Nurses' communication difficulties when providing end-of-life care in the oncology setting: a cross-sectional study.

PURPOSE: To (1) examine the communication difficulties nurses experience when providing end-of-life (EOL) care, (2) establish the correlation between communication difficulties across various stakeholders and (3) determine the impact sociodemographic factors has on the communication difficulties experienced. METHODS: 124/178 (69.7%) nurses from oncology wards of a tertiary hospital were recruited. Sociodemographic survey and three validated subscales: Communication with Patient and Family (CPF), Explanation to Family (EF) and Reassessment of Current Treatment and Nursing Care (RCTNC) were used to collect the data. Data were analysed with Independent Samples T test, One-Way Analysis of Variance and Pearson's correlation coefficient. RESULTS: Mean score was highest for CPF (8.75 ± 2.24) and lowest for RCTNC (6.32 ± 2.26). Positive correlations were found between CPF with EF (r = 0.613, p < 0.001), CPF with RCTNC (r = 0.243, p = 0.007) and EF with RCTNC (r = 0.370, p < 0.001). Age (p = 0.048), years of experience (p = 0.001), religion (p = 0.034) and EOL care training received (p = 0.040) were significant factors for CPF subscale while age (p = 0.011), years of experience (p = 0.001), educational qualification (p = 0.003) and EOL care training received (p = 0.026) were the significant factors for EF subscale. CONCLUSION: Nurses experienced more communication difficulties with patients and families than with the healthcare team. When nurses experience communication difficulties with the healthcare team, they also tend to experience communication difficulties with patients and families and when providing explanations to families. Nurses experienced greater communication difficulties when they are younger, are non-graduates, have less years of experience, adopted a religion or did not receive training in EOL care. TRIAL REGISTRATION: Clinical Trials.gov Identifier: 2019/00680 (Domain Specific Review Board).

Safety and tolerability of cryocompression as a method of enhanced limb hypothermia to reduce taxane-induced peripheral neuropathy.

PURPOSE: Severe peripheral neuropathy is a common dose-limiting toxicity of taxane chemotherapy, with no effective treatment. Frozen gloves have shown to reduce the severity of neuropathy in several studies but comes with the incidence of undesired side effects such as cold intolerance and frostbite in extreme cases. A device with thermoregulatory features which can safely deliver tolerable amounts of cooling while ensuring efficacy is required to overcome the deficiencies of frozen gloves. The role of continuous-flow cooling in prevention of neurotoxicity caused by paclitaxel has been previously described. This study hypothesized that cryocompression (addition of dynamic pressure to cooling) may allow for delivery of lower temperatures with similar tolerance and potentially improve efficacy. METHOD: A proof-of-concept study was conducted in cancer patients receiving taxane chemotherapy. Each subject underwent four-limb cryocompression with each chemotherapy infusion (three hours) for a maximum of 12 cycles. Cryocompression was administered at 16 °C and cyclic pressure (5-15 mmHg). Skin surface temperature and tolerance scores were recorded. Neuropathy was assessed using clinician-graded peripheral sensory neuropathy scores, total neuropathy score (TNS) and nerve conduction studies (NCS) conducted before (NCSpre), after completion (NCSpost) and 3 months post-chemotherapy (NCS3m). Results were retrospectively compared with patients who underwent paclitaxel chemotherapy along with continuous-flow cooling and controls with no hypothermia. RESULTS: In total, 13 patients underwent 142 cycles of cryocompression concomitant with chemotherapy. Limb hypothermia was well tolerated, and only 1 out of 13 patients required an intra-cycle temperature increase, with no early termination of cryocompression in any subject. Mean skin temperature reduction of 3.8 ± 1.7 °C was achieved. Cryocompression demonstrated significantly greater skin temperature reductions compared to continuous-flow cooling and control (p < 0.0001). None of the patients experienced severe neuropathy (clinician-assessed neuropathy scores of grade 2 or higher). NCS analysis showed preservation of motor amplitudes at NCS3m in subjects who underwent cryocompression, compared to the controls who showed significant deterioration (NCS3m cryocompression vs. NCS3m control: ankle stimulation: 8.1 ± 21.4%, p = 0.004; below fibula head stimulation: 12.7 ± 25.6%, p = 0.0008; above fibula head stimulation: 9.4 ± 24.3%, p = 0.002). Cryocompression did not significantly affect taxane-induced changes in sensory nerve amplitudes. CONCLUSION: When compared to continuous-flow cooling, cryocompression permitted delivery of lower temperatures with similar tolerability. The lower skin surface temperatures achieved potentially lead to improved efficacy in neurotoxicity amelioration. Larger studies investigating cryocompression are required to validate these findings.

