Elevated systolic pulmonary artery pressure is a substantial predictor of increased mortality after transcatheter aortic valve replacement in males, not in females.

BACKGROUND: While pulmonary hypertension (PH) in patients with severe aortic valve stenosis (AS) is associated with increased mortality after transcatheter aortic valve replacement (TAVR), there is limited data on gender differences in the effects on long-term survival. OBJECTIVE: The aim of this retrospective, multicenter study was to investigate the prognostic impact of pre-interventional PH on survival of TAVR patients with respect to gender. METHODS: 303 patients undergoing TAVR underwent echocardiography to detect PH prior to TAVR via measurement of systolic pulmonary artery pressure (sPAP). Different cut-off values were set for the presence of PH. The primary endpoint was all-cause mortality at 1, 3 and 5 years. RESULTS: Kaplan-Meier analysis by gender showed that only males exhibited significant increased mortality at elevated sPAP values during the entire follow-up period of 5 years (sPAP ≥ 40 mmHg: p ≤ 0.001 and sPAP ≥ 50 mmHg: p ≤ 0.001 in 1- to 5-year survival), whereas high sPAP values had no effect on survival in females. In Cox regression analysis based on the selected sPAP thresholds, male gender was an independent risk factor for long-term mortality after TAVR in all time courses. CONCLUSION: Male gender was an isolated risk factor for premature death after TAVR in patients with echocardiographic evidence of PH and severe AS. This could mean that, the indication for TAVR should be discussed more critically in men with severe AS and an elevated sPAP, while in females, PH should not be an exclusion criterion for TAVR.

Psychocardiological assessment in the acute phase of the takotsubo syndrome : Somatic and depressive disorders, resilience and illness perception.

OBJECTIVE: To analyze the psychocardiological profile and the clinical characteristics in the acute phase of takotsubo syndrome (TTS). METHODS: Prospective multicenter cohort study of TTS patients evaluating the clinical characteristics as well as the prevalence of somatic, depressive, panic, stress and anxiety disorders. Assessment of illness perception and resilience in the acute phase of the syndrome. RESULTS: All 27 evaluated TTS patients were female with a mean age of 68 years (±11.4 years). The apical type of TTS was found in 60% of patients, followed by the combined type of TTS in 30% of patients. Main clinical symptom leading to hospital admission was chest pain in nearly 80% of patients. An ST-segment elevation mimicking acute myocardial infarction was found in 44% of patients and T wave inversion in 26% of patients. An endogenous (emotional) stress event was found in 17 patients (63.0%), an exogenous (physical) stress event in 5 patients (18.5%) and a combined stress event in 2 patients (7.4%). In 11.1% of patients (n = 3) no stress event could be found. Moderate to high levels of illness threatening were found in 48% of patients and low to moderate resilience scores were found in 40% of patients. Somatic disorders were found in half of the patients (56%) followed by depressive disorders in 26% of patients. CONCLUSION: Moderate to low resilience scores and moderate to high levels of illness threatening can be seen in the acute phase of TTS, reflecting the severity of the experience as an adverse life event. Patients suffering from TTS present in the acute phase with a high prevalence of somatic disorders and relatively high prevalence of depressive disorders.

Soluble suppression of tumorigenicity 2 as outcome predictor after cardiopulmonary resuscitation: an observational prospective study.

Prognostication after cardiopulmonary resuscitation (CPR) is complex. Novel biomarkers like soluble suppression of tumorigenicity 2 (sST2) may provide an objective approach. A total of 106 post-CPR patients were included in this single-center observational prospective study. Serum sST2 levels were obtained 24 h after admission. Individuals were assigned to two groups: patients below and above the overall cohort's median sST2 concentration. Primary outcome was a combined endpoint at 6 months (death or Cerebral Performance Category > 2); secondary endpoint 30-day mortality. A uni- and multivariate logistic regression analysis were conducted. Elevated sST2-levels were associated with an increased risk for the primary outcome (OR 1.011, 95% CI 1.004-1.019, p = 0.004), yet no patients with poor neurological outcome were observed at 6 months. The optimal empirical cut-off for sST2 was 46.15 ng/ml (sensitivity 81%, specificity 53%, AUC 0.69). Levels above the median (> 53.42 ng/ml) were associated with higher odds for both endpoints (death or CPC > 2 after 6 months: 21% vs. 49%, OR 3.59, 95% CI 1.53-8.45, p = 0.003; death after 30 days: 17% vs. 43.3%, OR 3.75, 95% CI 1.52-9.21, p = 0.003). A positive correlation of serum sST2 after CPR with mortality at 30 days and 6 months after cardiac arrest could be demonstrated.

