Implementation of a patient blood management program in hematopoietic stem cell transplantation (Editorial, p. 2763).

BACKGROUND: Recipients of hematopoietic stem cell transplantation (HSCT) are among the highest consumers of allogeneic red blood cell (RBC) and platelet (PLT) components. The impact of patient blood management (PBM) efforts on HSCT recipients is poorly understood. STUDY DESIGN AND METHODS: This observational study assessed changes in blood product use and patient-centered outcomes before and after implementing a multidisciplinary PBM program for patients undergoing HSCT at a large academic medical center. The pre-PBM cohort was treated from January 1 through September 31, 2013; the post-PBM cohort was treated from January 1 through September 31, 2015. RESULTS: We identified 708 patients; 284 of 352 (80.7%) in the pre-PBM group and 225 of 356 (63.2%) in the post-PBM group received allogeneic RBCs (p < 0.001). Median (interquartile range [IQR]) RBC volumes were higher before PBM than after PBM (3 [2-4] units vs. 2 [1-4] units; p = 0.004). A total of 259 of 284 pre-PBM patients (91.2%) and 57 of 225 (25.3%) post-PBM patients received RBC transfusions when hemoglobin levels were more than 7 g/dL (p < 0.001). The median (IQR) PLT transfusion quantities was 3 (2-5) units for pre-PBM patients and 2 (1-4) units for post-PBM patients (p < 0.001). For patients with PLT counts of more than 10 × 109 /L, a total of 1219 PLT units (73.4%) were transfused before PBM and 691 units (48.8%) were transfused after PBM (p < 0.001). Estimated transfusion expenditures were reduced by $617,152 (18.3%). We noted no differences in clinical outcomes or transfusion-related adverse events. CONCLUSION: Patient blood management implementation for HSCT recipients was associated with marked reductions in allogeneic RBC and PLT transfusions and decreased transfusion-related costs with no detrimental impact on clinical outcomes.

Frequency of venous thrombotic events in patients with myelodysplastic syndrome and 5q deletion syndrome during lenalidomide therapy.

Lenalidomide is known to increase the risk of venous thromboembolism in patients with hematologic malignancies. The role of antithrombotic prophylaxis in patients receiving lenalidomide is well established in multiple myeloma. However, when used in patients with a myelodysplastic syndrome (MDS)-in particular, del(5q) patients-the risk of venous thromboembolism and the need for anticoagulation are unknown. We performed a retrospective for MDS patients with 5q deletion. The total number of patients was 64, and 24 (38%) were treated with lenalidomide. Of those who received lenalidomide, venous thrombotic events (VTE) occurred in 4 (17%). All events occurred after 1 year of lenalidomide therapy. Although limited by the cohort size, concurrent erythropoietin-stimulating agents (ESAs) were not associated with increased thrombotic events, and the diagnosis of VTE did not affect survival. Our data suggest an increased incidence of VTE with prolonged lenalidomide treatment, mainly if MDS responds to this therapy.

From clinical trials to clinical practice: outcome of NSABP-B27 neoadjuvant chemotherapy regimen for high-risk early-stage breast cancer.

PURPOSE: Majority of Jordanian breast cancer patients present at a relatively young age and with locally advanced disease highlight the importance of neoadjuvant chemotherapy. This study evaluated the efficacy and safety of NSABP-B27 regimen in high-risk patients in daily clinical practice. METHODS: Patients' medical records and hospital database were searched for all consecutive patients treated at our institution for breast cancer using neoadjuvant NSABP-B27 chemotherapy regimen. Chemotherapy was given at standard doses and schedule as originally reported in the NSABP-B27. RESULTS: 346 female patients (median age 51 years) were treated using this regimen. Majority had high-risk features including larger tumor size (>4 cm in 68.5%), positive axillary lymph nodes (78.3%), and Grade III disease (47.4%). While most patients tolerated and completed planned chemotherapy, 41 (11.8%) patients failed to complete all four cycles of docetaxel. Following neoadjuvant chemotherapy, complete pathological response (pCR) was achieved in 84 (25.0%) evaluable patients; pCR was higher in hormone receptor-negative disease (40.0 vs. 22.1%, p = 0.002), in patient with tumor size ≤4 cm (28.3 vs. 23.5%, p = 0.024) and in patients with node-negative disease (41.2 vs. 20.7%, p = 0.002). Age (<50 vs. ≥50) had no effect, with pCR of 24.2 and 26.4%, respectively (p = 0.607). Breast-conserving surgery was performed in 85 (24.6%). CONCLUSIONS: NSABP-B27 is an effective neoadjuvant regimen. Despite including higher risk patients, pCR is similar to the original NSABP-B27 and many other anthracycline-taxane-based regimens. Tumor size, LN status, hormone receptors status, but not age, were significant factors in achieving pCR.