Early detection of phlebitis among hematology-oncology patients: a best practice implementation project.

INTRODUCTION: Peripherally-inserted venous catheters (PIVC) are essential for cancer patients to receive treatment. Phlebitis is a major complication of PIVC. Currently, nurses' assessment of phlebitis mainly involves visual inspection. However, the latest literature suggests palpation for tenderness to promote the early detection of phlebitis. OBJECTIVES: This project evaluated the effectiveness of a bundle approach to increase nurses' compliance with PIVC site assessment to promote early detection of phlebitis (grade 2 and above). METHODS: The JBI Evidence Implementation Framework was used to conduct this project in a 28-bed hematology-oncology ward in a Singapore hospital. The bundle approach used in this project consisted of a training presentation, medical mannequin, and phlebitis scale card. The rate of nurses' compliance with best practice for PIVC site assessment was measured at 1 month and 6 months post-implementation. The incidence of phlebitis was monitored up until 12 months post-implementation. RESULTS: Baseline data indicated that only 18.75% (3 out of 16) nurses palpated for tenderness when assessing for phlebitis. Data at 1 month and 6 months post-implementation reported sustained high compliance rates of 85.71% (24 out of 28) and 89.29% (25 out of 28), respectively. Late detection of phlebitis was reduced by 66% (from three cases to one case) at 6 months post-implementation, and no patients required invasive interventions. CONCLUSIONS: The bundle approach used in this project facilitated early detection of phlebitis following the inclusion of palpation into nurses' assessment for phlebitis. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A204.

Prognostic factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia: a systematic review and meta-analysis.

Chemotherapy-induced febrile neutropenia patients are heterogeneous in their risk of adverse outcomes. Management strategies are tailored according to level of risk. Many emerging predictors for risk stratification remain controversial being based on single studies only. A systematic review was conducted to determine the strength of association of all identified predictors. Studies were obtained from electronic databases, grey literatures and reference lists. Methodological quality of studies was assessed for internal validity and representativeness. Seven studies (four prospective and three retrospective cohorts) investigating 22 factors were reported. Fixed effects meta-analysis showed: hypotension and thrombocytopenia were significant predictors for high-risk. Additional predictors that might enhance performance of current models include: tachypnoea, presence of central venous catheter, duration and severity of neutropenia. Further research to investigate new factors/markers is needed to develop a robust prognostic model, which is the key to enhance patient safety.

Reducing Chemotherapy Waiting Times in the Ambulatory Setting of a Tertiary Cancer Centre Using a Design Thinking Approach.

INTRODUCTION: Chemotherapy is complex. We hypothesized that a design thinking approach could redesign preparatory processes and reduce wait times. METHODS: A multidisciplinary process mapping exercise was undertaken to understand the current processes, followed by proposing and testing solutions. Proposals were selected based on desirability and feasibility. These focused on starting the morning treatments on time and scheduling pre-made regimens in these slots. The primary outcome measure was the time from the appointment to starting treatment. Treatments in the post-intervention study group were compared against a historical control group. RESULTS: The median time to start morning treatment decreased by 46%, from 83 min (with an interquartile range 50-127) in the control group to 45 min (with an interquartile range of 24-81 min) in the study group (p < 0.001). This translated into an overall improvement for the day, with the median time to start treatment decreasing from 77 min (with an interquartile range of 40-120 min) to 47 min (with an interquartile range of 20-79 min) (p < 0.001). Pre-makes increased by 258%, from 908 (28.5%) to 2340 (71.7%) regimens (p < 0.001). The number of patients starting treatment within an hour of their appointment increased from 1688 (32.8%) to 3355 (62.3%, p < 0.001). CONCLUSION: We have shown that a data-driven, design thinking approach can improve waiting times. This can be adapted to improve other processes in an empathetic, sustainable manner.

