Bing-Neel Syndrome, a Rare Presentation of Waldenström Macroglobulinemia-A Multicenter Report by the Polish Lymphoma Research Group.

Bing-Neel syndrome (BNS) is a rare presentation of Waldenström macroglobulinemia (WM). BNS is a consequence of the central nervous system (CNS) involvement by lymphoplasmacytic lymphoma (LPL) and, rarely, the peripheral nervous system. The data on BNS are extremely scarce. Therefore, we performed a multicenter retrospective analysis of BNS patients diagnosed and treated in centers aligned with the Polish Lymphoma Research Group. The analysis covers the years 2014-2021. Eleven patients were included, 55% females and the median age at BNS diagnosis was 61 years. The median time from WM to BNS was 3.5 years; 27% of patients did have a diagnosis of WM and BNS made simultaneously or within 30 days from each other. Isolated parenchymal involvement was the least frequent (20%). Patients were treated with different regimens, mostly able to cross the blood-brain barrier, including 18% treated with ibrutinib first line. The cumulative objective response to treatment was 73%. With the median follow-up of 20 months (95% CI, 2-32), the 36-month estimates were: overall survival (OS) 47%, progression-free survival (PFS) 33%, and cumulative incidence of BNS-associated death 41%. The performance status according to ECOG was significant for PFS (HR = 7.79) and the hemoglobin concentration below 11 g/dL was correlated with PFS. To conclude, BNS is a very rare manifestation of WM. It is associated with a poor outcome with most patients succumbing to BNS.

Allogeneic hematopoietic stem cell transplantation for adult HLH: a retrospective study by the chronic malignancies and inborn errors working parties of EBMT.

Hemophagocytic lymphohistiocytosis (HLH; hemophagocytic syndrome) is a rare syndrome of potentially fatal, uncontrolled hyperinflammation. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is indicated in primary, recurrent or progressive HLH, but information about its outcomes in the adult population is limited. We obtained data about 87 adult (≥18 years of age) patients retrospectively reported to the EBMT. The median survival time was 13.9 months. The three and five-year overall survival (OS) was 44% (95% CI 33-54%). Among 39 patients with a follow-up longer than 15 months, only three died. Relapse rate was 21% (95% CI 13-30%), while NRM reached 36% (95% CI 25-46%). Younger patients (<30 years of age) had better prognosis, with an OS of 59% (95% CI 45-73%) at three and five years vs 23% (95% CI 8-37%) for older ones. No difference in survival between reduced and myeloablative conditioning was found. To our knowledge, this is the largest report of adult HLH patients who underwent allo-HSCT. Patients who survive the first period after this procedure can expect a long disease-free survival. Both reduced intensity and myeloablative conditioning have therapeutic potential in adult HLH.

Impact of pre-transplantation sinus abnormalities assessed by Lund-Mackay scoring system on sinusitis occurrence after allogeneic hematopoietic cell transplantation in acute leukemia patients.

INTRODUCTION: Screening sinonasal evaluation is routinely performed before allogeneic hematopoietic cell transplantation (allo-HCT), however, data supporting such evaluation is inconsistent. O b j e c t i v e s: Assessment of the utility of screening sinonasal evaluation with computed tomography (CT). METHODS: A retrospective analysis of acute leukemia patients who underwent allo-HCT, for whom screening sinonasal CT scans were reevaluated, and for whom Lund-Mackay score (LMS) was calculated. R e s u l t s: Forty-eight patients, the median age at allo-HCT 38 years (18-58), 52% males, were included. 79% had acute myeloid leukemia (AML), 21% acute lymphoblastic leukemia (ALL). Conditioning intensity was myeloablative in 96% of patients, 21% of patients received total body irradiation. 19% of patients had a history of sinusitis before allo-HCT. Screening sinus CT was performed a median of 22 days before allo-HCT. The median LMS was 1 point (0- 10). The severity of sinus abnormalities was: no abnormalities (31%), mild (67%), moderate (2%), severe (0%). Mucosal thickening was the most frequent abnormality (69%). Eleven patients experienced sinusitis after a median of 93 days (11-607) after allo-HCT. 1-year cumulative incidence of sinusitis was 22%. No threshold of LMS and no type of sinus abnormalities were correlated with sinusitis development after allo-HCT. Mild sinus disease at screening did not negatively impact survival in comparison to no sinus disease. C o n c l u s i o n s: Despite the fact, that majority of analyzed patients had either no or mild sinus disease at screening a significant proportion of patients developed sinusitis after allo-HCT. Evaluation of LMS before allo-HCT did not help predict the development of sinusitis after the procedure.

