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AIM: Until the year 2000, allogeneic haematopoietic cell transplantation (HCT) was the standard treatment for young and fit chronic myeloid leukaemia (CML) patients. CML was the main indication for allogeneic HCT. The introduction of tyrosine kinase inhibitors changed the treatment of CML patients dramatically. Allogeneic HCT was rapidly replaced by tyrosine kinase inhibitors as first-line treatment for CML, and the indication shifted to the treatment of non-responders, patients intolerant to tyrosine kinase inhibitors and patients whose CML is transforming to the accelerated phase and blast crisis. This paper describes changes in the use of transplantation technology for CML patients in the face of rapid drug development. METHODS: All patients receiving a transplant for CML between 1997 and 2021 in Switzerland were included in the study. For the purpose of this analysis, time periods were analysed in quinquennia, 1997–2001 (Q1), 2002–2006 (Q2), 2007–2011 (Q3), 2012–2016 (Q4) and 2017–2021 (Q5), as the observation period spanned 25 years. RESULTS: Overall, 239 patients received a transplant. These included 96 in Q1, 56 in Q2, 25 in Q3, 34 in Q4 and 28 in Q5. Patient characteristics changed over time: recent patients were older and had a longer interval from diagnosis to transplantation because of tyrosine kinase inhibitor treatment. However, the proportions of patients receiving transplants during an early versus advanced disease stage differed little. Transplant technology changed, as well. Patients received intensive conditioning regimens less often due to higher age and more commonly had peripheral blood as opposed to bone marrow transplants. However, the type of stem cell donor selected did not differ. In a univariable analysis, there were no significant differences in survival, progression-free survival, non-relapse mortality, relapse incidence or incidences of acute and chronic graft-versus-host disease among the five quinquennia. In a multivariable analysis, older age, donors other than HLA-identical siblings and more advanced disease stage, but not the quinquennium, were associated with higher risk of death. CONCLUSION: Since the introduction of tyrosine kinase inhibitors haematopoietic cell transplantation has been used less frequently to treat CML. Patients in recent cohorts received transplants at an older age and later in the disease course; despite these higher risks, the outcome of allogeneic HCT has not worsened over time but has not improved, either. As the outcome is worse in advanced phases, it is important to conduct transplants before disease progression. Therefore, patients with advanced disease should be monitored closely and receive transplants in time.

We investigated ≥ grade 3 (CTC-AE) organ toxicities for commercial CD19 chimeric antigen receptor T cell (CAR-T cell) products in 492 patients (Axi-Cel; n = 315; Tisa-Cel; n = 177) with Large B-cell Lymphoma in the European Society for Blood and Marrow Transplantation (EBMT) CAR-T registry. The incidence of ≥ grade 3 organ toxicities during the first 100 days after CAR-T was low and the most frequent were: renal (3.0%), cardiac (2.3%), gastro-intestinal (2.3%) and hepatic (1.8%). The majority occurred within three weeks after CAR-T cell therapy. Overall survival was 83.1% [79.8-86.5; 95% CI] at 3 months and 53.5% [49-58.4; 95% CI] at one year after CAR-T. The most frequent cause of death was tumour progression (85.1%). Non-relapse mortality was 3.1% [2.3-4.1; 95% CI] at 3 months and 5.2% [4.1-6.5; 95% CI] at one year after CAR-T. The most frequent causes of non-relapse mortality were cell-therapy-related toxicities including organ toxicities (6.4% of total deaths) and infections (4.4% of total deaths). Our data demonstrates good safety in the European real-world setting.

