Mastocytosis and related entities: a practical roadmap.

Mastocytosis is a complex heterogenous multisystem disorder that is characterized by pathologic activation or accumulation of neoplastic mast cells (MCs) in one or more organs. This clonal MC expansion is often associated with a somatic gain-of-function mutation (D816V in most of the cases) in the KIT gene, encoding for the MC surface receptor KIT (CD117), a stem cell growth factor receptor. Based on clinical and biochemical criteria, the World Health Organization (WHO) divided mastocytosis into different subclasses. The exact prevalence of mastocytosis remains elusive, but it is estimated that the disease affects approximately 1 in 10,000 persons. The clinical presentation of mastocytosis varies significantly, ranging from asymptomatic patients to a life-threatening disease with multiple organ involvement, potentially leading to cytopenia, malabsorption, hepatosplenomegaly, lymphadenopathy, ascites or osteolytic bone lesions with pathological fractures. Patients with mastocytosis may experience symptoms related to release of MC mediators, such as flushing or diarrhea or even more severe symptoms such as anaphylaxis. Recently, a new genetic trait, hereditary alpha tryptasemia (HaT), was described which involves a copy number variation in the TPSAB1-gene. Its role as standalone multisystem syndrome is heavily debated. There is emerging evidence suggesting there might be a link between HaT and due to the increased prevalence of HaT in patients with SM. The aim of this review is to provide a practical roadmap for diagnosis and management of mastocytosis and its associated entities, since there are still many misconceptions about these topics.Abbreviations: AdvSM: Advanced systemic mastocytosis; ASM: Aggressive systemic mastocytosis; aST: acute serum tryptase; BM: Bone marrow; BMM: Bone marrow mastocytosis; bST: baseline serum tryptase; CM: Cutaneous mastocytosis; DCM: Diffuse cutaneous mastocytosis; HVA: Hymenoptera venom allergy; HaT: Hereditary alpha tryptasemia; ISM: Indolent systemic mastocytosis; MC: Mast cell; MCA: Mast cell activation; MCAS: Mast cell activation syndrome; MCL: Mast cell leukemia; MIS: Mastocytosis in the skin; MMAS: Monoclonal mast cell activation syndrome; MPCM: Maculopapular cutaneous mastocytosis; SM: Systemic mastocytosis; SM-AHN: Systemic mastocytosis with associated hematological neoplasm; SSM: Smouldering systemic mastocytosis; VIT: Venom immunotherapy.

Overexpression of FcεRI on Bone Marrow Mast Cells, but Not MRGPRX2, in Clonal Mast Cell Disorders With Wasp Venom Anaphylaxis.

Background: Uncertainties remain about the molecular mechanisms governing clonal mast cell disorders (CMCD) and anaphylaxis. Objective: This study aims at comparing the burden, phenotype and behavior of mast cells (MCs) and basophils in patients with CMCD with wasp venom anaphylaxis (CMCD/WVA+), CMCD patients without anaphylaxis (CMCD/ANA-), patients with an elevated baseline serum tryptase (EBST), patients with wasp venom anaphylaxis without CMCD (WVA+) and patients with a non-mast cell haematological pathology (NMHP). Methods: This study included 20 patients with CMCD/WVA+, 24 with CMCD/ANA-, 19 with WVA+, 6 with EBST and 5 with NMHP. We immunophenotyped MCs and basophils and compared baseline serum tryptase (bST) and both total and venom specific IgE in the different groups. For basophil studies, 13 healthy controls were also included. Results: Higher levels of bST were found in CMCD patients with wasp venom anaphylaxis, CMCD patients without anaphylaxis and EBST patients. Total IgE levels were highest in patients with wasp venom anaphylaxis with and without CMCD. Bone marrow MCs of patients with CMCD showed lower CD117 expression and higher expression of CD45, CD203c, CD63, CD300a and FcεRI. Within the CMCD population, patients with wasp venom anaphylaxis showed a higher expression of FcεRI as compared to patients without anaphylaxis. Expression of MRGPRX2 on MCs did not differ between the study populations. Basophils are phenotypically and functionally comparable between the different patient populations. Conclusion: Patients with CMCD show an elevated burden of aberrant activated MCs with a significant overexpression of FcεRI in patients with a wasp venom anaphylaxis.

