Hematopoietic cell transplantation and cellular therapies in Switzerland. Evolution over 25 years. A report from the stem cell transplantation and cellular therapies working groups of the SBST 1997-2021.

The Swiss Blood Stem Cell Transplantation and Cellular Therapy Group (SBST) leads a mandatory national registry for all hematopoietic stem cell transplants (HCT) and cellular therapies. After 25 years, information was available for 11,226 patients receiving an HCT (4031 allogeneic and 7195 autologous), including 925 pediatric patients. We compared patient characteristics and outcome by quinquennia 1997-2001, 2002-2006, 2007-2011, 2012-2016, and 2017-2021. There were numerous changes over time. Allogeneic transplant recipients became older (median age 33.7 vs. 54.3) and had more frequently unrelated donors and reduced intensity conditioning in later quinquennia. Similarly, age increased for recipients of autologous HCT (median 48.3 vs. 59.9). We did not see a significant drop in transplant activity during the SARS-CoV-2 pandemic. Analysis of outcome showed overall survival (relative risk (RR) of death 0.664 (0.529-0.832) and progression free survival (RR 0.708 (0.577-0.870) being improved over time comparing the latest to the first quinquennium adjusting for risk factors. Non-relapse mortality decreased in recipients of allogeneic HCT (RR: 0.371 (0.270-0.509)) over time but relapse risks did not. Outcome of autologous HCT improved as well across quinquennia, this improvement was mainly due to decreased relapse risks (RR 0.681 (0.597-0.777)), possibly related to maintenance treatment or rescue treatment for relapse mainly in myeloma patients. Cellular therapies other than allogeneic or autologous HCT, particularly chimeric antigen receptor T-cells (CAR-T) treatment have started to increase after 2019, year of approval of the first commercial CAR-T product in Switzerland. Data on chimeric antigen receptor T-cell treatment are too early for comparative analyses. Detailed analyses of changes over time are presented. This study includes all HCTs, and cellular therapies, data useful for quality assurance programs, health care cost estimation and benchmarking. Between 50% and 60% of patients are long-term survivors after both types of HCT, indicating growing populations of surviving patients requiring long-term care.

Immunomodulation with romiplostim as a second-line strategy in primary immune thrombocytopenia: The iROM study.

Thrombopoietin receptor agonists (TPO-RAs) stimulate platelet production, which might restore immunological tolerance in primary immune thrombocytopenia (ITP). The iROM study investigated romiplostim's immunomodulatory effects. Thirteen patients (median age, 31 years) who previously received first-line treatment received romiplostim for 22 weeks, followed by monitoring until week 52. In addition to immunological data, secondary end-points included the sustained remission off-treatment (SROT) rate at 1 year, romiplostim dose, platelet count and bleedings. Scheduled discontinuation of romiplostim and SROT were achieved in six patients with newly diagnosed ITP, whereas the remaining seven patients relapsed. Romiplostim dose titration was lower and platelet count response was stronger in patients with SROT than in relapsed patients. In all patients, regulatory T lymphocyte (Treg) counts increased until study completion and the counts were higher in patients with SROT. Interleukin (IL)-4, IL-9 and IL-17F levels decreased significantly in all patients. FOXP3 (Treg), GATA3 (Th2) mRNA expression and transforming growth factor-ß levels increased in patients with SROT. Treatment with romiplostim modulates the immune system and possibly influences ITP prognosis. A rapid increase in platelet counts is likely important for inducing immune tolerance. Better outcomes might be achieved at an early stage of autoimmunity, but clinical studies are needed for confirmation.

Safety and Feasibility of Immunoadsorption with Heparin Anticoagulation in Preparation of ABO-Incompatible Kidney Transplantation: A Retrospective Single-Center Study.