Implementing an evidence-based structured education and management program in an inpatient adult oncology setting to improve patients' pain control.

BACKGROUND AND AIMS: Cancer-related pain is prevalent across the cancer trajectory, and is probably one of the most feared of all cancer symptoms for patients and their families. Although there were guidelines and framework regarding the management of cancer pain, pain control among patients remain suboptimal. This best practice implementation project aimed to improve patients' perception on cancer pain management and pain control through implementing structured patient and family education and patient information leaflet (PIL) on managing cancer pain. METHODS: The current implementation project conducted in an adult oncology inpatient unit utilized the JBI Practical Application of Clinical Evidence System and Getting Research into Practice module for promoting evidence-based health care. RESULTS: A comparison between the preimplementation and postimplementation findings showed significant improvements for both audit criteria outcomes. The percentage of patients receiving verbal education rose from 0 to 69%, whereas the percentage of patients receiving PIL increased 0-100%. Patient compliance to analgesic regime increased from 0 to 100%. There was a significant improvement in patients' pain levels ( P  < 0.001), with majority rate having none-mild pain post intervention. CONCLUSION: A structured educational program on cancer-related pain improved patients' knowledge on cancer-related pain management and pain control. Despite the remarkable increase in the compliance rate, further interventions may still be required to achieve 100% compliance. Continuous audits will be held to guide follow-up interventions to ensure compliance and sustention of the project.

To reduce the average length of stay of patients who are admitted for DA-EPOCH-R chemotherapy regimen.

Healthcare institutions are often faced with bed crunch situation. As a result, patients requiring inpatient hospital stay for cancer treatment are delayed and this could lead to compromised overall disease response. Apart from the early discharge of patients to step-down care and explore alternatives of treatment setting, one of the ways to reduce length of stay is to improve on the efficiency of work processes. A baseline study demonstrated that delays in prescribing chemotherapy orders has led to an increased inpatient stay of seven days for a five day treatment regimen. This has profound consequences in terms of costs, patient safety, and utilisation of healthcare resources. A quality improvement project was initiated to review and revise the workflow and processes involved for the entire episode of treatment. A post-implementation review of the interventions showed cost savings, a reduction of average length of stay from seven days to six days (with a total of 28 days saved over six months), and improved patient and staff experience.

Prognostic factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia: a systematic review and meta-analysis.

