Fred Hutchinson transplant program pioneers treatment options for minority patients struggling to find a donor match.

Patients from ethnic minority and mixed-racial backgrounds are less likely to receive a lifesaving bone marrow transplant than Caucasian patients with the same disease due to lack of matching donors, according to the National Marrow Donor Program (NMDP).

The likelihood of a patient finding a bone marrow donor match is highly dependent on genetic similarities between the patient and donor. Seventy percent of patients in need of a transplant do not have a matching donor in their family, according to Be The Match, operated by the NMDP. These patients must instead turn to a donor registry or alternative methods for treatment. Unfortunately, few minority patients have either a matched family member or an identified matched unrelated donor. This is due to complex genetic factors and low donor-registration numbers.

Seattle Cancer Care Alliance (SCCA) is working with Fred Hutchinson Cancer Research Center to pioneer new lifesaving transplant procedures to reduce the need for matching bone marrow donors by providing bone marrow or blood stem cell transplants to patients who would not typically be candidates due to lack of a matching donor.

“The striking difference in donation levels echoes the need to raise awareness of the bone marrow and umbilical cord blood donation registries, while continuing the development of transplant programs that expand the availability of these life-saving treatment to more people,” said SCCA’s Colleen Delaney, M.D., MSc, director of the Cord Blood Transplant Program and associate member of the Clinical Research Division at Fred Hutch. “Thanks to innovative treatments developed at Fred Hutch and available today through the SCCA Transplant Program, nearly all patients in need of a bone marrow or blood stem cell transplant will be able to identify a donor. Our goal is to make sure every patient who needs a blood stem cell transplant will get one with survival rates that are equivalent to conventional unrelated donors.”

Delaney is a renowned expert in the development of novel methods to grow cord blood stem cells in the laboratory and has pioneered steps toward reducing the risk of life-threatening infections in patients who receive a cord blood transplant.

Cord blood is unique from other sources of stem cells for bone marrow transplants. This leftover blood in the umbilical cord, which is collected immediately after birth without harm to the infant or mother, contains immune cells that are protected from foreign invaders such as bacteria and viruses. Due to this protection, these “naive” immune cells do not perceive a patient’s unmatched stem cells as a threat. This means cord blood transplants do not require a near identical genetic match between donor and patient for successful treatment. Most cord blood transplants involve a genetically mismatched donor and patient.

While cord blood transplant recipients have been at high risk for early post-transplant complications due to the low number of cells available in a single cord blood unit, Delaney’s innovative methods for expanding the number of cord blood cells per unit prior to transplant have been able to reduce such risks.

Jessie Quinn, a patient of half-Caucasian and half-African American ancestry, knows first-hand the lifesaving promise of expanded cord blood cells method. A survivor of acute myelogenous leukemia (AML), Quinn was the first patient to participate in an SCCA clinical study led by Delaney using her novel approach with expanded cord blood cells. Quinn credits her survival to the Fred Hutchinson Transplant Program at SCCA and her doctors’ dedication to developing innovative options for patients unable to find a donor match.

The Fred Hutchinson Transplant Program at SCCA also provides successful haploidentical transplants for patients unable to find a relative who is a perfect match. Led by Paul O’Donnell, M.D., Ph.D., medical director of SCCA’s Adult Transplant Service and researcher in the Clinical Research Division at Fred Hutch, haploidentical transplants are performed when a patient’s relative offers a partial donor match. Through advances in drug therapies, physicians are able to control the adverse immune system responses that previously prevented these partially matched relatives from serving as donors. Haploidentical transplants are especially beneficial for pediatric patients using their parents or siblings as donors.

“Patients should not give up hope if they run into difficulties finding a donor,” O’Donnell said. “At SCCA, we are committed to turning cancer patients into cancer survivors. Sometimes that means exploring alternative options and looking into clinical trials to help our patients conquer cancer. The Fred Hutchinson Transplant Program at SCCA offers patients additional treatment plans when they often believe they are out of options.”

O’Donnell is currently leading a multi-center, randomized clinical trial to determine the effectiveness of double unrelated umbilical cord blood transplants versus haploidentical related bone marrow transplants in people with leukemia or lymphoma. He is actively recruiting patients. A multi-center randomized Phase II study led by Delaney is also currently recruiting patients to evaluate the clinical efficacy of giving study participants umbilical cord blood cells that have been expanded in the laboratory to increase the number of cells available for the transplant.