Introduction: Immunoadsorption (IA) of isohemagglutinins is an often-crucial procedure in preparation of major ABO blood group-incompatible living donor kidney transplantation (ABOi LDKT). Standard citrate-based anticoagulation during the procedure has potential disadvantages for distinct patient groups. In this study, we report our experience with an alternative anticoagulation scheme using heparin during IA for selected patients. Methods: We conducted a retrospective analysis of all patients who underwent IA with heparin anticoagulation between February 2013 and December 2019 at our institution with focus on the safety and efficacy of the adapted procedure. For further validation, we compared graft function, graft survival, and overall survival with those of all recipients of living donor kidney transplants with or without pretransplant desensitizing apheresis for ABO antibodies at our institution during the same period. Results: In thirteen consecutive patients prepared for ABOi LDKT with IA with heparin anticoagulation, no major bleeding or other significant complications were observed. All patients achieved sufficient isohemagglutinin titer reduction to proceed to transplant surgery. Graft function, graft survival, and overall survival did not significantly differ from patients treated with standard anticoagulation for IA or ABO compatible recipients of living donor kidneys. Conclusion: IA with heparin in preparation of ABOi LDKT is safe and feasible for selected patients after internal validation.

Indices of iron homeostasis in asymptomatic subjects with HFE mutations and moderate ferritin elevation during iron removal treatment.

We analysed iron biomarkers and their relationships in 30 subjects with HFE mutations and moderate hyperferritinaemia undergoing iron removal at our blood donation centre. Body mass index (BMI) and liver enzymes were assessed. Serum iron (SI), ferritin, transferrin saturation (TSAT), hepcidin and non-transferrin bound iron (NTBI) were measured serially. Seventeen subjects had p.C282Y/p.C282Y, nine p.C282Y/p.H63D, four p.H63D/p.H63D. Median age (p = 0.582), BMI (p = 0.500) and ferritin (p = 0.089) were comparable. At baseline, 12/17 p.C282Y/p.C282Y and 2/9 p.C282Y/p.H63D had measurable NTBI (p = 0.003). The p.C282Y/p.C282Y had higher TSAT (p < 0.001), lower hepcidin (p = 0.031) and hepcidin/ferritin ratio (p = 0.073). After treatment, iron indices were similar among groups, except TSAT (higher in p.C282Y/p.C282Y; p = 0.06). Strong relationships were observed between ferritin and TSAT (R = 0.71), NTBI and TSAT (R = 0.61), NTBI and SI (R = 0.54) in p.C282Y/p.C282Y. Hepcidin correlated weakly with ferritin in p.C282Y/p.C282Y (R = 0.37) but strongly in p.C282Y/p.H63D (R = 0.66) and p.H63D/p.H63D (R = 0.72), while relationships with TSAT were weak (R = 0.27), moderate (R = 0.55) and strong (R = 0.61), respectively. Low penetrance p.C282Y/p.C282Y phenotype displays hepcidin dysregulation and biochemical risk for iron toxicity.

Characterization of pathogen-inactivated COVID-19 convalescent plasma and responses in transfused patients.

BACKGROUND: Efficacy of donated COVID-19 convalescent plasma (dCCP) is uncertain and may depend on antibody titers, neutralizing capacity, timing of administration, and patient characteristics. STUDY DESIGN AND METHODS: In a single-center hypothesis-generating prospective case-control study with 1:2 matched dCCP recipients to controls according to disease severity at day 1, hospitalized adults with COVID-19 pneumonia received 2 × 200 ml pathogen-reduced treated dCCP from 2 different donors. We evaluated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in COVID-19 convalescent plasma donors and recipients using multiple antibody assays including a Coronavirus antigen microarray (COVAM), and binding and neutralizing antibody assays. Outcomes were dCCP characteristics, antibody responses, 28-day mortality, and dCCP -related adverse events in recipients. RESULTS: Eleven of 13 dCCPs (85%) contained neutralizing antibodies (nAb). PRT did not affect dCCP antibody activity. Fifteen CCP recipients and 30 controls (median age 64 and 65 years, respectively) were enrolled. dCCP recipients received 2 dCCPs from 2 different donors after a median of one hospital day and 11 days after symptom onset. One dCCP recipient (6.7%) and 6 controls (20%) died (p = 0.233). We observed no dCCP-related adverse events. Transfusion of unselected dCCP led to heterogeneous SARS CoV-2 antibody responses. COVAM clustered dCCPs in 4 distinct groups and showed endogenous immune responses to SARS-CoV-2 antigens over 14-21 days post dCCP in all except 4 immunosuppressed recipients. DISCUSSION: PRT did not impact dCCP anti-virus neutralizing activity. Transfusion of unselected dCCP did not impact survival and had no adverse effects. Variable dCCP antibodies and post-transfusion antibody responses indicate the need for controlled trials using well-characterized dCCP with informative assays.