Abstract Due to relatively high nonrelapse mortality (NRM), allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in non‐Hodgkin's lymphoma (NHL) remains the ultimate line of treatment but the only curable approach in a setting of relapse/refractory disease. Here, we conducted a retrospective, multicenter, registry‐based analysis on patients who underwent allo‐HSCT for NHL in Switzerland, over 30‐year (1985–2020) period. The study included 301 allo‐HSCTs performed for NHL patients in three University Hospitals of Switzerland (Zurich, Basel and Geneva) 09/1985 to 05/2020. We assessed in univariate and multivariable analysis the impact on survivals (overall survival [OS], relapse free survival [RFS], relapse incidence [RI], and non‐treatment related mortality [NRM]). The maximum follow‐up was 25 years with median follow‐up for alive patients of 61 months. The median age at allo‐HSCT was 51 years. Three‐ and ‐year OS was ‐ 59.5% and 55.4%; 3‐ and 5‐year PFS was 50% and 44%; 3‐ and 5‐year NRM was 21.7% and 23.6%. RI at 3 and 5 years was 27.4% and 34.9%. In conclusion, our analysis of the entire Swiss experience of allo‐HSCT in patients with NHL shows promising 5‐ and possibly 10‐year OS and relatively acceptable NRM rates for such population, the majority being not in complete remission (CR) at the time of transplantation.

Abstract Despite the high cure rate with initial therapy, approximately 10% of Hodgkin lymphoma (HL) patients are refractory to initial treatment, and up to 30% of patients will relapse after achieving initial complete remission. Despite promising initial results of treatment by immune checkpoint inhibitors, most patients will eventually progress. We analyzed 62 adult patients with relapsed or refractory HL (rrHL) treated by allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in one of three University Hospitals of Switzerland (Zurich, Basel, and Geneva) between May 2001 and January 2020. The primary endpoint was overall survival (OS). Secondary endpoints were relapse‐free survival (RFS), non‐relapse mortality (NRM), and relapse incidence, which were assessed in univariate analysis. The median follow‐up was 61 months (interquartile range 59–139). The 2‐ and 5‐year OS was 54% (standard error (SE) ±12) and 50.2% (SE ±13.3), respectively, and the 2‐ and 5‐year RFS was 40.7% (SE ±16.3) and 34.4% (SE ±19.0), respectively. NRM was 23.1% (SE ±2.2) and 27.4% (SE ±2.5) at 2 and 5 years, respectively. The cumulative incidence of relapse was 36.1% (SE ±5.6) at 2 years and 38.2% (SE ±6.6) at 5 years. Our analysis of allo‐HSCT outcomes in the context of rrHL shows encouraging OS and RFS rates, with the mortality rate reaching plateau at 50% at 2 years after allo‐HSCT. This confirms that allo‐HSCT still remains as a potentially curative option for half of patients with rrHL.

We investigated the incidence and outcome of anti-CD19 chimeric antigen receptor (CAR) T-cells-associated Common Terminology Criteria for Adverse Events (CTCAE) ≥grade 3 cytopenia. In the EBMT CAR-T registry, we identified 398 adult patients with large B-cell lymphoma who had been treated with CAR-T-cells with axicel (62%) or tisacel (38%) before August 2021 and had cytopenia status documented for the first 100 days. Most patients had received two or three previous lines of therapy, however, 22.3% had received four or more. Disease status was progressive in 80.4%, stable in 5.0% and partial/complete remission in 14.6%. 25.9% of the patients had received a transplantation before. Median age was 61.4 years (min–max; IQR=18.7–81; (52.9–69.5)).The cumulative incidence of ≥grade 3 cytopenia was 9.0% at 30 days (95% CI (6.5 to 12.1)) and 12.1% at 100 days after CAR T-cell infusion (95% CI (9.1 to 15.5)). The median time from CAR-T infusion to cytopenia onset was 16.5 days (min–max; IQR=1–90; (4–29.8)). Grade 3 and grade 4 CTCAE cytopenia occurred in 15.2% and 84.8%, respectively. In 47.6% there was no resolution.Severe cytopenia had no significant impact on overall survival (OS) (HR 1.13 (95% CI 0.74 to 1.73), p=0.57). However, patients with severe cytopenia had a poorer progression-free survival (PFS) (HR 1.54 (95% CI 1.07 to 2.22), p=0.02) and a higher relapse incidence (HR 1.52 (95% CI 1.04 to 2.23), p=0.03). In those patients who developed severe cytopenia during the first 100 days (n=47), OS, PFS, relapse incidence and non-relapse mortality at 12 months after diagnosis of severe cytopenia were 53.6% (95% CI (40.3 to 71.2)), 20% (95% CI (10.4 to 38.6)), 73.5% (95% CI (55.2 to 85.2)) and 6.5% (95% CI (1.7 to 16.2)), respectively.In multivariate analysis of severe cytopenia risk factors, only year of CAR-T infusion (HR=0.61, 95% CI (0.39 to 0.95), p=0.028) and total number of treatment lines before CAR-T infusion (one or two lines vs three or more, HR=0.41, 95% CI (0.21 to 0.83), p=0.013) had a significant positive association with the incidence of cytopenia. Other factors, such as previous transplantation, disease status at time of CAR-T, patient age and patient sex, had no significant association.Our data provide insight on frequency and clinical relevance of severe cytopenia after CAR T-cell therapy in the European real-world setting.