Overview of Current International Recommendations for Echocardiography Exams During the Covid-19 Pandemic and Its Local Implementation in Austria.

Since its first appearance in December 2019, the novel Coronavirus SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) has spread throughout the world at rapid pace causing the coronavirus disease 2019 (Covid-19). Originating in the Chinese province Hubei, more than 91.8 million people globally have now been infected with the coronavirus and more than 1.966.000 patients have died thus far from Covid-19 (as of January 13th 2021). The virus spreads primarily by droplet infection as well as via aerosols during close physical contact. Particularly in medical examinations with close physical contact between examiner and patient, like echocardiography, the risk of contracting the virus is increased. Therefore, the use of personal protective equipment is recommended for the protection of patients and medical personnel alike. In this article, the current recommendations of international professional associations on the use of personal protective equipment and their local implementation are presented.

[Echocardiographic examinations in times of the COVID-19 pandemic : International recommendations and implementation]. / Echokardiographieuntersuchungen in Zeiten der COVID-19-Pandemie : Internationale Empfehlungen und Umsetzung.

Since its first appearance in December 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread all over the world at a rapid pace causing the coronavirus disease 2019 (COVID-19). Originating from the Chinese province Hubei, more than 29.4 million people globally have now been confirmed to have contracted the coronavirus and more than 930,000 patients have died so far from COVID-19 (situation as of 15 September 2020). The virus is mainly spread during close contact by small droplets and aerosols. During the close contact in medical examinations, such as echocardiography, the risk of contracting the virus is increased. Therefore, the use of personal protective equipment is recommended for the protection of patients and medical personnel alike. This article summarizes the current recommendations of international societies and describes the local implementation in Austria.

Transcatheter aortic valve implantation without prior balloon valvuloplasty is associated with less pronounced markers of myocardial injury.

BACKGROUND: Aortic valve stenosis is the most common valvulopathy in developed countries. Transcatheter aortic valve implantation (TAVI) is a therapeutic alternative in symptomatic patients at high or prohibitive perioperative risk. Predilatation by balloon aortic valvuloplasty (BAV) under rapid ventricular pacing (RVP) has been a routine part of TAVI. However, both RVP and BAV carry substantial risks and an increasing number of interventional centers are performing TAVI without predilatation (direct TAVI). A transient decrease of left ventricular function and elevated markers of myocardial injury after TAVI with predilatation were observed in previous studies. In this study, we investigated whether direct TAVI was associated with a similar increase in cardiac biomarkers and decrease in ejection fraction in a cohort of our patients. METHODS: Consecutive patients undergoing TAVI without predilatation using a self-expanding system at a single center between April 2013 and December 2015 were followed up for one year and were retrospectively analyzed regarding mortality, safety and efficacy endpoints as well as common laboratory and echocardiographic parameters. RESULTS: A total of 164 patients (83±6 years; 56% female) were included in the analysis. According to the Valve Academic Research Consortium 2 (VARC-2) criteria the technical success rate was 96.3% and 89.1% of patients remained free of a combined safety endpoint at 30 days. Mortality rates at 30 days and 1 year were 3.0% (N.=5) and 10.4% (N.=17), respectively. TAVI without predilatation was highly effective in lowering aortic valve peak velocity from 4.4±0.6 m/s before to 1.7±0.5 m/s (P<0.01), and mean pressure gradient across the valve from 48.7±15.1 mmHg to 8.3±4.5 mmHg (<0.05). Left ventricular function remained unaltered after the intervention (51±10% prior to TAVI and 51±9% post TAVI), whereas high sensitive troponin T (hs-TnT), a well-established marker for myocardial injury, increased significantly from 26 ng/L (interquartile range=18.00-44.00) to 119 ng/L (interquartile range=73.25-166.00, P<0.001) during this time. Notably, an increase in the plasma levels of hs-TnT >15 times the upper limit of normal was associated with mortality both one month and one year after TAVI. CONCLUSIONS: TAVI without predilatation is feasible, safe and effective for aortic valve replacement in symptomatic patients with severe aortic stenosis who are at high perioperative risk. In contrast to a cohort of patients who underwent TAVI with predilatation previously published by another center, our patients did not suffer from transient impairment of left ventricular function. As a marker of myocardial injury, hs-TnT showed a less pronounced increase than reported previously. This might be a marker for a prognostic benefit as hs-TnT has been shown to be a strong predictor of outcome in patients undergoing TAVI. We conclude that direct TAVI is a less invasive option involving less myocardial stress.

