Fiona L. Dignan

Diagnosis and management of acute graft-versus-host disease

A joint working group established by the Haemato‐oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Society for Bone Marrow Transplantation (BSBMT) has reviewed the available literature and made recommendations for the diagnosis and management of acute graft‐versus‐host disease. This guideline includes recommendations for the diagnosis and grading of acute graft‐versus‐host disease as well as primary treatment and options for patients with steroid‐refractory disease. The goal of treatment should be effective control of graft‐versus‐host disease while minimizing risk of toxicity and relapse.

BCSH/BSBMT guideline: diagnosis and management of veno‐occlusive disease (sinusoidal obstruction syndrome) following haematopoietic stem cell transplantation

It is recommended that the diagnosis of veno‐occlusive disease (sinusoidal obstruction syndrome) [VOD (SOS)] be based primarily on established clinical criteria (modified Seattle or Baltimore criteria) (1A). Ultrasound imaging may be helpful in the exclusion of other disorders in patients with suspected VOD (SOS) (1C). It is recommended that liver biopsy be reserved for patients in whom the diagnosis of VOD (SOS) is unclear and there is a need to exclude other diagnoses (1C). It is recommended that liver biopsies are undertaken using the transjugular approach in order to reduce the risks associated with the procedure (1C). It is suggested that the role of plasminogen activator inhibitor 1 levels remains an area for further research but that these levels should not form part of the routine diagnostic work‐up for VOD (SOS) at present (2C).

Diagnosis and management of chronic graft-versus-host disease.

A joint working group established by the Haemato‐oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Society for Bone Marrow Transplantation (BSBMT) has reviewed the available literature and made recommendations for the diagnosis and management of chronic graft‐versus‐host disease (GvHD). This guideline includes recommendations for the diagnosis and staging of chronic GvHD as well as primary treatment and options for patients with steroid‐refractory disease. The goal of treatment should be the effective control of GvHD while minimizing the risk of toxicity and relapse.

Prophylactic defibrotide in allogeneic stem cell transplantation: minimal morbidity and zero mortality from veno-occlusive disease

Veno-occlusive disease (VOD) is a common and high-risk complication of allogeneic stem cell transplantation (SCT). Defibrotide has recently been used successfully to treat the disorder. We report on 58 patients who received defibrotide prophylaxis without concurrent heparin. No patients fulfilled the Baltimore criteria for VOD or died of the condition within 100 days of SCT. None of this group developed haemorrhagic complications secondary to defibrotide. These observations suggest that prophylaxis with defibrotide alone may reduce the incidence of VOD post-SCT although a randomised controlled trial is warranted to further evaluate its role.

Measuring Therapeutic Response in Chronic Graft-versus-Host Disease. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease

In 2005, the National Institutes of Health (NIH) Chronic Graft-versus-Host Disease (GVHD) Consensus Response Criteria Working Group recommended several measures to document serial evaluations of chronic GVHD organ involvement. Provisional definitions of complete response, partial response, and progression were proposed for each organ and for overall outcome. Based on publications over the last 9 years, the 2014 Working Group has updated its recommendations for measures and interpretation of organ and overall responses. Major changes include elimination of several clinical parameters from the determination of response, updates to or addition of new organ scales to assess response, and the recognition that progression excludes minimal, clinically insignificant worsening that does not usually warrant a change in therapy. The response definitions have been revised to reflect these changes and are expected to enhance reliability and practical utility of these measures in clinical trials. Clarification is provided about response assessment after the addition of topical or organ-targeted treatment. Ancillary measures are strongly encouraged in clinical trials. Areas suggested for additional research include criteria to identify irreversible organ damage and validation of the modified response criteria, including in the pediatric population.

Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation

Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate (>80%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation.

