High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) to rescue hematopoiesis is considered standard care for patients with a relapsed chemosensitive lymphoma, but diagnosis of lymphoma has been a risk factor for poor mobilization in several studies. The aim of this prospective noninterventional clinical audit was to review the mobilization strategies used by EBMT centers in relapsed lymphoma and to evaluate their efficacy. Between 2010 and 2014, 275 patients with relapsed lymphoma from 30 EBMT centers were prospectively registered. Almost all patients were mobilized with chemotherapy plus G-CSF (96%), but there was a large variation in chemotherapy schedules. Thirty (11%) of them were poor mobilizers (<2 × 106 CD 34+ cells/kg body weight) at the first mobilization. Poor mobilization was not associated with gender, age, bone marrow involvement at diagnosis, primary diagnosis, number of previous chemotherapy lines, previous radiotherapy or mobilization with G-CSF alone. The use of high dose cyclophosphamide alone was associated with mobilization failure (P = 0.0006), whereas the use of a platinum-containing regimen was associated with a good mobilization outcome (P = 0.013). Because failure rate is low, we can conclude from this study that PBSC mobilization failure in relapsed lymphomas is not an important problem in the EBMT centers.

• Klíčová slova
• relapsed lymphomas, stem cell mobilization,
• MeSH
• autologní transplantace MeSH
• dospělí MeSH
• klinický audit MeSH
• kmenové buňky z periferní krve patologie   MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfom krev   farmakoterapie   terapie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mobilizace hematopoetických kmenových buněk metody   MeSH
• neúspěšná terapie MeSH
• prospektivní studie MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• recidiva MeSH
• senioři MeSH
• transplantace periferních kmenových buněk MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinická studie MeSH
• multicentrická studie MeSH

Peripheral blood stem cells (PBSCs) are preferred source of hematopoietic stem cells for autologous transplantation. Mobilization of PBSCs using chemotherapy and/or granulocyte colony-stimulating factor (G-CSF) however fails in around 20%. Combining G-CSF with plerixafor increases the mobilizations success. We compared cost-effectiveness of following schemes: the use of plerixafor "on demand" (POD) during the first mobilization in all patients with inadequate response, the remobilization with plerixafor following failure of the first standard mobilization (SSP), and the standard (re)mobilization scheme without plerixafor (SSNP). Decision tree models populated with data from a first-of-a-kind patient registry in six Czech centers (n = 93) were built to compare clinical benefits and direct costs from the payer's perspective. The success rates and costs for POD, SSP and SSNP mobilizations were; 94.9%, $7,197; 94.7%, $8,049; 84.7%, $5,991, respectively. The direct cost per successfully treated patient was $7,586, $8,501, and $7,077, respectively. The cost of re-mobilization of a poor mobilizer was $5,808 with G-CSF only and $16,755 if plerixafor was added. The total cost of plerixafor "on-demand" in the sub-cohort of poor mobilizers was $17,120. Generally, plerixafor improves the mobilization success by 10% and allows an additional patient to be successfully mobilized for incremental $11,803. Plerixafor is better and cheaper if used "on demand" than within a subsequent remobilization.

• Klíčová slova
• cost-effectiveness, mobilization, on demand, plerixafor, poor mobilizers,
• MeSH
• analýza nákladů a výnosů MeSH
• benzylaminy MeSH
• cyklamy MeSH
• cytaferéza statistika a číselné údaje   MeSH
• délka pobytu statistika a číselné údaje   MeSH
• dítě MeSH
• dospělí MeSH
• ekonomické modely MeSH
• faktor stimulující kolonie granulocytů ekonomika   terapeutické užití   MeSH
• heterocyklické sloučeniny ekonomika   terapeutické užití   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfom ekonomika   chirurgie   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mnohočetný myelom ekonomika   chirurgie   MeSH
• mobilizace hematopoetických kmenových buněk ekonomika   metody   MeSH
• předškolní dítě MeSH
• rozhodovací stromy MeSH
• senioři MeSH
• transplantace periferních kmenových buněk ekonomika   MeSH
• výdaje na zdravotnictví MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Československo MeSH
• Názvy látek
• benzylaminy MeSH
• cyklamy MeSH
• faktor stimulující kolonie granulocytů MeSH
• heterocyklické sloučeniny MeSH
• plerixafor MeSH Prohlížeč