IntroductionThe type of donation may affect how susceptible a donor kidney is to injury from pre-existing alloimmunity. Many centers are, therefore, reluctant to perform donor specific antibody (DSA) positive transplantations in the setting of donation after circulatory death (DCD). There are, however, no large studies comparing the impact of pre-transplant DSA stratified on donation type in a cohort with a complete virtual cross-match and long-term follow-up of transplant outcome.MethodsWe investigated the effect of pre-transplant DSA on the risk of rejection, graft loss, and the rate of eGFR decline in 1282 donation after brain death (DBD) transplants and compared it to 130 (DCD) and 803 living donor (LD) transplants.ResultsThere was a significant worse outcome associated with pre-transplant DSA in all of the studied donation types. DSA directed against Class II HLA antigens as well as a high cumulative mean fluorescent intensity (MFI) of the detected DSA showed the strongest association with worse transplant outcome. We could not detect a significant additive negative effect of DSA in DCD transplantations in our cohort. Conversely, DSA positive DCD transplants appeared to have a slightly better outcome, possibly in part due to the lower mean fluorescent intensity (MFI) of the pre-transplant DSA. Indeed when DCD transplants were compared to DBD transplants with similar MFI (

# Introduction Haploinsufficiency of _GATA2_ leads to impaired genesis and function of hematopoietic stem and progenitor cells, resulting in impairment of all subsequent blood cell lineages. Germline mutations in _GATA2_ are transmitted by autosomal-dominant inheritance. Leading clinical symptoms of _GATA2_ deficiency syndromes are immunodeficiency, infections (mainly nontuberculous mycobacteria and human papillomavirus), predisposition to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), pulmonary alveolar proteinosis (PAP) and primary lymphedema. _GATA2_ mutations underlie not only Emberger syndrome (primary lymphedema and MDS), but also other syndromes like monocytopenia and mycobacterial infections syndrome (MonoMAC), dendritic cell/monocytopenia/natural killer (NK)-cell/B-cell lymphoid deficiency (DCML) and familial MDS/AML syndrome. We report the history of a Swiss family with Emberger syndrome extending over three generations. In addition, a review of the literature on _GATA2_ deficiencies is provided. # Methods Based on a general practitioner's observation of father and son sharing similar declined blood values and lymphedema, we examined the whole family for the presence of _GATA2_ mutation and a possible genotype-phenotype correlation. Publications on _GATA2_ deficiencies were researched on the PubMed database. # Results Six family members were diagnosed with _GATA2_ mutation, demonstrating individually variable penetrance and diversity of leading symptoms. # Conclusion Careful investigation of personal and family history, as well as meticulous examination, led to suspicion of the rare diagnosis of familial Emberger syndrome. Early diagnosis is mandatory for appropriate disease management. PEER REVIEWED ARTICLE