Carcinoid heart disease involving the left heart: a case report and biomarker analysis.

Herein, we report the case of a 67-year-old woman who was admitted to our hospital because of dyspnoea and oedema of the lower extremities. Transthoracic echocardiography revealed severe tricuspid and mitral regurgitation, and the leaflets of the tricuspid valve were found to be rigid and almost immobile. The plasma concentrations of serotonin and chromogranin A were elevated, and hence, suspicion for carcinoid heart disease was raised. In addition to the diagnostic workup and medical and surgical treatment, we analysed levels of novel cardiovascular biomarkers throughout the entire follow-up by means of enzyme-linked immunosorbent assay. A dopa positron emission tomography (DOPA-PET) was conducted and showed a neoplasm in the terminal ileum. Tricuspid valve replacement, mitral valve repair, and a closure of the patent foramen ovale (PFO) were conducted. Two months later, hemicolectomy and liver segment resection were performed. The tumour was resected, and the diagnosis of a neuroendocrine tumour (NET) was confirmed. Throughout the follow-up, we observed a decrease in the plasma levels of novel biomarkers [e.g. interleukin-8 (IL-8), soluble suppression of tumorigenicity-2 (sST2), and heart-type fatty acid-binding protein (H-FABP)] over the follow-up period. In our case, carcinoid heart disease resulted in a severe tricuspid regurgitation as commonly seen in these patients. Moreover, a pre-existent mitral regurgitation was likely aggravated by fibrotic remodelling, because a PFO has led to a right-to-left shunt and might have caused left heart involvement. As IL-8 was associated with adverse outcomes in patients with NETs, and sST2 and H-FABP were associated with adverse outcomes in patients with heart failure previously, these biomarkers could aid in the risk stratification of patients with NET.

Frailty scoring in transcatheter aortic valve replacement patients.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a less invasive treatment option for patients that are deemed too high a risk for surgical aortic valve replacement (SAVR). The aim of this review is to evaluate the frailty tools currently being used in patients referred for TAVR. METHODS: Using a literature search involving database search engines from CINAHL, PubMed, SAGE publications and European Society of Cardiology conducted from 2010 to the present, a critical evaluation of studies dealing with frailty assessment in patients referred for TAVR/SAVR is discussed. RESULTS: Eight studies met the criteria using frailty assessment in TAVR/SAVR patients. In all reviewed studies the impact of frailty on clinical outcome has been proved. Different instruments for measurements of frailty were used that have not been robustly evaluated. Frailty was defined differently and results may not be comparable. All reviewed studies used different cutoffs and scales and some a composite scoring system, although validity was limited. CONCLUSION: For frailty assessment implementation of validated standardized test protocols based on well-established assessment tools, covering all domains of frailty among TAVR centers is crucial for patient selection. Secondly, validated cutoffs and scoring systems are essential.

Rehospitalization rates after transcatheter aortic valve implantation.

AIMS: Comorbidities pose a major challenge to screening, selection and follow-up of transcatheter aortic valve implantation (TAVI) patients as well as to the procedure itself. The aim of the present study was to assess cardiac and non-cardiac readmission rates besides clinical endpoint data in the first 50 patients of a single center TAVI programme. METHODS AND RESULTS: TAVI was performed using the transfemoral CoreValve system. Procedural success rate was 94%; intraprocedural mortality was 2%. 82% of the patients remained free of a combined safety endpoint at 30 days, and 76.1% remained free of a combined efficacy endpoint at six months (modified criteria of the Valve Academic Research Consortium). At six months, among all surviving patients, 10.3% had experienced readmissions for cardiac causes, and 43.6% had experienced readmissions for non-cardiac causes. Causes of non-cardiac readmissions showed a wide distribution over various medical disciplines, reflecting the high rate of comorbidities. Beyond six months until a predefined reference date (mean follow up 9.9 months), the probability of hospitalization fell by half (1.54 vs. 0.74 hospital days per patient per month), driven by a decrease of non-cardiac readmissions. Karnofsky score before and after TAVI yielded a significant and sustained improvement of performance status, as assessed retrospectively at reference date. CONCLUSION: The findings of the present study suggest that the high prevalence of comorbidities in high-risk TAVI patients results in a high rate of non-cardiac rehospitalizations during the first 6 months of follow-up. Despite this fact, improvement of global everyday performance following TAVI as perceived by the patients seems to be substantial.