SCCA has been at the forefront of revolutionizing transplant treatment options since the clinical use of bone marrow and stem cell transplantation was first developed at the Fred Hutch more than 40 years ago. One of its founders, E. Donnall Thomas, M.D., won the 1990 Nobel Prize in physiology or medicine for this groundbreaking work. As a result of Thomas’ innovation, the world’s millionth blood stem cell transplant procedure took place in January of this year. To date, SCCA’s doctors have performed more than 14,000 bone marrow transplants and the clinic consistently ranks among the country’s top transplant centers in one-year patient survival rates.

Fred Hutch continues to lead transplant research and has pioneered the use of transplants to treat autoimmune disorders and other, non-cancerous diseases. By developing “mini-transplants” that use minimal doses of radiation resulting in reduce side effects, older patients who were not previously eligible for transplants now have an additional treatment option.

For more information about the Fred Hutchinson Transplant Program at SCCA, please visit:
http://www.seattlecca.org/diseases/bone-marrow-transplant-overview.cfm
.

Source: Fred Hutchinson Cancer Research Center

 

 

Earlier Mortality with Restless Legs Syndrome.

Results from a Health Professionals Follow-up Study analysis support an association.

To examine the controversial notion that restless legs syndrome (RLS) is associated with increased mortality, researchers tracked mortality among 18,425 participants in the Health Professionals Follow-up Study (HPFS) who answered a standardized questionnaire about the potential presence of RLS. Patients with diabetes, arthritis, or renal failure were excluded. The investigators documented deaths comprehensively using vital statistics, the National Death Index, family reports, and the postal system.

A total of 2765 deaths occurred between 2002 and 2010. After adjustment for age, RLS was associated with a significant increase in mortality (hazard ratio [HR], 1.39). The association was mildly weakened after adjustment for factors such as body-mass index, lifestyle, other chronic diseases, amount of sleep, and other sleep-related disorders (adjusted HR, 1.30). After excluding other chronic diseases associated with RLS (e.g., Parkinson disease), the association remained significant (adjusted HR, 1.92). Age, weight, short sleep duration, smoking, poor exercise, and a less healthy diet did not affect the association. The study did not include blood testing for iron deficiency.

Comment: Restless legs syndrome affects an estimated 5% to 10% of the population. Because of the association between RLS and chronic conditions such as renal disease, disentangling the mortality risk of RLS has been challenging. Strengths of the current study include accounting for all potential comorbidities such as diabetes, cardiovascular disease, and kidney disease, and establishment of the RLS diagnosis through the use of standardized questions. Not only was there an increased mortality with RLS in general, but this increased mortality occurred more commonly when there was concomitant respiratory dysfunction, endocrine disease, nutritional issues, or presence of metabolic disease or an immunologic disorder. Although observational studies do not prove causality, clinicians should be aware of the increased mortality risk in any patient presenting with RLS-type symptoms. This study was limited by the lack of information on use of dopaminergic medication, which is the best treatment for RLS. Neurologists and primary care doctors should to work together when treating RLS patients. Treating primary RLS symptoms and addressing sleep, blood pressure, cardiovascular, and other comorbidities could be helpful. However, we do not yet understand how to modify the increased mortality risk in patients with RLS.

Source: Journal Watch Neurology

 

Are isometric exercises a good way to build strength?

Isometric exercises are contractions of a particular muscle or group of muscles. During isometric exercises, the muscle doesn’t noticeably change length and the affected joint doesn’t move. Isometric exercises don’t effectively build strength but can help maintain muscle strength — most often in a rehabilitative setting.

Because isometric exercises are done in one position without movement, they’ll improve strength in only one particular position. You’d have to do various isometric exercises through your limb’s whole range of motion to improve muscle strength across the range. In addition, since isometric exercises are done in a static position, they won’t help improve speed or athletic performance.

Isometric exercises may be helpful to someone who’s been injured or has a condition such as arthritis, which could make movement painful or be aggravated by using muscles to move a joint through the full range of motion. For instance, if you injure your rotator cuff, your doctor or physical therapist might initially recommend isometric exercises involving the group of muscles that helps stabilize the shoulder to maintain shoulder strength during recovery.

It’s also important to note that isometric exercises generally aren’t recommended for people who have high blood pressure or heart problems, because the large increase in muscle tension caused by isometric exercises can dramatically increase blood pressure.

Source:
http://www.mayoclinic.com

 

 

Menopause weight gain: Stop the middle age spread.

Most women gain weight as they age, but excess pounds aren’t inevitable. To minimize menopause weight gain, step up your activity level and enjoy a healthy diet.

As you get older, you might notice that maintaining your usual weight becomes more difficult. In fact, many women gain weight around the menopause transition.

Menopause weight gain isn’t inevitable, however. You can reverse course by paying attention to healthy-eating habits and leading an active lifestyle.