BackgroundPre-transplant donor specific antibodies (DSA), directed at non-self human leukocyte antigen (HLA) protein variants present in the donor organ, have been associated with worse outcomes in kidney transplantation. The impact of the mean fluorescence intensity (MFI) and the target HLA antigen of the detected DSA has, however, not been conclusively studied in a large cohort with a complete virtual cross-match (vXM).MethodsWe investigated the effect of pre-transplant DSA on the risk of antibody-mediated rejection (ABMR), graft loss, and the rate of eGFR decline in 411 DSA positive transplants and 1804 DSA negative controls.ResultsPre-transplant DSA were associated with a significantly increased risk of ABMR, graft loss, and accelerated eGFR decline. DSA directed at Class I and Class II HLA antigens were strongly associated with increased risk of ABMR, but only DSA directed at Class II associated with graft loss. DSA MFI markedly affected outcome, and Class II DSA were associated with ABMR already at 500-1000 MFI, whereas Class I DSA did not affect outcome at similar low MFI values. Furthermore, isolated DSA against HLA-DP carried comparable risks for ABMR, accelerated eGFR decline, and graft loss as DSA against HLA-DR.ConclusionOur results have important implications for the construction and optimization of vXM algorithms used within organ allocation systems. Our data suggest that both the HLA antigen target of the detected DSA as well as the cumulative MFI should be considered and that different MFI cut-offs could be considered for Class I and Class II directed DSA.

In the past, our research group was able to successfully remove circulating tumor cells with magnetic nanoparticles. While these cancer cells are typically present in low numbers, we hypothesized that magnetic nanoparticles, besides catching single cells, are also capable of eliminating a large number of tumor cells from the blood ex vivo. This approach was tested in a small pilot study in blood samples of patients suffering from chronic lymphocytic leukemia (CLL), a mature B-cell neoplasm. Cluster of differentiation (CD) 52 is a ubiquitously expressed surface antigen on mature lymphocytes. Alemtuzumab (MabCampath®) is a humanized, IgG1κ, monoclonal antibody directed against CD52, which was formerly clinically approved for treating chronic lymphocytic leukemia (CLL) and therefore regarded as an ideal candidate for further tests to develop new treatment options. Alemtuzumab was bound onto carbon-coated cobalt nanoparticles. The particles were added to blood samples of CLL patients and finally removed, ideally with bound B lymphocytes, using a magnetic column. Flow cytometry quantified lymphocyte counts before, after the first, and after the second flow across the column. A mixed effects analysis was performed to evaluate removal efficiency. p < 0.05 was defined as significant. In the first patient cohort (n = 10), using a fixed nanoparticle concentration, CD19-positive B lymphocytes were reduced by 38% and by 53% after the first and the second purification steps (p = 0.002 and p = 0.005), respectively. In a second patient cohort (n = 11), the nanoparticle concentration was increased, and CD19-positive B lymphocytes were reduced by 44% (p < 0.001) with no further removal after the second purification step. In patients with a high lymphocyte count (>20 G/L), an improved efficiency of approximately 20% was observed using higher nanoparticle concentrations. A 40 to 50% reduction of B lymphocyte count using alemtuzumab-coupled carbon-coated cobalt nanoparticles is feasible, also in patients with a high lymphocyte count. A second purification step did not further increase removal. This proof-of-concept study demonstrates that such particles allow for the targeted extraction of larger amounts of cellular blood components and might offer new treatment options in the far future.