BACKGROUND: Increasing numbers of studies identify new prognostic factors for categorising chemotherapy-induced febrile neutropenia adult cancer patients into high- or low-risk groups for adverse outcomes. These groupings are used to tailor therapy according to level of risk. However many emerging factors with prognostic significance remain controversial, being based on single studies only. OBJECTIVES: A systematic review was conducted to determine the strength of association of all identified factors associated with the outcomes of chemotherapy-induced febrile neutropenia patients. INCLUSION CRITERIA: The participants included were adults of 15 years old and above, with a cancer diagnosis and who underwent cancer treatment.The review focused on clinical factors and their association with the outcomes of cancer patients with chemotherapy-induced febrile neutropenia at presentation of fever.All quantitative studies published in English which investigated clinical factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia were considered.The primary outcome of interest was to identify the clinical factors for risk stratification of adult cancer patients with chemotherapy-induced febrile neutropenia. SEARCH STRATEGY: Electronic databases searched from their respective inception date up to December 2011 include MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Science-Direct, Scopus and Mednar. METHODOLOGICAL QUALITY: The quality of the included studies was subjected to assessment by two independent reviewers. The standardised critical appraisal tool from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) was used to assess the following criteria: representativeness of study population; clearly defined prognostic factors and outcomes; whether potential confounders were addressed and appropriate statistical analysis was undertaken for the study design. DATA COLLECTION: Data extraction was performed using a modified version of the standardised extraction tool from the JBI-MAStARI. Prognostic factors and the accompanying odds ratio reported for the significance of these factors that were identified by multivariate regression, were extracted from each included study. DATA SYNTHESIS: Studies results were pooled in statistical meta-analysis using Review Manager 5.1. Where statistical pooling was not possible, the findings were presented in narrative form. RESULTS: Seven studies (four prospective cohort and three retrospective cohort) investigating 22 factors in total were included. Fixed effects meta-analysis showed: hypotension [OR=1.66, 95%CI, 1.14-2.41, p=0.008] and thrombocytopenia [OR=3.92, 95%CI, 2.19-7.01, p<0.00001)] were associated with high-risk of adverse outcomes for febrile neutropenia. Other factors that were statistically significant from single studies included: age of patients, clinical presentation at fever onset, presence or absence of co-morbidities, infections, duration and severity of neutropenia state. Five prognostic factors failed to demonstrate an association between the variables and the outcomes measured and they include: presence of pneumonia, total febrile days, median days to fever, recovery from neutropenia and presence of moderate clinical symptoms in association with Gram-negative bacteraemia. CONCLUSIONS: Despite the overall limitations identified in the included studies, this review has provided a synthesis of the best available evidence for the prognostic factors used in risk stratification of febrile neutropenia patients. However, the dynamic aspects of prognostic model development, validation and utilisation have not been addressed adequately thus far. Given the findings of this review, it is timely to address these issues and improve the utilisation of prognostic models in the management of febrile neutropenia patients. IMPLICATIONS FOR PRACTICE: The identified factors are similar to the factors in current prognostic models. However, additional factors that were reported to be statistically significant in this review (thrombocytopenia, presence of central venous catheter, and duration and severity of neutropenia) have not previously been included in prognostic models. This review has found these factors may improve the performance of current models by adding or replacing some of the factors. IMPLICATIONS FOR RESEARCH: The role of risk stratification of chemotherapy-induced febrile neutropenia patients continues to evolve as the practice of risk-based therapy has been demonstrated to be beneficial to patients, clinicians and health care organisations. Further research to identify new factors /markers is needed to develop a new model which is reliable and accurate for these patients, regardless of cancer types. A robust and well-validated prognostic model is the key to enhance patient safety in the risk-based management of cancer patients with chemotherapy-induced febrile neutropenia.

Risk factors for adverse outcomes and multidrug-resistant Gram-negative bacteraemia in haematology patients with febrile neutropenia in a Singaporean university hospital.

INTRODUCTION: Institutional febrile neutropenia (FN) management protocols were changed following the finding of a high prevalence of ceftazidime-resistant Gram-negative bacteraemia (CR-GNB) among haematology patients with FN. Piperacillin/tazobactam replaced ceftazidime as the initial empirical antibiotic of choice, whereas carbapenems were prescribed empirically for patients with recent extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae colonisation/infection. An audit was conducted to determine the impact of these changes. METHODS: Data from all FN episodes between October 2008 and December 2010 were collected prospectively, with mid-November 2009 demarking the transition between pre-intervention and intervention periods. Outcomes measured included 30-day mortality post-development of FN and the presence of CR-GNB. RESULTS: There were 427 FN episodes (200 in the pre-intervention period) from 225 patients. The prevalence of CRGNB was 10.3%, while the 30-day mortality was 4.7%, with no difference between pre-intervention and intervention periods. Independent risk factors for 30-day mortality included the presence of active haematological disease, vancomycin prescription and older age. Independent factors associated with initial CR-GNB were profound neutropenia, the presence of severe sepsis and active haematological disease. Recent ESBL-producing Enterobacteriaceae colonisation/infection was not predictive of subsequent CR-GNB (positive predictive value 17.3%), whereas a model based on independent risk factors had better negative predictive value (95.4%) but similarly poor positive predictive value (21.4%), despite higher sensitivity. CONCLUSION: A change in the FN protocol did not result in improved outcomes. Nonetheless, the audit highlighted that empirical carbapenem prescription may be unnecessary in FN episodes without evidence of severe sepsis or septic shock, regardless of previous microbiology results.