Eosinophilic gastroenteritis and graft-versus-host disease induced by transmission of Norovirus with fecal microbiota transplant.

Fecal microbiota transplantation (FMT) was performed to decolonize gastrointestinal tract from antibiotic-resistant bacteria before allogeneic hematopoietic cells transplantation (alloHCT). AlloHCT was complicated by norovirus gastroenteritis, acute graft-versus-host disease, and eosinophilic pancolitis. Norovirus was identified in samples from FMT material. Symptoms resolved after steroids course and second norovirus-free FMT from another donor.

Seasonal variation of human physiology does not influence the harvest of peripheral blood CD34+ cells from unrelated hematopoietic stem cell donors.

There are many reports on factors predicting the outcome of PBSC (peripheral blood stem cell) mobilization, such as the donor's gender, age, weight, white blood cell count, platelets pre apheresis, LDH and iron status. Although there are reports of seasonal variation in the physiology of the human immune system and hematopoiesis there are no data that such differences play a role in the response to G-CSF in healthy hematopoietic stem cell donors. The response to G-CSF could also impact the collection results during different seasons. To assess the possible impact of seasonal variation we performed a retrospective, single-center analysis of mobilization and harvest of PBSC in 330 healthy unrelated donors. We found no significant differences in the number of CD34+ cells in peripheral blood after G-CSF mobilization and in collection results when all donors were analyzed. In the subgroup of male donors the number of CD34+ stem cells after G-CSF mobilization was higher than average in summer and autumn (p = 0.036), however, it did not translate into clinically relevant differences in stem cell harvest. We conclude that although there is possible seasonal variation in the response to G-CSF in male donors there is no impact on PBSC harvest in healthy unrelated donors.

Tandem Allogeneic Hematopoietic Stem Cell Transplantation for Salvage Treatment of Acute Myeloid Leukemia Refractory to Induction Chemotherapy: A Case Report.

BACKGROUND: Primary refractory acute myeloid leukemia (AML) is associated with dismal prognosis. No standard treatment options are available, and it remains an unmet clinical need. Here, we report a case of a tandem allogeneic hematopoietic stem cell transplantation (allo-HSCT) performed in a patient who did not achieve remission after 2 courses of induction chemotherapy. METHODS CASE REPORT: The treatment was approved by the Bioethical Commission of the Medical University of Warsaw and was performed in accordance with the Declaration of Helsinki. The patient gave informed consent. RESULTS: A 41-year-old woman was diagnosed with AML, high cytogenetic risk, with concomitant skin and central nervous system involvement, bone marrow necrosis, and hemophagocytic lymphohistiocytosis. She received "3+7" induction and HAM (cytarabine, mitoxantrone) reinduction, after which she did not achieve remission and hematopoietic recovery. Tandem allo-HSCT was performed from the same HLA-identical brother---the first after reduced intensity conditioning (cladribine, cytarabine, mitoxantrone, melphalan) and the second after myeloablative conditioning (BuCy--busulphan, cyclophosphamide). The patient obtained complete remission after the first allo-HSCT and remains disease-free after the second for 5 years CONCLUSION: Tandem allo-HSCT may be a treatment option for primary refractory AML.