The prevalence of Behçet's disease in the north of Jordan: a hospital-based epidemiological survey.

OBJECTIVES: To estimate the prevalence of Behçet's disease (BD) in Jordan, with the additional aim of comparing this prevalence among hospital workers in other geographical areas. METHODS: In the first stage of our survey, 2,569 employees from 6 hospitals in north Jordan were interviewed using a screening questionnaire to identify individuals with recurrent oral ulcers (ROU), a previous diagnosis of BD (PDBD) and/or any major symptom related to BD. In the second stage, all individuals with ROU or PDBD identified at stage 1, were examined by 2 rheumatologists for the presence/confirmation of BD according to the International Study Group (ISG) criteria. Pathergy test was performed according to recommendations. RESULTS: ROU were present in 210 (8.2%) individuals. BD was confirmed in 10 employees with PDBD. Seven more BD patients were found. Mean age of 17 BD patients was 38.6±10.7 (range 26-65 y). M: F was 2.4:1. Pathergy test was positive in 8/17. A family history of ROU or BD was noted in 9 (52%) and 3 (25.0%), respectively, compared to 227 (8.9%) and 62 (2.6%) in the whole group, excluding the BD patients (p<0.001 and 0.008, respectively). The prevalence rate of BD in the north of Jordan was estimated as 66:10.000 (95% CI 34.8 to 97.5:10000). CONCLUSIONS: The results of this first ever survey indicated that the prevalence of BD in the north of Jordan is among the highest in the world. This prevalence can now be compared to hospital workers in other geographical areas.

Resolution of intracardiac and pulmonary thrombi without anticoagulation in a patient with Behçet's disease: a case report.

Intracardiac and pulmonary thrombi are rare but serious manifestations of Behçet's disease, the treatment of such cases is a challenge to the treating physician and use of anticoagulants can hold a great risk to some patients. We report a patient who was found to have multiple right intraventricular and bilateral pulmonary artery thrombi and was clinically diagnosed with Behçet's disease. Early in the course of his treatment, the patient developed massive haemoptysis which precluded the further use of anticoagulants. The patient was treated with immunosuppressants alone and had complete resolution of his symptoms and documented resolution of the thrombi. In a review of the literature, only 3 out of around 50 patients reported to have intracardiac thrombi complicating Behçet's disease were treated without anticoagulants (1, 2) even though there is no clear evidence to support the benefit of anticoagulation to treat arterial or thrombotic lesions (3). We conclude that intracardiac thrombi in patients with Behçet's disease may resolve with immunosuppressants without anticoagulation, which is especially important in patients with contraindication to anticoagulation.

Allogeneic Hematopoietic Stem Cell Transplantation in the Outpatient Setting: The Mayo Clinic Experience.

Hematopoietic stem cell transplantations (HSCT) are intensive and potentially curative modalities available for a variety of hematological diseases. Although alloHSCTs are typically performed in an inpatient setting, there has been increasing interest in moving them to the outpatient setting. AlloHSCTs are associated with a median length of hospital stay of 30 days. AlloHSCTs in the inpatient setting may increase patient exposure to nosocomial infections, drug-resistant organisms, rapid deconditioning with time spent in hospital beds, and loss of muscle mass. In this study, we aim to share outcomes of 856 consecutive alloHSCTs done in our institute over the past 2 decades. This is a single-center retrospective chart review encompassing 856 patients who underwent outpatient alloHSCTs between 2000 and 2017. Reduced-intensity conditioning, stem cell infusion, and much of the immediate follow-up in the early alloHSCT period was performed on an outpatient basis with daily evaluation, laboratory assessment, and intervention as needed. Rate of non-routine hospital admission was our primary outcome of interest. We also looked at various secondary outcomes, including causes of admission, median length of stay, and in-hospital mortality rate. Data analysis was performed using STATA statistical software Version 15. Descriptive statistics were used to summarize baseline demographic data and outcomes. Logistic regression modeling was used to identify predictors of hospital admission. We observed that about one third of our cohort never required admission to the hospital throughout the first 100 days after HSCT. Among those admitted, 6.6% experienced a direct admission to the intensive care unit, and the overall in hospital mortality was low at 5%. Furthermore, the median length of stay was noted to be decreased at 6 days compared to a median reported 30 days in existing literature. Overall, we observed favorable safety profile and outcomes with outpatient management of HSCTs.

Treatment of anemia in cancer patients undergoing chemotherapy with intravenous ferric carboxymaltose without erythropoiesis-stimulating agents.