What causes menopause weight gain?

The hormonal changes of menopause might make you more likely to gain weight around your abdomen than around your hips and thighs. Hormonal changes alone don’t necessarily trigger menopause weight gain, however. Instead, the weight gain is usually related to aging, as well as lifestyle and genetic factors.

For example, muscle mass typically diminishes with age, while fat increases. Loss of muscle mass decreases the rate at which your body uses calories, which can make it more challenging to maintain a healthy weight. If you continue to eat as you always have and don’t increase your physical activity, you’re likely to gain weight.

Genetic factors also might play a role in menopause weight gain. If your parents or other close relatives carry extra weight around the abdomen, you’re likely to do the same.

Sometimes factors such as the stress of children leaving — or returning — home, divorce, the death of a spouse, or other life changes might change your diet or exercise habits and contribute to menopause weight gain.

How risky is weight gain after menopause?

Menopause weight gain can have serious implications for your health. Excess weight increases the risk of heart disease, type 2 diabetes and various types of cancer, including colorectal cancer and breast cancer.

What’s the best way to prevent weight gain after menopause?

There’s no magic formula for preventing — or reversing — menopause weight gain. Simply stick to weight-control basics:

• Move more. Aerobic activity can help you shed excess pounds and maintain a healthy weight. Strength training counts, too. As you gain muscle, your body burns calories more efficiently — which makes it easier to control your weight. For most healthy adults, the Department of Health and Human Services recommends moderate aerobic activity, such as brisk walking, for at least 150 minutes a week or vigorous aerobic activity, such as jogging, for at least 75 minutes a week. In addition, strength training exercises are recommended at least twice a week. If you want to lose weight or meet specific fitness goals, you might need to exercise more.
• Eat less. To maintain your current weight — let alone lose excess pounds — you might need about 200 fewer calories a day during your 50s than you did during your 30s and 40s. To reduce calories without skimping on nutrition, pay attention to what you’re eating and drinking. Choose more fruits, vegetables and whole grains. Opt for lean sources of protein.
• Seek support. Surround yourself with friends and loved ones who’ll support your efforts to eat a healthy diet and increase your physical activity. Better yet, team up and make the lifestyle changes together.

Remember, successful weight loss at any stage of life requires permanent changes in diet and exercise habits. Take a brisk walk every day. Try a yoga class. Swap cookies for fresh fruit. Split restaurant meals with a friend. Commit to the changes and enjoy a healthier you!

 

Source:
http://www.mayoclinic.com

 

Obstructive sleep apnoea and type 2 diabetes mellitus: a bidirectional association.

Obstructive sleep apnoea and type 2 diabetes are common medical disorders that have important clinical, epidemiological, and public health implications. Research done in the past two decades indicates that obstructive sleep apnoea, through the effects of intermittent hypoxaemia and sleep fragmentation, could contribute independently to the development of insulin resistance, glucose intolerance, and type 2 diabetes. Conversely, type 2 diabetes might increase predisposition to, or accelerate progression of, obstructive and central sleep apnoea, possibly through the development of peripheral neuropathy and abnormalities of ventilatory and upper airway neural control. Although more research is needed to clarify the mechanisms underlying the bidirectional association between the two disorders, their frequent coexistence should prompt all health-care professionals to embrace clinical practices that include screening of a patient presenting with one disorder for the other. Early identification of obstructive sleep apnoea in patients with metabolic dysfunction, including type 2 diabetes, and assessment for metabolic abnormalities in those with obstructive sleep apnoea could reduce cardiovascular disease risk and improve the quality of life of patients with these chronic diseases.

Source: lancet

 

 

Magnesium sulphate in acute severe asthma in children (MAGNETIC): a randomised, placebo-controlled trial.

Background

Little evidence is available for the effect of nebulised magnesium sulphate (MgSO4) in acute asthma in children. We assessed the effect of MgSO4 treatment in children with severe acute asthma.

Methods

In this randomised placebo-controlled, multi-centre, parallel trial, we enrolled children (aged 2—16 years) with severe acute asthma who did not respond to standard inhaled treatment from 30 hospitals in the UK. Children were randomly allocated (1:1) to receive nebulised salbutamol and ipratropium bromide with either 2·5 mL of isotonic MgSO4 (250 mmol/L; 151 mg per dose; MgSO4 group) or 2·5 mL of isotonic saline (placebo group) on three occasions at 20-min intervals. Randomisation was done with a computer-generated randomisation sequence, with random block sizes of two to four. Both patients and researchers were masked to treatment allocation. The primary outcome measure was the Yung Asthma Severity Score (ASS) at 60 min post-randomisation. We used a statistical significance level of p<0·05 for a between-group difference, but regarded a between-group difference in ASS of 0·5 as the minimal clinically significant treatment effect. Analysis was done by intention to treat. This trial is registered with controlled-trials.com, number ISRCTN81456894.