Induction of immunological tolerance has been the holy grail of transplantation immunology for decades. The only successful approach to achieve it in patients has been a combined kidney and hematopoietic stem cell transplantation from an HLA-matched or -mismatched living donor. Here, we report the first three patients in Europe included in a clinical trial aiming at the induction of tolerance by mixed lymphohematopoietic chimerism after kidney transplantation. Two female and one male patient were transplanted with a kidney and peripherally mobilized hematopoietic stem cells from their HLA-identical sibling donor. The protocol followed previous studies at Stanford University: kidney transplantation was performed on day 0 including induction with anti-thymocyte globulin followed by conditioning with 10x 1.2 Gy total lymphoid irradiation and the transfusion of CD34+ cells together with a body weight-adjusted dose of donor T cells on day 11. Immunosuppression consisted of cyclosporine A and steroids for 10 days, cyclosporine A and mycophenolate mofetil for 1 month, and then cyclosporine A monotherapy with tapering over 9–20 months. The 3 patients have been off immunosuppression for 4 years, 19 months and 8 months, respectively. No rejection or graft-versus-host disease occurred. Hematological donor chimerism was stable in the first, but slowly declining in the other two patients. A molecular microscope analysis in patient 2 revealed the genetic profile of a normal kidney. No relevant infections were observed, and the quality of life in all three patients is excellent. During the SARS-CoV-2 pandemic, all three patients were vaccinated with the mRNA vaccine BNT162b2 (Comirnaty®), and they showed excellent humoral and in 2 out 3 patients also cellular SARS-CoV-2-specific immunity. Thus, combined kidney and hematopoietic stem cell transplantation is a feasible and successful approach to induce specific immunological tolerance in the setting of HLA-matched sibling living kidney donation while maintaining immune responsiveness to an mRNA vaccine (ClinicalTrials.gov: NCT00365846).

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, in which autoreactive T and B cells play important roles. Other lymphocytes such as NK cells and innate-like T cells appear to be involved as well. To name a few examples, CD56bright NK cells were described as an immunoregulatory NK cell subset in MS while innate-like T cells in MS were described in brain lesions and with proinflammatory signatures. Autologous hematopoietic stem cell transplantation (aHSCT) is a procedure used to treat MS. This procedure includes hematopoietic stem/progenitor cell (HSPC) mobilization, then high-dose chemotherapy combined with anti-thymocyte globulin (ATG) and subsequent infusion of the patients own HSPCs to reconstitute a functional immune system. aHSCT inhibits MS disease activity very effectively and for long time, presumably due to elimination of autoreactive T cells. Here, we performed multidimensional flow cytometry experiments in peripheral blood lymphocytes of 27 MS patients before and after aHSCT to address its potential influence on NK and innate-like T cells. After aHSCT, the relative frequency and absolute numbers of CD56bright NK cells rise above pre-aHSCT levels while all studied innate-like T cell populations decrease. Hence, our data support an enhanced immune regulation by CD56bright NK cells and the efficient reduction of proinflammatory innate-like T cells by aHSCT in MS. These observations contribute to our current understanding of the immunological effects of aHSCT in MS.

Background: Allogeneic hematopoietic stem cell transplantation (alloHSCT) has been proposed as curative approach for advanced cutaneous T–cell lymphomas (CTCL). Currently, there is no established consensus for the management of disease relapse after alloHSCT.Results: Ten patients, previously treated with multiple lines of systemic treatment, received alloHSCT. Six patients had achieved partial response (PR, N = 5) and complete response (CR, N = 1) prior to HSCT. Post—HSCT, seven patients (N = 7) relapsed after a median time of 3.3 months (0.5–7.4 months) and were subsequently treated with radiotherapy (RT, N = 1), RT and adoptive T-cell transfer with EBV specific cells (N = 1), R-CHOP (N = 1) and interferon alpha−2a combined either with donor lymphocyte infusion (N = 1) or with brentuximab—vedotin (N = 1). One patient (N = 1) achieved PR only after reducing the immunosuppression. Two patients relapsed again and received interferon alpha−2a and brentuximab—vedotin, respectively. After a median follow-up time of 12.6 months (3.5–73.7 months) six patients were alive (60%) and four had deceased, three (N = 3) due to CTCL and one (N = 1) due to GVHD.Conclusion: Disease relapse after alloHSCT can be controlled with available treatments. For most patients who ultimately relapsed, reduction of immunosuppression and interferon alpha−2a either administered alone or in combination with another systemic agent were preferred. Although interferon alpha−2a, similarly to immunosuppression reduction, may be beneficial for the achievement of graft–vs.–lymphoma effect, the risk of simultaneous worsening of GVHD must be carefully evaluated and taken into consideration.