Peripheral blood stem cells are widely used as stem cell source for allografting. Progenitor cells can be effectively mobilized into peripheral blood in majority of healthy donors with a brief administration of G-CSF. A mobilization course in 111 donors (median age 40years) was retrospectively studied and the factors influencing the efficacy of mobilization were analyzed. The median number of CD34+ cells per kg recipient weight 5.1x10(6) was obtained after a median of two aphereses. The target cell dose (4.0x10(6)/kg) was reached in 69% of donors. Circulating CD34+ count and CD34+ yield were negatively associated with donor's age. Other independent factors associated with superior yield were precollection platelet and WBC counts. In multivariate analysis only CD34+ precount predicted for CD34+ yield. G-CSF had an acceptable short-term safety profile. Our data confirm that apheresis is a safe procedure in healthy including aged donors and suggest that older donors could be poorer mobilizers than younger.

• MeSH
• antigeny CD34 MeSH
• dárci tkání * MeSH
• dospělí MeSH
• faktor stimulující kolonie granulocytů aplikace a dávkování   MeSH
• hematopoetické kmenové buňky * MeSH
• leukaferéza * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mobilizace hematopoetických kmenových buněk * MeSH
• počet leukocytů MeSH
• senioři MeSH
• transplantace periferních kmenových buněk * MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny CD34 MeSH
• faktor stimulující kolonie granulocytů MeSH

BACKGROUND: Peripheral blood stem cells are an important source of hematopoietic stem cells (HSCs) for allogeneic transplantations. Some allogeneic donors mobilize HSCs poorly in response to the granulocyte--colony-stimulating factor (G-CSF). The estimation of the mobilization result in an individual donor is difficult due to the absence of suitable predictive factors. STUDY DESIGN AND METHODS: We analyzed the concentrations and kinetics of certain cytokines induced by G-CSF in 76 healthy donors and compared them with the mobilization efficiency. RESULTS: The levels of the most cytokines increased after the G-CSF application: sICAM, sVCAM, MMP-9, interleukin (IL)-6, TNF-α, sE-selectin, and fibronectin. The concentrations of SDF-1α and IL-8 decreased and VEGF and fractalkine remained unchanged. The premobilization concentrations of IL-6 (p = 0.0093) and TNF-a (p = 0.0006) correlated with preapheresis CD34+ cell count. The comparison of premobilization cytokine levels between better and worse mobilizers showed a difference for TNF-α (p = 0.0006) and IL-6 (p = 0.0682). The TNF-α level below cutoff of 3.6 pg/mL implied approximately 20 times higher risk of poor mobilization (odds ratio, 19.9; p = 0.0002). The immunophenotyping of CD34+ cells suggested a negative correlation between Day +5 CD34+ count and expression of CD11a (p = 0.0319) and a positive correlation with CD44 antigen expression (p = 0.0096). CONCLUSION: The concentrations of certain cytokines corresponded to the quality of HSC mobilization in healthy donors. Their levels measured before mobilization could probably serve as predictive factors for mobilization efficacy and prospectively detect donors who might profit from new mobilization molecules.

• MeSH
• časové faktory MeSH
• cytokiny krev   MeSH
• dárci krve * MeSH
• dospělí MeSH
• faktor stimulující kolonie granulocytů farmakologie   MeSH
• filgrastim MeSH
• hematopoetické kmenové buňky účinky léků   MeSH
• imunofenotypizace MeSH
• krevní obraz MeSH
• leukaferéza MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mobilizace hematopoetických kmenových buněk * MeSH
• prospektivní studie MeSH
• rekombinantní proteiny MeSH
• transplantace periferních kmenových buněk MeSH
• výběr dárců * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH
• faktor stimulující kolonie granulocytů MeSH
• filgrastim MeSH
• rekombinantní proteiny MeSH