BACKGROUND: Anemia is commonly encountered in cancer patients receiving active chemotherapy. Due to adverse events and presumed negative effects on disease-progression and survival, erythropoiesis-stimulating agents are not frequently used. In this study, we assess the efficacy and safety of intravenous ferric carboxymaltose (FCM) to treat cancer-induced anemia (CIA). PATIENTS AND METHODS: We recruited adult cancer patients on active chemotherapy with a hemoglobin (Hb) level ⩽11.0 g/dL. Based on serum ferritin (sFr) and transferrin saturation (TSAT), patients were divided into 3 groups: group I (absolute iron deficiency, n = 26) with sFr < 30 ng/mL and TSAT < 20%; group II (functional iron deficiency, n = 24) with sFr 30-800 ng/mL and TSAT < 20%; and patients with TSAT ⩾ 20% were placed in group III as "others" (n = 34). All patients were treated with intravenous FCM. Serum hepcidin and C-reactive protein were used as biomarkers to predict response. RESULTS: A total of 84 patients with a median age (SD) of 53.8 (10.6) were recruited. Baseline median Hb level was 10.2 (range: 8.3-11.0) gm/dL. At week 12, there was a significant increment in Hb level for patients in groups I and II (median increment: 2.35 and 1.5 gm/dL, respectively), with limited response observed in group III, and most of the increment noted as early as week 3 (⩾1.0 g/dL). Responders tended to have lower levels of hepcidin. No clinically significant adverse events were reported; however, asymptomatic hypophosphatemia was observed in 39 (46.4%) patients. CONCLUSIONS: Intravenous FCM is a safe and effective treatment option for the management of a subgroup of patients with CIA.The study was registered at ClinicalTrials.gov [Identifier: NCT04246021].

Hematopoietic stem cell transplant in adults with acute lymphoblastic leukemia: the present state.

INTRODUCTION: Allogeneic hematopoietic stem cell transplant (allo-HSCT) has an important role in management of acute lymphoblastic leukemia (ALL). Proper patient selection is central to ensure optimal outcomes. Areas covered: This review covers various aspects of HSCT in ALL patients, including indications, donor selection, conditioning regimens, and post-transplant management. Expert commentary: Allo-HSCT is important in post-remission management of ALL but proper risk-stratification is a major challenge. Incorporation of minimal residual disease (MRD) and molecular testing will improve patient allocation. Patients receiving pediatric-inspired induction who achieve molecular remission might not need allo-HSCT in first remission. Allo-HSCT should be considered in patients who don't achieve MDR negativity, didn't receive intensive induction, or have high risk cytogenetic and molecular features. Despite improved responses with tyrosine kinase inhibitors (TKIs) in Philadelphia positive (Ph+) ALL, allo-HSCT remains standard. Matched sibling donors are the optimal graft source, but other sources are valid alternatives. There is no single optimal conditioning regimen and retrospective studies found myeloablative and reduced intensity regimens to be comparable. Following allo-HSCT, there is no role for maintenance therapy in Philadelphia-negative ALL. In Ph+ ALL, maintenance TKIs improve outcomes. The integration of targeted and immunotherapies in the peri-transplant period holds potential for improved outcomes.

Clinical Course and Complications of Catheter and Non-Catheter-Related Upper Extremity Deep Vein Thrombosis in Patients with Cancer.

Patients with cancer have an increased risk of venous thromboembolism. Upper extremity venous system is a peculiar site, and little is known about the clinical course in patients with cancer. Electronic medical records were searched for patients with cancer with a diagnosis of upper extremity venous thrombosis. Individual patient data were reviewed. Eighty-seven patients were identified, and the median age was 52.4. The most common underlying malignancies were breast (23.0%), colorectal (18.4%), and gastroesophageal (18.4%). Median time from cancer diagnosis to upper extremity venous thromboembolism (UEDVT) was 3.44 months. Subclavian vein was the most common involved site (56.3%) and 54.0% patients had a central venous catheter; 50.6% of patients developed a complication; pulmonary embolism (PE) in 9.2%, superior vena cava (SVC) syndrome in 14.9%, and 26.4% had postthrombotic syndrome. In patients with isolated single vein thrombosis, complications were higher in the subset with internal jugular vein involvement compared to other sites (68.2% vs 52.2%) as were complications in patients with non-catheter-related thrombosis compared to patients with a central venous catheter in place (55% vs 27.7%). Median overall survival from time of cancer and UEDVT diagnoses was 29.6 and 13.25 months, respectively. In conclusion, UEDVT is an uncommon event. Around 50% developed a complication including PE, SVC or postthrombotic syndromes. Larger studies are needed to better identify risks associated with thrombosis and the best therapeutic approach and duration in this unique subset of patients with cancer.

The Application of Current Proposed Venous Thromboembolism Risk Assessment Model for Ambulatory Patients With Cancer.