Rare T- or NK-cell lymphomas with cutaneous manifestation may display a highly aggressive clinical course and major diagnostic/therapeutic challenges. This report describes our experiences with different lymphomas of this rare category and the therapeutic options used. This retrospective, descriptive, monocentric, cross-sectional case study, identified 4 rare aggressive T-/NK-cell lymphomas with manifestation in the skin, which were diagnosed in a tertiary care centre over a period of 4 years. Two patients had an Epstein-Barr virus-associated extranodal NK/T-cell lymphoma and 2 patients had a primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma. Concomitant extracutaneous involvement was observed in 2 of all 4 patients. Two patients had fulminant disease progression and resistance to chemotherapy. Two patients underwent allogeneic haematopoietic stem cell transplantation, which resulted in one complete remission and one partial remission. This report emphasizes the importance of an early diagnostic work-up and a prompt aggressive therapeutic approach.

In 1997, the Swiss Blood Stem Cell Transplantation Group (SBST) initiated a mandatory national registry for all haematopoietic stem cell transplants (HCTs) in Switzerland. As of 2016, after 20 years, information was available for 7899 patients who had received an HCT (2781 allogeneic [35%] and 5118 autologous [65%]). As some patients had more than one transplant the total number of transplants was 3067 allogeneic and 6448 autologous. We compared patient characteristics and outcome of the first decade (1997–2006) and second decade (2007-2016) of the registry. There were numerous changes over time. For allogeneic HCT, transplant rates, and therefore use of HCT technology, increased from 14 to 21.8 HCTs per 1 million inhabitants per year from the first to the second decade. Likewise autologous HCTs increased from 24.8 to 37.2 annually corrected for population growth. Allogeneic transplant recipients were older (38.4 vs 48.3 years) and more frequently had unrelated donors in the second decade. Similarly, age increased for recipients of autologous HCT (50.8 vs 56.4 years). Analysis of outcome showed that the probabilities of overall and progression-free survival were stable over time, in spite of the treatment of older and higher risk patients. In multivariate analysis, nonrelapse mortality decreased in recipients of allogeneic HCT (relative risk 0.68, 95% confidence interval 0.52–0.87) over the two decades. Improvement in adjusted nonrelapse mortality compensated for the fact that higher risk patients were treated in more recent years, resulting in similar overall survival. Five-year survival probabilities were 56% (53–59%) in the first and 54% (51–57%) in the second decade for allogeneic HCT, and 59% (57–61%) in the first and 61% (59–63%) in the second decade for autologous HCT. Detailed analyses of changes over time are presented. This study included all HCTs performed in Switzerland during the period of observation and the data are useful for quality assurance programmes, healthcare cost estimation and healthcare planning. Between 50 and 60% of patients were long-term survivors after both types of HCT, indicating growing populations of surviving patients requiring long-term care and observation.

QUESTIONS UNDER STUDY: The optimal strategy of anti-infectious prophylaxis in patients with acute leukaemia undergoing intensive chemotherapy remains a matter of debate. We assessed the impact of primary prophylaxis with posaconazole and levofloxacin on the incidence of invasive fungal infections (IFI) and bacteraemia. METHODS: A retrospective single-centre study including two groups of adult patients with AML receiving intensive chemotherapy. Group one without anti-infective prophylaxis (September 2008 – February 2010), and group two with anti-infective prophyalaxis (March 2010 – April 2011). The primary end-point was IFI according to the EORTC/MSG 2008 definitions and bacteraemia. RESULTS: Baseline characteristics were similar in the non-prophylaxis (n = 43 patients; 99 chemotherapy cycles) and the prophylaxis (n = 45; 104 chemotherapy cycles) group. IFI were significantly reduced in the prophylaxis group (55.3% vs. 88.9%; p = 0.0032) and there was a trend of the projected IFI-free survival at 100 days to be increased (50.1% vs. 25%; p = 0.0526). One-hundred day overall survival (84.4% and 88.4%, p = 0.35) and 2-year overall survival (64.4% and 58.1%; p = 0.64) were unaffected. No difference in the occurrence of bacteraemia was observed (32.3% vs. 34.6%; p = 0.8). A total of two (3.6%) patients in the non-prophylaxis and three (6.7%) in the prophylaxis group died due to IFI, and two (3.6%) in the non-prophylaxis and none in the prophylaxis group patients had to stop leukaemia treatment due to IFI. CONCLUSIONS: The anti-infective prophylaxis with posaconazole and levofloxacin resulted in a significant reduction of ‘possible’ IFI with a number-needed to treat to prevent one IFI of only 3 but did not result in a reduction of the incidence of bacteraemia.