Safety and Efficacy of Antibiotic De-escalation and Discontinuation in High-Risk Hematological Patients With Febrile Neutropenia: A Single-Center Experience.

BACKGROUND: There is currently no consensus on optimal duration of antibiotic treatment in febrile neutropenia. We report on the clinical impact of implementation of antibiotic de-escalation and discontinuation strategies based on the Fourth European Conference on Infections in Leukaemia (ECIL-4) recommendations in high-risk hematological patients. METHODS: We studied 446 admissions after introduction of an ECIL-4-based protocol (hereafter "ECIL-4 group") in comparison to a historic cohort of 512 admissions. Primary clinical endpoints were the incidence of infectious complications including septic shock, infection-related intensive care unit (ICU) admission, and overall mortality. Secondary endpoints included the incidence of recurrent fever, bacteremia, and antibiotic consumption. RESULTS: Bacteremia occurred more frequently in the ECIL-4 group (46.9% [209/446] vs 30.5% [156/512]; P < .001), without an associated increase in septic shock (4.7% [21/446] vs 4.5% [23/512]; P = .878) or infection-related ICU admission (4.9% [22/446] vs 4.1% [21/512]; P = .424). Overall mortality was significantly lower in the ECIL-4 group (0.7% [3/446] vs 2.7% [14/512]; P = .016), resulting mainly from a decrease in infection-related mortality (0.4% [2/446] vs 1.8% [9/512]; P = .058). Antibiotic consumption was significantly reduced by a median of 2 days on antibiotic therapy (12 vs 14; P = .001) and 7 daily antibiotic doses (17 vs 24; P < .001) per admission period. CONCLUSIONS: Our results support implementation of ECIL-4 recommendations to be both safe and effective based on real-world data in a large high-risk patient population. We found no increase in infectious complications and total antibiotic exposure was significantly reduced.

A case of multisystem inflammatory syndrome (MIS-A) in an adult woman 18 days after COVID-19 vaccination.

We discuss a case of a young woman, presenting a constellation of clinical and biochemical features meeting the current case definition of multisystem inflammatory syndrome in adults (MIS-A), 18 days after receiving her first dose of the Oxford/AstraZeneca vaccine. Therapy by means of intravenous immunoglobulins was initiated, leading to clinical and biochemical recovery. Although a relationship between MIS-A and the preceding vaccination cannot be confirmed, it can also not be excluded, given the temporal association and the fact that there were no indicators of a preceding SARS-CoV-2 infection.

Diagnosis of Primary Mast Cell Disorders in Anaphylaxis: Value of KIT D816V in Peripheral Blood.

BACKGROUND: Anaphylaxis is frequent in patients suffering from primary mast cell disorders (PMCDs). In patients without mastocytosis in the skin (MIS) and a baseline serum tryptase (bST) less than 30 ng/mL, the diagnosis of PMCD is challenging. In these patients, detection of the KIT D816V mutation in peripheral blood (PB) has been suggested as screening tool for a PMCD. OBJECTIVE: In this study, we investigated whether KIT D816V in PB can contribute to the decision to perform a bone marrow (BM) biopsy in patients with anaphylaxis without MIS and a bST less than 30 ng/mL. METHODS: We selected 74 patients with severe anaphylaxis without MIS and a bST less than 30 ng/mL. All underwent a BM biopsy. KIT D816V mutation was quantified in both PB and BM using digital droplet polymerase chain reaction (ddPCR). RESULTS: Diagnosis of a PMCD was established in 40 patients (54%). Median bST for patients with and without PMCD was, respectively, 9.5 ng/mL (range 4.2-27 ng/mL) and 4.9 ng/mL (range 2.2-20.3 ng/mL) (P <.001). KIT D816V in PB was detected in 16 out of 40 (40%) patients with PMCD. KIT D816V in BM was detected in 22 out of 40 (55%) patients with PMCD. CONCLUSIONS: In patients without MIS and a bST less than < 30 ng/mL who experience anaphylaxis, determination of KIT D816V mutation in PB is of limited help in deciding when to proceed to a BM biopsy. Therefore, KIT D816V in PB mutation analysis should be interpreted together with scoring tools to make a better assessment in identifying patients who should undergo BM biopsy.

