Severe Acute Hemolytic Transfusion Reaction Treated with Ruxolitinib and Plasma Exchange.

INTRODUCTION: Acute hemolytic transfusion reaction is a rare but extremely mortal condition. Even small quantities of ABO-incompatible erythrocytes, as much as 50 mL, can lead to fatality. Since there is no successful standard therapy, preventive measures are very important. In this case report, we presented a 29-year-old woman who was transfused with 2 units of AB Rh-positive instead of 0 Rh-positive red blood cells following a cesarean section. As far as we know, this is the first patient in the literature for whom ruxolitinib was used as a part of therapy. CASE REPORT: The patient was referred to our center 22 h after the ABO-mismatched transfusion. On admission, she had severe hemolysis, acute renal failure, and disseminated intravascular coagulation. Massive plasma exchange, hemodialysis, and pulse steroid therapy were commenced. The patient was refractory to first-line therapies. She was intubated on day 2 due to hypoxia, respiratory failure and changes in consciousness. Ruxolitinib, 2 × 10 mg/day, was started on day 3. The patient's clinical status improved on day 6. Ruxolitinib was withdrawn on day 15, and the patient was discharged without any complications or sequels on day 26. CONCLUSION: Ruxolitinib may be life-saving in patients with ABO-incompatible transfusion reaction which follows a severe and catastrophic course.

Hematopoietic Stem Cell Transplantation for Patients with Paroxysmal Nocturnal Hemoglobinuria with or without Aplastic Anemia: A Multicenter Turkish Experience

Objective: Although inhibition of the complement system at different steps is a promising therapy modality in patients with paroxysmal nocturnal hemoglobinuria (PNH), allogeneic hematopoietic stem cell transplantation (HCT) is still the only curative therapy, especially for patients with intractable hemolysis or bone marrow failure. The aim of this study is to evaluate the outcomes of allogeneic HCT in PNH patients with aplastic anemia (PNH-AA) or without. Materials and Methods: Thirty-five PNH/PNH-AA patients who were treated with allogeneic HCT in 10 transplantation centers in Turkey were retrospectively analyzed. Results: Sixteen (45.7%) and 19 (54.3%) patients were diagnosed with classical PNH and PNH-AA, respectively. The median age of the patients was 32 (18-51) years. The 2-year overall survival (OS) rate and rate of graft-versus-host disease-free, failure-free survival (GFFS) was 81.2% and 78.1%, respectively. The 2-year OS in cases of classical PNH and PNH-AA was 81.3% and 79.9%, respectively (p=0.87), and 2-year GFFS in cases of PNH and PNH-AA was 79% and 76% (p=0.977), without statistical significance. The OS and GFFS rates also did not differ between transplantations with matched sibling donors (MSDs) and matched unrelated donors (MUDs). Conclusion: Allogeneic HCT with MSDs or MUDs is a good option for selected patients with classical PNH and PNH-AA. In particular, patients with debilitating and refractory hemolysis and patients with bone marrow failure might form an excellent group of candidates for allogeneic HCT.

Evaluation of Cardiac Repolarization in the Randomized Phase 2 Study of Intermediate- or High-Risk Smoldering Multiple Myeloma Patients Treated with Daratumumab Monotherapy.

