PR with initial DAC course. CLAM used as early second induction might improve CR/CRi rates for younger AML pts with poor early response to DAC induction, but may be associated with higher mortality.

Associations of Ficolins With Hematological Malignancies in Patients Receiving High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantations.

A prospective study of 312 patients [194 with multiple myeloma (MM) and 118 with lymphomas (LYMPH)] receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT) was conducted. Ficolins are innate immune defense factors, able to distinguish between "self" "abnormal self," and "non-self" and contribute to the elimination of the last two by direct opsonization and/or initiation of complement activation via the lectin pathway. Concentrations of ficolin-1, ficolin-2, and ficolin-3 in serially taken serum samples were determined as were the polymorphisms of the corresponding (FCN1, FCN2, and FCN3) genes. Serum samples were collected before conditioning chemotherapy, before HSCT, and once weekly post-HSCT (four to five samples in total); some patients were also sampled at 1 and/or 3 months post-transplantation. The control group (C) consisted of 267 healthy unrelated individuals. Median ficolin-1 and ficolin-2 (but not ficolin-3) levels in MM patients' sera taken before chemotherapy were lower (and correspondingly frequencies of the lowest concentrations were higher) compared with controls. That appeared to be associated with the malignant disease itself rather than with post-HSCT complications (febrile neutropenia, infections accompanied, or not with bacteremia). Higher frequencies of the FCN1 genotype G/A-C/C-G/G (corresponding to polymorphisms at positions -542, -144, and +6658, respectively) and FCN2 gene heterozygosity for the -857 C>A polymorphism were found among patients diagnosed with MM compared with the C group. Furthermore, FCN2 G/G homozygosity (-557 A>G) was found more frequently and heterozygosity G/T at +6424 less frequently among LYMPH patients than among the healthy subjects. Heterozygosity for +1637delC mutation of the FCN3 gene was more common among patients diagnosed with lymphomas who experienced hospital infections. Although no evidence for an association of low ficolin-1 or ficolin-2 with infections during neutropenia following chemotherapy before HSCT was found, we observed a possible protective effect of ficolins during follow-up.

The Role of Complement Activating Collectins and Associated Serine Proteases in Patients With Hematological Malignancies, Receiving High-Dose Chemotherapy, and Autologous Hematopoietic Stem Cell Transplantations (Auto-HSCT).

We conducted a prospective study of 312 patients (194 with multiple myeloma, 118 with lymphomas) receiving high-dose conditioning chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT). Polymorphisms of MBL2 and MASP2 genes were investigated and serial measurements of serum concentrations of mannose-binding lectin (MBL), CL-LK collectin and MASP-2 as well as activities of MBL-MASP-1 and MBL-MASP-2 complex were made. Serum samples were taken before conditioning chemotherapy, before HSCT and once weekly after (totally 4-5 samples); in minority of subjects also 1 and/or 3 months post transplantation. The results were compared with data from 267 healthy controls and analyzed in relation to clinical data to explore possible associations with cancer and with chemotherapy-induced medical complications. We found a higher frequency of MBL deficiency-associated genotypes (LXA/O or O/O) among multiple myeloma patients compared with controls. It was however not associated with hospital infections or post-HSCT recovery of leukocytes, but seemed to be associated with the most severe infections during follow-up. Paradoxically, high MBL serum levels were a risk factor for prolonged fever and some infections. The first possible association of MBL2 gene 3'-untranslated region polymorphism with cancer (lymphoma) in Caucasians was noted. Heterozygosity for MASP2 gene +359 A>G mutation was relatively frequent in lymphoma patients who experienced bacteremia during hospital stay. The median concentration of CL-LK was higher in myeloma patients compared with healthy subjects. Chemotherapy induced marked increases in serum MBL and MASP-2 concentrations, prolonged for several weeks and relatively slighter decline in CL-LK level within 1 week. Conflicting findings on the influence of MBL on infections following chemotherapy of myeloma and lymphoma have been reported. Here we found no evidence for an association between MBL deficiency and infection during the short period of neutropenia following conditioning treatment before HSCT. However, we noted a possible protective effect of MBL during follow-up, and suspected that to be fully effective when able to act in combination with phagocytic cells after their recovery.

miRNA-15a, miRNA-16, miRNA-126, miRNA-146a, and miRNA-223 expressions in autologous hematopoietic stem cell transplantation and their impact on engraftment.