Culturing cells with mast cell phenotype and function: Comparison of peripheral blood and bone marrow as a source.

BACKGROUND: Studies on the mechanisms that govern mast cell (MC) functions are hindered by the difficulties in isolating sufficient numbers of these tissue-resident cells. Therefore, many research groups use cultured human MCs obtained out of progenitor cells. However, these culture methods significantly differ regarding primary source material, culture durations and conditions. Consequently, the finally obtained cells are likely to exhibit morphological, phenotypical and/or functional heterogeneity. OBJECTIVE: To compare the phenotype and functionality of cells cultured from peripheral blood and bone marrow progenitor cells from patients with suspected clonal MC disease. These cells are designated as PBCMCs and BMCMCs, respectively. METHODS: Twenty paired PBCMCs and BMCMCs cultures starting from CD34+ progenitor cells were compared. Cells were cultured for 4 weeks. Phenotyping included Giemsa and CD117 staining and flow cytometric staining for CD117, CD203c, FcεRI, MRGPRX2, CD300a, CD32, CD63 and CD25. Functional assessment included measurement of the up-regulation of CD63 after cross-linking of the high affinity receptor for IgE (FcεRI) with anti-FcεRI and ligation of MRGPRX2 with substance P. RESULTS: PBCMCs and BMCMCs are phenotypically comparable. Functionally, after activation with anti-FcεRI and substance P, PBCMCs and BMCMCs show similar up-regulation of the lysosomal degranulation marker CD63. However, the yield of PBCMCs is higher than BMCMs and peripheral blood cultures are purer than bone marrow cultures. CONCLUSION: PBCMCs are an attractive alternative to the more difficult to obtain BMCMCs for the exploration of the complex mechanisms that govern IgE- and MRGPRX2-dependent MC activation and degranulation. Unlike BMCMCs, PBCMCs are easily accessible and enable repetitive analyses.

The tele-transition of toxicity management in routine oncology care during the severe acute respiratory syndrome (SARS-CoV-2) pandemic.

BACKGROUND: Telehealth modalities were introduced during the SARS-CoV-2 pandemic to assure continuation of cancer care and maintain social distance. METHODS: This is a retrospective cohort analysis of our telehealth expansion programme. We adapted two existing patient-reported outcome (PRO) telemonitoring tools that register and (self-)manage toxicities to therapy, while screening for SARS-CoV-2-related symptoms. Outpatients from a tertiary cancer centre were enrolled. The adapted PRO interface allowed for uniform registration of SARS-CoV-2-related symptoms and effective triage of patients at home where we also implemented systematic throat washings, when available. RESULTS: Three hundred and sixty patients registered to the telemonitoring systems from March 13 to May 15, 2020. Four prespecified SARS-CoV-2 alarms resulted in three patients with positive PCR testing. Other Covid-19 symptoms (fever 5× and cough 2×) led to pretreatment triage resulting in 1 seroconversion after initial negative testing. One of the 477 throat washings proved positive. CONCLUSIONS: The rapid adoption of an amended PRO (self-)registrations and toxicity management system was feasible and coordinated screening for Covid-19. Continued clinical cancer care was maintained, with significant decreased waiting time. The systemic screening with throat washings offered no real improvement.

Use of chimerism analysis after allogeneic stem cell transplantation: Belgian guidelines and review of the current literature.