Type 2 diabetes mellitus compromises the survival of diffuse large B-cell lymphoma patients treated with (R)-CHOP - the PLRG report.

Comorbidities impair the prognosis of diffuse large B-cell lymphoma (DLBCL). Type 2 diabetes mellitus (DMT2) increases the risk of other comorbidities, e.g., heart failure (HF). Thus, we hypothesized that pre-existing DMT2 may negatively affect the outcome of DLBCL. To verify this, DLBCL patients treated with (R)-CHOP were enrolled. 469 patients were eligible, with a median age of 57 years; 356 patients had advanced-stage DLBCL. 126 patients had high-intermediate and 83 high-risk international prognostic index (IPI). Seventy-six patients had DMT2, 46 HF; 26 patients suffered from both DMT2 and HF. In the analyzed group DMT2 or HF significantly shortened overall survival (OS) and progression free survival (PFS): the 5-year OS for patients with DMT2 was 64% vs 79% and for those with HF: 49% vs 79%. The 5-year PFS for DMT2 was 50.6% vs 62.5% and for HF 39.4% vs 63.2%. The relapse/progression incidence was comparable between groups; the non-relapse/progression mortality (NRPM) was significantly higher solely in DMT2 patients (5-year NRPM 22.5% vs 8.4%). The risk of death was higher in patients with higher IPI (HR = 1.85) and with DMT2 (HR = 1.87). To conclude, pre-existing DMT2, in addition to a higher IPI and HF, was a negative predictor for OS and PFS.

Hodgkin lymphoma transformation of chronic lymphocytic leukemia-A real life data from the Polish Lymphoma Research Group.

Richter transformation (RT) of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) to Hodgkin lymphoma (HL) is a rare and unexpected event in the course of the disease and data on this phenomenon is still limited. To better understand the clinical and histological characteristics and the outcomes of HL variant of RT (HvRS) the Polish Lymphoma Research Group performed a nationwide survey which identified 22 patients with histologically proven HvRS diagnosed between 2002 and 2016. There were 16 (73%) males. The median age at CLL/SLL and HvRS diagnosis was 59 (39-77) and 64 (40-77) years, respectively. The median interval between CLL/SLL and HvRS diagnosis was 38 months (range: 0-187). All patients had an advanced stage HL, and majority, 17 (77%), presented with B symptoms. The predominant subtypes of HL were nodular sclerosis (12; 55%) and mixed cellularity (9; 41%). Eighteen patients received non-palliative treatment, including 13 who received driamycin, bleomycin, vinblastine, and dacarbazine (ABVD) regimen first line. Objective response was: 50%, with 33% complete remissions (61% and 46% for ABVD, respectively). Median overall survival reached 13.3 months (95% CI, 3.7-NA). The only adverse prognostic factor for survival was a higher number (≤1 versus ≥2) of prior lines of treatment given for CLL/SLL with HR 3.57 (95% CI, 1.16-10.92). We conclude, HvRS harbors a poor prognosis, especially in patients heavily pretreated for CLL/SLL. Response to standard first-line anti-HL chemotherapy is unsatisfactory, and new agents should be tested to improve the outcome.

The Emerging Link Between the Complement Cascade and Purinergic Signaling in Stress Hematopoiesis.

