Sexual dimorphism during integrative endocrine and immune responses to ionizing radiation in mice.

Exposure to cosmic ionizing radiation is an innate risk of the spaceflight environment that can cause DNA damage and altered cellular function. In astronauts, longitudinal monitoring of physiological systems and interactions between these systems are important to consider for mitigation strategies. In addition, assessments of sex-specific biological responses in the unique environment of spaceflight are vital to support future exploration missions that include both females and males. Here we assessed sex-specific, multi-system immune and endocrine responses to simulated cosmic radiation. For this, 24-week-old, male and female C57Bl/6J mice were exposed to simplified five-ion, space-relevant galactic cosmic ray (GCRsim) radiation at 15 and 50 cGy, to simulate predicted radiation exposures that would be experienced during lunar and Martian missions, respectively. Blood and adrenal tissues were collected at 3- and 14-days post-irradiation for analysis of immune and endocrine biosignatures and pathways. Sexually dimorphic adrenal gland weights and morphology, differential total RNA expression with corresponding gene ontology, and unique immune phenotypes were altered by GCRsim. In brief, this study offers new insights into sexually dimorphic immune and endocrine kinetics following simulated cosmic radiation exposure and highlights the necessity for personalized translational approaches for astronauts during exploration missions.

Secondary hemophagocytic lymphohistiocytosis: an unusual complication in disseminated Mycobacterium tuberculosis.

Tuberculosis-associated hemophagocytic lymphohistiocytosis (TB-HLH) is a rare and life-threatening complication of tuberculosis infection. Early recognition and treatment of TB-HLH is crucial for improving outcomes. Treatment typically involves a combination of antituberculosis therapy and immunosuppressive therapy to control the immune system's overreaction. In this report, we present the case of a 53-year-old ambulance driver who was diagnosed with TB-HLH. His CT scan revealed splenic abscesses, hepatomegaly and bilateral lung consolidation. He subsequently developed multiorgan failure, including acute respiratory distress syndrome (ARDS), transaminitis and bone marrow dysfunction. The clinical course and simultaneous increase in serum ferritin raised the suspicion of HLH. His Hscore was 254, indicating a high probability of hemophagocytic syndrome. TB diagnosis was confirmed by positive endotracheal TB GeneXpert and bone marrow aspiration (BMA) which detected acid-fast bacilli organisms. The patient was promptly started on anti-TB, dexamethasone and IVIG. The patient responded well to treatment and made a full recovery without any lasting complications. This case highlights the importance of promptly recognising HLH and identifying the underlying cause. In critically ill patients, it is crucial not to delay HLH-specific treatment while working up for differential diagnosis.

Mechanism-Driven and Clinically Focused Development of Botanical Foods as Multitarget Anticancer Medicine: Collective Perspectives and Insights from Preclinical Studies, IND Applications and Early-Phase Clinical Trials.

Cancer progression and mortality remain challenging because of current obstacles and limitations in cancer treatment. Continuous efforts are being made to explore complementary and alternative approaches to alleviate the suffering of cancer patients. Epidemiological and nutritional studies have indicated that consuming botanical foods is linked to a lower risk of cancer incidence and/or improved cancer prognosis after diagnosis. From these observations, a variety of preclinical and clinical studies have been carried out to evaluate the potential of botanical food products as anticancer medicines. Unfortunately, many investigations have been poorly designed, and encouraging preclinical results have not been translated into clinical success. Botanical products contain a wide variety of chemicals, making them more difficult to study than traditional drugs. In this review, with the consideration of the regulatory framework of the USFDA, we share our collective experiences and lessons learned from 20 years of defining anticancer foods, focusing on the critical aspects of preclinical studies that are required for an IND application, as well as the checkpoints needed for early-phase clinical trials. We recommend a developmental pipeline that is based on mechanisms and clinical considerations.

Effectiveness of Educational Programs on Palliative and End-of-life Care in Promoting Perceived Competence Among Health and Social Care Professionals.