Prospective audit of post-chemotherapy febrile neutropenia in patients with solid cancer and lymphoma in two Singaporean cancer centres.

INTRODUCTION: Febrile neutropenia (FN) is a significant cause of mortality and morbidity in oncology and haematology units worldwide. The overall mortality in hospital surveys in Singapore surveys on post-chemotherapy FN has ranged between 3.0% and 8.8%. However, recent evidence indicates that outpatient management of patients with low-risk FN is safe and cost-effective. MATERIALS AND METHODS: We conducted a prospective audit on a cohort of adult patients with post-chemotherapy FN seen at 2 local public sector cancer centres over a 1-year period in order to define their epidemiological characteristics and outcomes, and also to assess the uptake of early discharge/outpatient management strategies for these patients. RESULTS: We reviewed 306 FN episodes from 248 patients. Patient characteristics and outcomes were similar between both institutions. Eleven (3.7%) FN episodes were managed as outpatient and none developed complications. Overall 30-day mortality was 6.6%, while the median length of stay (LOS) was 7 days (IQR: 4 to 11 days). The only independent risk factor for mortality was severe sepsis (OR:13.19; 95% CI: 1.98 to 87.7; P = 0.008). Factors independently associated with a longer LOS were vancomycin prescription (coefficient: 0.25; 95% CI: 0.08 to 0.41; P = 0.003), longer duration of intravenous antibiotics (coefficient: 0.08; 95% CI: 0.06 to 0.10; P <0.001), and prior review by an infectious diseases physician (coefficient: 0.16; 95% CI: 0.01 to 0.31; P = 0.034). CONCLUSION: This audit demonstrated that mortality from FN in our 2 cancer centres is low and comparable to international institutions. It also demonstrates that outpatient management of FN is safe in selected patients, and can be further expanded for right-siting of resources.

The experience of being a neutropenic cancer patient in an acute care isolation room: a systematic review of qualitative evidence.

BACKGROUND: Protective isolation is one of the precautionary measures put in place for neutropenic cancer patients, where patients will be placed in an isolation room during their medical treatment in the hospital. The purpose of this practice is to minimise neutropenic patients from contracting nosocomial infection and the length of stay in the isolation room varies depending on their medical condition. It has been reported in some literature that this group of patients experience social isolation, a wide range of emotions and psychological burdens such as depression and anxiety as a result of staying in the isolation room. Therefore, a systematic review on neutropenic cancer patients' experience in isolation room will add knowledge to the nursing science of providing high quality care for this particular group of patients. OBJECTIVES: The objectives of this review are to understand neutropenic cancer patients' experiences in the isolation room and their coping mechanisms. INCLUSION CRITERIA: The participants of interest were adults neutropenic cancer patients aged 18 years old and above.The phenomenon of interest i was the experience of neutropenic cancer patients who were nursed in an isolation room due to chemotherapy induced neutropenia or during the period of haematopoietic stem cell transplant.The studies of interests were are qualitative studies which focus on adult neutropenic cancer patients' experiences in an isolation room.The outcome of interest wai s patients' self reported experiences. SEARCH STRATEGY: An initial search to identify keywords was undertaken in MEDLINE and CINAHL. A second search using all identified keywords and index terms across the databases was performed subsequently. The final search included reference lists from included papers for additional studies. METHODOLOGICAL QUALITY: Six qualitative papers were included in this review. The papers were qualitative descriptive, phenomenological, qualitative exploratory and grounded theory. All the papers used interview as primary method to collect data except one study which had an additional art making directive method. DATA COLLECTION: Data were extracted using standardised data extraction tools from JBI-QARI. DATA SYNTHESIS: Categories were formed based on aggregation from the similar findings with like meaning. The categories were then read and reread to develop two synthesised findings that were presented as declamatory and generalisable statements to guide and inform clinical practice. RESULTS: Two syntheses were generated based on the meta-aggregation. The first synthesis was that health care workers need to be aware physical isolation could result in social isolation in patients that made them feel powerless. The second synthesis was that health care workers should encourage patients to use cognitive mechanisms to cope with isolation experiences. Family, friends and nurses should step in to provide help in any form whenever patients need it. CONCLUSIONS: Isolation room has a negative impact on the neutropenic cancer patients while they are hospitalised. However, they are coping effectively using cognitive mechanisms and receive adequate support externally.Offering patients more options especially having flexibility in their daily routine such as meal times could be a useful intervention to allow them to take some control. Notifying the patient in advance of their time of treatment and involving patients in their treatment care will promote their autonomy. Tracking the patients' coping mechanisms and offering support when necessary will ease the patients' isolation experience.The psychological effects of being cared for in isolation room may undermine the clinical benefits of infection control. Therefore, future research is needed to evaluate the effectiveness of isolation room in preventing neutropenic cancer patients from infection.