Plerixafor plus granulocyte-colony stimulating factor (G-CSF) enhances the mobilization of hematopoietic stem cells (HSCs) for collection and subsequent autologous hematopoietic stem cell transplantation (HSCT) in patients with multiple myeloma (MM). This international, multicenter, noninterventional registry study (NCT01362972), evaluated long-term outcomes for MM patients who received plerixafor versus other mobilization regimens. The comparisons were: G-CSF + plerixafor (G-CSF + P) versus G-CSF-; G-CSF + P versus G-CSF + chemotherapy (G-CSF + C); and G-CSF + P + C versus G-CSF + C. Propensity score matching was used to balance groups. Primary outcome measures were progression free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR) after transplantation. After propensity matching, 77 versus 41 patients in the G-CSF + P versus G-CSF cohorts, 129 versus 129 in the G-CSF + P versus G-CSF + C cohorts, and 117 versus 117 in the G-CSF + P + C versus G-CSF + C cohorts were matched, respectively. Propensity score matching resulted in a smaller sample size and imbalances were not completely overcome. For both PFS and OS, the upper limits of the hazard ratio 95% confidence intervals exceeded prespecified boundaries; noninferiority was not demonstrated. CIR rates were higher in the plerixafor cohorts. G-CSF + P remains an option for the mobilization of HSCs in poor mobilizers with MM with no substantial differences in PFS, OS, and CIR in comparison with other regimens.

• MeSH
• benzylaminy MeSH
• cyklamy MeSH
• heterocyklické sloučeniny * MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• mnohočetný myelom * terapie   MeSH
• mobilizace hematopoetických kmenových buněk MeSH
• registrace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• benzylaminy MeSH
• cyklamy MeSH
• heterocyklické sloučeniny * MeSH
• plerixafor MeSH Prohlížeč

• Klíčová slova
• AUDIOMETRY *, OTOSCLEROSIS/surgery *,
• MeSH
• audiologie * MeSH
• audiometrie * MeSH
• lidé MeSH
• mobilizace třmínku * MeSH
• otoskleróza chirurgie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Cyclophosphamide (Cy) plus granulocyte-colony stimulating factor (G-CSF) is currently a standard regimen for hematopoietic stem cell (HSC) mobilization in patients with multiple myeloma (MM). However, cytarabine (AraC) in intermediate doses plus G-CSF seems to have a higher mobilization efficacy. The aim of this study was to retrospectively compare mobilization using AraC and Cy. Thirty consecutive MM patients were mobilized by Cy + G-CSF, and the subsequent 40 patients by AraC + G-CSF. Both groups were comparable. The target yield of 10 × 106 CD34+ cells/kg (for tandem and 2 additional transplantations) was achieved in 98% (AraC) and 57% (Cy) of patients (p < 0.0001) by 1.2 and 2.1 apheresis (means), and by single apheresis in 83 and 17% of patients, respectively. AraC mobilization resulted in higher peak concentration of CD34+ cells in blood (median 238.0 vs. 87.9/µL, p < 0.0001) and higher CD34+ yield (median 28.6 × 106 vs. 10.4 × 106/kg, p < 0.0001) compared to Cy mobilization. Toxicities were comparable except for thrombocytopenia gr. 4, observed in 50% of patients after AraC (Cy 7%). In view of these results, we conclude that mobilization with AraC plus G-CSF is very effective with acceptable toxicity and could be considered in MM patients with planned or expected higher numbers of transplantations.

• MeSH
• autologní štěp MeSH
• cyklofosfamid aplikace a dávkování   škodlivé účinky   MeSH
• cytarabin aplikace a dávkování   škodlivé účinky   MeSH
• dospělí MeSH
• faktor stimulující kolonie granulocytů aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetný myelom * krev   terapie   MeSH
• mobilizace hematopoetických kmenových buněk * MeSH
• retrospektivní studie MeSH
• senioři MeSH
• transplantace kmenových buněk * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• cyklofosfamid MeSH
• cytarabin MeSH
• faktor stimulující kolonie granulocytů MeSH

This study (NCT01288573) investigated plerixafor's safety and efficacy in children with cancer. Stage 1 investigated the dosage, pharmacokinetics (PK), pharmacodynamics (PD), and safety of plerixafor + standard mobilization (G-CSF ± chemotherapy). The stage 2 primary endpoint was successful mobilization (doubling of peripheral blood CD34+ cell count in the 24 h prior to first apheresis) in patients treated with plerixafor + standard mobilization vs. standard mobilization alone. In stage 1, three patients per age group (2-<6, 6-<12, and 12-<18 years) were treated at each dose level (160, 240, and 320 µg/kg). Based on PK and PD data, the dose proposed for stage 2 was 240 µg/kg (patients 1-<18 years), in which 45 patients were enrolled (30 plerixafor arm, 15 standard arm). Patient demographics and characteristics were well balanced across treatment arms. More patients in the plerixafor arm (24/30, 80%) met the primary endpoint of successful mobilization than in the standard arm (4/14, 28.6%, p = 0.0019). Adverse events reported as related to study treatment were mild, and no new safety concerns were identified. Plerixafor + standard G-CSF ± chemotherapy mobilization was generally well tolerated and efficacious when used to mobilize CD34+ cells in pediatric cancer patients.