OBJECTIVE: To assess the prognostic value of various parameters including positron emission tomography / computed tomography (PET/CT) and identify risk factors for survival of patients with non-Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma (HL) treated with autologous stem cell transplantation (ASCT). METHODS: Patient charts and our prospective ASCT database were assessed for the impact of documented variables on event free survival (EFS) and overall survival (OS), including salvage and conditioning regimens used, and PET/CT results before and after ASCT. RESULTS: Overall, 180 patients with NHL (n = 134; 74%) or HL (n = 46; 26%) received ASCT from December 2000 to May 2011. Of the NHL patients, 59 (44%) had diffuse large B-cell lymphoma (DLBCL). Conditioning was mainly performed with cyclophosphamide, carmustine, etoposide (CBV) (n = 72; 40%) or carmustine, etoposide, cytarabine, melphalan (BEAM) (n = 103; 57%). Treatment-related mortality (TRM) was 1.7%. Outcome data are in line with previously reported studies, especially the data for salvage treatment and BEAM conditioning in DLBCL patients confirmed the outcome reported recently in a phase III study. Positive pre- and post-transplantation PET/CT was an adverse risk factor for survival (PET/CT+ before ASCT: hazard ratio (HR): 2.65 (1.11−6.33), p = 0.029; PET/CT+ after ASCT: HR: 7.11 (2.76−18.34), p

Haematopoietic stem cell transplantation (HSCT) is a highly specialised procedure used to treat malignancies of the lymphohaematopoietic system as well as some acquired and inherited disorders of the blood. This analysis by the Swiss Blood Stem Cell Transplantation Group, based on data from 2008–2011, describes, treatment rates in Switzerland for specific indications and compares this with data from Germany, France, Italy and the Netherlands, corrected for the size of the population. Differences in transplant rates, in rates for particular indications, and in the use of specific transplant technologies such as use of unrelated donors, use of cord blood or mismatched family donors are described. These data are put in correlation with donor availability from international registries and with number of transplant teams and number of procedures per team all corrected for population size.

Background Traditionally, single-unit red blood cell transfusions were believed to be insufficient to treat anemia, but recent data suggest that they may lead to a safe reduction of transfusion requirements. We tested this hypothesis by changing from a double- to a single-unit red blood cell transfusion policy.Design and Methods We performed a retrospective cohort study in patients with hematologic malignancies receiving intensive chemotherapy or hematopoietic stem cell transplantation. The major end-points were the reduction in the total number of red blood cell units per therapy cycle and per day of aplasia. The study comprised 139 patients who received 272 therapy cycles. Overall 2212 red blood cell units were administered in 1548 transfusions.Results During the periods of the double- and single-unit policies, one red blood cell unit was transfused in 25% and 84% of the cases and the median number of red blood cell units per transfusion was two and one, respectively. Single-unit transfusion led to a 25% reduction of red blood cell usage per therapy cycle and 24% per aplasia day, but was not associated with a higher out-patient transfusion frequency. In multivariate analysis, single-unit transfusion resulted in a reduction of 2.7 red blood cell units per treatment cycle (P=0.001). The pre-transfusion hemoglobin levels were lower during the single-unit period (median 61 g/L versus 64 g/L) and more transfusions were administered to patients with hemoglobin values of 60 gl/L or less (47% versus 26%). There was no evidence of more severe bleeding or more platelet transfusions during the single-unit period and the overall survival was similar in both cohorts.Conclusions Implementing a single-unit transfusion policy saves 25% of red blood cell units and, thereby, reduces the risks associated with allogeneic blood transfusions.