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment option in both adult and pediatric patients with malignant and non-malignant hematological diseases.  Chimerism analysis, which determines the donor or recipient origin of hematopoietic cells in HSCT recipients, is an essential aspect of post-HSCT follow-up.Objectives: To review the current literature and develop Belgian consensus guidelines for the use of chimerism analysis in the standard of care after allogeneic HSCT.Methods: Non-systematic review of the literature in consultancy with the members of the BHS transplantation committee.Results: Clinical application with regards to prediction of graft failure or relapse as well as cell source are reviewed. A consensus guideline on the use of chimerism analysis after HSCT is presented.Conclusion: Monitoring of the dynamics or kinetics of a patient's chimerism status by serial analysis at fixed time points, as well as on suspicion of relapse or graft failure, is needed to monitor engraftment levels, as well as disease control and possible relapse.

Current antimicrobial practice in febrile neutropenia across Europe and Asia: the EBMT Infectious Disease Working Party survey.

The aim of this survey was to summarize the current antimicrobial practice in febrile neutropenia and the presence of key aspects of antimicrobial stewardship. A questionnaire was sent to 567 centers, and complete responses were obtained from 194 (34.2%). Fluoroquinolone and co-trimoxazole prophylaxis are used in 57.1% and 89.1%, respectively. In 66.4%, the first-line empirical therapy is piperacillin/tazobactam, whereas 10.9% use carbapenems. Empirical combination therapy is used in stable patients without history of resistant pathogens in 37.4%. De-escalation to monotherapy is performed within 3 days in 35.3% and after 10 days in 19.1%. Empirical addition of a glycopeptide is performed when fever persists more than 2-3 days in 60.8%. Empirical escalation to a broader spectrum agent is performed when fever persists more than 3-5 days in 71.4%. In case of positive blood cultures with a susceptible pathogen and uncomplicated presentation, 76.7% of centers de-escalate and 36.6% discontinue before neutrophil recovery. In fever of unknown origin with uncomplicated presentation, 54.1% of centers de-escalate and 49.5% discontinue before neutrophil recovery. Recommendations put forward in the ECIL guidelines are not widely implemented in clinical practice. Specific problems include overuse of carbapenems and combination therapy and unjustified addition of glycopeptides without further de-escalation or discontinuation.

Comparison of the Power of Procalcitonin and C-Reactive Protein to Discriminate between Different Aetiologies of Fever in Prolonged Profound Neutropenia: A Single-Centre Prospective Observational Study.

Management of fever in prolonged, profound neutropenia remains challenging with many possible infectious and non-infectious causes. We investigated whether procalcitonin (PCT) is superior to C-reactive protein (CRP) in discriminating between different aetiologies of fever in this setting. CRP and PCT were tested daily during 93 neutropenic episodes in 66 patients. During this study period, 121 febrile episodes occurred and were classified into four categories based on clinical and microbiological findings: microbiologically documented infection (MDI); clinically documented infection (CDI); proven or probable invasive fungal disease (IFD); fever of unknown origin (FUO). Values of PCT and CRP at fever onset as well as two days later were considered for analysis of their performance in distinguishing aetiologies of fever. At fever onset, no significant difference in PCT values was observed between different aetiologies of fever, whereas median CRP values were significantly higher in case of IFD (median 98.8 mg/L vs 28.8 mg/L, p=0.027). Both PCT and CRP reached their peak at a median of 2 days after fever onset. Median PCT values on day 2 showed no significant difference between the aetiologies of fever. Median CRP values on day 2 were significantly higher in IFD (median 172 mg/L versus 78.4 mg/L, p=0.002). In MDI median CRP values rose > 100 mg/L, whereas they did not in CDI or FUO. PCT has no added value over CRP for clinical management of fever in prolonged, profound neutropenia. When performing reassessment 2 days after fever onset, CRP has better discriminatory power between aetiologies of fever.