Findings

Between Jan 3, 2009, and March 20, 2011, we recruited and randomly assigned 508 children to treatment: 252 to MgSO4and 256 to placebo. Mean ASS at 60 min was lower in the MgSO4 group (4·72 [SD 1·37]) than it was in the placebo group (4·95 [SD 1·40]; adjusted difference −0·25, 95% CI −0·48 to −0·02; p=0·03). This difference, however, was not clinically significant. The clinical effect was larger in children with more severe asthma exacerbation (p=0·03) and those with symptoms present for less than 6 h (p=0·049). We detected no difference in the occurrence of adverse events between groups.

Interpretation

Overall, nebulised isotonic MgSO4, given as an adjuvant to standard treatment, did not show a clinically significant improvement in mean ASS in children with acute severe asthma. However, the greatest clinical response was seen in children with more severe attacks (SaO2<92%) at presentation and those with preceding symptoms lasting less than 6 h.

Source: lancet

 

Intravenous or nebulised magnesium sulphate versus standard therapy for severe acute asthma (3Mg trial): a double-blind, randomised controlled trial.

Background

Previous studies suggested intravenous or nebulised magnesium sulphate (MgSO4) might improve respiratory function in patients with acute asthma. We aimed to determine whether intravenous or nebulised MgSO4 improve symptoms of breathlessness and reduce the need for hospital admission in adults with severe acute asthma.

Methods

In our double-blind, placebo-controlled trial, we enrolled adults (aged ≥16 years) with severe acute asthma at emergency departments of 34 hospitals in the UK. We excluded patients with life-threatening features or contraindication to study drugs. We used a central randomisation system to allocate participants to intravenous MgSO4 (2 g in 20 min) or nebulised MgSO4 (three 500 mg doses in 1 h) alongside standard therapy including salbutamol, or placebo control plus standard therapy alone. We assessed two primary outcome measures in all eligible participants who started treatment, according to assigned treatment group: the proportion of patients admitted to hospital within 7 days and breathlessness measured on a 100 mm visual analogue scale (VAS) in the 2 h after initiation of treatment. We adjusted for multiple testing using Simes’s method. The trial stopped before recruitment was completed because funding expired. This study is registered, number ISRCTN04417063.

Findings

Between July 30, 2008, and June 30, 2012, we recruited 1109 (92%) of 1200 patients proposed by the power calculation. 261 (79%) of 332 patients allocated nebulised MgSO4 were admitted to hospital before 7 days, as were 285 (72%) of 394 patients allocated intravenous MgSO4 and 281 (78%) of 358 controls. Breathlessness was assessed in 296 (89%) patients allocated nebulised MgSO4, 357 (91%) patients allocated intravenous MgSO4, and 323 (90%) controls. Rates of hospital admission did not differ between patients treated with either form of MgSO4 compared with controls or between those treated with nebulised MgSO4 and intravenous MgSO4. Change in VAS breathlessness did not differ between active treatments and control, but change in VAS was greater for patients in the intravenous MgSO4 group than it was in the nebulised MgSO4 group (5·1 mm, 0·8 to 9·4; p=0·019). Intravenous or nebulised MgSO4 did not significantly decrease rates of hospital admission and breathlessness compared with placebo: intravenous MgSO4 was associated with an odds ratio of 0·73 (95% CI 0·51 to 1·04; p=0·083) for hospital admission and a change in VAS breathlessness of 2·6 mm (—1·6 to 6·8; p=0·231) compared with placebo; nebulised MgSO4 was associated with an odds ratio of 0·96 (0·65 to 1·40; p=0·819) for hospital admission and a change in VAS breathlessness of −2·6 mm (—7·0 to 1·8; p=0·253) compared with placebo.

Source: lancet

 

 

Pulmonary hypertension in β thalassaemia.

Pulmonary hypertension is one of the leading causes of morbidity and mortality in patients with haemolytic disorders and is a frequent finding in echocardiographic screening of patients with β thalassaemia. Substantial progress has been made in understanding of the multifactorial pathophysiology of pulmonary hypertension in β thalassaemia. Haemolysis, reduced nitric oxide bioavailability, iron overload, and hypercoagulopathy are among the main pathogenetic mechanisms. Various disease-directed therapeutic methods, such as transfusion, chelation, and splenectomy, have important roles in the development of pulmonary hypertension in β thalassaemia. Studies investigating the prevalence of pulmonary hypertension in β thalassaemia are mostly based on echocardiographic findings, and are thus limited by the scarcity of information derived from right heart catheterisation. Invasive pulmonary haemodynamic data are needed to clarify the true prevalence of pulmonary hypertension in β thalassaemia, to better understand the underlying pathophysiology and risk factors, and to define the optimum therapy for this devastating complication.