INTRODUCTION: Daratumumab is a CD38-targeting monoclonal antibody that has demonstrated clinical benefit for multiple myeloma. Daratumumab inhibition of CD38, which is expressed on immune cell populations and cardiomyocytes, could potentially affect cardiac function. This QTc substudy of the phase 2 CENTAURUS study investigated the potential effect of intravenous daratumumab monotherapy on QTc prolongation and other electrocardiogram (ECG) parameters, including concentration-QTc effect modeling. METHODS: Patients had intermediate- or high-risk smoldering multiple myeloma. Patients with QT interval corrected by Fridericia's formula (QTcF) > 470 ms, QRS interval ≥ 110 ms, or PR interval ≥ 200 ms were excluded. Triplicate ECGs were collected at screening, Dose 1, and Dose 8. Analyses of on-treatment ECGs were conducted with a time-matched baseline (primary analysis). By time-point, pharmacokinetic-pharmacodynamic (PK/PD), and outlier analyses were conducted. RESULTS: Of 123 patients in CENTAURUS, 31 were enrolled in the QTc substudy. Daratumumab produced a small increase in heart rate (5-12 beats per minute) of unclear significance. There was a small but clinically insignificant effect on QTc, as measured by both time-matched time-point and PK/PD analyses. The primary analysis demonstrated a maximum mean increase in QTcF of 9.1 ms (90% 2-sided upper confidence interval [CI], 14.1 ms). The primary PK/PD analysis predicted a maximum QTcF increase of 8.5 ms (90% 2-sided upper CI, 13.5 ms). No patient had an abnormal U wave, a new QTcF > 500 ms, or > 60 ms change from baseline for QTcF. CONCLUSION: Analysis of ECG intervals and concentration-QTc relationships showed a small but clinically insignificant effect of daratumumab. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02316106.

Total body irradiation + fludarabine compared to busulfan + fludarabine as "reduced-toxicity conditioning" for patients with acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation in first complete remission: a study by the Acute Leukemia Working Party of the EBMT.

The optimal conditioning for patients with acute myeloid leukemia in first complete remission treated with allogeneic hematopoietic cell transplantation (allo-HCT) has not been defined so far. In this retrospective study, we compared two "reduced-toxicity" regimens: intravenous busulfan at a total dose of 9.6 mg/kg (3 days) + fludarabine (Bu3/Flu) and total body irradiation at a dose of 8 Gy + fludarabine (TBI8Gy/Flu). In the entire study cohort (n = 518), the probabilities of overall survival (OS), leukemia-free survival (LFS), relapse and non-relapse mortality (NRM) at 2 years for Bu3/Flu and TBI8Gy/Flu were 62% vs. 72.5% (p = 0.051), 59.5% vs. 65% (p = 0.15), 30% vs. 20% (p = 0.01), and 10% vs. 14% (p = 0.18), respectively. In multivariate model for patients <50 years old, TBI8Gy/Flu was associated with improved LFS (hazard ratio (HR) = 0.5, p = 0.04), OS (HR = 0.31, p = 0.004), and survival free from both graft-versus-host disease and relapse (HR = 0.55, p = 0.03), as well as tendency to reduced risk of relapse (HR = 0.53, p = 0.08). Among patients aged 50 years or older the use of TBI8Gy/Flu was associated with increased incidence of NRM (HR = 3.9, p = 0.0009), with no significant impact on other outcome measures. We conclude that the use of TBI8Gy/Flu as "reduced-toxicity" regimen may be advised in younger patients with AML referred for allo-HCT.

Incidence and risk factors for hepatic sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation: A retrospective multicenter study of Turkish hematology research and education group (ThREG).

Hepatic sinusoidal obstruction syndrome (HSOS) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively evaluated the incidence, risk factors, treatment and survival for HSOS after allo-HSCT in Turkey. We also reported our experience of defibrotide (DF) for HSOS prophylaxis in high-risk (HR) patients. Across Turkey, 1153 patients from 10 centers were enrolled in the study. We evaluated the medical records of patients who were treated with allo-SCT between January 2012 and December 2015. The study included 1153 patients (687 males/466 females) with median age of 38 (15-71) years. The incidence of HSOS was 7.5 % (n = 86). The incidences of HSOS in the HR/DF+, HR/DF- and standard risk (SR) group were 8%, 66.7 % and 6.2 %, respectively. The rate of HSOS development was not statistically different between HR/DF + and SR group (p = 0.237). HSOS prophylaxis (defibrotide) was significantly decreased HSOS-related mortality (p = 0.004). The incidence of HSOS was found similar to literature in this large Turkish cohort. Defibrotide prophylaxis appears to be associated with low incidence of HSOS development and reduced HSOS-related mortality. Although these results are promising, future studies are needed to support the efficacy of defibrotide prophylaxis in patients with risk of HSOS.

Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience.

Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, in approximately one-third of the responding patients, the disease relapses following completion of therapy. One of the drugs that have been approved for the treatment of relapsed/refractory cHL is nivolumab, an immune check point inhibitor that shows its effects by blocking the programmed death 1 (PD-1) receptor. In this study, we present a retrospective "real-life" analysis of the usage of nivolumab in patients with relapsed/refractory cHL that have joined the named patient program (NPP) for nivolumab, reflecting 4 years of experience in the treatment of relapsed/refractory cHL. We present a retrospective analysis of 87 patients (median age, 30) that participated in the NPP in 24 different centers, who had relapsed/refractory cHL and were consequently treated with nivolumab. The median follow-up was 29 months, and the median number of previous treatments was 5 (2-11). In this study, the best overall response rate was 70% (CR, 36%; PR, 34%). Twenty-eight of the responding patients underwent subsequent stem cell transplantation (SCT). Among 15 patients receiving allogeneic stem cell transplantation, 9 patients underwent transplantation with objective response, of which 8 of them are currently alive with ongoing response. At the time of analysis, 23 patients remained on nivolumab treatment and the rest discontinued therapy. The main reason for discontinuing nivolumab was disease progression (n = 23). The safety profile was acceptable, with only nine patients requiring cessation of nivolumab due to serious adverse events. The 24-month progression-free and overall survival rates were 58.5% (95% CI, 0.47-0.68) and 78.7% (95% CI, 0.68-0.86), respectively. Eighteen patients died during the follow-up and only one of these was regarded to be treatment-related. With its efficacy and its safety profile, PD-1 blockers became an important treatment option in the heavily pretreated cHL patients.

Long-term results of brentuximab vedotin in relapsed and refractory Hodgkin lymphoma: multi-center real-life experience.

Classical Hodgkin lymphoma (cHL) is considered a curable disease; however, approximately one-third of responders experience disease relapse following first-line therapy. Several studies have shown the efficacy of brentuximab vedotin (BV) in patients with relapsed/refractory HL. We present a retrospective analysis of 58 patients with relapsed/refractory HL treated with BV in a named patient program from 11 centers. The median follow-up duration was 20 (range, 4-84) months. The best overall response rate was 64% (complete response [CR], 31%; partial response [PR], 33%). The 5-year progression-free survival (PFS) and overall survival (OS) rates were 12% (95% confidence interval [CI], 0.05-0.22) and 26% (95% CI, 0.16-0.38), respectively. Among patients who achieved CR, the estimated 5-year PFS and OS rates were 32% (95% CI, 0.13-0.54) and 60% (95% CI, 0.33-0.78), respectively. A total of 26 patients underwent subsequent stem cell transplantation. The 5-year PFS and OS rates for 10 patients who had consolidative stem cell transplantation were 28% and 30%, respectively. Twenty-seven patients required further therapy following BV. At the time of the analysis, 12 patients (21%) were alive. Five patients (9%) had long-term remission after achieving CR with BV monotherapy, with a median PFS of 76 months. Three of them (5%) did not receive any other treatment following BV and their median PFS was 75 months. Our long-term results showed that a small subset of patients with relapsed/refractory cHL may benefit from and even be cured with BV monotherapy.

Recommendations for Risk Categorization and Prophylaxis of Invasive Fungal Diseases in Hematological Malignancies: A Critical Review of Evidence and Expert Opinion (TEO-4).