Providing both autologous and allogeneic hematopoietic stem cell transplants (HSCT) may have a stronger impact on the outcome of autologous HSCT in adult patients than activity levels or implementation of JACIE at Belgian transplant centres.

While performance since the introduction of the JACIE quality management system has been shown to be improved for allogeneic hematopoietic stem cell transplants (HSCT), impact on autologous-HSCT remains unclear in Europe. Our study on 2697 autologous-HSCT performed in adults in 17 Belgian centres (2007-2013) aims at comparing the adjusted 1 and 3-yr survival between the different centres & investigating the impact of 3 centre-related factors on performance (time between JACIE accreditation achievement by the centre and the considered transplant, centre activity volume and type of HSCT performed by centres: exclusively autologous vs both autologous & allogeneic). We showed a relatively homogeneous performance between Belgian centres before national completeness of JACIE implementation. The 3 centre-related factors had a significant impact on the 1-yr survival, while activity volume and type of HSCT impacted the 3-yr survival of autologous-HSCT patients in univariable analyses. Only activity volume (impact on 1-yr survival only) and type of HSCT (impact on 1 and 3-yr survivals) remained significant in multivariable analysis. This is explained by the strong relationship between these 3 variables. An extended transplantation experience, i.e., performing both auto & allo-HSCT, appears to be a newly informative quality indicator potentially conveying a multitude of underlying complex factors.

EBV-associated hemophagocytic lymphohistiocytosis complicated by severe coagulation disorders and opportunistic infections: case report of a survivor.

The possibility of hemophagocytic lymphohistiocytosis should always be kept in mind when examining/treating a patient with fever of unknown origin and sepsis-like symptoms. Early diagnosis leading to prompt initiation of immunosuppressive therapy as well as aggressive supportive care, including correction of coagulation abnormalities and treatment of opportunistic infections, can decrease mortality.

Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia.

Relapse is a major problem in acute myeloid leukemia (AML) and adversely affects survival. In this phase 2 study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms' tumor 1 (WT1) messenger RNA (mRNA) as postremission treatment in 30 patients with AML at very high risk of relapse. There was a demonstrable antileukemic response in 13 patients. Nine patients achieved molecular remission as demonstrated by normalization of WT1 transcript levels, 5 of which were sustained after a median follow-up of 109.4 months. Disease stabilization was achieved in 4 other patients. Five-year overall survival (OS) was higher in responders than in nonresponders (53.8% vs 25.0%; P = .01). In patients receiving DCs in first complete remission (CR1), there was a vaccine-induced relapse reduction rate of 25%, and 5-year relapse-free survival was higher in responders than in nonresponders (50% vs 7.7%; P < .0001). In patients age ≤65 and >65 years who received DCs in CR1, 5-year OS was 69.2% and 30.8% respectively, as compared with 51.7% and 18% in the Swedish Acute Leukemia Registry. Long-term clinical response was correlated with increased circulating frequencies of polyepitope WT1-specific CD8+ T cells. Long-term OS was correlated with interferon-γ+ and tumor necrosis factor-α+ WT1-specific responses in delayed-type hypersensitivity-infiltrating CD8+ T lymphocytes. In conclusion, vaccination of patients with AML with WT1 mRNA-electroporated DCs can be an effective strategy to prevent or delay relapse after standard chemotherapy, translating into improved OS rates, which are correlated with the induction of WT1-specific CD8+ T-cell response. This trial was registered at www.clinicaltrials.gov as #NCT00965224.

Passenger Lymphocyte Syndrome (PLS): A Single-center Retrospective Analysis of Minor ABO-incompatible Liver Transplants.