OBJECTIVE: MicroRNAs engaged in angiogenesis and hematopoiesis can influence hematopoietic stem cells (HSCs) homing after transplantation by targeting bone marrow niche microenvironment. This study aimed to examine the kinetics of miRNA-15a, miRNA-16, miRNA-126, miRNA-146a, and miRNA-223 in autologous HSC transplantation settings. METHODS: The study comprised of 51 patients with hematological malignancies (42 multiple myeloma, 9 lymphoma). Samples were taken at four time points: before conditioning, after chemotherapy but prior to autologous HSC transplantation (day 0), on day +7, and +14 days after HSCT. The miRNA levels were evaluated by the real-time PCR method. RESULTS: A significant, steady decline of all tested microRNAs in the course of transplantation, as compared to the baseline, was found. The study revealed that higher levels of miRNA-15a, miRNA-16, miRNA-126, and miRNA-146a on day 0 correlated with longer time to engraftment. Additionally, a positive correlation between the levels of miRNA-15a, miRNA-146a, and miRNA-223 assessed on day +7 and the time to engraftment was observed. CONCLUSIONS: In conclusion, all investigated microRNAs changed significantly in the course of transplantation. Our results suggest that the miRNAs may participate in hematopoietic recovery in the early post-transplant period and influence engraftment efficiency after HSCT.

The Influence of Comprehensive Cardiac Rehabilitation on Heart Rate Variability Indices after CABG is More Effective than after PCI.

The aim of this study was to evaluate the influence of cardiac rehabilitation (CR) on heart rate variability (HRV) indices in men with coronary artery disease (CAD) treated with percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). The study population consisted of 131 male patients with CAD prospectively and consecutively admitted to CR after PCI n = 72, or CABG n = 59. Participants performed cycle ergometer interval training for 45 min three times a week for 8 weeks. At baseline and after 8 weeks, all patients underwent the HRV assessment. HRV indices in CAGB survivals were significantly lower in comparison to PCI patients at baseline. Significant increases were seen for SDNN, rMSSD, and HF in the CABG group and only in HF component in PCI group after 8 weeks of CR. Eight weeks of CR seems to be more effective in CABG patients than patients after PCI.

VEGF, ANGPT1, ANGPT2, and MMP-9 expression in the autologous hematopoietic stem cell transplantation and its impact on the time to engraftment.

As a site of complicated interactions among cytokines, bone marrow niche has been the subject of many scientific studies, mainly in the context of the proteins influencing damage or recovery of endothelium after allogeneic hematopoietic stem cell transplantation (HSCT). In this study, we aimed at exploring mutual correlations of bone marrow niche cytokines involved in the homing and mobilization of hematopoietic stem cells, as well as in angiogenesis. The aim of our study was to evaluate levels of cytokines: VEGF, angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2), and matrix metalloproteinase 9 (MMP-9) during autologous HSCT and to examine their influence on hematological recovery. Forty-three patients with hematological malignancies (33 multiple myeloma, 10 lymphoma) were enrolled in the study. Plasma samples were taken at five time points: before conditioning treatment (BC), on transplantation day (0) and 7 (+7), 14 (+14), and 21 (+21) days after HSCT. The cytokine levels were evaluated by ELISA method. Our study revealed decreased levels of VEGF, ANGPT1, and MMP-9 in the early post-transplant period as compared to the baseline (BC). ANGPT2 was decreased after conditioning treatment, but tended to increase from day +7. On day +7, positive correlations between ANGPT1 level as well as MMP-9 and the time to engraftment were observed. As opposite to ANGPT1, negative correlation between ANGPT2 level on day +7 after HSCT and the time to hematological recovery was noticed. Our study suggests that investigated cytokines are an important part of bone marrow environment and significantly influence the time to engraftment after HSCT.

Safety and feasibility of therapeutic platelet depletion with Spectra Optia in a pregnant woman.

INTRODUCTION: Thrombocytapheresis is an alternative treatment beneficial in rare circumstances, when cytoreductive agents are contraindicated, drug therapy gave no response or the expected response would be too slow. Here we present a case of a pregnant woman who underwent 5 thrombocytaphereses using Spectra Optia device to reduce circulating platelets (PLT) count and prepare for Cesarian section. PATIENT CHARACTERISTICS AND PERFORMED TREATMENT: A 39-year-old woman with diagnosed chronic myeloid leukemia (CML) was treated with interferon because of too high PLT count. The treatment was well tolerated but the effect was not satisfactory (PLT count remained high). Because of high risk of bleeding during childbirth, the healthcare providers decided to perform thrombocytapheresis to reduce circulating PLT count below 1000×10E3/µl, and to prepare the patient for a planned Cesarean section. The results are presented as mean±SD. RESULTS: Five therapeutic aphereses procedures were performed, with a Spectra Optia device (TerumoBCT). A mean of 1.3±0.3 total blood volume was processed and we observed a mean PLT drop of 42.3±17.7%. Each apheresis procedure resulted in a PLT level ≤1000×10E3/µl. PLT CE1 was high 50.6±2.6% and reproducible. The white blood cell (WBC) loss was low (18.5%±11.0%). No adverse effects were observed. CONCLUSION: Therapeutic platelet depletion using the Spectra Optia™ Apheresis System can be effective and safe during pregnancy. Thrombocytapheresis procedures were reproducible and Spectra Optia system successfully adjusted settings to each procedure conditions. Thrombocytapheresis seems to be a viable and safe option even in pregnant women.