BACKGROUND: There is a growing need for palliative care for patients near the end of life and their caregivers. Palliative and end-of-life care (EoLC) education are recommended for all health care (e.g., physicians, nurses, and allied health practitioners) and social care professionals (e.g., social workers) to ensure the quality of services. However, less attention has been afforded to generic, in contrast to specialized, EoLC education. This study evaluated the effectiveness of a series of short-term generic EoLC educational programs for health and social care professionals. METHOD: A pre-post survey design was adopted, focusing on different EoLC core competences. RESULTS: Significant improvement was observed in all perceived competences after the educational programs, regardless of participants' occupation or EoLC experience. Perceived competence in self-care was rated significantly higher than all other competences prior to the programs. Healthcare professionals rated significantly higher on competence in symptom management than social workers. Scores on communication skill and self-care competences were significantly higher following longer (i.e., 16-24 hours) than shorter (i.e., 4-8 hours) programs. CONCLUSION: Generalist palliative/EoLC educational programs may enable health and social care professionals to refresh and extend their knowledge and skills and enhance their perceived competence in providing EoLC. Further research on generalist palliative/EoLC education is needed to examine the impact of continuing training on professionals' actual practice in EoLC and palliative care.

Multicentre, randomised clinical trial comparing intravitreal aflibercept monotherapy versus aflibercept combined with reduced-fluence photodynamic therapy (RF-PDT) for the treatment of polypoidal choroidal vasculopathy.

PURPOSE: To compare the efficacy and safety of intravitreal aflibercept (IVA) monotherapy versus aflibercept combined with reduced-fluence photodynamic therapy (RF-PDT) (IVA+RF-PDT) for the treatment of polypoidal choroidal vasculopathy (PCV). METHODS AND ANALYSIS: Multicentred, double-masked, randomised controlled trial to compare the two treatment modalities. The primary outcome of the study is to compare the 52-week visual outcome of IVA versus IVA+RF PDT. One hundred and sixty treatment-naïve patients with macular PCV confirmed on indocyanine green angiography will be recruited from three centres in Singapore. Eligible patients will be randomised (1:1 ratio) into one of the following groups: IVA monotherapy group-aflibercept monotherapy with sham photodynamic therapy (n=80); combination group-aflibercept with RF-PDT (n=80). Following baseline visit, all patients will be monitored at 4 weekly intervals during which disease activity will be assessed based on best-corrected visual acuity (BCVA), ophthalmic examination findings, optical coherence tomography (OCT) and angiography where indicated. Eyes that meet protocol-specified retreatment criteria will receive IVA and sham/RF-PDT according to their randomisation group. Primary endpoint will be assessed as change in BCVA at week 52 from baseline. Secondary endpoints will include anatomical changes based on OCT and dye angiography as well as safety assessment. Additionally, we will be collecting optical coherence tomography angiography data prospectively for exploratory analysis. ETHICS AND DISSEMINATION: This study will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the ICH E6 guidelines of Good Clinical Practice and the applicable regulatory requirements. Approval from the SingHealth Centralised Institutional Review Board has been sought prior to commencement of the study. TRIAL REGISTRATION NUMBER: NCT03941587.

Piper sarmentosum Roxb. Attenuates Beta Amyloid (Aß)-Induced Neurotoxicity Via the Inhibition of Amyloidogenesis and Tau Hyperphosphorylation in SH-SY5Y Cells.

BACKGROUND: In Alzheimer's disease, accumulation of beta amyloid (Aß) triggers amyloidogenesis and hyperphosphorylation of tau protein leading to neuronal cell death. Piper sarmentosum Roxb. (PS) is a traditional medicinal herb used by Malay to treat rheumatism, headache and boost memory. It possesses various biological effects, such as anti-cholinergic, anti-inflammatory, anti-oxidant and anti-depressant-like effects. OBJECTIVE: The present study aimed to investigate neuroprotective properties of PS against Aß-induced neurotoxicity and to evaluate its potential mechanism of action. METHODS: Neuroprotective effects of hexane (HXN), dichloromethane (DCM), ethyl acetate (EA) and methanol (MEOH) extracts from leaves (L) and roots (R) of PS against Aß-induced neurotoxicity were investigated in SH-SY5Y human neuroblastoma cells. Cells were pre-treated with PS for 24 h followed by 24 h of induction with Aß. The neuroprotective effects of PS were studied using cell viability and cellular reactive oxygen species (ROS) assays. The levels of extracellular Aß and tau proteins phosphorylated at threonine 231 (pT231) were determined. Gene and protein expressions were assessed using qRT-PCR analyses and western blot analyses, respectively. RESULTS: Hexane extracts of PS (LHXN and RHXN) protected SH-SY5Y cells against Aß-induced neurotoxicity, and decreased levels of extracellular Aß and phosphorylated tau (pT231). Although extracts of PS inhibited Aß-induced ROS production, it was unlikely that neuroprotective effects were simply due to the anti-oxidant capacity of PS. Further, mechanistic study suggested that the neuroprotective effects of PS might be due to its capability to regulate amyloidogenesis through the downregulation of BACE and APP. CONCLUSION: These findings suggest that hexane extracts of PS confer neuroprotection against Aß- induced neurotoxicity in SH-SY5Y cells by attenuating amyloidogenesis and tau hyperphosphorylation. Due to its neuroprotective properties, PS might be a potential therapeutic agent for Alzheimer's disease.