Frequency, reactivity and evolution of human leukocyte antigen and human platelet antigen antibodies in the setting of hematopoietic cell transplantation.

BACKGROUND AND OBJECTIVES: Antibodies (Ab) against HLA and HPA antigens play an important role in HCT. In this prospective study we evaluated prevalence and kinetics of HLA- and HPA-Ab after HCT, including a possible donor-recipient transfer and their clinical relevance in respect to platelet transfusion refractoriness (PTR). MATERIALS AND METHODS: Patients were consecutively recruited. Ab were determined by microbead assay technique and a mean fluorescence intensity cut-off of 1,000. RESULTS: At baseline, 21 donors (42 %) and 27 patients (54 %) had HLA-Ab with a mean panel reactivity (cPRA) of 34.9 ± 29.4 % and 46.1 ± 36.5 %, respectively. We observed a significant higher number of HLA-Ab specificities in female donors and patients and a predominance of HLA-class I Ab. At day 0 we detected an increase of HLA-Ab (from 526 to 673) and cPRA (55.2 ± 31.9 %). Thirty-six patients (72 %) developed new HLA-Ab, mainly 3 weeks after HCT. In 7 patients an HLA-Ab with the same specificity as detected in the corresponding donor emerged, suggesting a possible transfer from the donor to the recipient. Overall, MFI showed a high variation. Type and number of transfusions were not associated with number and intensity of HLA-Ab (ρ: -0.05 - 0.02). Number of HLA-Ab, cPRA and intensity were not associated with PTR, which occurred in 9 patients (18 %) and none had bleeding WHO > 2. CONCLUSIONS: Although a considerable number of patients have and develop HLA-Ab before and early after HCT, we found no association with PTR and bleeding and management should be individualized.

Pathogen inactivation treatment of triple-dose apheresis platelets with amotosalen and ultraviolet a light.

BACKGROUND: A triple storage (TS) set allows for pathogen inactivation (PI) treatment of triple-dose apheresis platelet products with amotosalen + UVA. We evaluated the quality and metabolic parameters of platelet concentrates (PCs) pathogen inactivated and stored for 7 days. MATERIALS AND METHODS: Twelve triple-dose products collected with two different apheresis platforms were treated with amotosalen+UVA. Products were split into three single-dose units. Testing was made pretreatment, after splitting, at days 5 and 7 of storage. RESULTS: Single-dose PI PCs had a mean platelet content of 2.89 ± 0.35 x 1011 . From baseline to day 7, pH remained stable (7.1 ± 0.1 vs. 7.0 ± 0.1), pO2 increased (11.3 ± 2.4 vs. 18.3 ± 3.5 kPa) as did LDH (201 ± 119 vs. 324 ± 203 U/L) and lactate (3.6 ± 1.7 vs. 12.1 ± 1.5 mmol/L) (all p < 0.01); pCO2 decreased (4.1 ± 0.8 vs. 1.5 ± 0.7 mmHg; p < 0.01) and so did bicarbonate (6.6 ± 1.1 vs. 2.5 ± 1.4 mmol/L), glucose (5.6 ± 1.2 vs. 0.4 ± 0.4 mmol/L) and ATP (3.4 ± 0.9 vs. 2.5 ± 1.4 nmol/108 platelets) (all p < 0.05). CONCLUSION: Triple-dose PCs processed with the TS sets fulfilled the quality requirements and displayed metabolic changes of expected extent during 7-day storage.

Long-Term Course of Haemoglobin and Ferritin Values in High-Frequency Donors of Whole Blood and Double Erythrocyte Apheresis.