Prospective audit of febrile neutropenia management at a tertiary university hospital in Singapore.

INTRODUCTION: Febrile neutropenia (FN) remains a major cause of morbidity and mortality in Oncology/Haematology units. We launched a new protocol for FN management that incorporates risk stratification at our institute from October 2008. An audit was performed concurrently to evaluate the protocol and to define the epidemiology of FN locally. MATERIALS AND METHODS: Case records of all inpatients with FN between October 2008 and June 2009 were reviewed prospectively. Clinical and microbiological characteristics were collated along with outcomes and programme adherence. Statistical testing was performed using Stata 10.1. RESULTS: There were 178 FN episodes (50 in patients with solid cancers) from 131 patients. Forty-two (23.6%) episodes were classified as high-risk according to MASCC criteria. Initial blood cultures were positive in 49 (27.5%) episodes, of which gram-negative bacilli (GNB) predominated. Overall compliance to the protocol was 56.7%, with the main issue being disinclination to use oral antibiotics as fi rst-line empirical therapy for low-risk episodes. Overall mortality was 7.3% and infection-related mortality was 4.5%. High-risk FN and the presence of central venous catheters were independently associated with bacteraemia on multivariate analysis, but there were no independent predictors of infection-related mortality. CONCLUSIONS: GNB accounted for the majority of bloodstream infections at our institute, unlike data from developed countries. Uptake of the new FN protocol was satisfactory, although the use of oral antibiotics as fi rst-line empirical therapy can be improved. A better method for predicting infections caused by antibiotic-resistant GNB is urgently required, and antibiotic resistance trends should be monitored to enable the implementation of more appropriate antibiotic regimens over time.

Nutritional Status and Nutritional Knowledge of Malay Pregnant Women in Selected Private Hospitals in Klang Valley / Jurnal Sains Kesihatan Malaysia