This is the last of a series of articles on invasive fungal infections prepared by opinion leaders in Turkey. The aim of these articles is to guide clinicians in managing invasive fungal diseases in hematological malignancies and stem cell transplantation based on the available best evidence in this field. The previous articles summarized the diagnosis and treatment of invasive fungal disease and this article aims to explain the risk categorization and guide the antifungal prophylaxis in invasive fungal disease.

The effect of trans-resveratrol on platelet-neutrophil complex formation and neutrophil burst in hypercholesterolemic rats.

Transresveratrol (t-resveratrol; 3,5,4'-trihydroxy-trans-stilbene) is a polyphenolic compound found in fresh grapes, grape juice and wine, and has been found to reduce the total cholesterol level in hypercholesterolemic rats. The objective of the present study was to assess the effects of t-resveratrol on platelet-neutrophil complex formation and neutrophil reactive oxygen species (ROS) status in control and hypercholesterolemic rats using a modified flow cytometric method. Rats (n=80) were divided into five groups (control, ethanol, resveratrol, hypercholesterolemic and resveratrol-administered hypercholesterolemic groups), comprising 16 animals per group. Serum levels of lipids and H2O2 were determined using commercially available kits, while platelet-neutrophil complex formation and neutrophil ROS status were determined using a modified flow cytometric method. Serum total cholesterol and low-density lipoprotein cholesterol levels were found to be increased and the high-density lipoprotein cholesterol level was found to be decreased in the HC group compared with the control group (P<0.001). Treatment of HC rats with t-resveratrol significantly lowered total cholesterol and low-density lipoprotein cholesterol levels (P<0.001). In the hypercholesterolemic group, levels of serum H2O2 platelet-neutrophil complex formation and neutrophil ROS status were significantly increased (P<0.001). On the other hand, in the resveratrol-administered hypercholesterolemic group, serum H2O2 levels, platelet-neutrophil complex formation and neutrophil ROS status were decreased compared with the hypercholesterolemic group (P<0.001). Serum H2O2 levels, platelet-neutrophil complex and neutrophil ROS status were positively correlated with one another. The present study is the first to demonstrate the protective effect of t-resveratrol against hypercholesterolemia-induced platelet-neutrophil complex formation and neutrophil ROS burst. Further investigations on its plausible role in antihypercholesterolemic treatment are warranted.

Aberrations of chromosomes 9 and 22 in acute lymphoblastic leukemia cases detected by ES-fluorescence in situ hybridization.

A reciprocal translocation between chromosomes 9 and 22 creates oncogenic BCR/ABL fusion in the breakpoint region of the derivative chromosome 22. The aim of this study was to evaluate the importance of atypical fluorescence in situ hybridization (FISH) signal patterns in pediatric and adult acute lymphoblastic leukemia (ALL) cases. We evaluated t(9;22) translocation in 208 cases with ALL (294 tests), including 139 childhood and 69 adult cases by FISH technique using BCR/ABL extra signal (ES) probe. FISH signal patterns observed in pediatric ALL cases were as follows; Major-BCR/ABL (M-BCR/ABL) (1.4%), minor-BCR/ABL (m-BCR/ABL) (3.6%), trisomy 9 (4.3%), trisomy 22 (4.3%), trisomy or tetrasomy of both chromosomes 9 and 22 (2.9%), monosomy 9 (1.4%), monosomy 22 (0.7%), ABL gene amplification (1.4%), derivative chromosome 9 deletion (1.4%), and extra copies of the Philadelphia chromosome (1.4%). FISH signal patterns observed in adult ALL cases were as follows; M-BCR/ABL (5.8%), m-BCR/ABL (11.6%), two different cell clones with major and minor BCR/ABL signal pattern (2.9%), extra copies of Philadelphia chromosome (4.3%), derivative chromosome 9 deletion (1.4%), trisomy 9 (2.9%), tetraploidy (1.4%), monosomy 9 (1.4%), trisomy 22 (1.4%), and coexistence of both trisomy 22 and monosomy 9 (1.4%). Trisomy 9, trisomy 22, and polyploidy of chromosomes 9 and 22 were specific atypical FISH signal patterns for childhood B cell acute lymphoblastic leukemia (B-ALL) patients. However, monosomy 9 and ABL gene amplification were highly specific for childhood T cell acute lymphoblastic leukemia (T-ALL) patients. Our report presents the correlation between atypical FISH signal patterns and clinical findings of a large group of ALL cases.