Innate immunity plays an important role in orchestrating the immune response, and the complement cascade (ComC) is a major component of this ancient defense system, which is activated by the classical-, alternative-, or mannan-binding lectin (MBL) pathways. However, the MBL-dependent ComC-activation pathway has been somewhat underappreciated for many years; recent evidence indicates that it plays a crucial role in regulating the trafficking of hematopoietic stem/progenitor cells (HSPCs) by promoting their egress from bone marrow (BM) into peripheral blood (PB). This process is initiated by the release of danger-associated molecular patterns (DAMPs) from BM cells, including the most abundant member of this family, adenosine triphosphate (ATP). This nucleotide is well known as a ubiquitous intracellular molecular energy source, but when secreted becomes an important extracellular nucleotide signaling molecule and mediator of purinergic signaling. What is important for the topic of this review, ATP released from BM cells is recognized as a DAMP by MBL, and the MBL-dependent pathway of ComC activation induces a state of "sterile inflammation" in the BM microenvironment. This activation of the ComC by MBL leads to the release of several potent mediators, including the anaphylatoxins C5a and desArgC5a, which are crucial for egress of HSPCs into the circulation. In parallel, as a ligand for purinergic receptors, ATP affects mobilization of HSPCs by activating other pro-mobilizing pathways. This emerging link between the release of ATP, which on the one hand is an activator of the MBL pathway of the ComC and on the other hand is a purinergic signaling molecule, will be discussed in this review. This mechanism plays an important role in triggering defense mechanisms in response to tissue/organ injury but may also have a negative impact by triggering autoimmune disorders, aging of HSPCs, induction of myelodysplasia, and graft-versus-host disease after transplantation of histoincompatible hematopoietic cells.

Autologous peripheral blood stem cell transplantation in dialysis-dependent multiple myeloma patients-DAUTOS Study of the Polish Myeloma Study Group.

INTRODUCTION: Dialysis-dependent (DD) multiple myeloma patients (MM) have a poor prognosis and high tumour burden, thus may benefit from autologous peripheral blood stem cell transplantation (auto-PBSCT), however, these patients have an increased risk of toxicity. AIMS: To evaluate the outcomes (toxicity, PFS, OS) of high dose therapy followed by auto-PBSCT during an observational study and after propensity score matching. PATIENTS AND METHODS: Between 2004-2015, 24 DD patients, (aged 38-67 years), ISS 3, treated with auto-PBSCT, requiring dialysis at diagnosis and auto-PBSCT were evaluated, matched and compared to 55 normal renal function MM patients (NRF) with ISS 3 for outcomes of interest. RESULTS: In DD patients compared to NRF patients risk of mucositis (88% vs 55%), infection (79% vs 51%), parenteral nutrition (50% vs 24%), diarrhoea (71% vs 38%), prolonged duration of hospitalisation (medians: 30 vs 21 days), requirement for RBC transfusion (83% vs 36%) were significantly higher, while no significant differences were found in post-transplant response (ORR; 75% vs 87%), 5-year PFS (36% vs 20%) and OS (39% vs 50%). Subgroup analyses based on toxicity supported these results. CONCLUSIONS: Despite the increased risk of toxicity in DD patients these events do not significantly affect both the PFS and OS.

Continuous Mononuclear Cell Collection (cMNC) protocol impact on hematopoietic stem cell collections in donors with negative collection predictors.

BACKGROUND: Recently, novel protocol utilizing Continuous Mononuclear Cell Collection (cMNC) have been introduced for leukapheresis. We compared the efficacy of cMNC with an older protocol - mononuclear cell collection (MNC) for CD34+ cell collection in unrelated donors with negative stem cell collection predictors. MATERIAL AND METHODS: Retrospective data from a series of 258 consecutive unrelated hematopoietic stem cell donors was included in this single-center study (80 donors collected with cMNC and 178 with MNC). The donors with poor predictors for collection such as low number of circulating CD34+ cells and/or weight disproportion were assigned to the cMNC arm. RESULTS: The cMNC protocol yielded a higher number of CD34 + cells per donor body weight (7.63 × 106/kg vs 6.82 × 106/kg, p = 0.027). One apheresis was sufficient for collection of target cell number in 89% individuals from both groups despite negative predictors in the cMNC group. In donors with CD34 + cell count <100/µL and a body weight disproportion between donor and recipient one apheresis was sufficient in 83% of donors in cMNC group and in 58% in MNC group (p = 0.0345) with collection efficiency CE2% values of 61% for cMNC and 62% for MNC (p = 0.77). CONCLUSION: cMNC protocol is more efficient in donors with low pre-apheresis CD34+ cell count and weight disproportion between donor and recipient. This suggests that the use of cMNC in unrelated donors could possibly further improve the results of HSC collections.