Background and Aims: Due to the shortage of donor livers, minor ABO-incompatible liver transplantations are commonly performed. Together with the allograft, immunocompetent B-lymphocytes, called passenger lymphocytes, are transplanted. In case of minor ABO-incompatibility, these passenger lymphocytes produce antibodies directed towards the recipient's red blood cells, which causes immune-mediated hemolysis, also known as the passenger lymphocyte syndrome (PLS). Although this is a self-limiting disorder, serious complications can occur, including graft failure. Retrospectively, we evaluated the role of PLS in minor ABO-incompatible liver transplantations performed at our center. Methods: A retrospective analysis was conducted for all minor ABO-incompatible liver transplantations performed at the Antwerp University Hospital between 2003 and 2015. All patient files were inspected for clinical and laboratory findings. In cases of PLS diagnosis, the applied treatment was also studied. Results: In total, 10 patients underwent a minor ABO-incompatible liver transplantation and 4 showed signs of PLS. All 4 PLS patients were treated with different therapeutic strategy, corresponding to the severity of hemolysis. In all 4 cases, PLS resolved following treatment. Conclusion: When performing minor ABO-incompatible liver transplantations, knowledge of PLS is elemental. Next to a high index of clinical suspicion, we suggest routine screening for markers of hemolysis, with emphasis on haptoglobin level and direct antiglobulin test, weekly in the first 4 weeks post-transplantation as well as in case of a sudden hemoglobin drop within the first 3 months after transplantation. Peri- and postoperative transfusion support using donor-compatible blood has been suggested to prevent the occurrence or limit the extent of hemolysis.

Adult acute precursor B-cell lymphoblastic leukemia presenting as hypercalcemia and osteolytic bone lesions.

BACKGROUND: Osteolytic bone lesions and hypercalcemia without peripheral blasts B-cell acute lymphoblastic leukemia (B-ALL) is reported in children but rarely seen in adults. CASE PRESENTATION: We describe the case of a 34-year old man presenting with hypercalcemia and symptomatic osteolytic bone lesions of vertebrae and ribs who was initially suspected as having a solid malignancy. Diagnostic work-up including peripheral blood examination, radiographic and nuclear studies could, however, not detect a primary tumor. Because of a mild thrombocytopenia and the lack of a primary focus, a bone marrow biopsy was performed leading to the diagnosis of Philadelphia chromosome positive precursor B-ALL. After correction of the hypercalcemia with intravenous fluid administration, corticoids and bisphosphonates, the patient was treated according to the HOVON 100 protocol achieving complete molecular remission after the first cycle of induction chemotherapy. CONCLUSION: Hypercalcemia and osteolytic bone lesions are rare complications of adult B-ALL and can occur in the absence of peripheral blastosis. With this case report we would like to emphasize the importance of clinical awareness. Immediate treatment of hypercalcemia and initiation of antileukemic treatment is mandatory as a delay of diagnosis might pose a real and possible life-threatening risk in these patients.

Detection of a case of chronic myeloid leukaemia with deletions at the t(9;22) translocation breakpoints by a genome-wide non-invasive prenatal test.

OBJECTIVE: Non-invasive prenatal tests (NIPTs) interrogating the complete genome are able to detect not only fetal trisomy 13, 18 or 21 but additionally provide information on other (sub)chromosomal aberrations that can be fetal or maternal in origin. We demonstrate that in a subset of cases, this information is clinically relevant and should be reported to ensure adequate follow-up. METHOD: Genome-wide NIPT was carried out and followed by a software analysis pipeline optimized to detect subchromosomal aberrations. RESULTS: The NIPT profile showed deletions on chromosomes 9 and 22: NIPT 9q33.3q34.12(129150001-133750000)x1,22q11.23(23550001-25450000)x1,22q13.1(37850001-39600000)x1. This result was confirmed by single nucleotide polymorphism array on maternal genomic DNA, which also demonstrated that the deletions were somatic in nature. Fluorescence in situ hybridization and quantitative real-time polymerase chain reaction revealed that the deletions were flanking the translocation breakpoint on the derivative chromosome 9 as the result of a t(9;22)(q34;q11.2) translocation with BCR-ABL1 fusion typical for chronic myeloid leukaemia (CML). Multidisciplinary counselling, together with complete blood count, taught that the woman was in an early chronic phase CML. The woman was followed up closely, and treatment could be postponed until after delivery. CONCLUSION: Genome-wide NIPT identified a CML in chronic phase caused by the typical t(9;22)(q34;q11.2) translocation and accompanied by deletions flanking the translocation breakpoints. © 2016 John Wiley & Sons, Ltd.