Array comparative genomic hybridization analysis of adult acute leukemia patients.

We have performed a retrospective array-based comparative hybridization (array-CGH) study on 41 acute leukemia samples [n=17 acute lymphoblastic leukemia (ALL) patients only at diagnosis, n=3 ALL patients both at diagnosis and relapse; n=20 acute myeloid leukemia (AML) patients only at diagnosis and n=1 AML patient both at diagnosis and relapse] using an Agilent 44K array. In addition to previously detected cytogenetic aberrations, we observed cryptic aberrations in 95% of ALL and 90.5% of AML cases. ALL-specific recurrent abnormalities were RB1 (n=3), PAX5 (n=4), and CDKN2B (n=3) deletions; AML-specific recurrent abnormalities were HOXA9 and HOXA10 (n=2) deletions and NOTCH1 duplication (n=2). Recurrent duplication of the ELK1 oncogene was observed in both ALL (n=2) and AML (n=3) cases. Our results demonstrate that oligo-array CGH (oaCGH) is an effective method for defining copy number alterations and identification of novel recurring unbalanced abnormalities. At least for now, however, the use of oaCGH for routine diagnosis still has some restrictions.

Primary follicular lymphoma of the cervix uteri: a review.

Primary non-Hodgkin's lymphoma of the cervix is a rare disease, of which a subgroup of follicular lymphoma constitutes only 8.5%. There is not an established treatment protocol neither for primary cervical lymphoma nor for its follicular subgroup. We presented a case with Ann Arbor stage IEA (Extra-nodal involvement and absence of weight loss, fever, night sweat) primary follicular lymphoma of the cervix. She was treated with chemotherapy followed by pelvic radiotherapy. Upon relapse with a nodal neck mass, she was treated with rituximab alone. She remained well for 23 months after rituximab. In the 39 months of follow-up, there was no evidence of disease. In the light of our case, we reviewed the reported cases of primary follicular lymphoma of the cervix while discussing their treatment protocols and the cases of primary cervix lymphoma treated with rituximab.

Hemodialysis shortens long in vitro closure times as measured by the PFA-100.

BACKGROUND: Hemorrhagic complications are commonly encountered in patients with end-stage renal disease (ESRD). Uremic patients show a bleeding diathesis mainly due to abnormalities in platelet function. There are several tests to detect and measure impairment of hemostasis in these patients, but none appear to be ideal. In recent years, the PFA-100 (platelet function analyzer) was introduced to measure primary, platelet-dependent hemostasis. In this study, the effect of hemodialysis on platelet function was evaluated using the PFA-100 in patients with ESRD. MATERIAL/METHODS: The study was performed on 45 patients with ESRD undergoing regular hemodialysis aged between 20-76 years (median: 54 years). Collagen/epinephrine (CEPI) and collagen/ADP (CADP) closure times were measured before and after the hemodialysis session using the PFA. RESULTS: CEPI (normal range: 85-165 sec) was significantly shortened from 230+/-60 to 206+/-63 sec after hemodialysis (p<0.05). The CADP (normal range: 71-118 sec) was also shortened by hemodialysis from 177+/-69 to 169+/-71 sec (p>0.05). CEPI closure times of 10 (26%) in 38 patients with long CT returned to normal after hemodialysis. CADP closure times of 9 (25%) of 36 patients with long CT returned to normal after hemodialysis. CONCLUSIONS: This study confirms the existence of a dysfunction of primary hemostasis in patients with ESRD, and hemodialysis has the ability to correct some part of the hemostatic disturbances. As a sensitive, specific, reproducible, easy to perform, and noninvasive test for platelet-related primary hemostasis, the PFA-100 system may become a useful tool for an overall evaluation of primary hemostasis in patients with ESRD.