Venous thromboembolism (VTE) is a commonly encountered problem in patients with cancer. In recent years, cancer treatment paradigm has shifted with most therapy offered in ambulatory outpatient settings. Excess of half VTEs in patients with cancer occur in outpatient settings without prior hospitalization, where current practice guidelines do not recommend routine prophylaxis. Risk assessment models (RAMs) for VTE in such patients were recently introduced. This study aims to assess the practical application of one of these models in clinical practice. Medical records and hospital electronic database were searched for patients with cancer having VTE. Known risk factors were collected, and risk assessment was done using the Khorana RAM. Over a 10-year period, 346 patients developed VTE in ambulatory settings. Median age was 57 and 59.0% were females. Lower extremities were involved in 196 (56.6%), while 96 (27.7%) had pulmonary embolism. Most (76.6%) patients had stage IV disease, only 9.0% had stage I or II disease. Only 156 (45.1%) patients were on active chemotherapy, for whom Khorana risk assessment score was calculated. In these patients, high risk was identified in 31 (19.9%) patients, while 81 (51.9%) had intermediate risk and 44 (28.2%) had low risk. No patients were on prophylaxis prior to VTE. Most ambulatory patients with cancer who developed VTE were not on chemotherapy, and many of those who were on active treatment had low Khorana risk scores. This illustrates the need to modify the model or develop a new one that takes into consideration this group of patients.

Four cycles of adriamycin and cyclophosphamide followed by four cycles of docetaxel (NSABP-B27) with concomitant trastuzumab as neoadjuvant therapy for high-risk, early-stage, HER2-positive breast cancer patients.

BACKGROUND: The majority of breast cancer patients in Jordan are diagnosed at a young age and present with metastatic or locally advanced disease. The National Surgical Adjuvant Breast and Bowel Project Protocol B27 (NSABP-B27) (four cycles of adriamycin and cyclophosphamide [AC] followed by four cycles of docetaxel) is a standard neoadjuvant regimen in our institution. In this study, we report the efficacy of adding trastuzumab to docetaxel in this regimen for high-risk human epidermal growth factor receptor 2 (HER2)-positive early-stage disease. PATIENTS AND METHODS: Consecutive HER2-positive breast cancer patients treated with this regimen were included. Treatment was given at standard doses and schedules as reported in NSABP-B27. Trastuzumab was given with docetaxel and then continued for 1 year. RESULTS: A total of 121 patients (mean age 45.4 years) were included. The majority had high-risk features including large tumor size, positive axillary lymph nodes, and grade III disease. Three patients did not complete the planned cycles of AC due to a lack of response. Eight (6.6%) patients missed at least one cycle of docetaxel. Following neoadjuvant therapy, 119 patients underwent surgery, of whom 59 (49.6%) patients achieved pathological complete response. The response was higher in node-negative patients (64.0 vs 45.7%; P=0.03) and in hormone receptor-negative disease patients (69.7 vs 41.9%; P=0.018). Breast-conserving surgery was performed in 21.5% of the patients. The median disease-free survival (DFS) for the whole group was not reached while the 3- and 5-year DFS rates were 84.2 and 74.1%, respectively. CONCLUSION: Trastuzumab added to the NSABP-B27 regimen is a unique combination. When used in high-risk patients, as in our study, outcomes similar to reported data were achieved without unexpected toxicities.

Anti-TNF therapy in Jordan: a focus on severe infections and tuberculosis.

BACKGROUND: A high rate of infection has been reported in patients receiving treatment with anti-tumor necrosis factor (anti-TNF). This study describes the rate of and risk factors for serious infections in patients receiving anti-TNF agents in Jordan. METHODS: This retrospective observational study was conducted at a large tertiary referral center in the north of Jordan. Between January 2006 and January 2012, 199 patients who received an anti-TNF agent (infliximab, adalimumab, or etanercept) were included. Patients received the anti-TNF treatment for rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, or other conditions. A serious infection was defined as any bacterial, viral, or fungal infection that required hospitalization, administration of appropriate intravenous antimicrobial therapy, and temporary withholding of anti-TNF treatment. RESULTS: The mean duration of anti-TNF treatment was 26.2 months. Steroids were used in 29.1% of patients, while 54.8% were given additional immunosuppressant therapy (methotrexate or azathioprine). Only one anti-TNF agent was given in 70.4% of patients, while 29.6% received different anti-TNF agents for the duration of treatment. Serious infections were documented in 39 patients (19.6%), including respiratory tract infections (41%), urinary tract infections (30.8%), and skin infections (20.5%), and extrapulmonary tuberculosis in three patients (7.7%). Exposure to more than one anti-TNF agent was the only factor associated with a significant increase in the rate of infection (relative risk 1.9, 95% confidence interval 1.06-4.0, P=0.03). CONCLUSION: Serious infections, including tuberculosis, were a common problem in patients receiving anti-TNF agents, and exposure to more than one anti-TNF agent increased the risk of serious infection.