BACKGROUND: High-intensity donation is a risk factor for iron deficiency in blood donors. Interdonation intervals for whole blood (WB) donation and double unit red blood cell apheresis (2RBC) vary among countries. We retrospectively evaluated the course of haemoglobin (Hb) and ferritin values in men regularly donating WB 4 times a year or 2RBC twice a year (i.e., maximal frequency) over a period of 48 months. METHODS: Data of male donors with 16 WB or 8 2RBC consecutive donations were analysed. The minimum Hb levels for WB donation and 2RBC apheresis (collection of 360 mL RBC) were 135 and 140 g/L, respectively. There was no lower limit set for ferritin, and no iron was substituted. RESULTS: We identified 294 WB (mean age 53 years, SD 11) and 151 2RBC donors (mean age 48 years, SD 9) who donated at a mean interval of 97 (SD 18) and 201 days (SD 32), respectively, between January 1, 2008, and December 31, 2013. At baseline, Hb and ferritin values were lower in WB donors compared to 2RBC donors, with a mean Hb of 153 g/L (SD 13) versus 159 g/L (SD 8) and a mean ferritin of 44 µg/L (SD 52) versus 73 µg/L (SD 56; p < 0.001 for both parameters), respectively. Ferritin was below 15 µg/L in 40 WB (14%) and in 4 (3%) 2RBC donors. In WB donors, the mean Hb levels at baseline versus last donation showed no significant difference (153 vs. 152 g/L, p = 0.068), whereas the mean ferritin levels decreased significantly (44 vs. 35 µg/L, p < 0.001). The 2RBC donor group displayed a statistically different decrease in both the mean Hb levels (158 vs. 157 g/L; p < 0.05) and the mean ferritin levels (73 vs. 66 µg/L; p = 0.052). The lowest Hb was measured at the 11th WB donation (152 g/L; p < 0.05) and at the 4th 2RBC apheresis (157 g/L; p < 0.05). There was no deferral due to low Hb at any time. The lowest ferritin was shown at the 4th WB (37 µg/L) and at the 3rd 2RBC donation (60 µg/L), respectively. At the last visit, ferritin was below 15 µg/L in 23 WB donors (8%) and in 2 2RBC donors (1%). CONCLUSIONS: High-intensity male donors with an interdonation interval of 12 weeks for WB donation and 24 weeks for 2RBC apheresis maintain acceptable Hb levels and, after an initial decline, stable ferritin levels despite ongoing blood donation.

Low arginine vasopressin levels in patients with diabetes insipidus are not associated with anaemia.

OBJECTIVE: Arginine vasopressin (AVP) is released upon osmotic stimulation or hypovolaemia in order to maintain water balance. A recent study showed a role of AVP in haematopoiesis by stimulating red blood cell precursors, suggesting a higher risk of anaemia in patients with AVP deficiency. The objective was to explore the effect of low AVP levels in patients with central diabetes insipidus (cDI) and primary polydipsia (PP) on haemoglobin and the prevalence of anaemia. METHODS: A total of 164 patients with either cDI (70, 43%) or PP (94, 57%) and 30 healthy volunteers from two prospective diagnostic studies performed in Switzerland, Germany and Brazil were studied. A standardized clinical and biochemical (eg copeptin, full blood count) assessment was performed. Haemoglobin and haematocrit levels and prevalence of anaemia (defined as haemoglobin values of <120 g/L in women and <130 g/L in men) were analysed. RESULTS: Mean copeptin values were 2.63 pmol/L (±1.08) and 3.91 pmol/L (±4.28) in patients with cDI and PP and 24.76 pmol/L (±5.75) in healthy volunteers, P = .02. The prevalence of anaemia was low in all participants with 7.1%, 2.2% and 10% in cDI, PP and in healthy volunteers, P = .15. Mean haemoglobin values were similar in all groups: 139 g/L (±15.85), 140 g/L (±13.16) and 139 g/L (±13.05) in patients with cDI, PP and healthy volunteers, P = .90, as were mean haematocrit values with 41% in all groups (P = .85). CONCLUSION: Chronic low AVP levels in patients with cDI and PP do not affect haemoglobin levels and prevalence of anaemia.

Very long-term follow-up of aplastic anemia treated with immunosuppressive therapy or allogeneic hematopoietic cell transplantation.

INTRODUCTION: Since the 1970s outcome of aplastic anemia (AA) patients has improved significantly due to the introduction of immunosuppressive therapy (IST) and allogeneic hematopoietic transplantation (HCT). However, patients may suffer from persistent disease, relapse, clonal evolution, graft-versus-host disease and other late effects. Here, we analyse very long-term outcome of all AA patients at our institution comparing not only survival, but also response status and complications. METHODS: Patient charts of all 302 AA patients treated between 1973 and 2017 at the University Hospital Basel, Switzerland, were retrospectively analysed. RESULTS: First line treatment was IST in 226 (75%) and HCT in 76 (25%) patients. Overall survival at 30 years was similar in patients treated initially by HCT and IST (44% (±14%), and 40% (± 9%) respectively, with better results in more recent years. Partial and no response occurred more frequently after IST, relapse incidence after IST was 24 %, whereas non-engraftment and graft failure was documented in 15 patients (19 %) after HCT. Clonal evolution to myelodysplastic syndrome / acute myeloid leukemia was 16 % at 25 years in IST patients, 1.3 % in HCT patients, iron overload (18 versus 4 %, p = 0.002) and cardiovascular events (11 versus 1 %, p=0.011) occured significantly more often in IST than HCT treated patients. The majority of long-term survivors, 96% of those alive at 25 years, were in complete remission at last follow up, irrespective of the initial treatment modality. CONCLUSION: Very long term survivors after AA are those with stable hematopoietic recovery.