Double dose plateletpheresis by continuous and intermittent flow devices increases platelet-neutrophil complex formation in healthy donors without noticeable neutrophil activation.

Several reports have demonstrated that during a single plateletpheresis procedure, platelets may form heterotypic aggregates which may predispose certain donors to thrombotic complications. In this study, changes in the expression of neutrophil adhesion molecules (CD11b/CD18, CD50/54, CD62L) and platelet-neutrophil complex (PNC) formation were investigated by a flow cytometric method in healthy donors following a double dose plateletpheresis (DDP) procedure. Our results show that DDP which are carried out by the Fresenius AS.TEC 204 and Haemonetics MCS+ cause a significant increase in PNC formation in donors. Additionally, the Fresenius AS.TEC 204 device caused a decrease in CD62L expression which is a sign of mild neutrophil activation. Although the clinical significance of these laboratory changes is not clear, the occurrence of neutrophil activation and increased PNC formation might predispose certain donors to thrombotic complications following DDP.

Cytomegalovirus antigenemia and outcomes of patients undergoing allogeneic peripheral blood stem cell transplantation: effects of long-term high-dose acyclovir prophylaxis and preemptive ganciclovir treatment.

Cytomegalovirus (CMV) disease is a frequent cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. In order to investigate the relationships between antigenemia, high-dose acyclovir (HDACV) prophylaxis, preemptive ganciclovir (GCV) therapy, and outcomes, we analyzed the records of 105 patients, including both pediatric and adult populations, who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) and who were at risk for CMV reactivation and disease (both recipient and donor seropositive). All received HDACV until neutrophil engraftment, but prophylaxis was continued till post-transplant day 180 only in pediatric patients in conjunction with weekly CMV pp65 antigenemia monitoring. Antigenemia-guided preemptive strategy with GCV was used for all patients. CMV antigenemia developed in 45 patients (42.9%) and CMV disease in 13 (12.4%). The frequencies for antigenemia were 31.3 and 63.2% in pediatric and adult groups (P = 0.002). All CMV diseases were in the adult group (P<0.001). Age at transplantation, underlying disease, long-term HDACV prophylaxis and acute graft versus host disease (aGVHD) were all found to be a significant risk factors for antigenemia. All of these factors other than aGVHD and conditioning regimen were also the significant risk factors for CMV disease. However, when we analyzed the pediatric and adult patients separately, dropping "long-term HDACV prophylaxis," none of these parameters were significant risk factors for CMV disease. In conclusion, we hypothesize that long-term HDACV prophylaxis in the GCV era results in a low incidence of CMV reactivation and disease in patients undergoing PBSCT.

rHuG-CSF increases the platelet-neutrophil complex formation and neutrophil adhesion molecule expression in volunteer granulocyte and stem cell apheresis donors.