• MeSH
• autologní štěp MeSH
• benzylaminy MeSH
• cyklamy MeSH
• dítě MeSH
• heterocyklické sloučeniny * MeSH
• lidé MeSH
• mladiství MeSH
• mobilizace hematopoetických kmenových buněk MeSH
• nádory * terapie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• klinické zkoušky, fáze II MeSH
• práce podpořená grantem MeSH
• Názvy látek
• benzylaminy MeSH
• cyklamy MeSH
• heterocyklické sloučeniny * MeSH
• plerixafor MeSH Prohlížeč

Autologous peripheral blood stem cell transplantation is performed in an increasing number of chronic lymphocytic leukaemia (CLL) patients who are in the first remission following fludarabine treatment. There are contradictory data about the adverse impact of fludarabine on stem cell harvest. We analysed retrospectively mobilization results in 56 poor-risk CLL patients (median age: 56 years) who underwent first-line treatment with fludarabine and cyclophosphamide. The mobilization, consisting of cyclophosphamide 3 g/m(2) and granulocyte colony-stimulating factor (G-CSF) 10 microg/kg per day, was performed with a median of 77 days following the last fludarabine course. The target yield was >or=2.0x10(6) CD34+ cells/kg. The procedure was successful in 23 (41%) patients. A median of 3.3x10(6) CD34+ cells/kg was collected per patient. The successful mobilization was associated with a longer interval from the last chemotherapy (>2 months). The mobilization result was not influenced by the number of fludarabine cycles. No correlation was found in other parameters such as disease stage at diagnosis, disease status at stimulation or age. The poorly mobilized patients had significantly lower prestimulation blood counts (platelets, WBC and haemoglobin). Our data show that fludarabine does not generally prevent the stem cell mobilization; nevertheless, mechanisms related to the impact of fludarabine on stem cell harvest must be further investigated.

• MeSH
• autologní transplantace MeSH
• chronická lymfatická leukemie krev   terapie   MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• dospělí MeSH
• faktor stimulující kolonie granulocytů aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mobilizace hematopoetických kmenových buněk * metody   MeSH
• počet leukocytů MeSH
• protinádorové látky aplikace a dávkování   MeSH
• senioři MeSH
• transplantace periferních kmenových buněk MeSH
• vidarabin aplikace a dávkování   analogy a deriváty   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cyklofosfamid MeSH
• faktor stimulující kolonie granulocytů MeSH
• fludarabine MeSH Prohlížeč
• protinádorové látky MeSH
• vidarabin MeSH

Changes in both the concentration of non-esterified fatty acids in serum and white (epididymal) adipose tissue, serum glycerol, and basal and L-noradrenaline-stimulated release of NEFA and glycerol from white adipose tissue in vitro were monitored 1, 6, 24, 48 and 72 h after a single whole-body irradiation of rats with a lethal X-ray dose of 14.35 Gy (1 500R). The NEFA concentration in serum and white adipose tissue was higher 1 h after irradiation as compared with that of sham-irradiated (control) animals; the free glycerol concentration in serum of the irradiated rats was lower than that of control rats. Basal release of NEFA was higher 1 h after irradiation, and lower 6 and 72 h after irradiation; the simulated release of NEFA did not change significantly. Basal and stimulated release of glycerol from the adipose tissue of irradiated rats was higher 6 h after irradiation. The relation between the changes in lipolysis and lipid mobilization and the changes in serum and tissue lipids in the irradiated organisms are discussed.

• MeSH
• chemická stimulace MeSH
• epididymis MeSH
• glycerol krev   metabolismus   MeSH
• krysa rodu Rattus MeSH
• kyseliny mastné neesterifikované krev   metabolismus   MeSH
• lipolýza účinky záření   MeSH
• mobilizace lipidů účinky záření   MeSH
• noradrenalin farmakologie   MeSH
• rentgenové záření MeSH
• tuková tkáň metabolismus   účinky záření   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• glycerol MeSH
• kyseliny mastné neesterifikované MeSH
• noradrenalin MeSH