Long-term follow-up for up to 5 years on the risk of leukaemic progression in thrombocytopenic patients with lower-risk myelodysplastic syndromes treated with romiplostim or placebo in a randomised double-blind trial.

BACKGROUND: Treatment options for thrombocytopenia in myelodysplastic syndromes are scarce. As described previously in a randomised phase 2 study (n=250), 58 weeks of romiplostim treatment in patients with International Prognostic Scoring System (IPSS)-defined lower-risk (low-risk or intermediate-1 risk) myelodysplastic syndromes led to reduced platelet transfusions (p<0·0001) and increased International Working Group-defined haematological improvement-platelet rates (p<0·0001) versus placebo. However, the study drug was discontinued because of the potential risk for progression to or incorrect diagnosis or treatment for acute myeloid leukaemia, based on an acute myeloid leukaemia interim hazard ratio (HR) of 2·5; the subsequent 58-week acute myeloid leukaemia HR was 1·2 (95% CI 0·4-3·8). METHODS: This study is a 5-year follow-up of a phase 2, multicentre, double-blind trial of romiplostim treatment in patients with lower-risk myelodysplastic syndromes. Eligible patients were recruited at 109 centres in North America, Europe, Russia, and Australia, were aged 18-90 years, and had platelets of 20 × 109 per L or less with or without a history of bleeding or 50 × 109 platelets per L or less with a history of bleeding. Patients were randomly assigned by interactive voice response system with stratification by baseline platelet count (≥20 × 109 per L or <20 × 109 per L) and IPSS risk (low or intermediate-1) to receive either placebo or 750 µg romiplostim subcutaneously once per week for 58 weeks. The primary outcomes for this long-term follow-up were survival and progression to acute myeloid leukaemia. Progression to acute myeloid leukaemia was defined as either 20% blasts or more after 4 weeks from romiplostim discontinuation; as per pathology; or by initiation of antileukaemia treatment. The primary outcome was assessed per protocol in all patients with available data. This study is registered with ClinicalTrials.gov, NCT00614523. FINDINGS: Patients were recruited from July 21, 2008, to Dec 16, 2010. 167 patients were assigned to receive romiplostim treatment and 83 were assigned to receive placebo. 210 (84%) of 250 patients entered the 5-year long-term follow-up (139 patients in the romiplostim group and 83 in the placebo group). At the end of follow-up, proportions of patients with acute myeloid leukaemia (20 [12%] of 167 in the romiplostim group vs nine [11%] of 83 in the placebo group; HR 1·06 [95% CI 0·48-2·33]; p=0·88) and proportions who died (93 [56%] vs 54 [54%]; HR 1·03 [0·72-1·47]; p=0·89) were not significantly different between the two groups. INTERPRETATION: Following the decision to stop the study drug, 5-year long-term follow-up HRs for transformation to acute myeloid leukaemia and HRs for death did not differ between patients treated with romiplostim and those treated with placebo, indicating that use of romiplostim is probably not associated with any increased risk of acute myeloid leukaemia or death, despite initial concerns. FUNDING: Amgen Inc.

Incidence of Second Primary Malignancies after Autologous Transplantation for Multiple Myeloma in the Era of Novel Agents.