Source: lancet

Reproductive organ involvement in non-Hodgkin lymphoma during pregnancy: a systematic review.

Data for pregnancy-associated non-Hodgkin lymphoma are limited to case reports, making it difficult to define this disorder. We did a systematic search for articles published between 1967 and 2011 with the aim to determine the characteristics, management, and outcome of pregnancy-associated non-Hodgkin lymphoma. We identified 121 patients from 74 papers. Most patients with stage information available presented with stage IV disease (75%, 82 of 108 patients). Patients were classified into three clinical groups; those with indolent lymphomas accounted for 5% (five of 108), aggressive lymphomas (diffuse large B-cell lymphoma and T-cell lymphomas) made up 48% of patients (52 of 108), and highly aggressive lymphomas (Burkitt’s lymphoma, immunoblastic lymphoma, and unspecified highly aggressive lymphomas) accounted for 47% of patients (51 of 108). Reproductive organ involvement (breast, ovary, uterus, placenta) was reported in 49% of 110 patients with information available on extranodal involvement, and prevailed in endemic Burkitt’s lymphoma (100%, 19 of 19), followed by non-endemic Burkitt lymphoma (70%, 14 of 20), immunoblastic lymphoma (67%, two of three), peripheral T-cell lymphoma (46%, six of 13), and indolent (40%, two of five) and diffuse large cell lymphoma (23%, nine of 40). Most patients received antepartum (45%, 55 of 121) or postpartum therapy (45%, 54 of 121), resulting in 6-month survival of 53% for mothers and a livebirth rate of 83%. Pregnancy-associated non-Hodgkin lymphoma has unique clinical characteristics with frequent reproductive organ involvement. Collaborative prospective studies are needed to further characterise pathophysiological and clinical aspects of this complication.

Source: lancet

 

 

Galactomannan and PCR versus culture and histology for directing use of antifungal treatment for invasive aspergillosis in high-risk haematology patients: a randomised controlled trial.

Background

Empirical treatment with antifungal drugs is often used in haematology patients at high risk of invasive aspergillosis. We compared a standard diagnostic strategy (culture and histology) with a rapid biomarker-based diagnostic strategy (aspergillus galactomannan and PCR) for directing the use of antifungal treatment in this group of patients.

Methods

In this open-label, parallel-group, randomised controlled trial, eligible patients were adults undergoing allogeneic stem-cell transplantation or chemotherapy for acute leukaemia, with no history of invasive fungal disease. Enrolled patients were randomly assigned (1:1) by a computer-generated schedule to follow either a standard diagnostic strategy (based on culture and histology) or a biomarker-based diagnostic strategy (aspergillus galactomannan and PCR) to direct treatment with antifungal drugs. Patients, were followed up for 26 weeks or until death. Masking of the use of different diagnostic tests was not possible for patients, treating physicians, or investigators. The primary endpoint was empirical treatment with antifungal drugs in the 26 weeks after enrolment (for the biomarker-based diagnostic strategy, a single postive galactomannan or PCR result was deemed insufficient to confirm invasive aspergillosis, so treatment in this context was classified as empirical). This outcome was assessed by an independent data review committee from which the study allocations were masked. Analyses were by intention to treat and included all enrolled patients. This study is registered withClinicalTrial.gov, number NCT00163722.

Findings

240 eligible patients were recruited from six Australian centres between Sept 30, 2005, and Nov 19, 2009. 122 were assigned the standard diagnostic strategy and 118 the biomarker-based diagnostic strategy. 39 patients (32%) in the standard diagnosis group and 18 (15%) in the biomarker diagnosis group received empirical antifungal treatment (difference 17%, 95% CI 4—26; p=0·002). The numbers of patients who had hepatotoxic and nephrotoxic effects did not differ significantly between the standard diagnosis and biomarker diagnosis groups (hepatotoxic effects: 21 [17%] vs 12 [10%], p=0·11; nephrotoxic effects: 52 [43%] vs 60 [51%], p=0·20).

Interpretation

Use of aspergillus galactomannan and PCR to direct treatment reduced use of empirical antifungal treatment. This approach is an effective strategy for the management of invasive aspergillosis in high-risk haematology patients.

Source: lancet