Polypharmacy and inappropriate prescribing in elderly internal-medicine patients in Austria.

OBJECTIVE: The aim of the study was to assess the prevalence of polypharmacy and inappropriate drug use in elderly internal-medicine patients in one Austrian center and to define the impact of these and other identified predictors on the occurrence of adverse drug events. METHODS: All patients>or=75 years admitted to selected internal wards of a university hospital were included in a monocentric prospective cohort study over a period of three months. The pre-admission medication of the patients was analyzed with respect to appropriateness by a multidisciplinary team consisting of pharmacists and physicians trained in internal medicine. The medication was evaluated for the occurrence of adverse drug events. RESULTS: A total of 543 patients were analyzed (median age 82 years; 60.2% female). The mean number of drugs taken was 7.5+/-3.8, with women taking significantly more drugs than men (7.8 vs. 6.8, P=0.013). Overall, 58.4% of the patients fulfilled the given criteria for polypharmacy (>6 drugs). The following factors were associated with polypharmacy: female sex, need for nursing care, high number of discharge diagnoses and high Charlson comorbidity score. Unnecessary drugs were found prescribed in 36.3% of all patients, drugs to avoid (Beers criteria) in 30.1%, duplication in 7.6%, wrong dosage in 23.4% and possible drug-drug interactions in 65.8%. Adverse drug events were identified in 17.8% of the patients (97/543), among whom the adverse drug event was the reason for hospital admission in 56.7% of the cases and a drug-drug interaction was involved in 18.7%. Risk factors for adverse drug events were female sex, polymorbidity, renal dysfunction and inappropriate prescribing. CONCLUSION: Polypharmacy, inappropriate prescribing and adverse drug events were highly prevalent in a cohort of elderly internal-medicine patients in Austria. To improve drug safety in this high-risk population, appropriate prescribing might be more important than simply reducing the number of prescribed drugs.

Massive infiltration of bone marrow in colon carcinoma after treatment with activated protein C.

We present an unusual case of localized colorectal carcinoma complicated by sepsis which was treated with activated protein C (APC). Shortly after treatment the patient developed symptomatic metastases to the bone marrow (BM). Destruction of bones by colorectal cancer (CRC) is rare, although BM micrometastases are frequently observed. However, overt symptomatic BM metastasis is an exotic rarity. APC interacts with molecules and modulates pathways that are unquestionably involved in tumorigenesis and formation of metastases. Therefore a possible contributory role of the anti-inflammatory and immunomodulatory therapy in the rapid evolution of the disease cannot be excluded. Questions concerning the relevance and contribution of sepsis, treatment with APC, exquisitely high levels of non-thrombosis-associated D-dimer and CA19-9 to this highly uncommon course of disease are discussed. The lesson learned from this case is that APC may have contributed to the massive invasion of BM by colonic cancer cells in our patient and that APC should therefore be used with extreme restraint in patients with potentially curable cancer.

Bone marrow microvessel density and its prognostic significance in AML.

Microvessel density reportedly is increased in various hematologic disorders including acute lymphatic and myeloid leukemias. In these patients the bone marrow microvessel density (BM-MVD) appears to be associated with an unfavorable prognosis. In the present study, we have retrospectively analyzed the BM-MVD (at diagnosis) in 31 patients with acute myeloid leukemia (AML) (median age: 38 years; range: 21-53 years; f:m-ratio: 1:1,4) who underwent conventional chemotherapy and consecutive allogeneic bone marrow transplantation (BMT). The median BM-MVD at diagnosis was 30/mm2 (range: 17-48/mm2) and thus was significantly higher compared to controls (n = 9; BM-MVD: median 7/mm2, range 2-11/mm2; P < 0.05). In patients who failed to achieve a complete remission (CR) in response to induction chemotherapy, the BM-MVD was significantly higher (median: 41.5/mm2) at diagnosis than in patients who entered CR (median: 28.5/mm2, P < 0.05). In addition, patients with high BM-MVD ( > 30 mm2) had a significantly shorter overall survival compared to patients with a lower BM-MVD ( < 30 mm2, P < 0.05). Moreover, patients with a high BM-MVD ( > 30 mm2) were found to have a significantly higher risk of relapse (P < 0.05). In 4 patients in whom a continuous complete remission was documented after BMT, the BM-MVD levels were analyzed at diagnosis as well as between day + 80 and day + 100 after BMT. In all 4 patients, the BM-MVD was found to decrease in response to BMT until day 100 (P < 0.05). Together, our data suggest that the BM-MVD could be a prognostic parameter concerning survival in patients with AML undergoing allogeneic BMT.