The advent of novel agents for multiple myeloma (MM) is cause for a re-examination of the incidence of second primary malignancies (SPMs). We examined the SPM rate in MM patients who were enrolled in the prospective observational CALM (Collaboration to Collect Autologous Transplant outcome in Lymphoma and Myeloma) study. Between 2008 and 2012, 3204 patients with MM underwent a first autologous hematopoietic stem cell transplantation. Plerixafor was used as a mobilizing agent for patients with poor (or potentially poor) stem cell mobilization as defined by the respective centers. A total of 135 patients developed SPMs, with a cumulative incidence of 5.3% (95% confidence interval, 4.4 to 6.3) at 72 months. Ninety-four patients developed solid tumors, 30 developed hematologic malignancies, and 11 developed an SPM of an unknown type. The cumulative incidence of known hematologic and solid malignancies were 1.4% and 3.6%, respectively, at 72 months. In a univariate analysis, use of radiotherapy, type of induction regimen, hematopoietic stem cell dose, poor mobilizer status, plerixafor use, and sex did not influence the cumulative incidence of SPMs. Only age over 65 years was statistically associated with an increased incidence. Overall, the incidence of SPMs was comparable to earlier estimations of SPMs in MM.

Melphalan 140 mg/m2 or 200 mg/m2 for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party.

Melphalan at a dose of 200 mg/m2 is standard conditioning prior to autologous hematopoietic stem cell transplantation for multiple myeloma, but a dose of 140 mg/m2 is often used in clinical practice in patients perceived to be at risk of excess toxicity. To determine whether melphalan 200 mg/m2 and melphalan 140 mg/m2 are equally effective and tolerable in clinically relevant patient subgroups we analyzed 1964 first single autologous transplantation episodes using a series of Cox proportional-hazards models. Overall survival, progression-free survival, cumulative incidence of relapse, non-relapse mortality, hematopoietic recovery and second primary malignancy rates were not significantly different between the melphalan 140 mg/m2 (n=245) and melphalan 200 mg/m2 (n=1719) groups. Multivariable subgroup analysis showed that disease status at transplantation interacted with overall survival, progression-free survival, and cumulative incidence of relapse, with a significant advantage associated with melphalan 200 mg/m2 in patients transplanted in less than partial response (adjusted hazard ratios for melphalan 200 mg/m2versus melphalan 140 mg/m2: 0.5, 0.54, and 0.56). In contrast, transplantation in very good partial or complete response significantly favored melphalan 140 mg/m2 for overall survival (adjusted hazard ratio: 2.02). Age, renal function, prior proteasome inhibitor treatment, gender, or Karnofsky score did not interact with overall/progression-free survival or relapse rate in the melphalan dose groups. There were no significant survival or relapse rate differences between melphalan 200 mg/m2 and melphalan 140 mg/m2 patients with high-risk or standard-risk chromosomal abnormalities. In conclusion, remission status at the time of transplantation may favor the use of melphalan 200 mg/m2 or melphalan 140 mg/m2 for key transplant outcomes (NCT01362972).

Nutritional Status of Hematological Patients before Hematopoietic Stem Cell Transplantation and in Early Posttransplantation Period.

Hematopoietic stem cell transplantation (HSCT) is an aggressive method of treatment affecting patient's homeostasis. The aim of the study was to evaluate the initial nutritional status of HSCT patients and nutritional status in early posttransplantation period. The prospective study included 100 consecutive patients with hematological malignancies subjected to HSCT. The nutritional status evaluation was made using the nutritional screening scales, anthropometric and biochemical parameters, as well. On the day +7 following HSCT significant decrease in concentration of total protein (5.8 g/dl), albumin (3.6 g/dl) and transferrin (165 mg/dl) were observed (P < 0.001), although the mean body mass/BMI were within the normal range. On the day +14, the biochemical parameters of the nutritional status were even lower (P < 0.001). Poorer nutritional status was associated with worse performance status and mucositis escalation. The adequate nutritional support plan is important element of the whole transplantation procedure.

Biosimilar G-CSF versus filgrastim and lenograstim in healthy unrelated volunteer hematopoietic stem cell donors.