Expanding Indications for Liver Transplant: Tumor and Patient Factors.

During the past few decades, liver transplant has developed from a high-mortality procedure to an almost routine procedure with good survival outcomes. The development of living donor liver transplant has increased the availability of liver grafts, and the scope of indications for liver transplant has been expanding ever since. The aim of this review is to provide an overview of such an expansion of scope. Various criteria have been proposed to expand the eligibility of patients with hepatocellular carcinoma exceeding the Milan criteria for liver transplant. Furthermore, liver transplant is increasingly performed as a treatment modality for cholangiocarcinoma, neuroendocrine liver metastasis and colorectal liver metastasis. The number of elderly patients receiving liver transplant is on the rise. Combined organ transplantation has also been adopted to treat patients with multiple organ failure. Going forward, further development of preoperative noninvasive predictors in tumor, patient and even donor factors is needed to identify patients at risk of poor outcomes and hence optimize patient management.

Shortwave infrared polymethine fluorophores matched to excitation lasers enable non-invasive, multicolour in vivo imaging in real time.

High-resolution, multiplexed experiments are a staple in cellular imaging. Analogous experiments in animals are challenging, however, due to substantial scattering and autofluorescence in tissue at visible (350-700 nm) and near-infrared (700-1,000 nm) wavelengths. Here, we enable real-time, non-invasive multicolour imaging experiments in animals through the design of optical contrast agents for the shortwave infrared (SWIR, 1,000-2,000 nm) region and complementary advances in imaging technologies. We developed tunable, SWIR-emissive flavylium polymethine dyes and established relationships between structure and photophysical properties for this class of bright SWIR contrast agents. In parallel, we designed an imaging system with variable near-infrared/SWIR excitation and single-channel detection, facilitating video-rate multicolour SWIR imaging for optically guided surgery and imaging of awake and moving mice with multiplexed detection. Optimized dyes matched to 980 nm and 1,064 nm lasers, combined with the clinically approved indocyanine green, enabled real-time, three-colour imaging with high temporal and spatial resolutions.

Piper sarmentosum Roxb. Root Extracts Confer Neuroprotection by Attenuating Beta Amyloid-Induced Pro-Inflammatory Cytokines Released from Microglial Cells.

BACKGROUND: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that eventually leads to severe cognitive impairment. Although the exact etiologies of AD still remain elusive, increasing evidence suggests that neuroinflammation cascades mediated by microglial cells are associated with AD. Piper sarmentosum Roxb. (PS) is a medicinal plant reported to possess various biological properties, including anti-inflammatory, anti-psychotic and anti-oxidant activity. However, little is known about the anti-inflammatory activity of PS roots despite their traditional use to treat inflammatory- mediated ailments. OBJECTIVE: This study aimed to evaluate the anti-inflammatory and neuroprotective properties of extracts obtained from the roots of PS against beta-amyloid (Aß)-induced microglial toxicity associated with the production of pro-inflammatory mediators. METHOD: BV2 microglial cells were treated with hexane (RHXN), dichloromethane (RDCM), ethyl acetate (REA) and methanol (RMEOH) extracts of the roots of PS prior to activation by Aß. The production and mRNA expression of pro-inflammatory mediators were evaluated by Griess reagent, ELISA kits and RT-qPCR respectively. The phosphorylation status of p38α MAPK was determined via western blot assay. BV2 conditioned medium was used to treat SH-SY5Y neuroblastoma cells and the neuroprotective effect was assessed using MTT assay. RESULTS: PS root extracts, in particular RMEOH significantly attenuated the production and mRNA expression of IL-1ß, IL-6 and TNF-α in Aß-induced BV2 microglial cells. In addition, RHXN, REA and RMEOH extracts significantly reduced nitric oxide (NO) level and the inhibition of NO production was correlated with the total phenolic content of the extracts. Further mechanistic studies suggested that PS root extracts attenuated the production of cytokines by regulating the phosphorylation of p38α MAPK in microglia. Importantly, PS root extracts have protective effects against Aß-induced indirect neurotoxicity either by inhibiting the production of NO, IL-1ß, IL-6, and TNF-α in BV2 cells or by protecting SHSY5Y cells against these inflammatory mediators. CONCLUSIONS: These findings provided evidence that PS root extracts confer neuroprotection against Aß- induced microglial toxicity associated with the production of pro-inflammatory mediators and may be a potential therapeutic agent for inflammation-related neurological conditions including Alzheimer's disease (AD).