Adequate nutrition is important for mothers and their offspring during and after birth. This cross sectional study was conducted to determine nutritional status and nutritional knowledge of pregnant women from two selected private hospitals in Klang Valley, Malaysia. A total of 236 Malay pregnant women aged between 20 to 45 years old (mean age 31+5 years) were recruited through convenient sampling method. Socio-demographic data, nutritional knowledge and a 24-hours diet recall were obtained through a self-administered questionnaire. Anthropometric and haemoglobin data were obtained from the antenatal records in the respective hospitals. The percentages of participants who were underweight, normal, overweight and obese before pregnancy were 12.7%, 55.1%, 25.0% and 7.2% respectively. Among those who were obese before pregnancy, a total of 59.7% had inadequate weight gain, 24.6% gained adequate weight and 15.7% gained excessive gestational weight. About 33.5% of subjects were anaemic (Hb < 11.0g/dL). The mean daily energy intake of the participants was 1748 ± 526 kcal which was 76% of RNI. Calcium (73% of RNI), folic acid (36% of RNI), niacin (89% of RNI) and vitamin D (40% of RNI). The nutritional knowledge level of subjects was moderate (51.9 ± 13.8%). Lower monthly household income (p < 0.001), educational level (p < 0.001) and gestational stage (p < 0.05) of participants were associated with a lower nutritional knowledge level. Nutritional knowledge score was positively correlated with gestational weight gain (r = 0.166, p < 0.05) and haemoglobin level (r = 0.200, p < 0.05). Subjects who claimed practising food taboos had higher nutritional knowledge score (54.9 ± 12.5%) than those who did not (49.9 ± 14.4%)(p < 0.05). A comprehensive nutrition education should be integrated in the antenatal classes to improve nutritional status of pregnant women

Impact of postgrafting immunosuppressive regimens on nonrelapse mortality and survival after nonmyeloablative allogeneic hematopoietic stem cell transplant using the fludarabine and low-dose total-body irradiation 200-cGy.

The development of nonmyeloablative (NM) hematopoietic cell transplantation (HCT) has extended the potential curative treatment option of allografting to patients in whom it was previously contraindicated because of advanced age or comorbidity. Acute and chronic graft versus host disease (GVHD) and its consequent nonrelapse mortality (NRM), remains the major limitation of NM HCT. In this report, we analyzed the outcome of 67 patients (median age, 45 years) with hematologic diseases receiving NM conditioning with fludarabine 90 mg/m(2) and total body irradiation (TBI) 200-cGy, followed by filgrastim-mobilized peripheral blood stem cell transplant from HLA identical (n = 61), 5/6 antigen-matched related (n = 1), 6/6 antigen-matched unrelated (n = 3), and 5/6 antigen-matched unrelated (n = 2) donors. The first cohort of 21 patients were given cyclosporine (CSP) and mycophenolate mofetil (MMF) as postgrafting immunosuppression, whereas the subsequent cohort was given additional methotrexate (MTX) and extended duration of CSP/MMF prophylaxis in an attempt to reduce graft-versus-host disease (GVHD). Sixty-four (95%) patients engrafted and 3 (5%) had secondary graft failure. Myelosuppression was moderate with neutrophil counts not declining below 500/microL in approximately 25% of patients, and with more than half of the patients not requiring any blood or platelet transfusion. The 2-year cumulative interval (CI) of grade II-IV, grade III-IV acute GVHD and chronic GVHD were 49%, 30%, and 34%, respectively. The 2-year probability of NRM, overall (OS), and progression-free (PFS) survival were 27%, 43%, and 28%, respectively. GVHD-related death accounted for 85% of NRM. Compared with patients receiving CSP/MMF, patients receiving extended duration of CSP/MMF with additional MTX in postgrafting immunosuppression had a significantly lower risk of grade III-IV acute GVHD (CI 20% versus 52%; P = .009) and NRM (CI at 2 years: 11% versus 62%; P < .001), without any significant adverse impact on the risk of relapse (CI at 2 years: 59% versus 33%; P = .174) Subgroup analysis of a cohort of patients given MTX/CSP/MMF showed that patients with "standard risk" diseases (n = 21) had a 3-year OS and PFS of 85% and 65%, respectively. This compares favorably to the 41% (P = .02) and 23% (P = .03) OS and PFS, respectively, in patients with "high-risk" diseases (n = 25). In conclusion, the addition of MTX onto the current postgrafting immunosuppression regimen with extended CSP/MMF prophylaxis duration provides more effective protection against severe GVHD, and is associated with more favorable outcome in patients receiving NM fludarabine/TBI conditioning than in patients receiving fludarabine/TBI conditioning with CSP and MMF without MTX.