The World Marrow Donor Organization recommends original granulocyte-colony stimulating factor (G-CSF) for the mobilization of stem cells in healthy unrelated hematopoietic stem cell donors. We report the comparison of a biosimilar G-CSF (Zarzio) with two original G-CSFs (filgrastim and lenograstim) in mobilization in unrelated donors. We included data of 313 consecutive donors who were mobilized during the period from October 2014 to March 2016 at the Medical University of Warsaw. The primary endpoints of this study were the efficiency of CD34+ cell mobilization to the circulation and results of the first apheresis. The mean daily dose of G-CSF was 9.1 µg/kg for lenograstim, 9.8 µg/kg for biosimilar filgrastim, and 9.3 µg/kg for filgrastim (p < 0.001). The mean CD34+ cell number per microliter in the blood before the first apheresis was 111 for lenograstim, 119 for biosimilar filgrastim, and 124 for filgrastim (p = 0.354); the mean difference was even less significant when comparing CD34+ number per dose of G-CSF per kilogram (p = 0.787). Target doses of CD34+ cells were reached with one apheresis in 87% donors mobilized with lenograstim and in 93% donors mobilized with original and biosimilar filgrastim (p = 0.005). The mobilized apheresis outcomes (mean number of CD34+ cells/kg of donor collected during the first apheresis) was similar with lenograstim, biosimilar filgrastim, and filgrastim: 6.2 × 106, 7.6 × 106, and 7.3 × 106, respectively, p = 0.06. There was no mobilization failure in any of the donors. Biosimilar G-CSF is as effective in the mobilization of hematopoietic stem cells in unrelated donors as original G-CSFs. Small and clinically irrelevant differences seen in the study can be attributed to differences in G-CSF dose and collection-related factors. Active safety surveillance concurrent to clinical use and reporting to donor outcome registry (e.g., EBMT donor outcome registry or WMDA SEAR/SPEAR) might help to evaluate the possible short- and long-term complications of biosimilar G-CSF.

Bone marrow harvest from unrelated donors-up-to-date methodology.

OBJECTIVES: Bone marrow harvesting is one of the essential sources of stem cells for hematopoietic stem cell transplantation. We describe here the current "up-to-date" standard of the bone marrow harvest in unrelated stem cell donors. METHODS: We analyzed medical data of 187 unrelated hematopoietic stem cell donors who underwent bone marrow harvest without previous peripheral blood stem collection at the center between 2011 and 2015. The methodology of marrow collection includes multiple cells aimed at safety of the procedure, for example, educational movie, modified skin disinfection protocol, cell enumeration during the procedure, reduction of the contamination surfaces, and ongoing monitoring of the quality of work of the doctors. RESULTS: The total nucleated cell count over 2×108 per kg of recipient has been reached in 93.6% of harvests. All of the donors harvested more than 1×108 per kg of the recipient. There were no donors who required transfusions or had serious adverse events during and after the harvest. CONCLUSION: We describe here the current up-to-date standard of bone marrow harvest, which leads to excellent results in majority of donors without causing significant complications during the donation.

Similar but not the same: Differential diagnosis of HLH and sepsis.

Differential diagnosis of hemophagocytic lymphohistiocytosis (HLH; hemophagocytic syndrome) and sepsis is critically important because the life-saving aggressive immunosuppressive treatment, required in the effective HLH therapy, is absent in sepsis guidelines. Moreover, HLH may be complicated by sepsis. Hyperinflammation, present in both states, gives an overlapping clinical picture including fever and performance status deterioration. The aim of this review is to provide aid in this challenging diagnostic process. Analysis of clinical features and laboratory results in multiple groups of patients (both adult and pediatric) with either HLH or sepsis allows to propose criteria differentiating these two conditions. The diagnosis of HLH is supported by hyperferritinemia, splenomegaly, marked cytopenias, hypofibrinogenemia, low CRP, characteristic cytokine profile and, only in adults, hypertriglyceridemia. In the presence of these parameters (especially the most characteristic hyperferritinemia), the other HLH criteria should be assessed. Genetic analyses can reveal familial HLH. Hemophagocytosis is neither specific nor sensitive for HLH.