The response of Escherichia coli to the alkylating agents chloroacetaldehyde and styrene oxide.

DNA damage is ubiquitous and can arise from endogenous or exogenous sources. DNA-damaging alkylating agents are present in environmental toxicants as well as in cancer chemotherapy drugs and are a constant threat, which can lead to mutations or cell death. All organisms have multiple DNA repair and DNA damage tolerance pathways to resist the potentially negative effects of exposure to alkylating agents. In bacteria, many of the genes in these pathways are regulated as part of the SOS reponse or the adaptive response. In this work, we probed the cellular responses to the alkylating agents chloroacetaldehyde (CAA), which is a metabolite of 1,2-dichloroethane used to produce polyvinyl chloride, and styrene oxide (SO), a major metabolite of styrene used in the production of polystyrene and other polymers. Vinyl chloride and styrene are produced on an industrial scale of billions of kilograms annually and thus have a high potential for environmental exposure. To identify stress response genes in E. coli that are responsible for tolerance to the reactive metabolites CAA and SO, we used libraries of transcriptional reporters and gene deletion strains. In response to both alkylating agents, genes associated with several different stress pathways were upregulated, including protein, membrane, and oxidative stress, as well as DNA damage. E. coli strains lacking genes involved in base excision repair and nucleotide excision repair were sensitive to SO, whereas strains lacking recA and the SOS gene ybfE were sensitive to both alkylating agents tested. This work indicates the varied systems involved in cellular responses to alkylating agents, and highlights the specific DNA repair genes involved in the responses.

Expression of Intracellular Reactive Oxygen Species in Hematopoietic Stem Cells Correlates with Time to Neutrophil and Platelet Engraftment in Patients Undergoing Autologous Bone Marrow Transplantation.

Reactive oxygen species (ROS) play important roles in hematopoiesis and regulate the self-renewal, migration, and myeloid differentiation of hematopoietic stem cells (HSCs). This study was conducted to determine whether ROS levels in donor HSCs correlate with neutrophil and platelet engraftment in patients after bone marrow transplantation. Cryopreserved HSC samples from 51 patients who underwent autologous transplantation were studied. Levels of intracellular ROS were assessed by flow cytometry using 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) in the CD45+/CD34+ HSC population. Colony forming unit assays were performed on HSCs isolated from the ROShigh and ROSlow populations to assess the differentiation potential of these 2 cell subsets. Distinct populations of ROShigh and ROSlow cells were evident in all patient samples. The median percentage of ROShigh expressing HSCs in the study cohort was 75.8% (range, 2% to 95.2%). A significant correlation was identified between the percentage of ROShigh stem cells present in the hematopoietic progenitor cells collected by apheresis product infused and the time to neutrophil engraftment (P < .001, r = -.54), as well as time to plt20, plt50, and plt100 (P < 0.001; r = -.55, -.59, and -.56 respectively). The dose of CD34+/ROShigh/kg infused also inversely correlated with a shorter time to neutrophil engraftment; time to engraftment for patients receiving > or ≤3 × 106 cells/kg was 11.5 days (range, 9 to 23) versus 14 days (range, 10 to 28), respectively (P = .02). The dose of ROShigh HSCs delivered did not correlate with platelet engraftment. Collectively, these data suggest that the dose of ROShigh stem cells delivered to patients may predict time to neutrophil engraftment after autologous transplantation.