An early CT-diagnosis-based treatment strategy for invasive fungal infection in allogeneic transplant recipients using caspofungin first line: an effective strategy with low mortality

Empirical antifungal therapy is frequently used in allogeneic transplant patients who have persistent febrile neutropenia and can be associated with high cost, toxicity and breakthrough infections. There are limited reports of strategies for early diagnosis of invasive fungal infection (IFI) and, to our knowledge, no reports of treatment strategies based only on high-resolution computerized tomography (HRCT) scans. We used an early treatment strategy for IFI in 99 consecutive patients undergoing allogeneic transplantation. Patients received caspofungin if they had antibiotic-resistant neutropenic fever for more than 72 h and a positive HRCT scan. Fifty-three of 99 patients (54%) had antibiotic-resistant neutropenic fever at 72 h and would have received parenteral antifungal treatment if an empirical approach had been used. The HRCT-based strategy reduced the use of parenteral antifungal agents to 17/99 patients (17%), a 68% reduction. No subsequent diagnoses of IFI occurred within 100 days in patients with a negative HRCT. Only one patient died from IFI within 100 days. These data suggest that this non-empirical strategy may be feasible and that caspofungin may be effective in this setting. A randomized controlled trial is warranted to further assess these results.

Efficacy of bimonthly extracorporeal photopheresis in refractory chronic mucocutaneous GVHD

Extracorporeal photopheresis (ECP) has become a recognised treatment for steroid-refractory chronic GVHD (cGVHD), but the optimal frequency and duration of treatment are yet to be established. We report on 82 consecutive patients with mucocutaneous cGVHD who received a bimonthly regimen of ECP treatment for two consecutive days, which could be subsequently tapered to a monthly regimen depending on response. Patients were steroid-refractory, steroid-dependent or steroid-intolerant, and 29 (35%) had multiorgan involvement. The median duration of treatment was 330 days (42–987). The median number of ECP cycles was 15 (1.5–32). Response was assessed by clinical assessment and reduction in immunosuppression after 6 months. 69/82 (84%) had completed 6 months of ECP and 65/69 (94%) had ⩾50% improvement in symptoms and signs of cGVHD. A total of 77% of patients who completed 6 months of ECP had a reduction in immunosuppression dose and 80% had decreased their steroid dose (27.5% stopped, 30% had ⩾75% reduction, 17.5% had ⩾50% reduction and 25% had <50% reduction). OS at 3 years from the start of ECP was 69%. This study reports the largest series of patients receiving bimonthly ECP treatment for cGVHD, and confirms that ECP allows successful reduction of immunosuppression.

Organ-specific management and supportive care in chronic graft-versus-host disease

A joint working group established by the Haemato‐oncology subgroup of the British Committee for Standards in Haematology and the British Society for Bone Marrow Transplantation has reviewed the available literature and made recommendations for the supportive care and management of organ‐specific complications of chronic graft‐versus‐host disease (cGvHD). This guideline includes recommendations for the specific therapy of skin, oral, liver, gut, lung, ocular and genital manifestations of cGvHD and for the supportive care of these patients, including vaccinations and prophylaxis against infection. The goal of treatment should be effective control of GvHD while minimizing the risk of toxicity and relapse.

Long-term Trends in Thyroid Carcinoma: A Population-Based Study in Olmsted County, Minnesota, 1935-1999

OBJECTIVE To determine whether there was a significant increase in the incidence of thyroid carcinoma in Olmsted County, Minnesota, that may be attributed to the widespread use of therapeutic head and neck irradiation between 1920 and the 1950s or to exposure to atomic fallout at the Nevada Test Site in the 1960s. METHODS Rochester Epidemiology Project resources were used to identify potential cases of thyroid carcinoma among residents of Olmsted County between 1935 and 1984. We extended this earlier study through 1999. RESULTS During the study period, thyroid carcinoma was newly diagnosed in 263 residents. In women, the age-adjusted incidence increased from 2.7 per 100,000 person-years (p-y) in 1935-1949 to 9.2 per 100,000 p-y in 1990-1999 (P = .001); In men, the rate increased from 0.8 to 5.0 per 100,000 p-y (P = .007). However, most of the increase occurred before 1965 and remained relatively stable thereafter. Similar trends were observed for papillary carcinoma alone. CONCLUSION Although the Incidence of thyroid carcinoma increased significantly between 1935 and 1964, no significant Increases have been seen since 1965, suggesting that neither atmospheric atomic fallout from the Nevada Test Site nor use of ionizing radiation to treat conditions of the head and neck significantly affected the incidence of thyroid carcinoma in Olmsted County.