Are myelodysplastic syndromes underdiagnosed in Poland? A report by the Polish Adult Leukaemia Group.

OBJECTIVES: The epidemiology of myelodysplastic syndromes (MDS) differs among countries. Here, we present the first epidemiological indices determined for Poland. METHODS: Twenty-one haematological centres participated in the study. Patients diagnosed with MDS and acute myeloid leukaemia (AML) with 20-29% blasts were enrolled. Data collection was conducted for strictly predefined period. RESULTS: The overall crude incidence rate for all MDS subtypes was 1.95 (95% CI, 1.81-2.09) per 100 000 person-years: 2.46 (95% CI, 2.24-2.69) for males and 1.47 (95% CI, 1.31-1.65) for females; after excluding AML cases, the indices were as follows: 2.35 (95% CI, 2.08-2.66) for males and 1.27 (95% CI, 1.08-1.5) for females. Prevalence rate was 6.2 per 100 000 persons (95% CI, 5.96-6.45), that is 6.86 (95% CI, 6.49-7.24) for males and 5.58 (95% CI, 5.26-5.92) for females. Both incidence and prevalence increased with increasing age. The most frequently diagnosed MDS subtype was refractory cytopenia with multilineage dysplasia (RCMD), responsible for 30.3% of all newly diagnosed MDSs. CONCLUSIONS: RCMD is the most frequent MDS subtype in Poland. Incidence and prevalence indices are lower than those reported for other populations, which probably results from inadequate diagnosis of potential cases of this disease.

Red Blood Cell Transfusion Dependency and Hyperferritinemia Are Associated with Impaired Survival in Patients Diagnosed with Myelodysplastic Syndromes: Results from the First Polish MDS-PALG Registry.

BACKGROUND: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders characterized by ineffective hematopoiesis, cytopenias and a risk of progression to acute myeloid leukemia (AML). Anemia is the most frequent cytopenia diagnosed in patients with MDS. Regular RBC transfusions are the only treatment option for about 40% of patients. Transfusion-dependent patients develop secondary iron overload. The influence of serum ferritin (SF) concentration on survival and acute myeloid leukemia transformation in MDS patients remains controversial. The data for the Central European population is scarce and so far there is no description for Poland. OBJECTIVES: The aim of this study was to perform a retrospective analysis of the relationship of SF concentration with red blood cell transfusion dependency, survival and transformation to acute myeloid leukemia. MATERIAL AND METHODS: We retrospectively evaluated the data of the 819 MDS patients (58% male; median age 70 years) included in the MDS Registry of the MDS Section of the Polish Adult Leukemia Group (PALG). RESULTS: Analyses were performed on 190 patients diagnosed with MDS, maximal 6 months before inclusion to the registry in order to avoid selection bias (a shorter survival of higher risk MDS patients). Patients with hyperferritinemia higher than 1000 ng/L vs. patients with SF concentration lower than 1000 ng/L had a median survival of 320 days vs. 568 days, respectively (p log-rank = 0.014). The following factors were found to significantly worsen survival: RBC-transfusion dependence (p = 0.0033; HR 2.67L), platelet transfusion dependence (p = 0.0071; HR 3.321), hemoglobin concentration lower than 10 g/dL (p = 0.0036; HR 2.97), SF concentration higher than 1000 ng/L (p = 0.0023; HR = 2.94), platelet count lower than 10 G/L (p = 0.0081 HR = 5.04), acute leukemia transformation (p = 0.0081; HR 1.968). CONCLUSIONS: Taking into account the relatively low number of patients in previous studies exploring hyperferritinemia in MDS, the results of the first Polish MDS Registry provide important insights. Hyperferritinemia higher than 1000 ng/L can be an important indicator of poor prognosis in MDS.