Piper sarmentosum Roxb. confers neuroprotection on beta-amyloid (Aß)-induced microglia-mediated neuroinflammation and attenuates tau hyperphosphorylation in SH-SY5Y cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper sarmentosum Roxb. (PS), belonging to Piperaceae family, is an edible plant with medicinal properties. It is traditionally used by the Malays to treat headache and boost memory. Pharmacological studies revealed that PS exhibits anti-inflammatory, anti-oxidant, anti-acetylcholinesterase, and anti-depressant-like effects. In view of this, the present study aimed to investigate the anti-inflammatory actions of PS and its potential neuroprotective effects against beta-amyloid (Aß)-induced microglia-mediated neurotoxicity. MATERIALS AND METHODS: The inhibitory effects of hexane (LHXN), dichloromethane (LDCM), ethyl acetate (LEA) and methanol (LMEOH) extracts from leaves of PS on Aß-induced production and mRNA expression of pro-inflammatory mediators in BV-2 microglial cells were assessed using colorimetric assay with Griess reagent, ELISA kit and real-time RT-PCR respectively. Subsequently, MTT reduction assay was used to evaluate the neuroprotective effects of PS leaf extracts against Aß-induced microglia-mediated neurotoxicity in SH-SY5Y neuroblastoma cells. The levels of tau proteins phosphorylated at threonine 231 (pT231) and total tau proteins (T-tau) were determined using ELISA kits. RESULTS: Polar extracts of PS leaves (LEA and LMEOH) reduced the Aß-induced secretion of pro-inflammatory cytokines (IL-1ß and TNF-α) in BV-2 cells by downregulating the mRNA expressions of pro-inflammatory cytokines. The inhibition of nitric oxide (NO) production could be due to the free radical scavenging activity of the extracts. In addition, conditioned media from Aß-induced BV-2 cells pre-treated with LEA and LMEOH protected SH-SY5Y cells against microglia-mediated neurotoxicity. Further mechanistic study suggested that the neuroprotective effects were associated with the downregulation of phosphorylated tau proteins. CONCLUSIONS: The present study suggests that polar extracts of PS leaves confer neuroprotection against Aß-induced microglia-mediated neurotoxicity in SH-SY5Y cells by attenuating tau hyperphosphorylation through their anti-inflammatory actions and could be a potential therapeutic agent for Alzheimer's disease.

Serum levels, safety and tolerability of new formulation SUBA-itraconazole prophylaxis in patients with haematological malignancy or undergoing allogeneic stem cell transplantation.

OBJECTIVES: To assess therapeutic levels, safety and tolerability of a novel formulation SUBA-itraconazole (where SUBA stands for SUper BioAvailability) when compared with conventional itraconazole liquid when used as antifungal prophylaxis in patients undergoing allogeneic HSCT or in haematological malignancy patients with an intermediate/high risk of invasive fungal infection (IFI). METHODS: This was a single-institution, prospective cohort study using a historical control group as the comparator. RESULTS: A total of 57 patients were assessed: 27 in the SUBA-itraconazole cohort and 30 in the liquid itraconazole cohort. Therapeutic concentrations were achieved significantly more quickly in the SUBA-itraconazole group: median of 6 (95% CI 5-11) days versus 14 (95% CI 12-21) days in the liquid itraconazole group (P < 0.0001). At day 10, therapeutic concentrations were achieved in 69% (95% CI 44%-81%) of the SUBA-itraconazole group versus 21% (95% CI 7%-33%) of the liquid itraconazole group (P < 0.0001). The mean trough serum concentrations at steady-state of SUBA-itraconazole were significantly higher, with less interpatient variability [1577 ng/mL, coefficient of variation (CV) 35%] versus liquid itraconazole (1218 ng/mL, CV 60%) (P < 0.001). There were two (7.4%) treatment failures in the SUBA-itraconazole group, both due to cessation of therapy for mucositis, compared with seven (23.3%) treatment failures in the liquid itraconazole group, due to subtherapeutic levels (five), mucositis (one) and gastrointestinal intolerance (one) (P = 0.096). CONCLUSIONS: The use of the SUBA-itraconazole formulation was associated with more rapid attainment of therapeutic levels with less interpatient variability compared with conventional liquid itraconazole when used as IFI prophylaxis in allogeneic HSCT or intermediate-/high-IFI risk haematological malignancy patients.

Traumatic spondyloptosis of the cervical spine: A case report and discussion of worldwide treatment trends.

BACKGROUND: Cervical spondyloptosis is defined as the dislocation of the spinal column most often caused by trauma. Due to compression or transection of the spinal cord, severe neurological deficits are common. Here, we review the literature and report a case of traumatic C5-6 spondyloptosis that was successfully treated using an anterior-only surgical approach. METHODS: The patient presented with quadriplegia and absent sensation distal to the C5 dermatome following a rollover motor vehicle accident. The preoperative American Spinal Injury Association Impairment Scale was A. Computed tomography of the cervical spine revealed C5-6 spondyloptosis, lamina fractures on the right side at the C3-4 level, and widened facet joint on the right side at C6-7. RESULTS: The patient underwent cervical traction and anterior cervical discectomy and fusion at the C5-6, C6-7 levels; no 360° fusion was warranted. Six months postoperatively, the patient remained quadriplegic below the C5 level. CONCLUSION: Presently, no consensus is present regarding the best treatment for spondyloptosis. Worldwide, the 360° approach is the most commonly used (45%), followed by anterior-only surgery (31%) and posterior-only surgery (25%). The surgical choice depends upon patient-specific features but markedly varies among geographical regions.