Long-term follow up of patients with multiple myeloma after high-dose chemotherapy and allogeneic stem cell transplantation.

OBJECTIVES: Allogeneic transplantation may offer a curative approach to multiple myeloma (MM). We retrospectively analyzed the outcome of patients with multiple myeloma undergoing allogeneic stem cell transplantation in the context of beta(2) microglobulin and chromosome 13q. METHODS: All 13 patients with MM, who were referred to our center for allogeneic stem cell transplantation, were evaluated. Median age of patients was 38 yr, eight patients had chemo-sensitive disease, and median time between diagnosis of MM and transplantation was 15 months. Engraftment, acute and chronic graft vs. host disease, response to treatment, disease-free survival, and overall survival were evaluated according to standard criteria. RESULTS: There was one transplant-related death. Among 12 evaluable patients, seven patients (58%) achieved a complete remission (CR), and four patients (33%) achieved a partial remission. Acute graft vs. host disease occurred in 46% of patients, and chronic graft vs. host disease in 42% of available patients. After a median follow-up of 69.5 months (range, 5-128) nine patients (70%) are still alive, and six of them have remained progression free. Among five patients with low beta(2) microglobulin and normal chromosome 13q, four patients achieved a CR, with CR duration >5 yr in three of them. Among seven patients with elevated ss(2) microglobulin and/or deletion of chromosome 13q, only three CR were observed, with two patients still in CR on days +920 and +161, respectively. CONCLUSIONS: Allogeneic stem cell transplantation in patients with MM results in promising rates of CR, but durable remissions are predominantly seen in patients with favorable prognostic parameters.

Removal of persisting isohaemagglutinins with Ig-Therasorb immunoadsorption after major ABO-incompatible non-myeloablative allogeneic haematopoietic stem cell transplantation.

BACKGROUND: Major ABO-incompatibility can be associated with haemolysis, prolonged red cell aplasia (PRCA) and higher peri-transplant mortality resulting from organ toxicity after conventional and non-myeloablative allogeneic haematopoietic stem cell transplantation. Different therapeutic strategies have been developed to allow erythroid reconstitution in these patients. METHODS: We present three patients, who developed PRCA after non-myeloablative allogeneic haematological stem cell transplantation for haematological malignancies. The patients were treated with Ig-Therasorb immunoadsorption (five treatments per week) to remove persisting incompatible isohaemagglutinins. RESULTS: Two patients became transfusion independent after 12 and 14 treatments. In one patient, however, no reduction of the isohaemagglutinin titres could be observed after 25 treatments, probably due to persistence of his underlying disease. CONCLUSIONS: Although Ig-Therasorb immunoadsorption was effective in only two patients, it seems to be a promising therapeutic option for patients with PRCA after allogeneic non-myeloablative haematological stem cell transplantation.

ABO mismatch increases transplant-related morbidity and mortality in patients given nonmyeloablative allogeneic HPC transplantation.

BACKGROUND: ABO mismatch has not been thought to affect the outcome of patients undergoing myeloablative conditioning and allogeneic HPC transplantation. Data on transplant-related complications after ABO-mismatched transplantation after nonmyeloablative conditioning are limited. STUDY DESIGN AND METHODS: Therefore, 40 patients were analyzed after nonmyeloablative conditioning with regard to ABO compatibility. Eleven received a minor and bidirectional and 8 a major ABO-mismatched graft. RESULTS: Four patients had evidence of hemolysis during engraftment, being lethal in one, and three developed pure RBC aplasia. Six patients in the ABO-mismatched group developed thrombotic microangiopathy, and three of them died. ABO-identical and ABO-mismatched patients had a similar incidence of GVHD. Viral infections occurred in both groups in equal shares. Patients with an ABO-mismatch had to be rehospitalized until Day 100 for a median of 19 days versus 0 days in the identical group (p < 0.05). Overall survival was 60 and 57 percent in the ABO-identical and ABO-mismatch groups, respectively. The probability of transplant-related mortality was 0 versus 28 percent in the identical group compared to patients with an ABO mismatch (p < 0.05). The probability of relapse or progression was 76 versus 25 percent in the ABO-identical group compared to the ABO-mismatched group, respectively. CONCLUSION: Significantly more patients with ABO mismatch showed transplant-associated complications and died as a result of transplant-related causes.