Report of a 'consensus' on the lines of therapy for primary immune thrombocytopenia in adults, promoted by the Italian Gruppo di Studio delle Piastrine.

Despite the publication in 2009 of a paper on 'terms and definitions of immune thrombocytopenia' (ITP), some unresolved issues remain and are reflected by the disagreement in the treatment suggested for primary ITP in adults. Considering that these disagreements could be ascribed to non-shared goals, we generated a 'consensus' on some terms, definitions, and assertions useful for classifying the different lines of treatment for primary ITP in adults according to their indications and goals. Agreement on the appropriateness of the single assertions was obtained by consensus for the following indicators: 1. classification of four 'lines of therapy'; 2. acceptance of the expression 'sequences of disease' for the indications of the respective four lines of treatment; 3I . practicability of splenectomy; 3Ib . acceptance, with only some exceptions, of a 'timing for elective splenectomy of 12 months'; and 4a-d . 'goals of the four lines of therapy.' On the basis of the consensus, a classification of four lines of treatment for primary ITP in adults was produced. In our opinion, this classification, whose validity is not influenced by the recently published new guidelines of the American Society of Hematology (ASH) and reviews, could reduce the disagreement that still exists regarding the treatment of the disease.

Extracorporeal Photopheresis in Graft-versus-Host Disease.

BACKGROUND AND SUMMARY: Extracorporeal photopheresis (ECP) is a leukapheresis-based procedure used in the therapy of acute and chronic graft-versus-host disease (aGvHD, cGvHD) and other diseases. Based on the substantial efficacy and the excellent safety profile in the absence of immunosuppression ECP has established itself as a major treatment form for steroid-refractory GvHD. Here we review the current literature on ECP as a treatment option for patients with aGvHD as well as cGvHD. KEY MESSAGES: ECP is a well-established second-line therapy for cGvHD. Its role in the treatment of aGvHD is less clear but also points towards an effective second-line therapy option. In the future ECP could play a role in the prevention of GvHD. More experimental and randomized controlled trials are needed to define the best patient selection criteria, settings, and therapy regimens for GvHD.

[Thrombocytopenia as an incidental finding]. / Thrombozytopenie als Zufallsbefund.

Thrombocytopenia as an incidental finding Abstract. Platelets play an important role in normal hemostasis and their number in the periphereal blood is normally very stable. Thrombocytopenia is frequently encountered in the clinic. As a first step, one has to exclude so called pseudothrombocytopenia due to preanalytic (EDTA as an anticoagulant) conditions. This can be done by determination of platelet counts in citrate or alternative (e. g. Thrombo-Exact) tubes or by performing a blood smear, where platelets are seen clumped. A blood smear is also the mainstay of further work-up as the differential diagnosis is very broad. In bleeding patients early therapeutic interventions have to be considered. Further work-up should be done stepwise and in collaboration with a hematologist. A definite diagnosis is essential in order to define specific therapeutic interventions, mainly in bleeding patients, in patients scheduled for surgery or patients taking antiaggregation and / or anticoagulation therapy.

The value of the post-thaw CD34+ count with and without DMSO removal in the setting of autologous stem cell transplantation.