Factors determining pbsc mobilization efficiency and nonmobilization following ICE with or without rituximab (R-ICE) salvage therapy for refractory or relapsed lymphoma prior to autologous transplantation.

ICE/R-ICE (ifosfamide, carboplatin, and etoposide without or with rituximab) chemotherapy followed by autologous stem cell transplantation is an established regimen in refractory/relapsed lymphoma. Few studies have addressed which factors are important in determining peripheral blood stem cell (PBSC) mobilization efficiency or nonmobilization following ICE/R-ICE. Between 2004 and 2013, 88 patients with refractory/relapsed lymphoma who received ICE/R-ICE salvage-chemotherapy prior to granulocyte colony stimulating factor (G-CSF) stimulated PBSC mobilization at a single center were identified. Mobilization efficiency was assessed by time from ICE/R-ICE to day of harvest, duration of G-CSF use, days to peripheral blood (PB) CD34(+) ≥15/µL, PB CD34(+) number on harvest day, CD34(+) yield and nonmobilization rate. Median PB CD34(+) at harvest were 54/µL (7-524); median days to first apheresis was 15 (11-30); median harvested total CD34(+) were 5.46 × 10(6) /kg (0.96-44.36); 71 patients (80.7%) successfully mobilized; 20 (22.7%) patients were poor mobilizers; 14 (15.9%) patients were considered nonmobilizers with maximal PB CD34(+) <7/µL and did not proceed to apheresis. Six of 20 poor mobilizers were apheresed with PB CD34(+) 7-12/µL, 50% were successfully harvested. No differences were found between ICE and R-ICE regimens. Impaired mobilization efficiency was associated with age, remission status, >1 line of induction chemotherapy, four cycles ICE/R-ICE and grade 4 neutropenia. Prior bone marrow (BM) involvement was associated with nonmobilization. The majority of patients can be successfully mobilized with ICE/R-ICE. Prior BM involvement is associated with high rates of nonmobilization following ICE/R-ICE. Such patients may benefit from novel mobilization agents and/or alternative salvage regimens to ICE/R-ICE.

Factors predicting haematopoietic recovery in patients undergoing autologous transplantation: 11-year experience from a single centre.

Engraftment outcomes following autologous transplantation correlate poorly to infused stem cell number. We evaluated 446 consecutive patients who underwent autologous transplantation at our centre between 2001 and 2012. The impact of pre-transplant and collection factors together with CD34(+) dosing ranges on engraftment, hospital length of stay (LOS) and survival endpoints were assessed in order to identify factors which might be optimized to improve outcomes for patients undergoing autologous transplantation using haemopoietic progenitor cells-apheresis (HPC-A). Infused CD34(+) cell dose correlated to platelet but not neutrophil recovery. Time to platelet engraftment was significantly delayed in those receiving low versus medium or high CD34(+) doses. Non-remission status was associated with slower neutrophil and platelet recovery. Increasing neutrophil contamination of HPC-A was strongly associated with slower neutrophil recovery with infused neutrophil dose/kg recipient body weight ≥3 × 10(8)/kg having a significant impact on time to neutrophil engraftment (p = 0.001). Higher neutrophil doses/kg in HPC-A were associated with days of granulocyte colony stimulation factor (G-CSF) use, HPC-A volumes >500 ml and higher NCC in HPC-A. High infused neutrophil dose/kg and age >65 years were associated with longer hospital LOS (p = 0.002 and 0.011 respectively). Only age, disease and disease status predicted disease-free survival (DFS) and overall survival (OS) in our cohort (p < 0.005). Non-relapse mortality was not affected by low dose of CD34(+) (<2 × 10(6)/kg). In conclusion, our study shows that CD34(+) remains a useful and convenient marker for assessing haemotopoietic stem cell content and overall engraftment capacity post-transplant. Neutrophil contamination of HPC-A appears to be a key factor delaying neutrophil recovery. Steps to minimize the degree of neutrophil contamination in HPC-A product may be associated with more rapid neutrophil engraftment and reduced hospital LOS.