BACKGROUND: Transfusing blood products may induce inflammatory reactions within the vascular compartment potentially leading to a systemic inflammatory response. Experiments were designed to assess the inflammatory potential of different blood products in an endothelial cell-based in vitro model and to compare baseline levels of potentially activating substances in transfusion products. METHODS: The inflammatory response from pre-activated (endotoxin-stimulated) and non-activated endothelial cells as well as neutrophil endothelial transmigration in response to packed red blood cells (PRBC), platelet concentrates (PC) and fresh frozen plasma (FFP) was determined. Baseline inflammatory mediator and lipid concentrations in blood products were evaluated. RESULTS: Following incubation with all blood products, an increased inflammatory mediator release from endothelial cells was observed. Platelet concentrates, and to a lesser extent also FFP, caused the most pronounced response, which was accentuated in already pre-stimulated endothelial cells. Inflammatory response of endothelial cells as well as blood product-induced migration of neutrophils through the endothelium was in good agreement with the lipid content of the according blood product. CONCLUSION: Within the group of different blood transfusion products both PC and FFP have a high inflammatory potential with regard to activation of endothelial cells. Inflammation upon blood product exposure is strongly accentuated when endothelial cells are pre-injured. High lipid contents in the respective blood products goes along with an accentuated inflammatory reaction from endothelial cells.

Background The possibility that allogeneic hematopoietic stem cell transplantation performed across the ABO blood group-barrier is associated with an increase of graft-versus-host disease, in particular endothelial damage, has not been elucidated so far. For this reason, we investigated the level of endothelial cell chimerism after allogeneic hematopoietic stem cell transplantation in order to delineate the role of hematopoietic stem cells in endothelial replacement.Design and Methods The frequency of donor-derived endothelial cells was analyzed in 52 hematopoietic stem cell transplant recipients, in 22 normal skin biopsies, in 12 skin samples affected by graft-versus-host disease, various tissues from five autopsies and four secondary solid tumors by ABH immunohistochemistry, XY fluorescence in situ hybridization and short tandem repeat analysis of laser captured endothelial cells.Results Skin biopsies from two patients transplanted with minor ABO-incompatible grafts (i.e. O in A) showed 3.3% and 0.9% H antigen-positive donor-derived endothelial cells by ABH immunohistochemistry. Tumor biopsies from two recipients showed 1.2% and 2.5% donor-derived endothelial cells by combined immunohistochemistry/ fluorescence in situ hybridization. All other skin samples, heart, liver, bone-marrow, and tumor tissues failed to reveal donor-type endothelial cells up to several years after ABO-incompatible hematopoietic stem cell transplantation.Conclusions Endothelial cell replacement by bone marrow-derived donor cells after allogeneic hematopoietic stem cell transplantation is a rare event. It does not seem to represent a major mechanism of physiological in vivo blood vessel formation, tumor neoangiogenesis, vascular repair after graft-versus-host disease episodes or acceptance of ABO-incompatible grafts.

Background Persistent anti-donor isoagglutinins after major ABO blood group incompatible hematopoietic stem cell transplantation may cause delayed red blood cell engraftment and post-transplant pure red cell aplasia.Design and Methods We investigated the effect of pretransplant anti-donor isoagglutinin reduction by in vivo absorption and/or plasmapheresis on the incidence of pure red cell aplasia and the time to red blood cell engraftment in 153 hematopoietic stem cell transplant recipients with major ABO incompatibility.Results Twelve patients (8%) developed pure red cell aplasia, 3/98 (3%) with, and 9/55 (16%) without prior isoagglutinin reduction (p=0.009). Red blood cell engraftment was faster in patients with isoagglutinin reduction; in addition, peripheral blood hematopoietic stem cell transplantation, acute graft-versus-host disease, and younger age were associated with faster red blood cell engraftment in Cox regression analysis. In patients with pure red cell aplasia the mean red blood cell engraftment occurred after 225 days (p