Several reports have shown that granulocyte colony-stimulating factor (G-CSF) administration induces a transient, mild hypercoagulable state, which might predispose certain donors to thrombotic complications. In the present study, changes in the expression of neutrophil adhesion molecules (CD11b/CD18, CD62L) and platelet-neutrophil complex formation following rHuG-CSF administration were investigated in normal granulocyte and stem cell donors. For granulocyte apheresis (N = 10), rHuG-CSF (5 microg/kg) was given subcutaneously every 12 h three times and apheresis was carried out two hours after the last dose. For stem cell apheresis (N = 8), rHuG-CSF (10 microg/kg/day) was given subcutaneously for 5 days and apheresis was carried out when peripheral CD34+ cell counts exceeded 20 cell/microL. Expression of neutrophil adhesion molecules (CD11b/CD18, CD62L) and platelet-neutrophil complex formation following rHuG-CSF administration were investigated in donors by a flow cytometric method. A significant increase in neutrophil counts (P < 0.001), and decreases in platelet counts (P < 0.01) and hemoglobin levels (P < 0.01) occurred following G-CSF administration. The expression of CD11b/CD18 significantly increased (P < 0.001) over pretreatment values with G-CSF administration and returned to baseline 1 week after stopping the drug. In contrast, CD62L expression was decreased (P < 0.01) with G-CSF and returned to normal after cessation of the drug. rHuG-CSF caused more than a two-fold increase (from 0.3 to 7.0 x 10(9)/L) in circulating platelet-neutrophil complexes (P < 0.01), which returned to normal after 1 week. Although clinical significance of these laboratory changes is not clear, the occurrence of neutrophil activation and increased platelet-neutrophil complex formation might predispose certain donors or patients to thrombotic complications following G-CSF administration.

Peritoneal macrophages function modulation by L-carnitine in aging rats.

BACKGROUND AND AIMS: The aging process is associated with a progressive decline in physiological functions involving immune response in most species. The aim of the present study was to determine the effect of L-carnitine on impaired macrophages function in aged rats. METHODS: Superoxide anion production, chemotaxis and phagocytic activity were studied in peritoneal macrophages obtained from young (2 months old) and aged (24 months old) rats. L-carnitine (50 mg/kg bw) or control vehicle was orally gavaged into young and aged rats for 30 consecutive days. RESULTS: The peritoneal macrophages of the aged rats exhibited an increase in superoxide anion generation and a decline in chemotaxis and phagocytic index by comparison with the young rats. Superoxide anion production in aged rats was significantly reduced by L-carnitine treatment, as accompanied by a significant enhancement of chemotactic activity, which was restored to control levels observed in young rats. The age-related reduction in phagocytic index was only slightly, but not significantly, restored by L-carnitine administration, however. CONCLUSION: The findings suggest that L-carnitine administration may be useful in reversing some age-related changes.

Effects of L-carnitine on neutrophil functions in aged rats.

Several age-related alterations occur at the cellular level in the immune system leading to a decrease in the immune response. The present study was designed to determine the effect of L-carnitine on impaired neutrophil functions of aged rats. For this reason, superoxide anion radical production, chemotaxis and phagocytic activity were studied in the neutrophils obtained from the peripheral blood of young and old rats. We orally gavaged L-carnitine (50 mg/kg b.w. per day) or control vehicle into young (2 months) and aged (24 months) rats for 30 consecutive days. The neutrophils of aged rats exhibited an increase in superoxide anion production and decline in phagocytosis and chemotaxis when compared with that in young rat neutrophils. Superoxide anion production in aged rats was significantly decreased by L-carnitine treatment which was accompanied with a significant enhancement of chemotactic and phagocytic activity being restored to control levels. These findings demonstrated that L-carnitine is capable of restoring the age-related changes of neutrophil functions.

Apoptosis of cord blood neutrophils and their response to colony-stimulating factors.

Neutrophil production and functions are immature in newborns. Although neutrophil kinetics during neonatal period have been widely studied, little is known about the effect of apoptosis on these defects. In this study, we examine the apoptosis of neonatal neutrophils and the effects of colony-stimulating factors (CSF) on this process. The study was performed using three different methodologies (morphological analysis, surface Fas expression, and mitochondrial 7A6 antigen expression) and the results were compared with adult controls. Neonatal neutrophils more rapidly underwent apoptosis in comparison to adult neutrophils. The above-mentioned three different methods gave similar results. Granulocyte-CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF) decreased the apoptosis of neutrophils in newborns and adults. This effect was significantly more pronounced in adults than newborns in morphological analysis. Increased apoptosis may contribute to qualitative and quantitative defects of neutrophils during neonatal period and may be an explanation for the proneness of newborn to develop neutropenia during systemic infections.