Rapid establishment of long-term culture-initiating cells of donor origin after nonmyeloablative allogeneic hematopoietic stem-cell transplantation, and significant prognostic impact of donor T-cell chimerism on stable engraftment and progression-free survival.

BACKGROUND: Nonmyeloablative allogeneic hematopoietic stem-cell transplantation (NST) allows establishment of donor hematopoiesis without eradication of recipient stem cells by chemoradiotherapy. Quantification of donor chimerism may predict graft failure and relapse. METHODS: We quantified donor long-term culture-initiating cells (LTC-IC) in nine patients during the early phase after NST and lineage-specific donor cells of myeloid (CD33+, CD34+, granulocytes) and lymphoid lineage (CD3+, CD4+, CD8+, CD56+) in 38 patients with a median follow-up of 40 weeks after NST. Conditioning therapy consisted of fludarabine 90 mg/m2 followed by total body irradiation of 2 Gy. RESULTS: Only rapid establishment of donor T-cell chimerism was essential for stable donor engraftment. Patients with less than 90% of donor T cells 4 weeks after NST had a significantly higher risk of relapse, graft rejection, or both (14 of 18 patients) than patients with donor T-cell chimerism of 90% and higher (3 of 20 patients). Although conditioning therapy was nonmyeloablative, a significant decrease of repopulating stem cells defined as LTC-IC was seen after 2 weeks followed by rapid recovery of LTC-IC to pretransplant values. Interestingly, all LTC-IC were from donor origin 2 and 4 weeks after NST, but rapid establishment of donor LTC-IC was not predictive for progression-free survival. CONCLUSIONS: Rapid establishment of lymphoid but not myeloid donor chimerism is a prognostic factor for stable donor engraftment after NST. It seems that an immunologic shield of alloreactive donor T cells is essential for early hematopoietic progenitors.

Continuous complete clinical and molecular remission in two patients with refractory lymphoid malignancies after autografting followed by allogeneic stem cell transplantation with reduced intensity conditioning.

We present a 60-year-old patient with primary refractory non-Hodgkin's lymphoma and a 58-year-old patient with multiple myeloma with relapse after first autologous stem cell transplantation (ASCT), who underwent ASCT followed by allogeneic stem cell transplantation (alloSCT) with reduced intensity conditioning consisting of fludarabine and a single dose of total body irradiation. For graft-versus-host disease prophylaxis cyclosporine and mycophenolate mofetyl were given. Complete donor chimaerism was observed on d 28 after SCT. Both patients achieved sustained complete haematological and molecular remission of the immunoglobulin kappa light chain (Igkappa) rearrangement and are alive and well 17 and 16 months after SCT respectively.

Ex vivo expansion of long-term culture initiating marrow cells by IL-10, SCF, and IL-3.

BACKGROUND: Ex vivo expansion of progentior cells may shorten hematopoietic regeneration after myeloablative chemoradiotherapy, increase target cells for gene therapy, and improve purging of progenitor cell components. STUDY DESIGN AND METHODS: Marrow cells were incubated for 1 week in suspension culture with and without IL-10, IL-3, and SCF. As long-term culture initiating cells (LTC-ICs) represent early hematopoietic progenitors in vitro, these cells were quantified at initiation and after a 1-week culture period in a limiting dilution assays. Additionally, immunophenotyping of cells before and after culture was performed. RESULTS: In six experiments, marrow cells cultured for 1 week with IL-10, IL-3, and SCF showed a significant increase (almost doubling) in LTC-ICs as compared with marrow cells before expansion. Additionally, an increased proliferative capacity of LTC-ICs was achieved with a sevenfold increase of committed colony-forming cells and a 10-fold proliferation of high proliferative potential colony-forming cells. Immunophenotyping revealed a sevenfold increase of CD34+ CD45 RA- cells in IL-10-, IL-3-, SCF-stimulated suspension cultures. In unstimulated cultures, no LTC-ICs were maintained after 1 week. CONCLUSION: Expansion of LTC-ICs by IL-10, IL-3, and SCF has not been shown so far. This in vitro model allows expansion of LTC-IC if compared with the input of progenitor cells without extensive progenitor cell manipulation. This should be an attractive model for in vitro purging, gene transfer, or expansion of progenitor cells to allow rapid engraftment after myeloablative chemotherapy.