BACKGROUND: CD34+ cell count correlates with engraftment potency after autologous stem cell transplantation. Assessment of CD34+ mainly occurs after apheresis and before cryopreservation with dimethyl sulfoxide (DMSO). The influence of postthaw CD34+ cell numbers over time to engraftment is not well studied, and determination of postthaw CD34+ cell counts is challenging for a variety of reasons. The aim of this retrospective study was to systematically assess the value of postthaw CD34+ cell counts in autologous grafts with and without DMSO removal. STUDY DESIGN AND METHODS: Between January 2008 and December 2015, 236 adult patients underwent a total of 292 autologous stem cell transplantations. Median age at transplantation was 56 years, and the main indication was multiple myeloma (60%). DMSO removal was done in 96 grafts (33%), either by centrifugation or by Sepax method. RESULTS: Patients receiving grafts containing DMSO showed a significantly faster platelet (p = 0.02) and RBC (p = 0.001) engraftment. DMSO removal was not associated with fewer infusion-related adverse events. We observed a good correlation between CD34+ cell count after apheresis and CD34+ cell count after thawing/washing (r = 0.931). Ninety grafts (31%) showed a significant loss of viable CD34+ cells, which translated into a delayed engraftment. CONCLUSION: DMSO removal was associated with delayed platelet and RBC engraftment without preventing adverse events. CD34+ cell enumeration after thawing remains difficult to perform, but grafts showing higher cell loss during cryopreservation and thawing are associated with slower engraftment. Prospective studies on the role of DMSO removal and postthaw CD34+ enumeration using defined protocols are needed.

Clinical impact of amotosalen-ultraviolet A pathogen-inactivated platelets stored for up to 7 days.

BACKGROUND: Universal pathogen inactivation of platelet concentrates (PCs) using amotosalen/ultraviolet A with 7-day storage was implemented in Switzerland in 2011. Routine-use data were analyzed at the University Hospital Basel, Switzerland. STUDY DESIGN: A retrospective two-cohort study of patient and PC characteristics, component usage, patient outcomes, count increments (CIs), and adverse events were analyzed for two consecutive 5-year periods with either 0- to 5-day-old conventional PC (C-PC) (n = 14,181) or 0- to 7-day-old pathogen-inactivated PC (PI-PC) (n = 22,579). RESULTS: In both periods, PCs were issued for transfusion on a "first in, first out" basis. With 7-day PI-PC, wastage was reduced from 8.7% to 1.5%; 16.6% of transfused PI-PCs were more than 5 days old. Transfusion of PI-PC more than 5 days old compared with 5 days old or less did not increase platelet and RBC use on the same or next day as an indirect measure of hemostasis and did not increase transfusion reactions. Mean corrected count increments (CCIs) for PI-PC stored for 5 days or less were 22.6% lower than for C-PC (p < 0.001), and declined with increasing storage duration for both, although the correlation was weak (r2 = 0.005-0.014). Mean number of PCs used per patient and duration of PC support were not different for hematology/oncology, allogeneic and autologous hematopoietic stem cell transplant (HSCT), and general medical/surgical patients, who used the majority (~92.0%) of PI-PCs. Five-year treatment-related mortality in allogeneic HSCT was unchanged in the PI-PC period. CONCLUSIONS: PI-PCs with 7-day storage reduced wastage and did not increase PC or red blood cell utilization or adverse reactions compared with fresh PI-PC or a historical control group, demonstrating preserved efficacy and safety.

Red Blood Cells: Exchange, Transfuse, or Deplete.

Erythrocytapheresis, red blood cell (RBC) depletion, and RBC exchange transfusions are apheresis techniques used to rapidly lower the circulating RBC mass or to exchange the patient erythrocyte mass with donor RBC. Automated RBC exchange is performed using an apheresis device, while manual RBC exchange is based on sequential phlebotomies and isovolemic replacement. Compared to simple RBC transfusions, RBC exchange offers several advantages, e.g., a lower risk for iron accumulation and efficient control of pathological erythrocyte populations. Disadvantages are the higher costs of the procedure, the increased use of donor RBC, and the requirement of apheresis devices and trained hospital staff. The most frequent indication for RBC exchange is sickle cell disease (SCD). RBC exchange transfusions are standard treatment in SCD patients with a history of or a risk for acute stroke and are clinical options for other acute complications of SCD. The most common indication for RBC depletion is the removal of donor RBC from the bone marrow grafts in major ABO-incompatible allogeneic hematopoietic stem cell transplantation to avoid immediate hemolysis. Rare indications for RBC exchange are severe infections with intraerythrocytic pathogens such as malaria or babesiosis and severe erythrocytosis or hereditary hemochromatosis where the aim is to rapidly decrease RBC populations or the iron content. However, only few high-quality studies are available looking at the efficacy of RBC exchange in the different disease entities, and treatment is often based on low levels of evidence and should therefore be decided in close collaboration with a transfusion medicine specialist.