Clinical and microbiological impact of discontinuation of fluoroquinolone prophylaxis in patients with prolonged profound neutropenia.

BACKGROUND: Infections remain a leading cause of morbidity and mortality in patients with reduced immunity caused by haematological disease and chemotherapy-induced neutropenia. We evaluated the clinical and microbiological impact of discontinuing fluoroquinolone prophylaxis in these patients. METHODS: We analysed 154 admissions in three sequential periods of 8 months: long-standing use, discontinuation of prophylaxis and reintroduction of prophylaxis. Clinical endpoints were occurrence of febrile neutropenia, bacteraemia, severe sepsis, septic shock, response to antibiotic therapy, total antibiotic consumption and duration of hospital stay. Microbiological analysis included bacterial isolates from stool and blood cultures and their resistance pattern. RESULTS: No significant increase in serious infectious complications was seen with the discontinuation of prophylaxis. The overall incidence of bacteraemia did not change, but a higher proportion of bacterial isolates were Gram-negative (22.2% vs. 5.9% & 8.6%; P = 0.030), more often multisusceptible (50% vs. 0%) and less fluoroquinolone resistant (10% vs. 100%). Screening of stools showed a higher prevalence of organisms in the discontinuation period (86.7% vs. 37.3% & 55.2%; P ≤ 0.001), but they were more frequently multisusceptible (53.8% vs. 10.5% & 6.3%; P ≤ 0.001). After discontinuation of prophylaxis, fluoroquinolone resistance decreased rapidly from 73.7 to 7.7%, in association with a significant decrease in extended spectrum beta-lactamase (ESBL)-producing isolates from 42.1 to 10.3%. Resistance figures immediately returned to prediscontinuation values after reinstitution of prophylaxis. CONCLUSIONS: No clinically relevant short-term drawbacks were observed with the discontinuation of fluoroquinolone prophylaxis in patients with chemotherapy-induced prolonged profound neutropenia, which led to a significant decrease in fluoroquinolone resistance as well as occurrence of ESBL-producing isolates.

Determining factors predictive of CD34+ cell collection efficiency in an effort to avoid extended and repeated apheresis sessions.

INTRODUCTION: Collection efficiency (CE) is a reflection of the proportion of cells passing through a cell separator that is harvested. The aim of our study was to evaluate which factors influence CE independently in order to find ways to improve CE and therefore minimize the costs and risks of leukapheresis and graft processing. MATERIALS AND METHODS: A total of 206 consecutive apheresis procedures performed on 128 donors/patients were studied retrospectively. We explored the association between CE and the following factors: age, sex, weight, mobilization (granulocyte-colony-stimulating factor with or without chemotherapy), collection type (autologous versus allogeneic), venous access (peripheral versus central), total processed blood volume (TPV), hematocrit, white blood cell (WBC) count, thrombocyte count, and peripheral blood CD34+ cell concentration (PBCD34+). RESULTS: Stepwise multiple regression analysis showed WBC count to be the single best predictor of CE, accompanied by TPV. When performing subgroup analysis for autologous apheresis procedures, the inverse correlation of WBC count and TPV with CE becomes stronger (r = -0.563 with P < 0.001 and r = -0.198 with P = 0.020 respectively), whereas those correlations disappear when analyzing only allogeneic apheresis procedures. CONCLUSION: The negative correlation between TPV and CE present only in autologous collection procedures can be explained by the limited intra-apheresis recruitment of CD34+ cells into the blood which is negatively influenced by extensive pre-treatment. As a result of this study we decided to limit TPV to a maximum of three times the patient's blood volume in autologous apheresis procedures at our center.