The Remarkable Journey of a Low-Frequency Alloantibody.

Herein we describe a case of febrile non-hemolytic reaction (FNHTR) in a 64-year-old male 20 min after the transfusion of one red blood cell unit. 20 days prior the patient had undergone an allogeneic hematopoietic stem cell transplantation (HCT) from an unrelated donor with minor ABO disparity. The patient had been treated for plasma cell myeloma with multiple transfusions in the past, but no transfusion reactions or alloimmunization had been reported.

[Cellular therapies]. / Zelluläre Therapien.

Cellular therapies Abstract. Transfusion medicine and allogeneic stem cell transplantation are well known and established cellular therapies in hematology. Since decades many efforts have been made, in order to re-program the patient's own immune system in order to clear malignancies. A breakthrough was achieved with the manufacturing and optimizing of so-called chimeric antigen receptor (CAR) T-cells, genetically engineered cells, specifically directed against tumor antigens. In this review we discuss the structure of CAR T-cells, their manufacturing and the different steps of a CAR T-cell treatment according to the current licensing. Furthermore, we give an outlook on future prospects of cellular therapies including the major issues in the field.

Handling, processing and disposal of stem cell products in Europe: A survey by the cellular therapy and immunobiology working party of the European Society for Blood and Marrow Transplantation.

BACKGROUND: There is considerable heterogeneity in processing of stem cells for hematopoietic stem cell transplantation across Europe. The Foundation for the Accreditation of Cellular Therapy (FACT)-Joint Accreditation Committee International Society for Cellular Therapy and European Society for Blood and Marrow Transplantation (EBMT) (JACIE) standards provide minimum guidelines that, however, leave room for significant variations in practices at the individual transplantation center (TC). METHODS: To better understand the extent of heterogeneity in storage conditions, quality controls (QCs), graft processing and disposal, a questionnaire was developed, reviewed by the Cellular Therapy and Immunobiology Working Party (CTIWP) and sent to all EBMT TCs. RESULTS: In this study, 288 TCs from 46 countries (32 European, 14 associated) responded to the survey. Long-term storage is performed mainly either in liquid nitrogen or in the vapor phase of liquid nitrogen with 10% dimethyl sulfoxide (DMSO; 58% of centers). In case of microbiological contamination, most TCs make a case-by-case decision in collaboration with the clinicians. CD34+ counts are performed routinely either before and/or after thawing. Some centers perform additional QCs. DMSO is generally not removed (83%) and the graft is thawed at the bedside (68%) in a water bath (78%). There is heterogeneity between the centers regarding duration of storage and graft disposal. DISCUSSION: Overall, this survey demonstrates that the majority of responding TCs uses standardized procedures (intracenter standardization). However, significant intercenter variations persist, which warrant further standardization and investigations on clinical and financial consequences. Additionally, efforts should be undertaken to provide more specific international guidelines on storage duration and graft disposal, which may also have an important impact on health care services worldwide.

A comparative prospective observational study of children and adults with immune thrombocytopenia: 2-year follow-up.

Comparative clinical studies of children and adults with immune thrombocytopenia (ITP) are poorly covered in the literature. However, the accepted classification of ITP-childhood ITP and adult ITP-results in considerable differences in treatment protocols and practice guidelines. The analysis of the Pediatric and Adult Registry on Chronic ITP (PARC-ITP) of patients at first presentation demonstrated fewer differences in clinical and laboratory findings at initial diagnosis between children and adults than expected. The present report of 2-year follow-up data supports the hypothesis that there are common aspects of childhood and adult ITP. Data of 3360 children and 420 adults were collected during the time of 2004 until 2015 at initial diagnosis. Follow-up information was available for 51% and 33% of children and 66% and 49% of adults at 12- and 24-months, respectively. Similarities were found in unexpected areas of ITP, such as the rate of late remission at 12 and 24 months, reported bleeding sites, platelet count in bleeders, and the frequency of treated patients with persistent or chronic ITP. Differences were confirmed for the overall rate of remission and treatment modalities. Unexpected differences were found in the percentage of nonbleeders, with more adults in the nonbleeder group. More studies are needed to investigate different age groups with the aim to optimize their management.